Download Autofluorescence in blunt trauma Cataract surgery in

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Autofluorescence in blunt trauma
Cataract surgery in Paraguay
Lutein-based dye for capsulorhexis
Conjunctival melanoma in Mexico
Pediatric cataracts
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1. Morgan PB et al. Ocular physiology and comfort in neophyte subjects fitted with daily disposable silicone hydrogel contact lenses. Cont. Lens Anterior Eye. 2013 Jun;36(3):118-25. 2. MEYLER, J.; VEYSAND , J. Do new daily
disposable lenses improve patient comfort? Optician. 2006; 6046(231): 34-6 3. RUSTON , D.; MOODY, K. A daily disposable designed for healthy contact lens wear. Optician. 01.10.09: 34-37CLMTruEye.
Narafilcon A - 111-DAY ACUVUE® TRUEYE® com HYDRACLEAR® 1: Reg.ANVISA 80148620065. VENDA SOB PRESCRIÇÃO MÉDICA REFRACIONAL. Johnson & Johnson Industrial Ltda. Rod. Pres. Dutra, Km 154 - S. J. dos
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Referências Bibliográficas: 1) Patente de Laboratoires Théa. 2) Bula do produto: Hyabak. Registro MS nº 8042140002.
HYABAK®. Solução sem conservantes para hidratação e lubrificação dos olhos e lentes de contacto. Frasco ABAK®. COMPOSIÇÃO: Hialuronato de sódio 0,15g. Cloreto de sódio, trometamol, ácido clorídrico, água para preparações injetáveis q.b.p. 100 mL. NOME E MORADA DO FABRICANTE: Laboratoires Théa, 12 rue Louis
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esteja danificado. MANTER FORA DO ALCANCE DAS CRIANÇAS. INTERAÇÕES: É conveniente aguardar 10 minutos entre a administração de dois produtos oculares. COMO UTILIZAR ESTE DISPOSITIVO: POSOLOGIA: 1 gota em cada olho durante o dia, sempre que necessário.
Nos utilizadores de lentes: uma gota em cada lente ao colocar e retirar as lentes e também sempre que necessário ao longo do dia. MODO E VIA DE ADMINISTRAÇÃO: INSTILAÇÃO OCULAR. STERILE A - Para uma utilização correta do produto é necessário ter em conta determinadas
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cima. O tempo de aparição de uma gota é mais longo do que com um frasco clássico. Tapar o frasco após a utilização. Ao colocar as lentes de contato: instilar uma gota de HYABAK® na concavidade da lente. FREQUÊNCIA E MOMENTO EM QUE O PRODUTO DEVE SER ADMINISTRADO:
Distribuir as instilações ao longo do dia, conforme necessário. EFEITOS NÃO PRETENDIDOS E INCÔMODOS (EFEITOS INDESEJÁVEIS): Rara possibilidade de ligeiras irritações oculares. CONSERVAÇÃO DE DISPOSITIVO: NÃO EXCEDER O PRAZO LIMITE DE UTILIZAÇÃO, INDICADO
NA EMBALAGEM EXTERIOR. PRECAUÇÕES ESPECIAIS DE CONSERVAÇÃO: Conservar a uma temperatura inferior a 25ºC. Depois de aberto, o frasco não deve ser conservado mais de 8 semanas. DATA DE REVISÃO DESTE FOLHETO INFORMATIVO: 04/2009. Registro MS nº 80424140002.
Material dirigido exclusivamente a profissionais habilitados a prescrever e/ou dispensar medicamentos.
Produzido em: Fev/2014
uso compátivel com
lentes de contato2
facilita a colocação
e a retirada, e proporciona
conforto imediato
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ISSN 0004-2749
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ISSN 1678-2925
(Electronic version)
Frequency of publication: Bimonthly
Arq Bras Oftalmol. São Paulo, v. 77, issue 3, pages 139-208, May/Jun. 2014
Contents
V
Editorial
Open-angle glaucoma surgery: the current standing
Cirurgia do glaucoma de ângulo aberto: estado atual
Ivan Maynart Tavares
Original Articles
Fundus autofluorescence in blunt ocular trauma
139
Autofluorescência do fundo de olho no trauma ocular contuso
Ricardo Luz Leitão Guerra, Igor Sandes Pessoa da Silva, Eduardo Ferrari Marback, Otacílio de Oliveira Maia Jr., Roberto Lorens Marback
143
Pediatric cataracts: clinical aspects, frequency of strabismus and chronological, etiological, and morphological features
Márcia Beatriz Tartarella, Gloria Fátima Britez-Colombi, Suanne Milhomem, Márcia Cordeiro Emery Lopes, João Borges Fortes Filho
148
Measurement of choroid thickness in pregnant women using enhanced depth imaging optical coherence tomography
Sertan Goktas, Ahmet Basaran, Yasar Sakarya, Muammer Ozcimen, Zehra Kucukaydin, Rabia Sakarya, Mustafa Basaran, Erkan Erdogan, Ismail Alpfidan
152
Ocular biometry and central corneal thickness in children: a hospital-based study
Adem Gul, Cagatay Caglar, Adnan Cınal, Tekin Yasar, Adil Kılıc
155
Conjunctival melanoma: survival analysis in twenty-two Mexican patients
Rosa Angélica Salcedo-Hernández, Kuauhyama Luna-Ortiz, Leonardo Saúl Lino-Silva, Ángel Herrera-Gómez, Verónica Villavicencio-Valencia,
Miriam Tejeda-Rojas, José F. Carrillo
159
Static cyclotorsion measurements using the Schwind Amaris laser
Daoud C. Fahd, Elyse Jabbour, Charbel D. Fahed
Catarata pediátrica: aspectos clínicos, frequência de estrabismo e características cronológicas, etiológicas e morfológicas
Medição da espessura da coroide em gestantes utilizando tomografia de coerência óptica com profundidade de imagem aprimorada
Biometria ocular e espessura corneana central em crianças: um estudo de base hospitalar
Melanoma conjuntival: análise de sobrevivência em vinte e dois pacientes mexicanos
Medições da ciclotorção estática usando o laser Schwind Amaris
Is the cost the primary barrier for cataract surgery in Paraguay?
164
A taxa para a cirurgia é a principal barreira para a adesão à cirurgia de catarata no Paraguai?
Harumi G. Burga, Celeste N. Hinds, Van C. Lansingh, Margarita Samudio, Susan Lewallen, Paul Courtright, Rainald Duerksen, Pablo Cibils, Manuel Zegarra
168
Expression of TNF-α and IL-6 cytokines in the choroid and sclera of hypercholesterolemic rabbits
Rogil José de Almeida Torres, Andrea Luchini, Lucas Younes Barberini, Leonardo Precoma,Caroline Luzia de Almeida Torres, Robson Antonio de Almeida Torres,
Lucia de Noronha, Bruna Olandoski Erbano, Antonio Marcelo Barbante Casella, Dalton Bertolim Precoma
Expressão das citocinas TNF-α and IL-6 na coroide e esclera de coelhos hipercolesterolêmicos
173
Efficacy of a lutein-based dye (PhacodyneTM) for visualizing anterior capsulorhexis during cataract surgery by
phacoemulsification
Eficácia de corante à base de luteína (PhacodyneTM) para observação da capsulorrexis anterior em cirurgia de facoemulsificação
Lucas Monferrari Monteiro Vianna, Marcos J. Cohen, Cristina Muccioli, Acácio Lima, Diogo Sousa-Martins, Maurício Maia, Rubens Belfort Jr.
178
Ophthalmologic findings in hepatitis C patients treated with pegylated interferon α-2b and ribavirin
Fernando José de Novelli, André Przysiezny, Evandro Luis Rosa, Raquel Francine Liermann Garcia, Mário Junqueira Nóbrega
Achados oftalmológicos nos pacientes portadores de hepatite C em tratamento com
interferon peguilado α-2b e ribavirina
Case Reports
scleral dellen as an early complication of pterygium excision with simple conjunctival closure
182 Severe
and review of the literature
“Dellen” escleral grave como complicação precoce de excisão de pterígio com fechamento conjuntival simples e revisão da literatura
Jose Javier Garcia-Medina, Mónica del-Rio-Vellosillo, Vicente Zanon-Moreno, Amanda Ortiz-Gomariz, Manuela Morcillo-Guardiola, Maria Dolores Pinazo-Duran
185
Transient spectral domain optical coherence tomography findings in classic mewds: a case report
Luciana Castro Lavigne, David Leonardo Cruvinel Isaac, José Osório Duarte Júnior, Marcos Pereira de Ávila
188
Susac syndrome: diverse clinical findings and treatment
Ricardo Canto Bardal, Emmerson Badaro, Jayme Arana, Fabio Alves, Eduardo Cunha de Souza, Pedro Paulo Bonomo, Ezequiel Portella, Mauricio Maia
Alterações transitórias evidenciadas na tomografia de coerência óptica de domíno espectral em quadro clássico de mewds: relato de caso
Síndrome de Susac: achados clínicos diversos e tratamento
Intrastromal crosslinking in post-LASIK ectasia
191
“Crosslinking” intraestromal em ectasia pós-LASIK
Bernardo Kaplan Moscovici, Mauro Campos
Review Articles
Is
dry eye an environmental disease?
193
O olho seco é uma doença relacionada a exposição ambiental?
Monica Alves, Priscila Novaes, Monica de Andrade Morraye, Peter Sol Reinach, Eduardo Melani Rocha
Letters to the Editor
Bilateral acute depigmentation of the iris (BADI): first reported case in Brazil
201
Saban Gonul, Banu Bozkurt
Reply
201
Heloisa Andrade Maestrini
203
Refractive error in school children in Campinas, Brazil
Rodrigo Pessoa Cavalcanti Lira, Italo Fernandes do Espírito Santo, Gustavo Lima do Valle Astur, Diana Maziero, Thais Helena Moreira Passos, Carlos Eduardo Leite Arieta
Erros refrativos em escolares de Campinas, Brasil
205 Instructions to Authors
Editorial
Open-angle glaucoma surgery: the current standing
Cirurgia do glaucoma de ângulo aberto: estado atual
Ivan Maynart Tavares
Glaucoma is an optic neuropathy characterized by progressive degeneration of retinal ganglion cells(1). It is
the main cause of irreversible blindness in the world, and affects more than 70 million people worldwide, being
10% bilaterally blind(2). Glaucoma can remain asymptomatic until it is severe, leading glaucoma filtration surgery
to be performed in advanced cases, often by general ophthalmologists, which may be, in part, responsible for
the wrong impression of its low success-rates and high incidence of complications. Therefore, glaucoma surgery
is feared by patients and even by some ophthalmologists. Nevertheless, recently published studies on glaucoma
surgery safety and efficacy have reported a different reality.
First, due to recent diagnostic and therapeutic advancements, including improvements in surgery techniques, the 20-year probability of glaucoma-related blindness in at least one eye was reduced to half during the
period from 1965 to 2009(3). One of these enhancements was the advent of the safe trabeculectomy technique,
proposed by Peng Khaw from the Moorfields Eye Hospital(4). Moreover, a multicenter analysis showed that good
trabeculectomy outcomes with low rates of surgical complications can be achieved, but intensive proactive
postoperative care is required. These authors showed an intraocular pressure (IOP) equal or less than 18 mmHg
in 86% of the patients after a two-year follow-up period, when included hypotensive medication use(5). They also
reported antifibrotics use in 93% of the cases, what corroborated the current practice pattern among glaucoma specialists. The use of mitomycin-C (MMC) during trabeculectomy has not only enhanced its IOP-lowering
effect, but also made the postoperative period more challenging. Suture manipulation (including massage, laser
suture lysis, etc.), bleb needling and subconjunctival 5-fluorouracil injections are directly related to success, and
demand both time and expertise. In the same report, 31 patients (7%) had late-onset hypotony (three of them
with visual acuity decreased by >2 Snellen lines), and two patients developed bleb-related endophthalmitis(5).
Incidentally, another recent paper reported that visual loss after surgery, the “wipe-out” phenomenon, is rare,
even in patients with advanced glaucomatous visual field loss and split fixation(6).
The Ex-Press® implantation during glaucoma filtration surgery should be considered as a modification in
trabeculectomy, and not as an entirely new procedure. A recent meta-analysis of randomized clinical trials comparing both procedures reported similar efficacy in IOP-lowering, medication reduction, vision recovery, qualified operative success-rates, and a greater incidence of most complications, with the exception of hyphema(7).
Controversy over its application in daily practice exists, as its efficacy and safety are similar to trabeculectomy,
however it makes the procedure more costly.
Non-penetrating surgical procedures, including deep sclerectomy (DS), are more difficult to perform and
require a longer learning curve. The addition of MMC to DS not only decreased the difference in the reduction
in IOP (from -2.65 to -0.83 mmHg), but also increased the incidence of complications, when compared to trabeculectomy with MMC. Even though, the absolute risk of complications is higher in the trabeculectomy group(8).
Hence, good result reports with this technique have been limited to a select group of skilled surgeons.
With regard to glaucoma drainage devices (GDD), the Tube versus Trabeculectomy Study (TVT), a multicenter, randomized clinical trial, demonstrated that IOP in the low-teens could be achieved with GDD (350 mm2
Baerveldt implant; Abbot Medical Optics Inc., USA), in patients with previous cataract extraction or trabeculectomy(9). Although the TVT study has expanded the use of tube shunts beyond refractory glaucoma, a major shift
in glaucoma surgical practice patterns has not been seen, and GDD continue to be often used either after two
failed filtration surgeries or in cases in which these procedures are not indicated.
Cyclodestructive procedures, both trans-scleral and endoscopic, have been reserved for cases in which other
surgical techniques have failed. Though they are effective, potential for serious complications exists(10); therefore
they are seldom indicated before filtration procedures or GDD.
Submitted for publication: June 30, 2014
Accepted for publication: June 30, 2014
Funding: No specific financial support was available for this study.
Glaucoma Service, Department of Ophthalmology and Visual Sciences, Universidade Federal de
São Paulo - Escola Paulista de Medicina - UNIFESP - São Paulo (SP) - Brazil.
Corresponding author: Ivan Maynart Tavares. Rua Botucatu, 821 - São Paulo, SP - 04023-062 - Brazil
E-mail: [email protected]
http://dx.doi.org/10.5935/0004-2749.20140035
Disclosure of potential conflicts of interest: The author has any potential conflicts of interest to disclose.
V
Open-angle glaucoma surgery: the current standing
Finally, the advent of new devices and innovative techniques led on to new procedures, the minimally
invasive glaucoma surgeries (MIGS). MIGS are ab interno and ab externo procedures, with limited manipulation
of the sclera, little or no manipulation of the conjunctiva, and no bleb formation. Trabectome (NeoMedix, USA),
Hydrus (Ivantis, USA), iStent (Glaukos, USA) and canaloplasty are some examples of MIGS approved in the USA
or Europe. They are indicated for mild to moderate glaucoma, whereas IOP is reduced to mid-to-high teens,
preferably combined with cataract extraction. Furthermore, most MIGS are fast to perform, have a more rapid
visual recovery, and have a lower complication rate than filtration surgery(11,12). Nonetheless, there is limited data
on costs, as well as on how they could negatively affect a future trabeculectomy. Unfortunately, none of the
MIGS devices is approved in Brazil, in part due to regulatory authorities costly and bureaucratic procedures and
requirements for registration of medical devices, what have limited our armamentarium for glaucoma treatment
and hampered science development.
REFERENCES
1. Weinreb RN, Aung T, Medeiros FA. The pathophysiology and treatment of glaucoma:
a review. JAMA. 2014;311(18):1901-11.
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Original Article
Fundus autofluorescence in blunt ocular trauma
Autofluorescência do fundo de olho no trauma ocular contuso
Ricardo Luz Leitão Guerra1, Igor Sandes Pessoa da Silva2, Eduardo Ferrari Marback3, Otacílio de Oliveira Maia Jr.2, Roberto Lorens Marback3
ABSTRACT
RESUMO
Purpose: To describe the findings of fundus autofluorescence (FAF) imaging in
patients with blunt ocular trauma.
Methods: In this non-interventional retrospective study, we reviewed medical
records and imaging examination results. The data analyzed included gender, age,
laterality, trauma etiology, time between trauma and imaging, visual acuity, changes
in the retinal periphery, fundus examination results, and FAF imaging findings. FAF
imaging was performed using a Topcon TRC-50DX Retinal Camera (Tokyo, Japan).
Results: Eight eyes from 8 patients were studied. The mean age was 27.6 years
(range, 19-43 years). Men (n=7) were more frequently affected by blunt ocular
trauma than women (n=1). Physical aggression was the most common trauma
etiology (n=3), followed by accidents with fireworks (n=2). Other causes were car
accidents (n=1), occupational trauma caused by a grinder (n=1), or being hit by a
stone (n=1). Visual acuity ranged from 20/80 to light perception. Traumatic pigment
epitheliopathy (TPE) was identified in 5 cases, choroidal rupture in 3 cases, subretinal
hemorrhage in 3 cases, and Purtscher’s retinopathy in 1 case. Hypoautofluorescence was observed in cases of choroidal rupture, recent subretinal hemorrhage,
and intraretinal hemorrhage, and in two cases of TPE. Hyperautofluorescence was
observed in cases of old subretinal hemorrhage and at the edge of the lesion in
two cases of choroidal rupture. Mild hyperautofluorescence was observed in the
posterior pole in Purtscher’s retinopathy. Three cases of TPE exhibited hypoautofluorescence with diffuse hyperautofluorescent areas.
Conclusion: FAF imaging is a non-invasive method for assessing changes in the
posterior segment of the eye resulting from blunt ocular trauma. Furthermore,
this technique provides valuable information. We described the findings of FAF
imaging in cases of TPE, choroidal rupture, subretinal hemorrhage, and Purtscher’s
retinopathy.
Objetivo: Descrever os achados do exame de autofluorescência do fundo de olho
(AFF) em pacientes vítimas de trauma ocular contuso.
Métodos: Estudo retrospectivo, não intervencionista, realizado através da revisão de
prontuários e exames de imagem. Os dados analisados foram: sexo, idade, lateralida­­
de, etiologia do trauma, tempo decorrente entre o trauma e a realização do exame,
acuidade visual, alterações na periferia da retina, diagnóstico fundoscópico e achados
ao exame de AFF (realizada no aparelho Topcon TRC-50DX Retinal Camera).
Resultados: Oito olhos de 8 pacientes foram estudados. A idade média foi de 27,6
anos (de 19 a 43 anos), o sexo masculino (n=7) foi mais acometido do que o feminino (n=1), agressão física foi a etiologia mais comum do trauma (n=3), seguido de
acidente com fogos de artifício (n=2). Outras causas foram acidente automobilístico
(n=1), trauma ocupacional com lixadeira (n=1) e pedrada (n=1). A acuidade visual
variou de 20/80 a percepção luminosa. Epiteliopatia pigmentar traumática (EPT) foi
identificada em 5 casos, rotura de coroide em 3, hemorragia sub-retiniana em 3 e
retinopatia de Purtscher em 1 caso. Hipoautofluorescência foi observada nos casos
de rotura de coroide, hemorragia sub-retiniana recente, hemorragia intrarretiniana
e em 2 casos de EPT. Hiperautofluorescência foi visualizada nos casos de hemorra­gia
sub-retiniana em degradação, na borda de 2 casos de roturas de coroide e discretamente no polo posterior na retinopatia de Purtcher. Três casos de EPT apresentaram
hipoautofluorescência com pontos hiperautofluorescentes difusos.
Conclusão: O exame de AFF permite avaliar as alterações do segmento posterior do
olho decorrentes do trauma ocular contuso de forma não invasiva, somando informações valiosas. Foram descritos achados do exame em casos de epiteliopatia pigmentar
traumática, rotura de coroide, hemorragia sub-retiniana e retinopatia de Purtscher.
Keywords: Trauma; Retinal pigment epithelium; Retinal diseases; Ocular trauma
IntroduCTION
Blunt ocular trauma is an injury that does not compromise the
in­­tegrity of the eye wall(1). It manifests in various ways in the posterior
segment of the eye and causes serious sequelae(1). Vitreous hemorrhage, retinal edema (commotio retinae), choroidal rupture, macular
holes, retinitis sclopetaria, retinal rupture, and retinal dialysis are complications involving the posterior segment in blunt ocular trauma(1).
Fundus autofluorescence (FAF) imaging is a method that uses
a non-invasive imaging technique to evaluate the integrity of the
retinal pigment epithelium (RPE)(2). A homogeneous pattern on FAF
images indicates normal metabolic activity of the PER cells, whereas
decreased fluorescence (hypoautofluorescence) suggests impairment
of photoreceptors or PER cells(3).
Submitted for publication: December 19, 2013
Accepted for publication: April 2, 2014
Study conducted at Retina and Vitreous Service, Hospital São Rafael, Fundação Monte Tabor,
Salvador, BA, Brazil.
Clínica de Olhos Leitão Guerra, Salvador, BA, Brazil.
Hospital São Rafael, Fundação Monte Tabor, Salvador, BA, Brazil.
3
Faculdade de Medicina da Bahia, Universidade Federal da Bahia, Salvador, BA, Brazil.
1
Descritores: Trauma; Epitélio pigmentado da retina; Doenças retinianas; Traumatismos oculares
The usefulness of FAF imaging is well described in several eye
conditions such as retinal dystrophies(2) and pigmented intraocular
tumors(4). This study aimed to describe the findings of FAF imaging
in patients with blunt ocular trauma. In the reviewed literature, we
only found three articles describing the findings of FAF imaging in
patients that showed changes in the posterior segment associated
with blunt ocular trauma(5-7).
METHODS
This was a non-interventional retrospective study. In this study,
the medical records and imaging results of patients, who were
diagnosed with injury caused by blunt ocular trauma involving the
posterior segment, were reviewed.
Funding: No specific financial support was available for this study.
Disclosure of potential conflicts of interest: None of the authors have any potential conflicts of
interest to disclose.
Corresponding author: Ricardo Leitão Guerra. Rua Catarina Paraguaçu, 8 - Salvador (BA) 40150-200 - Brazil - E-mail: [email protected]
2
http://dx.doi.org/10.5935/0004-2749.20140036
Arq Bras Oftalmol. 2014;77(3):139-42
139
Fundus autofluorescence in blunt ocular trauma
All patients were submitted to an ophthalmologic examination,
color fundus photography, and FAF at Hospital São Rafael-Fundação
Monte-Tabor in Salvador, Bahia-Brazil from 02/01/2011 to 01/31/2013.
Patient selection was based on a diagnosis of ocular blunt trauma
collected from the institution’s fundus photography registry book.
Patients with incomplete data were excluded from the study. This
study was approved by the research ethics committee of the same
institution (CAAE - 14929313.4.0000.0048).
The data analyzed included sex, age, laterality, trauma etiology,
time between trauma and imaging, visual acuity, changes in the re­tinal
periphery, fundus examination results, and FAF imaging findings. FAF
imaging was performed using a Topcon TRC-50DX Retinal Camera
(Tokyo, Japan).
RESULTS
Eight eyes in 8 patients were studied. No patient was excluded
from the study. A summary of the cases is shown in table 1; color fundus photography and FAF findings are shown in figures 1 and 2. The
mean age was 27.6 years (range, 19-43 years), and men (n=7) were
more frequently affected by blunt ocular trauma than women (n=1),
and the right eye (n=5) was more affected than the left eye (n=3).
Physical aggression was the most common trauma etiology
(n=3), followed by accidents with fireworks (n=2). Other causes were
car accidents (n=1), occupational trauma caused by a grinder (n=1),
and being hit by a stone (n=1).
Visual acuity ranged from 20/80 to light perception, and 2 pa­­
tients exhibited changes on peripheral retinal examination that
included retinal dialysis with peripheral retinal detachment (n=1) and
rupture of the retina without retinal detachment (n=1).
Traumatic pigment epitheliopathy (TPE) was the most common
finding (n=5), followed by choroidal rupture (n=3), subretinal hemorrhage (n=3), and Purtscher’s retinopathy (n=1). Hypoautofluo­
rescence was observed in cases of choroidal rupture, recent sub­­
retinal hemorrhage, intraretinal hemorrhage, and in 2 cases of TPE.
Hyperautofluorescence was observed in cases of old subretinal
hemorrhage and at the edge of the lesion in 2 cases of choroidal
rupture. Mild hyperautofluorescence was observed in the posterior
pole in Purtscher’s retinopathy. Three cases of TPE exhibited hypoau­
tofluorescence with diffuse hyperautofluorescent areas. These fin­
dings are summarized in table 2.
DISCUSSION
TPE
TPE usually occurs in cases of severe trauma following resolution
of commotio retinae(5,8). When the macular region is involved, TPE is
associated with poor visual prognosis(5,8). In these cases, FAF imaging
shows a hypoautofluorescent area alternating with punctiform hyperautofluorescent lesions(5,6).
In this series of cases, 5 of the 8 patients had TPE (cases 4, 5, 6, 7,
and 8). Three patients (cases 6, 7, and 8) exhibited the characteristic
pattern on FAF images, which is described above. In the other 2 cases
(cases 4 and 5), FAF imaging showed a hypoautofluorescent lesion
corresponding to the affected region. We observed that FAF imaging
was more effective than color fundus photography for the identification and definition of the areas affected by TPE.
Choroidal rupture
Choroidal rupture can be observed on FAF images as a hypoauto­
fluorescent line, and in some cases, FAF imaging provides better
visualization and definition of the lesion than color fundus photography(5,7). In some cases, there is a hyperautofluorescent ring surrounding the lesion, which may correspond to hyperplasia of RPE that
occurs as the rupture heals(5).
In the 3 patients with choroidal rupture (cases 2, 3, and 4), FAF
imaging showed a hypoautofluorescent lesion corresponding to the
site of rupture. In 2 cases (cases 3 and 4), a hyperautofluorescent ring
was observed at the edge of the lesion. The time elapsed between
the trauma and examination was longer for these patients, which
confirms the hypothesis of hyperautofluorescence at the edge of the
lesion is related to the healing process of a choroidal rupture.
Subretinal hemorrhage
Recent subretinal hemorrhage (when there is no degradation of
blood cells) presents itself as a hypoautofluorescent lesion on FAF images(5). As erythrocytes are degraded and the blood turns yellowish,
the appearance on FAF images becomes hyperautofluorescent(5).
We note that, in this situation, devitalized blood cells are har­mful to
photoreceptors and are associated with a poorer visual prognosis(5,9).
Three cases described in this study exhibited signs of subretinal
hemorrhage; 1 case of recent hemorrhage (case 2) and 2 cases of old
hemorrhage (cases 3 and 4). The results of the FAF imaging examinations in these patients agreed with those described in the literature,
and they allowed us to better define the extension of a subretinal
hemorrhage, both in recent cases and in cases wherein blood cell
degradation was observed. The authors believe that this characteristic makes FAF imaging a useful tool for identifying and monitoring
patients who have subretinal hemorrhage for which there is no indication of surgical treatment.
Purtscher’s retinopathy
One patient (case 1) was diagnosed with Purtscher’s retinopathy,
and FAF imaging was performed during the acute phase. We did not
find in the literature a description of FAF imaging for similar cases
(following trauma). We searched for the terms “Purtscher”, “Retinopathy”, and “Autofluorescence” in MEDLINE and SCIELO databases.
Only 1 report of a Purtscher-like retinopathy case (following pan­­­
creatitis) was found in the literature, which described the results of
Table 1. Summary of cases studied
Gender
Age
Eye
Trauma etiology
Time
VA
Periphery
Diagnosis
Case 1
M
27
LE
Car accident
6 days
20/200
Normal
Purtscher
Case 2
M
25
LE
Grinder
5 days
20/200
Dialysis
CR
Case 3
F
19
RE
Physical aggression
3 months
20/80
Normal
CR
Case 4
M
43
RE
Fireworks
8 months
20/200
Normal
CR + MH + TPE
Case 5
M
19
LE
Stone
3 months
CF
Normal
EPT
Case 6
M
16
RE
Fireworks
1 month
CF
Normal
CR + TPE
Case 7
M
32
RE
Physical aggression
1 month
CF
Normal
CR + TPE
Case 8
M
40
RE
Physical aggression
2 months
LP
Rupture
TPE
M= male; F= female; RE= right eye; LE= left eye; VA= visual acuity; CF= counting fingers; LP= light perception; CR= choroidal rupture; MH= macular hole; TPE= traumatic epitheliopathy.
140
Arq Bras Oftalmol. 2014;77(3):139-42
Guerra RLL, et al.
A
B
C
D
E
F
G
H
Figure 1. A) Purtscher’s retinopathy. B) FAF exhibits hypoautofluo­
rescence in the areas corresponding to intraretinal hemorrhage
and mild perimacular hyperautofluorescence. C) Recent subretinal
hemorrhage in the macular region, secondary to choroidal rupture
temporal to the macula. D) FAF exhibits an extensive hypoauto­
fluorescent area in the region affected by the hemorrhage and a
hypoautofluorescent line corresponding to choroidal rupture. E)
Choroidal rupture with subretinal hemorrhage showing degrada­
tion of subretinal blood. F) FAF exhibits hyperautofluorescence
corresponding to the degraded blood. Choroidal rupture as a
hypoautofluorescent line associated with the hyperautofluo­
rescent areas. G) Choroidal rupture, degraded subretinal blood,
and macular hole 8 months after blunt trauma. H) FAF exhibits
a hypoautofluorescent line corresponding to choroidal rupture,
a hyperautofluorescent line caused by degraded blood, and
moderate hypoautofluorescence in the posterior pole and in the
peripapillary region corresponding to the involvement of RPE.
FAF examination(10). In this report, we describe hypoautofluorescence
in the areas corresponding to Purtscher’s spots, hyperautofluorescence in veins affected by ischemia during the acute phase of retinopathy, and a granular pattern of hyperautofluorescence and hypoau­
tofluorescence in the region previously affected by the Purtscher’s
spots after the retinopathy had been resolved(10).
Contrary to this finding, FAF imaging of the patient described in
the present study showed hypoautofluorescence in the areas corresponding to intraretinal hemorrhage and mild hyperautofluorescence
surrounding the macular region, corresponding to the sites where
Purtscher’s spots were observed.
Despite the similar clinical presentation, the difference between
the pathophysiological mechanism of Purtscher’s retinopathy and
that of Purtscher-like retinopathy may explain the disparate results
among examinations. The lack of experimental studies or other data
in the literature precludes a definitive conclusion.
Moreover, we propose that in the case of the patient who sus­­tained
trauma, a different change associated with Purtscher’s retinopathy,
such as commotio retinae, contributed to hyperautofluorescence in
the posterior pole. This hypothesis is consistent with the results described by Lavinsky et al(5). Three cases of commotio retinae exhibited
A
B
C
D
E
F
G
H
Figure 2. A) Hyperchromic lesion in the papillomacular bundle
surrounded by hyperchromic and hypochromic pigment changes
in the macular region. B) FAF exhibits a large hypoautofluorescent
area affecting the macula. C) Choroidal rupture with extensive
subretinal fibrosis, mobilization of the pigment in the posterior
pole, and retinal architecture anomalies. D) FAF exhibits a hy­
poautofluorescent lesion with diffuse hyperautofluorescent
areas affecting the posterior pole. E) Subretinal hemorrhage near
the area of subretinal fibrosis affecting the temporal macular
region. Toward the upper arcade, there is a change in RPR pig­
mentation. F) FAF exhibits a hypoautofluorescent area with
dif­f u­se hyperautofluorescent areas in the affected region, with a
prevalence of hypoautofluorescent lesions. G) Slightly decreased
RPE pigmentation in the peripapillary region. H) FAF exhibits a
hy­poautofluorescent lesion with diffuse hyperautofluorescent
areas. In this case, FAF resulted in improved delimitation of the
lesion compared with color fundus photography.
Table 2. Correlation between the findings of fundus examination and
FAF imaging
Fundus
examination
n
FAF imaging
n
Choroidal rupture
3
Hypoautofluorescence at the site of rupture
3
Hyperfluorescence at the edge of the lesion
2
Alternating hypoautofluorescence and
hyperautofluorescence
3
Hypoautofluorescence
2
Traumatic pigment
epitheliopathy
5
Recent subretinal
hemorrhage
1
Hypoautofluorescence
1
Old subretinal
hemorrhage
2
Hyperautofluorescence
2
Purtscher’s
retinopathy
1
Perimacular hyperautofluorescence and
hypoautofluorescence corresponding to
hemorrhage
1
n= number of eyes that exhibited the finding.
mild hyperautofluorescence during the acute phases of the disease,
which progressed to TPE in a few weeks(5). In the present study, we
Arq Bras Oftalmol. 2014;77(3):139-42
141
Fundus autofluorescence in blunt ocular trauma
were not able to follow this case because the patient did not return
for subsequent visits.
Clinical application
After analyzing the results of this study and comparing them with
the reviewed literature, we believe that FAF imaging plays an important
role evaluation of patients who sustain blunt ocular trauma. The main
advantages of FAF, according to the literature(5,7), are better lesion definition than color and red free fundus photography that improves the
quality of patient follow-up. Longitudinal studies are necessary to establish further advantages of FAF imaging in cases of blunt ocular trauma.
CONCLUSION
FAF examination is a non-invasive method for assessing changes
in the posterior segment of the eye that result from blunt ocular trauma. It provides valuable information. We described the findings of
FAF imaging in cases of TPE, choroidal rupture, subretinal hemorrha­ge,
and Purtscher’s retinopathy.
REFERÊNCIAS
1.Posterior segment manifestations of trauma. In: Basic and Clinical Science Course,
Section 12: Retina and vitreous. American Academy of Ophthalmology. 2011. p.315-33.
2. Coco M, Baba NT, Sallum JM. Avaliação da autofluorescência do fundo de olho nas
distrofias de retina com o aparelho Heidelberg Retina Angiograph2. Arq Bras Oftalmol. 2007;70(5):739-45.
3.Ishida T, Ohno-Matsui K, Kaneko Y, Tobita H, Hayashi K, Shimada N, Mochizuki M.
Autofluorescence of metastatic choroidal tumor. Int Ophthalmol. 2009;29(4):309-13.
4. Materin MA, Raducu R, Bianciotto C, Shields CL. Fundus autofluorescence and optical
coherence tomography findings in choroidal melanocytic lesions. Middle East Afr J
Ophthalmol. 2010;17(3):201-6.
5.Lavinsky D, Martins EN, Cardillo JA, Farah ME. Fundus autofluorescence in patients
with blunt ocular trauma. Acta Ophthalmol. 2011;89(1):89-94.
6.Mustafa MS, McBain VA, Scott CM. Autofluorescence imaging - a useful adjunct in
imaging macular trauma. Clin Ophthalmol. 2010;4:1497-8.
7. Kolomeyer AM, Szirth BC, Nayak NV, Khouri AS. Complimentary imaging technologies
in blunt ocular trauma. Oman J Ophthalmol. 2013;6(2):108-11.
8. Sawa M, Ober MD, Spaide RF. Autofluorescence and retinal pigment epithelial atrophy
after subretinal hemorrhage. Retina. 2006;26(1):119-20.
9. Yang CS, Chou TF, Liu JH, Hsu WM. Air bag associated posterior segment ocular trauma.
J Chin Med Assoc. 2004;67(8):425-31.
10. Giani A, Deiro AP, Sabella P, Eandi CM. Spectral domain-optical coherence tomography
and fundus autofluorescence findings in a case of Purtscher-like retinopathy. Retinal
Cases & Brief reports. 2011;5(2):167-70.
II Congresso de Estética Periocular da
Sociedade Brasileira de Cirurgia Plástica Ocular
(SBCPO)
7 e 8 de novembro 2014
Rio Othon Palace
Rio de Janeiro - RJ
Informações:
Site: www.ciopcongressos.com.br
142
Arq Bras Oftalmol. 2014;77(3):139-42
Original Article
Pediatric cataracts: clinical aspects, frequency of strabismus and chronological,
etiological, and morphological features
Catarata pediátrica: aspectos clínicos, frequência de estrabismo e características cronológicas,
etiológicas e morfológicas
Márcia Beatriz Tartarella1, Gloria Fátima Britez-Colombi1, Suanne Milhomem1, Márcia Cordeiro Emery Lopes1, João Borges Fortes Filho2
ABSTRACT
RESUMO
Purpose: This study aimed to evaluate the frequency of strabismus and chronological, etiological, and morphological features in patients with pediatric cataracts.
Methods: Medical records of pediatric patients were evaluated at the Congenital
Cataract Section, Department of Ophthalmology, Federal University of São Paulo,
from 2001 to 2011. Patients with congenital cataract or developmental cataract
were included. The patients with traumatic cataract, cataract secondary to uveitis,
radiation or drugs, aphakic or pseudophakic patients who underwent surgery in
another hospital, patients with glaucoma, non-lenticular leukocorias (retinoblastoma, retinopathy of prematurity, prelenticular leukocorias), and lens subluxation
were excluded from the study. The following outcomes were evaluated: frequency
of chronological, etiological, and morphological features, laterality, and occurrence
of associated strabismus.
Results: A total of 207 patients were included. One hundred and seventeen patients (56.5%) had congenital cataract and 90 patients (43.5%) had developmental
cataract. One hundred and nine patients (52.6%) had unilateral cataract. In terms
of morphology, 72 children (33.8%) had zonular cataract and 66 (31.9%) had total
cataract. Idiopathic cataract affected 150 patients (72.5%). There were 108 patients
(52.2%) with strabismus, mainly secondary esotropia.
Conclusion: Idiopathic etiology was the most frequent cause in this group of
pa­­tients. Zonular cataract was the main morphological type of cataract in the
study. Unilateral cataract occurred more frequently in patients with persistent fetal
vasculature (PFV). Strabismus presented in 52% of the patients. The current analysis
may help establish an earlier and more accurate diagnosis of pediatric cataracts.
Objetivos: Avaliar as frequências do estrabismo e as características cronológica,
etiológica e morfológica das cataratas pediátricas.
Método: Estudo retrospectivo dos prontuários de crianças atendidas no Ambulatório
de Catarata Congênita do Departamento de Oftalmologia da Universidade Federal de
São Paulo no período entre 2001 e 2011. Foram incluídos pacientes com diagnóstico de
catarata congênita ou de desenvolvimento. Foram excluídos os pacientes com catarata
traumática; secundárias a uveíte, radiação ou medicamentos; pacientes operados em
outro serviço; pacientes com glaucoma; leucocorias não cristalinianas (retinoblastoma,
retinopatia da prematuridade, leucocorias pré-cristalinianas), e com sub-luxação do
cristalino. Foram avaliadas: as frequências cronológicas, etiológicas e morfológicas
das cataratas; a lateralidade e a ocorrência de estrabismo associado nestes pacientes.
Resultados: Foram incluídos 207 pacientes. Cento e dezessete (56,5%) apresentavam
catarata congênita e 90 (43,5%) apresentavam catarata de desenvolvimento. Cento e
nove (52,6%) pacientes eram portadores de catarata unilateral. Quanto à morfologia,
72 crianças (33,8%) apresentavam catarata zonular e 66 (31,9%) apresentavam catarata total. A etiologia idiopática foi a mais frequente (72,5%) afetando 150 pacientes.
Foram observados 108 pacientes (52,2%) com estrabismo associado, especialmente
endotropias secundárias.
Conclusões: A etiologia idiopática foi a mais frequente neste estudo. O tipo morfológico
zonular foi o mais frequentemente diagnosticado. Cataratas unilaterais ocorreram
mais frequentemente em pacientes com persistência da vasculatura fetal. O estrabismo
associado ocorreu em 52% dos pacientes. A análise dos resultados deste estudo pode
contribuir para diagnosticar a catarata pediátrica precocemente e de modo mais preciso.
Keywords: Cataract; Congenital; Diagnosis; Strabismus; Persistent fetal circulation
syndrome; Humans; Pediatric
Descritores: Catarata/congênito; Catara/diagnóstico; Estrabismo; Síndrome da per­­­
sistência do padrão de circulação fetal; Humanos; Criança
INTRODUCTION
Cataract is a major cause of visual impairment during childhood.
Pediatric cataract often leads to amblyopia and secondary strabismus(1-4). Early diagnosis and treatment to prevent lateral geniculate
body atrophy during the critical period of visual development is
important for the visual prognosis of children affected by cataract(5-7).
Pediatric cataracts are classified according to their time of onset
(chronological), etiology, and morphology. The chronological classification is based on the time of onset of the opacity in the lens(8). When
lens opacity is detected within the first 3 months of life after birth, the
disease is classified as congenital cataract. When the diagnosis or the
onset of opacity occurs after 3 months of life, the disease is classified
as developmental cataract or infantile cataract. Early developmental
cataract occurs within the first 12 months of life and late developmental cataract occurs after the first year of life(8-10). The chronological
classification helps establish the visual prognosis in patients.
Pediatric cataracts have different etiologies including hereditary,
secondary to congenital infections associated with systemic syndromes and ocular abnormalities [aniridia, persistent fetal vasculature
(PFV), Peters anomaly, anterior segment dysgenesis, prior ocular surgery and uveitis], secondary to external agents, such as drugs (e.g.,
corticosteroids), radiotherapy, or environmental factors, and ocular
Submitted for publication: August 13, 2013
Accepted for publication: January 29, 2014
Funding: No specific financial support was available for this study.
Study conducted at Congenital Cataract Section, Department of Ophthalmology, Federal University
of São Paulo (UNIFESP), São Paulo, SP, Brazil.
1
Department of Ophthalmology, Federal University of São Paulo (UNIFESP), São Paulo, SP, Brazil.
Department of Ophthalmology, Hospital de Clínicas de Porto Alegre, Federal University of Rio
Grande do Sul (UFRGS), Porto Alegre, RS, Brazil.
Disclosure of potential conflicts of interest: None of the authors have any potential conflicts of
interest to disclose.
Corresponding author: João Borges Fortes Filho. Rua Ramiro Barcelos, 2.350 - Porto Alegre (RS) 90035-903 - Brazil - E-mail: [email protected]
2
http://dx.doi.org/10.5935/0004-2749.20140037
Arq Bras Oftalmol. 2014;77(3):143-7
143
Pediatric cataracts: clinical aspects, frequency of strabismus and chronological, etiological, and morphological features
trauma(10-14). Cataracts with undetermined causes are classified as
idiopathic(15).
Morphologically, pediatric cataracts are classified into total cataract, zonular cataract (lamellar, pulverulent, nuclear, sutural), capsular
cataract (anterior subcapsular, posterior subcapsular, lenticonus), and
membranous cataract(16). When associated with syndromes, metabolic
diseases, or inherited cataracts, the morphological features of the
cataract may provide clues to the possible etiology(14).
The objective of the present study was to evaluate the frequency
of strabismus as well as the chronological, etiological, and morphological features of the disease in pediatric cataract patients.
METHODS
This retrospective and descriptive study was conducted at the
Congenital Cataract Section, Department of Ophthalmology, Universidade Federal de São Paulo (UNIFESP), Brazil, from February 2001 to
January 2011. Patients diagnosed with congenital or developmental
cataract were included in the study. Exclusion criteria were the following:
traumatic cataract, cataract secondary to uveitis, radiation, or drugs,
aphakic or pseudophakic patients who underwent surgery at an un­
re­lated service, patients with glaucoma, non-lenticular leukocorias
(re­­tinoblastoma, retinopathy of prematurity, prelenticular leukocorias),
and patients with lens subluxation.
Data collected from the patient files at the first presentation in­­­­­
cluded gestational, familial, and personal health information. Eye
examination included analysis of the cataract morphology at biomicroscopy. Patients underwent ocular ultrasound when the opacity of
the lens prevented the examination of the ocular fundus by binocular
indirect ophthalmoscopy. For the outcomes evaluated, we collected
the following data: time of onset of the cataract, laterality, etiology,
morphology, and evaluated the ocular alignment by Hirschberg test.
We also performed strabismus detection with the help of cover test.
The visual acuity was assessed by the age-paired tests, Teller cards
acuity test, Lea Hyvarigen test, or Snellen visual acuity test.
Cataract was classified chronologically according to the time
when the disease was detected. Cases showing lens opacity within
the first 3 months of life following birth were classified as congenital
cataracts. Cases in which diagnosis or the onset of opacity occurred
after the first 3 months of life were classified as developmental cataract. To establish the etiology of the disease, children were referred
to a pediatrician for clinical evaluation and routine tests. Children
up to 18 months of age were requested to undergo routine serologic tests for the detection of any possible toxoplasmosis, rubella,
syphilis, and cytomegalovirus. The following laboratory tests were
performed routinely: complete blood count test, blood glucose test,
neonatal heel prick test (Guthrie test), and total serum calcium test.
Patients with cataracts of suspected genetic etiology were referred to
the Section of Genetics of the Pediatric Department at the UNIFESP.
After the required tests were performed at the institute, the patients
with no identifiable cause for cataracts were included in the group
of idiopathic etiology.
Cataract was classified according to the morphology as total
(Fi­­­gure 1), zonular, polar, capsular, and membranous. Zonular cataracts, which effect the fetal nucleus of the lens, were further classified
as lamellar (Figure 2), pulverulent (Figure 3), nuclear (Figure 4), and sutural. According to the site of lens opacity, polar cataracts were classi­fied
as anterior, posterior, or pyramidal (Figure 5). Capsular cataracts were
further classified as anterior, posterior, and lenticonus. When multiple
morphological types of cataract co-exist in the same child or in the
same eye, they are considered as mixed cataract.
RESULTS
We analyzed a total of 428 medical files. However, only 207 of these
files contained complete medical history, time of onset of the disease,
144
Arq Bras Oftalmol. 2014;77(3):143-7
etiology, and morphology of the cataract. Therefore, only these 207
cases were included in our study. Age of the patients ranged from 19
days to 12 years.
Of the 207 patients included in the study, 117 had congenital ca­­
taract (56.5%), and 90 patients (43.5%) had developmental cataract.
At the time of diagnosis, 109 patients (52.6%) had unilateral cataract.
Of these patients, 51.3% had congenital cataract and 54.4% had developmental cataract. The frequencies of congenital and develop­mental
cataracts, according to their laterality, are shown in table 1.
Figure 1. Total cataract.
Figure 2. Lamellar cataract.
Figure 3. Pulverulent cataract.
Tartarella MB, et al.
Of the 207 patients, 150 (72.5%) had idiopathic cataract. Among
these 150 cases, 74 (49.3%) had bilateral cataract. Infectious etiology
was present in 18 patients (8.7%). Congenital rubella occurred in 14
patients (6.8%) and accounted for 77.8% of the cases in which infection
was identified as the etiology. PFV was diagnosed in 17 patients
(8.2%), of which 16 had unilateral cataract (94.1%). Familial history of
pediatric cataracts was confirmed in 14 cases (6.8%). Hereditary patterns
detected were either autosomal dominant or autosomal recessive.
The etiology established in the present study is shown in table 2.
Serum calcium test was performed to detect parathyroid disorders.
Total serum calcium was within the normal range in all the patients
(between 6.7 and 10.7 mg/dL).
Total cataract was diagnosed in 66 patients (31.9%), whereas 72
cases (33.8%) had zonular cataract. Among the different types of
zonular cataract, lamellar cataract was the most frequent and was
detected in 46 cases. As shown in table 3, mixed cataracts were present in 33 patients (15.9%).
The association between the etiology of detected cataract and
the morphological types is shown in table 4. Zonular (60 cases) and
total (43 cases) cataracts were more frequent in the idiopathic etiology group. PFV had more cases of posterior capsular cataracts (10
cases) than the entire group.
Strabismus was diagnosed in 108 (52.2%) patients, of which 65
(55.55%) were children with congenital cataracts and 43 were children (47.77%) with developmental cataracts.
Esotropia and exotropia were diagnosed in 60 (55.6%) and 48
(44.4%) patients, respectively. Esotropia was present in 40 (34.2%) patients with congenital cataracts and 20 (22.22%) patients with developmental cataracts. Vertical deviations were found in three patients.
However, all three cases were associated with horizontal deviation.
The distribution of the cases of strabismus among the patients with
cataract is shown in table 5.
Visual acuity ranged from light perception in total cataract cases
to 20/20 in lamellar cataracts. Only children with visual acuities worse
than 20/70 were selected for surgery.
DISCUSSION
The present study demonstrated a similar frequency of occurrence of congenital and developmental cataracts (56.5% vs. 43.5%,
Table 2. Etiology of laterality
Etiology
Unilateral
Bilateral
Total
Idiopathic
076
74
150 (72.5%)
Infectious
015
03
Congenital rubella
Figure 4. Nuclear cataract.
0013
Toxoplasmosis
002
018 (08.7%)
01
14 (77.8% in the group)
02
4 (22.2% in the group)
Secondary to PFV
016
01
17 (08.2%)
Hereditary
001
13
14 (06.8%)
Syndromes
001
07
08 (03.9%)
Down syndrome
000
06
6 (75% in the group)
Other
001
01
2 (25% in the group)
Total of patients
109
98
207 (100%)
PFV= persistent fetal vasculature.
Table 3. Morphology of pediatric cataracts and laterality
Morphological characteristics
Figure 5. Polar cataract.
Unilateral
Bilateral
Total
Total cataract
043
23
66 (31.9%)
Zonular
026
46
72 (33.8%)
Lamellar
012
36
48
Pulverulent
000
02
02
Nuclear
008
06
14
Sutural
006
02
08
Capsular
Table 1. Distribution of laterality in congenital and developmental
cataracts
Congenital cataract
Developmental cataract
Total
P=0.976.
013
03
Anterior subcapsular
000
00
Posterior subcapsular
013
03
Polar
016
04
Unilateral
Bilateral
Total
060 (51.3%)
57 (48.7%)
117 (56.5%)
Anterior
001
04
090 (43.5%)
Posterior
015
00
049 (54.4%)
109 (52.6%)
41 (45.6%)
98 (47.4%)
207 (100%)
16 (07.7%)
00
16
20 (09.7%)
05
15
Mixed
011
22
33 (15.9%)
Total of patients
109
98
207 (100%)
Arq Bras Oftalmol. 2014;77(3):143-7
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Pediatric cataracts: clinical aspects, frequency of strabismus and chronological, etiological, and morphological features
Table 4. Analysis of the etiology and morphology of pediatric cataracts
Total Cataract Zonular Capsular Polar Mixed Total
Infectious
11
03
00
02
02
018
Syndromes
04
03
00
00
01
008
Hereditary
03
06
00
01
04
014
PFV
05
00
10
00
02
017
Idiopathic
43
60
06
17
24
150
Total of patients
66
72
16
20
33
207
PFV= persistent fetal vasculature.
Table 5. Association between pediatric cataract and the occurrence
of strabismus
Orthophoria
Esotropia
Exotropia
Total
Congenital
52 (44.4%)
40 (34.2%)
25 (21.3%)
117
Developmental
47 (52.2%)
20 (22.2%)
23 (25.5%)
090
Total of patients
99
60
48
207
Cataract
respectively), as well as similar rates of cataract laterality (47.3% of bi­­­
lateral cataract vs. 52.7% unilateral cataract). Laterality may indicate
the etiology. In this study, we found that bilateral cataracts were usually
associated with syndromes or a familial history (hereditary) of the disease. Unilateral cataracts occurred more frequently in cases of PFV and
congenital rubella. A previous study of unilateral congenital cataracts
found that almost all unilateral cases were due to PFV(17).
Analysis of the etiology revealed that idiopathic cataracts occurred most frequently (72.5%) followed by cataracts caused by congenital infections (8.7%) such as rubella. In agreement with the results
of an earlier study, we found that 17 patients (8.2%) had cataracts
associated with PFV and majority of these cases (16 patients, 94.1%)
had unilateral cataracts(18). Among 8 patients with genetic disorders,
7 had bilateral cataract (87.5%) and all 8 cases had Down’s syndrome.
Hereditary cataracts accounted for only 6.8% of the cases. This rate
is substantially lower than an earlier reported study, which noted
that nearly one-third of the cases were inherited(19). Further, a study
of 85 patients conducted in Tunisia found that 32.5% of the patients
had idiopathic cataract, 42.3% had hereditary cataract, and 4.7% had
cataract caused by infection(20).
To establish the etiology of pediatric cataracts the routine work
up protocol should include tests for metabolic disease markers, urine
reducing substance test, and eye examination of relatives (patient’s
parents, grandparents, and siblings). In the recent years, DNA analysis
has been widely used to identify the affected genes. Accordingly,
mutations in crystallins and connexins have been identified to play
important role in the development of cataracts. To date, more than
30 independent loci have been mapped and identified as playing key
roles in inherited cataracts(21-25).
Other measures that could improve the identification of the etio­
logy of pediatric cataracts include a questionnaire regarding exposure
to environmental risk factors or chemicals and implementation of
polymerase chain reaction (PCR)-based tests to detect viral infection
of the lens. We performed serum calcium test to detect parathyroid
disorders and found that total serum calcium was normal in all the
patients.
Accurate diagnosis of the etiology of pediatric cataract is important for epidemiological studies and future preventive actions.
Pediatric cataracts exhibit substantial heterogeneity. The opacity
of the lens may affect the lens nucleus or alternatively the nucleus
could remain transparent while the cortex or the lamellae surrounding the nucleus become opaque. The morphological diversity makes
the morphological classification a challenging task. Additionally, there
exists the possibility for overlapping morphologies. We found that
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Arq Bras Oftalmol. 2014;77(3):143-7
zonular cataracts occurred with the highest frequency, in 72 (33.8%)
patients. Among these cases, the lamellar subtype (Figure 2) was the
most common (66.7%). Total cataract occurred in 66 (31.9%) patients
(Figure 1).
Morphology or laterality of pediatric cataract may be indicative
of its etiology. Hereditary cataracts display a variety of phenotypes,
more frequently display a zonular morphology (Figure 3), and are
usually bilateral. In most cases, the opacity of the lens caused by PFV
are unilateral posterior subcapsular, which progress into complete
opacity of the lens. We found that among the PFV patients, 52.94%
had posterior subcapsular cataract (Table 4). Nuclear cataract (Figure 4)
is usually detected at birth, whereas lamellar cataract (Figure 2) develops at a later stage and can be progressive. Visual prognosis may
depend on the morphological type, with less favorable outcomes in
cases of total cataracts(26).
As described earlier, strabismus was diagnosed in 108 (52.2%)
pa­­­­tients. A total of 65 (55.55%) children with congenital cataracts and
43 children (47.77%) with developmental cataracts had strabismus;
this suggested that the earlier the onset of the visual deprivation, the
greater the involvement of the visual pathways. Esotropia was more
frequent in patients with congenital cataracts (34.2%) (Table 5).
In a previous study of children with congenital cataract who underwent lensectomy, strabismus was present in 54.8% of the patients
and esotropia accounted for 64.7% of the cases(27).
A study of ocular alignment after surgery conducted in 41 children
with dense cataracts, among which 27 (66%) developed strabismus,
demonstrated that congenital cataract was associated with a greater
risk for the occurrence of strabismus than developmental cataract.
The study concluded that laterality and the time of onset of the
cataract were not significant risk factors for the development of strabismus. Further, the study showed that there is a significant risk for
the occurrence of strabismus in cases where the visual deprivation
lasted longer than 6 weeks(28). A separate study that analyzed 113
patients who underwent surgery for developmental cataract found
strabismus in 39 patients (34%), a higher incidence rate than that
of the general population. The authors concluded that strabismus
might have an impact on visual acuity in cases of unilateral and total
cataracts. The occurrence of strabismus in children with cataract
can be related to four factors that could affect the visual perception:
reduced vision in one eye with the presence of amblyopia, asymmetry
in visual acuity in bilateral cataract cases, loss of stereopsis, and anisometropia. Parents must be made aware that these patients may
have difficulty in viewing three-dimensional (3D) images in movies
and computers(29).
Programs implementing the red reflex test to detect leukocoria
in newborn and the administration of visual acuity screening tests in
pre-school children are of importance. These tests will enable the
early diagnosis of pediatric cataract, particularly since approximately
50% of pediatric cataract patients do not present with strabismus and
might not be referred on time for appropriate treatment(30).
CONCLUSIONS
Idiopathic etiology was the most frequent cause of cataract in the
group of patients studied. Zonular cataracts were the main morphological type of cataract. Unilateral cataracts occurred more frequently
in cases of PFV. Strabismus was present in 52% of the patients. The
results of our study may help establish a program for earlier and more
accurate diagnosis of pediatric cataracts.
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Arq Bras Oftalmol. 2014;77(3):143-7
147
Original Article
Measurement of choroid thickness in pregnant women using enhanced depth
imaging optical coherence tomography
Medição da espessura da coroide em gestantes utilizando tomografia de coerência óptica com
profundidade de imagem aprimorada
Sertan Goktas1, Ahmet Basaran2, Yasar Sakarya1, Muammer Ozcimen1, Zehra Kucukaydin2, Rabia Sakarya1, Mustafa Basaran2, Erkan Erdogan1, Ismail Alpfidan1
aBSTRACT
RESUMO
Purpose: To investigate choroidal thickness in healthy pregnant women during
different trimesters using enhanced depth imaging optical coherence tomography (EDI-OCT).
Methods: This prospective study included 90 healthy pregnant women in
their first, second, or third trimester (groups 1, 2, and 3, respectively) and 30
non-pregnant healthy women (group 4). The age range for all groups was 18-40
years. Spectral domain optical coherence tomography scans were obtained to
estimate the average choroidal thickness. Using EDI-OCT, we measured choroidal
thickness manually from the outer border of the retinal pigment epithelium to
the inner scleral border at the subfovea, 3 mm temporal, and 3 mm nasal to the
fovea. Differences among groups were analyzed by one-way ANOVA.
Results: We found a statistically significant difference between groups 2 and
group 4 for subfoveal, temporal, and nasal mean choroidal thickness (p=0.007,
p<0.001, p=0.026, respectively). The mean choroidal thickness for group 2 was 395 ±
80 µm, 338 ± 74 µm, and 233 ± 61 µm at the regions subfoveal, temporal, and nasal to
the fovea, respectively. In comparison, the mean choroidal thickness for group 4
was 335 ± 86 µm, 274 ± 54 µm, and 200 ± 53 μm at the regions subfoveal, temporal, and nasal to the fovea, respectively. No statistically significant differences
were found for choroidal thickness among groups 1-4 (p=0.214, p=0.177, p=0.094,
respectively) and between groups 3-4 (p=0.105, p=0.261, p=0.695, respectively)
for all measured points.
Conclusion: Our results suggest that choroidal thickening can occur at the regions
subfoveal, temporal, and nasal to the fovea in the second trimester.
Objetivo: Investigar a espessura da coroide em gestantes saudáveis durante os di­
ferentes trimestres utilizando tomografia de coerência óptica com profundidade de
imagem aprimorada (EDI-OCT).
Métodos: Este estudo prospectivo incluiu 90 gestantes saudáveis nos primeiro,
segundo e terceiro trimestres da gravidez (grupos 1, 2 e 3, respectivamente) e 30 mulheres saudáveis não-gestantes (grupo 4) com faixa etária de 18-40 anos de idade. Foi
realizada tomografia de coerência óptica espectral para estimar a espessura média
da coroide. A espessura da coroide foi medida manualmente da borda externa do
epitélio pigmentar da retina até o limite interno da esclera nas regiões subfoveal, 3 mm
temporal e 3 mm nasal à fóvea utilizando EDI-OCT. As diferenças entre os grupos
foram analisadas com o teste ANOVA unicaudal.
Resultados: Houve diferença estatística significativa na espessura média da coroide
entre os grupos 2 e 4 nas regiões subfoveal, temporal e nasal à fóvea (p=0,007; p<0,001;
p=0,026, respectivamente). A espessura média da coroide no grupo 2 foi: 395 ± 80 µm,
338 ± 77 µm e 233 ± 61 µm nas regiões subfoveal, temporal e nasal à fóvea, respecti­
vamente. Em comparação, a espessura média da coroide no grupo 4 foi de: 335 ±
86 µm, 275 ± 54 µm e 200 ± 53 µm, nas regiões subfoveal, temporal e nasal à fóvea,
respectivamente. Não foi encontrada diferença estatística significativa entre os
grupos 1-4 (p=0,214, p=0,177, p=0,094, respectivamente) e os grupos 3-4 (p=0,105,
p=0,261, p=0,695 respectivamente), para todas as medidas.
Conclusão: Nossos resultados sugerem que há espessamento da coroide nas regiões
subfoveal, temporal e nasal à fóvea no segundo trimestre gestacional.
Keywords: Choroid/anatomy & pathology; Choroid/pathology; Enhanced depth
imaging; Tomography, optical coherence; Diagnostic techniques, ophthalmological; Pregnancy
Descritores: Coroide/anatomia & histologia; Coroide/patologia; Tomografia de coe­
rência óptica; Técnicas de diagnóstico oftalmológico; Gravidez
Introduction
Pregnancy is associated with metabolic, hormonal, and hemody­
namic changes. The renin-angiotensin system regulates salt and
water hemostasis in the body, and both renin and angiotensin levels
increase during pregnancy. These changes lead to increasing blood
volume beginning in the first trimester(1,2). Systemic vascular resistance decreases during pregnancy(3,4), and hemodynamic changes
affect blood pressure. In normal pregnancy, blood pressure initially
decreases until the eighteenth to twentieth gestation week, but then
increases until delivery(5,6). One study reported that total macular volume and foveal retinal thickness increase during pregnancy in the
second and third trimesters because of fluid accumulation(7). During
pregnancy, hemodynamic changes affect other parts of the body,
including choroidal flow.
The choroid is the vascular layer between the retina and the sclera
that provides the blood supply to the eye and plays an important role
in ocular nutrition. Histopathological examination showed that it is
0.22 mm thick posteriorly(8). The choroid is composed of a vascular network that contributes to ocular nutrition through volume regulation
and is extremely sensitive to blood pressure changes. The choroidal
thickness is affected by blood flow and perfusion pressure(9). Therefore,
hemodynamic alterations can affect choroidal thickness.
Submitted for publication: February 12, 2014
Accepted for publication: March 24, 2014
Funding: No specific financial support was available for this study.
Study conducted at Konya Training and Research Hospital, Konya, Turkey.
1
Department of Opthalmology, Konya Training and Research Hospital, Konya, Turkey.
Department of Obstetrics and Gynecology, Konya Training and Research Hospital, Konya, Turkey.
2
148
Arq Bras Oftalmol. 2014;77(3):148-51
Disclosure of potential conflicts of interest: None of the authors have any potential conflicts of
interest to disclose.
Corresponding author: Sertan Goktas. Department of Opthalmology. Konya Research and Training
Hospital, 42090 Meram - Konya, Turkey - E-mail:[email protected]
http://dx.doi.org/10.5935/0004-2749.20140038
Goktas S, et al.
Optical coherence tomography (OCT) provides high-resolution,
cross-sectional digital images of live biological tissues in vivo. With
the use of enhanced depth imaging optical coherence tomography
(EDI-OCT), choroid images can be obtained and the choroidal thickness can be measured. Using OCT, one study reported the choroid
thickness as 287 μm, 261 μm, and 145 μm at subfoveal regions, 3 mm
temporal to the fovea, and 3 mm nasal to the fovea, respectively, in
healthy individuals(10). The change in the choroid thickness may play
a role in the pathophysiology of various ocular conditions.
In the present study, we used EDI-OCT to examine choroidal thickness at each trimester in healthy pregnant women, and then compared these measures with those for non-pregnant healthy women.
Methods
We examined 4 groups in the present study. Group 1 consisted of
30 eyes in 30 healthy women in the first trimester, group 2 consisted
of 30 eyes in 30 healthy women in the second trimester, and group
3 consisted of 30 eyes of 30 healthy women in the third trimester.
Group 4 was the control group and consisted of 30 eyes in 30 healthy
non-pregnant women. Only the right eye was assessed in each study
participant. This study followed the tenets of the Declaration of
Helsinki. All participants provided informed consent. The inclusion
criteria for groups 1, 2, and 3 were healthy pregnant women in their
first, second, or third trimester Inclusion criteria for the control group
(group 4) included an age of 18-40 years old, non-pregnant healthy
regularly menstruating women. High myopic and hyperopic refractive errors greater than -1.0 or +1.0 diopters, or intraocular surgical
intervention were excluded from the study. Subjects with systemic
diseases or conditions that might affect retinal or choroidal thickness
were excluded. For example, patients with diabetes mellitus were
excluded. Pregnant with high blood pressure was excluded. In addition,
patients with any retinal or choroidal abnormalities detected in
spectral-domain OCT scans were excluded.
All subjects underwent a thorough ocular examination, including
an auto-refractometer, best-corrected visual acuity measurement,
slit-lam­­­p examination, intraocular pressure measurement, and dila­­­ted
funduscopy. Choroidal thickness was measured using a spectraldo­­­main OCT device (Spectralis: wavelength, 870 nm; Heidelberg
Engineering, Germany) with an enhanced depth-imaging mode
after pupil dilation. All measurements were performed in the morning. The horizontal section running through the center of the fovea
was selected for further analysis. The OCT images were assessed
independently by 2 ophthalmologists.
The choroidal thickness was measured from the outer portion of
the hyperreflective line, corresponding to the retinal pigment epi-
thelium, to the inner surface of the sclera. Choroidal thickness was
measured at the fovea and at positions 3 mm temporal, and nasal to
the fovea. The values of the measurements were compared for each
observer and then averaged for analysis.
Diastolic blood pressure, systolic blood pressure, and ocular perfusion pressure were measured for each subject. Ocular perfusion
pressure was calculated according to the following formula(11): Ocular
perfusion pressure = mean blood pressure - intraocular pressure.
Statistical calculations were performed using SPSS (Statistical
Package for Social Sciences version 15.0; SPSS, Inc., Chicago, IL). Choroidal thickness is presented as the mean ± standard deviation. The
Kolmogorov-Smirnov test was used to assess correlations for data
with a normal distribution. Groups were compared with an analysis
of variance (ANOVA) and post hoc tests. The differences in choroidal
thickness detected by ANOVA and post hoc tests between healthy
(control group) and pregnant individuals were also analyzed by the
t-test. P values less than 0.05 were considered significant.
Results
Ninety eyes in 90 healthy pregnant women and 30 eyes of 30
age-matched healthy non-pregnant women were included. The
mean gestational age was 7.4 ± 2.6, 19.2 ± 2.9, and 33.1 ± 2.8 weeks
in groups 1, 2, and 3, respectively. Mean age was 28.5 ± 6.4, 26.6 ±
4.2, 26.9 ± 6.2, and 29.4 ± .2 years, in groups 1, 2, 3, and 4, respectively. There were no statistically significant differences in age among
the groups (p=0.183). Representative EDI-OCT scans for a pregnant
women and the control group is presented in figure 1. Table 1 shows
the mean choroidal thickness values for the groups that were mea­
sured at subfoveal regions, and those 3 mm nasal to fovea, and 3 mm
temporal to fovea. There were statistically significant differences
in subfoveal, temporal, and nasal choroidal thickness among the
groups (p<0.05). The mean subfoveal, temporal, and nasal choroidal
thickness was significantly greater in group 2 compared with the
control group (p=0.007, p<0.001, p=0.026, respectively). There was no
difference in mean subfoveal, nasal, and temporal choroidal thickness
between group 1 and the control group (p=0.214, p=0.177, p=0.094,
respectively). There was also no statistical significance among the 3
groups and control group for the mean subfoveal, temporal, and nasal
choroidal thickness (p=0.105, p=0.261, p=0.695, respectively). Figure 2
shows the distribution of choroidal thickness according to group.
The ocular perfusion pressure was 36.3 ± 3.5 mmHg in pregnant
women and 37.3 ± 2.8 mmHg in the control group. No significant
correlations were found between the choroidal thickness and ocular
perfusion pressure, gestational week.
A
B
Figure 1. A) Optical coherence tomography image from the control group demonstrating enhanced depth imaging on Spectralis
(Heidelberg Engineering). The choroidal thickness was measured from the outer portion of the hyperreflective line, corresponding
to the retinal pigment epithelium to the inner surface of the sclera at the subfovea, 3 mm temporal, and 3 mm nasal to the fovea.
Calipers were positioned manually using computer software provided by the manufacturer. B) Optical coherence tomography
image from second trimester, which depicts the increased the choroidal thickness.
Arq Bras Oftalmol. 2014;77(3):148-51
149
Measurement of choroid thickness in pregnant women using enhanced depth imaging optical coherence tomography
Table 1. Mean choroidal thickness values (µm) for each group
Location
Group 1
(n=30)
first
trimester
Group 2
(n=30)
second
trimester
Group 3
(n=30)
third
trimester
Group 4
(n=30)
P* control
Subfoveal
362 ± 81
395 ± 80
368 ± 70
335 ± 86
0.037
Temporal
297 ± 73
338 ± 74
293 ± 72
274 ± 54
0.004
Nasal
225 ± 60
233 ± 61
205 ± 46
200 ± 53
0.044
Values are presented as the mean ± SD.
*= ANOVA test.
Figure 2. Graph showing subfoveal, temporal, and nasal choroidal thickness distribu­
tion according to groups.
Discussion
Pregnancy can affect the eyes. Non-pathological events occurring
during pregnancy includes reduced corneal sensitivity and increased
corneal thickness related to the water retention. Choroidal thickness
changes can be expected because of this water retention. There are
some additional pathologic conditions reported to develop during
pregnancy such as central serous chorioretinopathy(12). However, few
studies have investigated choroid thickness in pregnant women(13-15).
Takahashi et al. have demonstrated that there was no significant
difference in choroidal thickness between healthy pregnant and
non-pregnant women at the subfoveal and other measurement
points(13). However, only the pregnant women in the third trimester
were included in that study. Similarly, we did not find any difference
in choroidal thickness measurement between pregnant women in
the third trimester and the control group. Kara et al. investigated
pregnant women in 15-38 weeks of gestational age(14). They reported
that subfoveal choroidal thickness increased in pregnant women
but no significant correlation between the choroidal thickness and
gestational age was found. Sayin et al. investigated pregnant women
in 17-37 weeks of gestational age(15). They reported that subfoveal
choroidal thickness increased in pregnant women and found that negative correlation between the choroidal thickness and gestational
age. As distinct from these studies, we examined the mean choroidal
thickness in pregnant subjects in each trimester via EDI-OCT. To our
knowledge, the current study is the first to investigate the choroidal
thickness in three trimesters compared with non-pregnant healthy
women. It can be considered as an important finding that the choroidal thickness significantly increased in the second trimester but it
did not change in the first and third trimesters.
While blood volume progressively increases, a rapid increase is typically noted until mid-pregnancy, with a slower increase thereafter.
150
Arq Bras Oftalmol. 2014;77(3):148-51
Additionally, during pregnancy, vascular resistance decreases from the
fifth week of the gestation due to hormonal change(3,4). As vascular
resistance decreases, vascular compliance increases(16). The decrease
of the vascular resistance results in reduced blood pressure particularly in the mid-pregnancy. Thereafter, systemic pressure begins to
increase again and ultimately reaches or exceeds the pre-pregnancy
level(17). The reduction of blood pressure and systemic vascular resistance, which is observed particularly in the middle of preg­nancy, may
explain the increase in choroidal thickness in the second trimester.
During pregnancy blood flow increases in many organs, including
the kidneys, extremities, and skin(18-20). One study reported increa­sed
ocular blood flow during pregnancy caused by vasodilation due to
estrogen change(21). We suggest that increased choroidal thickness
may be secondary to increased blood flow.
Choroidal changes during pregnancy may play a vital role in the
pathophysiology of ocular diseases such as central serous chorioretinopathy. Choroidal vasodilation and choroidal vascular hyperpermeability causes subsequent vascular leakage resulting in increased
hydrostatic pressure in the choroid. Recent studies demonstrated a
significantly increased choroidal thickness in patients with acute central serous chorioretinopathy(22,23). Central serous chorioretinopathy
may be caused by an increased hydrostatic pressure in the choroid.
Pregnancy is one of the several known risk factors for central serous
chorioretinopathy, which commonly develops in the third trimester(24).
We speculate the increased choroidal thickness observed in the second trimester may be the causative factor underlying development
of central serous chorioretinopathy in the third trimester. This may
explain why central serous chorioretinopathy is more commonly
observed in the third trimester.
The current study has several limitations. First, we did not measure ocular blood flow. Color Doppler imaging can measure the velocity
of blood and vascular resistance within each vessel(25). Although this
technique is useful for determining choroidal blood flow, it does not
provide three-dimensional anatomical information about the choroidal layers. In our study, ocular blood flow was not examined; the­
refore, our study cannot determine the relationship between cho­­­roidal
thickness and ocular blood flow. We can speculate that the thicker
choroid may indicate an overall increase in choroidal blood flow in
pregnant women, as was previously demonstrated with a pulsatile
ocular blood flow pneumotonometer(21). Therefore, it is likely that
the increased choroidal thickness may be related to increased ocular
blood flow. Another limitation of our study was the small number of
participants.
High refraction and age affect the thickness of the choroid(10,26).
Consequently, in our study we included similar groups with respect
to meaningful characteristics, such as age and refraction, for both the
pregnant and control groups.
In conclusion, our study showed a significant increase in choroidal thickness in the second trimester whereas there was no increase
in the choroidal thickness during the first and third trimesters. These
data favor the idea that in pregnant women, increased choroidal
thi­ckness may lead to increased vascular permeability, which can
explain the relationship between pregnancy and central serous cho­
rioretinopathy. Further studies with a larger number of subjects should
be performed in a pregnant population to correlate choroidal blood
flow with choroidal thickness.
References
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thickness measured by spectral domain optical coherence tomography: factors
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13. Takahashi J, Kado M, Mizumoto K, Igarashi S, Kojo T. Choroidal thickness in pregnant
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14.Kara N, Sayin N, Pirhan D, Vural AD, Araz-Ersan HB, Tekirdag AI, et al. Evaluation of
sub­foveal choroidal thickness in pregnant women using enhanced depth imaging
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15. Sayin N, Kara N, Pirhan D, Vural A, Araz Ersan HB, Tekirdag AI, et al. Subfoveal choroidal thickness in preeclampsia: comparison with normal pregnant and nonpregnant
women. Semin Ophthalmol. 2014;29:11-7.
16. Spaanderman ME1, Willekes C, Hoeks AP, Ekhart TH, Peeters LL. The effect of pregnancy
on the compliance of large arteries and veins in healthy parous control subjects and
women with a history of preeclampsia. Am J Obstet Gynecol. 2000;183(5):1278-86.
17. Duvekot JJ, Cheriex EC, Pieters FA, Menheere PP, Peeters LH. Early pregnancy changes
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18. Dunlop W. Serial changes in renal hemodynamics during normal human pregnancy.
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21. Centofanti M, Migliardi R, Bonini S, Manni G, Bucci MG, Pesavento CB, et al. Pulsatile
ocular blood flow during pregnancy. Eur J Ophthalmol. 2002;12(4):276-80.
22.Tan CS, Cheong KX, Sadda SR. Change in subfoveal choroidal thickness in central
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24. Gass JDM. Central serous chorioretinopathy and white subretinal exudation during
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VII Congresso Brasileiro da SOBLEC
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Informações:
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Arq Bras Oftalmol. 2014;77(3):148-51
151
Original Article
Ocular biometry and central corneal thickness in children: a hospital-based study
Biometria ocular e espessura corneana central em crianças: um estudo de base hospitalar
Adem Gul1, Cagatay Caglar2, Adnan Cınal3, Tekin Yasar4, Adil Kılıc5
ABSTRACT
RESUMO
Purpose: To investigate the distribution of axial length, anterior chamber depth,
lens thickness, vitreous chamber depth, and central corneal thickness in children
at different age groups.
Methods: We studied 364 eyes in 182 children with ages between 1 and 12 years.
Axial length, anterior chamber depth, lens thickness, and vitreous chamber depth
were measured by ultrasound biometry. Central corneal thickness was measured
by ultrasound pachymetry in all children.
Results: The mean age was 6.54 ± 3.42 years. The axial length was 20.95 mm in
1-2 years old and 22.95 mm in 11-12 years old. The central corneal thickness was 556 µm
in 1-2 years old and 555 µm in 11-12 years old. The mean anterior chamber depth
and vitreous chamber depth increased with age (3.06 mm to 3.44 mm in anterior
chamber depth, 13.75 mm to 15.99 mm in vitreous chamber depth), and the lens
thickness decreased as age increased (3.67-3.51 mm).
Conclusion: The axial length increased with age and reached adult levels by the
age of 9-10 years. The lens thickness gradually decreased until 12 years. The central
corneal thickness measurements did not yield a linear algorithm.
Objetivo: Investigar a distribuição do comprimento axial, profundidade da câmara
anterior, espessura do cristalino, profundidade da câmara vítrea e espessura corneal
central em crianças em diferentes faixas etárias.
Métodos: Foram estudados 364 olhos de 182 crianças entre 1 e 12 anos de idade. O
comprimento axial, a profundidade da câmara anterior , a espessura do cristalino e a
profundidade da câmara vítrea foram medidos por biometria ultrassônica. A espessu­ra
corneal central foi medida por paquimetria ultrassônica em todas as crianças.
Resultados: A idade média foi de 6,54 ± 3,42 anos. O comprimento axial foi 20,95
mm no grupo de 1-2 anos de idade e 22,95 mm no grupo de 11-12 anos de idade. A
espessura corneal central foi 556 µm no grupo de 1-2 anos de idade e 555 µm no grupo
de 11-12 anos de idade. A profundidade da câmara anterior média e profundidade da
câmara vítrea aumentou com a idade (3,06 mm a 3,44 mm de profundidade da câmara
anterior, 13,75 mm a 15,99 mm de profundidade da câmara vítrea) e da espessura do
cristalino diminuiu com o aumento da idade (3,67 mm a 3,51 mm).
Conclusões: Em nosso estudo, os valores do comprimento axial aumentou com a
idade e atingiu os níveis adultos aos 9-10 anos de idade. A espessura do cristalino
diminuiu gradualmente até os 12 anos de idade. As medições de espessura corneal
central não seguiu um algoritmo linear.
Keywords: Biometry; Cornea/anatomy & histology; Axial length eye; Child
Descritores: Biometria; Córnea/anatomia & histologia; Comprimento axial do olho;
Criança
INTRODUCTION
Ocular biometry, the refractive status of developing human eyes
and how they change with age, is essential for understanding the
ocular growth and development of other ocular pathologies.
Many published studies have examined ocular biometry in older
populations and have provided significant data. However, there are
few population-based age norms for ocular biometry in children
due to the technical difficulties in measuring biometric parameters,
particularly in small children(1). When we searched for pediatric ocular
biometric studies in the ophthalmology literature, we noted some
restrictions in the design of previous studies, particularly those with
school-age children. There was a paucity of data regarding biometry
and central corneal thickness in preschool children. We decided to
search for both preschool and school age children to investigate
the normal distribution of axial length and central corneal thickness
among children in different age groups.
Ocular biometric status varies in different ethnicities. Therefore,
data from different areas and ethnicities should be studied. In this
article, we present data for ocular biometry and central corneal thickness in a pediatric population. This data contributes to the literature
by studying the Caucasian population in the eastern region of Turkey.
Submitted for publication: November 22, 2013
Accepted for publication: March 20, 2014
Funding: No specific financial support was available for this study.
Study conducted at Yuzuncu Yil University, Van, Turkey.
Ophthalmology Department, Ondokuz Mayis University, Samsun, Turkey.
Ophthalmology Department, Hitit University, Corum, Turkey.
Beyoglu Eye Research and Training Hospital, Istanbul, Turkey.
4
Ophthalmology Department, Yuzuncu Yil University, Van, Turkey.
5
Ophthalmology Department, Balikesir University, Balikesir, Turkey.
1
2
METHODS
This study was carried out in Yuzuncu Yil University, Faculty of Medicine, Ophthalmology Department. It was approved by the Human
Ethics Committee at Yuzuncu Yil University. The research adhered to
the tenets of the Declaration of Helsinki.
The study was performed prospectively. Subjects were children
between the ages of 1 and 12 years. The subjects were divided according to age into six groups: 1-2 years, 3-4 years, 5-6 years, 7-8 years,
9-10 years, and 11-12 years. The exclusion criteria were an ocular trauma, ocular surgery, uveitis, glaucoma, cataract, corneal pathologies,
vitreous pathologies, retinal pathologies, or premature retinopathy. We
did not include children younger than 12 months.
Disclosure of potential conflicts of interest: None of the authors have any potential conflicts of
interest to disclose.
Corresponding author: Adem Gul. Korfez Mah. Mehmet Akif Ersoy Bulvari, 84/15 - Atakum, Samsun
- Turkey - E-mail: [email protected]
3
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Arq Bras Oftalmol. 2014;77(3):152-4
http://dx.doi.org/10.5935/0004-2749.20140039
Gul A, et al.
We measured axial length (AL), anterior chamber depth (ACD),
lens thickness (LT), vitreous chamber depth (VCD), and central corneal
thickness (CCT). AL and CCT measurements were performed with
the US-1800 Echoscan (Nidek, Japan) using of A-scan biometry and
pachymetry probes via the contact method. The measurements were
taken after instilling anesthetic drops (proparacaine) on the cornea.
On average, 5 measurements were taken with the pachymetry probe and 10 measurements were taken with the biometry probe to
obtain better results. All measurements were taken between 08:30
and 11:30 a.m.
In this study, 364 eyes in 182 individuals were examined. Bilateral
evaluation was performed for all patients. The measurements were
taken under general anesthesia for 67 patients who had an intervention (probing) for naso-lacrimal dacryostenosis. The measurements
were taken during the pre-intervention period in patients who had
probing. All measurements were taken by the same ophthalmologist.
Statistical analyses were completed with independently paired
t-tests, ANOVAs, and correlation tests.
RESULTS
The mean age was 6.54 ± 3.42 years. For girls, the mean age was
6.61 ± 3.50 years in girls and 6.41 ± 3.30 years in boys. There was no signi­
ficant age difference between boys and girls. Among all subjects, 63%
were boys and 37% were girls; the ratio was 1.70 (n: boys/girls: 115/67).
The mean CCT was 556 ± 34 µm. There was a significant dif­­ference
between the age groups in terms of CCT. The mean AL, ACD, LT, and
VCD were 22.02 ± 1.19, 3.22 ± 0.36, 3.58 ± 0.23, and 15.17 ± 1.11 mm,
respectively. Details for the age groups are given in table 1. Significant
differences in the age groups were observed in the AL, ACD, LT, and
VCD results.
Increasing age was significantly correlated with increasing AL,
ACD, and VCD (p=0.000, p=0.000, p=0.000, respectively). Although
there was a significant positive correlation between AL, ACD, and
VCD, there was also a significant negative association between all
of the above measurements and the LT (p=0.054, p=0.000, p=0.000,
respectively). An important finding was that LT decreased as the age
increased (p=0.000).
When we compared girls and the boys, there were significant
differences in AL, ACD, and VCD (p=0.000, p=0.001, p=0.000, respectively), but there was no correlation in terms of CCT and LT (p=0.128,
p=0.147, respectively). The AL was 0.74 mm longer in boys than in
girls (Graphic 1).
the distributions of ocular biometry and CCT were documented in
a hospital-based sample of children between 1 and 12 years of age.
When we reviewed the literature on ocular biometry with focusing
on children, most data was from older children between 5 and 16
years of age(4-7).
In the literature, AL in newborns ranged from 17 to 17.3 mm, and
rapid increase was found in the postnatal period. The AL reached
20.6 mm after the first year of life. This rapid increase continued until
the third year of life. After this rapid phase, increases in AL slowed until
the seventh year and reached adult size at 10 years old(8-10). Our study
found similar results showing that AL reached 20.49 mm after the first
year of life and reached adult levels between 9 and 10 years of age.
Gordon et al. performed a study with age groups that reported
eye growth increased approximately 1 mm/year during the first 2
years of life, 0.4 mm/year between 2 and 5 years, and 0.1 mm/year
between 5 and 15 years(9). In our study, similar findings showed that
eye growth increased about 1 mm/year in the first 2 years of life and
increased 0.3 to 0.4 mm/year after 2 years. The average annual growth
rate in our study was 0.26 mm, and we did not observe a linear increase in AL.
Our study also examined whether there were differences between
girls and boys. Girls tended to have shorter eyes compared to boys.
The males are typically have a deeper anterior chamber and a larger
vitreous chamber. In the present study, the AL was 0.74 mm longer in
boys than in girls. This finding is consistent with Zadnik et al., who reported that AL was longer in boys(10). Twelker et al. and Ojaimi et al. studied AL in school-age children and reported the same findings(11,12).
In our study, lens thickness was 3.67 mm in the first 2 years of
life and 3.51 mm in 11-12 years (Graphic 2). Zadnik et al. studied
869 children between 6 and 14 years of age and reported that there
was a decrease in lens thickness between 6 and 10 years(13). Saw et
al. studied myopic children who were between 7 and 9 years of age
and reported a decrease of about 0.01 mm in lens thickness over 3
years(14). The same finding was also present in Shih et al.’s study, which
DISCUSSION
The most striking aspect of our study was that it was not performed with postmortem subjects or with congenital cataract patients,
as could be observed in some studies(2,3).
Ocular biometry
Graphic 1. Axial length in boys and girls.
Most of the studies with A-scans were conducted with adolescent and adult subjects. In this study, children were studied and
Table 1. Results by age group
1-2
years
3-4
years
5-6
years
7-8
years
9-10
years
11-12
years
n
30
29
30
33
32
28
CCT
556
547
565
563
550
555
AL
020.49
021.81
021.97
022.25
022.66
022.95
ACD
003.06
003.20
003.02
003.30
003.31
003.44
LT
003.67
003.63
003.59
003.56
003.54
003.51
VCD
013.75
014.94
015.30
015.34
015.76
015.99
n= number; CCT= central corneal thickness (µm); AL= axial length (mm); ACD= anterior
chamber depth (mm); LT= lens thickness (mm); VCD= vitreous chamber depth (mm).
Graphic 2. Lens thickness in age groups.
Arq Bras Oftalmol. 2014;77(3):152-4
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Ocular biometry and central corneal thickness in children: a hospital-based study
showed that a decrease was present in children between the ages of
7 and 11 years(15). Our study found that lens thickness continuously
decreased until 12 years of age. Therefore, we can say that there was
a decrease in lens thickness during the first 12 years of life.
Central corneal thickness
The literature included different results about CCT in children,
ranging from 529 to 564 µm(16-21). The average CCT in our study was
556 µm, and the range was between 448 and 678 µm.
Portellinha et al. reported that CCT is 573 µm in the newborn
and decreases after birth(22). However, they did not find differences
between boys and girls. In our study, there was only a 6-µm difference
between boys and girls, which was not statistically significant.
Prost et al. studied 360 children between 0 and 14 years old(23). In
newborns, the average CCT was 537 µm, and at 14 years of age, the
average was 567 µm. Parentin et al. hypothesized that this decrease
took place during the first and second years of life. They claimed that
rearrangements in collagen bundles and remodeling occurred in the
early years of life(24).
Hussein et al. studied children between the ages of 7 months and
14 years and reported that CCT was 538 µm in children under 2 years
old, 546 µm in children between 2 and 4 years, 565 µm between 5 and
9 years, and 555 µm between 10 and 14 years old. The mean CCT for
all age groups was 549 µm(16). Our present results are similar to that
study. As table 1 indicates, CCT was 556 µm in the first 2 years, 547 µm
between 3 and 4 years, 564 µm between 5 and 8 years, and 553 µm
between 9 and 12 years. We did not identify a gradual decrease or
increase, unlike that reported in other studies(16,22,23) in terms of CCT
during the first 12 years of life. The limitations of our study for CCT
are an insufficient number of subjects and the extreme measurement
results in age groups that make it difficult to obtain a linear algorithm.
In conclusion, axial length was 20.49 mm in first 2 years. It was
increasingly reached adult levels of approximately 22.66 mm during
years 9-10. Lens thickness was 3.67 mm in first 2 years and continuously decreased to 3.51 mm up to 11-12 years old. Central corneal
thickness was 556 µm in the first 2 years, and 555 µm in years 11-12.
There was no linear increase/decrease in central corneal thickness
measurements, which may be due to an insufficient subject number
and extreme values in age groups.
The results of this study may contribute to the literature, parti­
cularly in the aspect of understanding pediatric eye growth and
trea­ting the most common surgical entity (congenital cataract) in
early childhood period.
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8.Isenberg SJ. Physical and refractive characteristics of the eye at birth and during
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Components and Age, Gender, and Ethnicity. Optom Vis Sci. 2009;86(8):918-35.
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Refraction in a Population-Based Study of Australian Children. Invest Ophthalmol Vis
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13.Zadnik K, Mutti DO, Fusaro RE, Adams AJ. Longitudinal evidence of crystalline lens
thinning in children. Invest Ophthalmol Vis Sci. 1995;36(8):1581-7.
14. Saw SM, Chua WH, Gazzard G, Koh D, Tan DT, Stone RA. Eye growth changes in myopic
children in Singapore. Br J Ophthalmol. 2005;89(11):1489-94.
15. Shih YF, Chiang TH, Lin LL. Lens thickness changes among schoolchildren in Taiwan.
Invest Ophthalmol Vis Sci. 2009;50(6):2637-44.
16. Hussein MA, Paysse EA, Bell NP, et al. Corneal thickness in children. Am J Ophthalmol.
2004;138(5):744-8.
17. Shimmyo M, Ross AJ, Moy A, et al. Intraocular pressure, Goldmann applanation tension,
corneal thickness, and corneal curvature in Caucasians, Asians, Hispanics and African
Americans. Am J Ophthalmol. 2003;136(4):603-13.
18. Muir KW, Jin J, Freedman SF. Central corneal thickness and its relationship to intraocu­
lar pressure in children. Ophthalmology. 2004;111(12):2220-3.
19. Yildirim N, Sahin A, Basmak H, Bal C. Effect of central corneal thickness and radius of the
corneal curvature on intraocular pressure measured with the Tono-Pen and noncontact
tonometer in healthy schoolchildren. J Pediatr Ophthalmol Strabismus. 2007;44(4):
216-22.
20. Sahin A, Basmak H, Yildirim N. The influence of central corneal thickness and corneal
curvature on intraocular pressure measured by tono-pen and rebound tonometer
in children. J Glaucoma. 2008;17(1):57-61.
21.Coste R, Cornand E, Denis D. [Central corneal thickness in a pediatric population
using a noncontact specular microscope: a study of 405 cases]. J Fr Ophtalmol. 2008;
31(3):273-8. French.
22. Portellinha W. Belfort R Jr. Central and peripheral corneal thickness in newborns. Acta
Ophthalmol. 1991;69(2):247-50.
23. Prost ME, Oleszczyńska-Prost E. Central corneal thickness measurements in children.
Klin Oczna. 2005;107(7-9):442-4.
24.Parentin F, Pensiero S. Central corneal thickness in children with growth hormone
de­ficiency. Acta Ophthalmol. 2010;88(6):692-4.
Original Article
Conjunctival melanoma: survival analysis in twenty-two Mexican patients
Melanoma conjuntival: análise de sobrevivência em vinte e dois pacientes mexicanos
Rosa Angélica Salcedo-Hernández1, Kuauhyama Luna-Ortiz1,2, Leonardo Saúl Lino-Silva3, Ángel Herrera-Gómez1, Verónica Villavicencio-Valencia1,
Miriam Tejeda-Rojas1, José F. Carrillo1
ABSTRACT
RESUMO
Purpose: To describe the cases of conjunctival melanoma (CM) and report the
disease-free interval (DFI) and overall survival (OS).
Methods: The charts of 22 patients who were admitted to two hospitals between
1985 and 2006 were reviewed for pertinent data, including demographics, site of
involvement in the conjunctiva and sub-sites, surgical treatment, and adjuvant
treatment.
Results: There were 10 (45.45%) males and 12 (54.55%) females. Mean age was
52.3 years. In this group, 15 patients (68.1%) involved the bulbar conjunctiva, and 7
(31.9%) involved the palpebral conjunctiva. Of the 22 patients, 72.72% had a history
of conjunctival melanosis. The average tumor size was 20.4 mm. Eight (36.36%)
patients underwent orbital exenteration, 2 (9.06%) had enucleation, 5 (22.72%)
had wide excision of the lesion followed by radiotherapy, 2 (9.06%) had orbital
exenteration with neck dissection, and the remaining 5 patients (22.72%) were
considered adequately treated only with wide excision. Eight (36.36%) patients
received adjuvant treatment. Disease-free survival at 5 years was 51% and the
overall survival at 5 and 10 years was 50% and 37%, respectively.
Conclusion: Conjunctival melanoma is a rare entity. Tumor behavior is aggressive,
and the optimal treatment is surgery with adjuvant therapy.
Objetivo: Descrever o intervalo livre de doença (DFI) e sobrevida global (OS) de pa­
cientes com melanoma conjuntival (CM).
Método: Prontuários de 22 pacientes que foram internados em dois hospitais entre
1985 e 2006 foram revisados para dados pertinentes, incluindo dados demográficos,
local de envolvimento na conjuntiva e outros locais de acometimento, tratamento
cirúrgico e tratamento adjuvante.
Resultados: Dez (45,45%) homens e 12 (54,55%) mulheres foram selecionados. A
mé­­­dia de idade foi de 52,3 anos. Em 15 pacientes (68,1%) CM envolveu a conjuntiva
bulbar, e em 7 (31,9%) envolveu a conjuntiva palpebral. Dos 22 pacientes, 72,72%
tinham história de melanose conjuntival. O tamanho médio do tumor foi de 20,4 mm.
Oito (36,36%) pacientes foram submetidos à exenteração orbital, 2 (9,06% ) à enu­­clea­­ção,
5 (22,72%) à ampla excisão da lesão seguida de radioterapia, 2 (9,06%) à exenteração
orbital com esvaziamento cervical e os restantes 5 pacientes (22,72%) foram considerados adequadamente tratados apenas com excisão ampla. Oito (36,36%) pacientes
receberam tratamento adjuvante. Sobrevida livre de doença em 5 anos foi de 51% e
sobrevida global em 5 e 10 anos foi de 50% e 37%, respectivamente.
Conclusão: Melanoma conjuntival é uma entidade rara. Comportamento do tumor
é agressivo, e o melhor tratamento é a cirurgia com terapia adjuvante.
Keywords: Conjunctival neoplasms/surgery; Melanoma; Disease-free survival; Sur­­
vival analysis
Descritores: Neoplasias da conjuntiva/cirurgia; melanoma; Sobrevida livre de doença;
Análise de sobrevivência
INTRODUCTION
Ocular melanomas may arise from the eyelids, conjunctiva, and
intraocular and orbital structures. Conjunctival melanoma and primary acquired melanosis (PAM) are pigmented lesions of the ocular
surface. The incidence of conjunctival melanoma is low, estimated
to occur in 0.2 to 0.5 cases/million of the Caucasian population. In
a study of 4,836 patients with melanomas, 5.2% occurred in ocular
structures, from which 85% occurred in the uvea and 4.8% in the
conjunctiva(1,2). However, in recent years there has been a significant
increase in the number of cases of conjunctival melanoma in males,
whereas the incidence of conjunctival melanoma has remained unchanged in females(1,3). Conjunctival melanomas constitute 1% of the
ocular melanomas and can originate from a PAM in 75% of cases or
develop de novo. Generally, it presents as a pigmented lesion although
30% are amelanic(4). Twenty-six percent of cases with metastasis have
been reported without nodular involvement. Other authors have
reported lymph node disease in 41% of patients, with the most affected
lymph nodes being pre-auricular(5). The most significant factors
reported for recurrence and metastatic disease are the presence of
multi-focal tumors, myxoid cells, depth >4 mm, unfavorable locations
(such as palpebral, caruncle, and cornea), scleral extension, advanced tumor node metastasis staging (TNM) and incomplete surgical
excision(4,5). Treatment options for conjunctival melanoma include
surgical excision, excision combined with cryotherapy, radiotherapy,
and topical chemotherapy(6,7). Mortality at 10 years related to the tumor is between 10 and 30%(3). The purpose of this study is to report
the natural history and results of treatment and follow-up of a series
of cases with conjunctival melanoma recorded in a single Mexican
oncology center.
Submitted for publication: February 25, 2014
Accepted for publication: April 22, 2014
Funding: No specific financial support was available for this study.
Study conducted at Instituto Nacional de Cancerología, México, D.F., México.
Department of Head and Neck Surgery, Instituto Nacional de Cancerología, México, D.F., México.
División de Estudios de Posgrado, Universidad Nacional Autónoma de México (UNAM), México,
D.F., México.
3
Departament of Anatomic Pathology, Instituto Nacional de Cancerología, México, D.F., México.
1
2
http://dx.doi.org/10.5935/0004-2749.20140040
METHODS
This is a retrospective study from 1985 to 2006. Thirty clinical charts
of patients diagnosed with conjunctival melanoma were reviewed.
Eight patients were excluded because they refused treatment. The
cases analyzed had been subjected to biopsy in one center spe­cia­
Disclosure of potential conflicts of interest: None of the authors have any potential conflicts of
interest to disclose.
Correspondence address: Leonardo Saúl Lino-Silva. Instituto Nacional de Cancerología, Anatomic
Pathology. Av. San Fernando #22, Col. Sección XVI, Tlalpan, México, D.F., 14080
E-mail: [email protected]
Approval of the Institutional Review Board (IRB): This work was approved for The Comité de
Ética del Instituto Nacional de Cancerología de México, although evaluation of the project by the
Committee was not necessary.
Arq Bras Oftalmol. 2014;77(3):155-8
155
Conjunctival melanoma: survival analysis in twenty-two Mexican patients
lizing in oncology (Instituto Nacional de Cancerología). They were
subsequently surgically resected in our institution or arrived with a previous surgery for evaluation at our centers for a possible subsequent
treatment. All patients had a diagnosis of conjunctival melanoma
confirmed by histology, and all underwent liver function tests, chest
x-ray, and liver ultrasound to rule out distant metastases. Computed
tomography (CT) was performed when the exam results showed
suspicious findings of local infiltration. The 2010 American Joint
Com­­mittee on Cancer (AJCC) staging system was applied to patients
in this series. Treatment with chemotherapy or radiotherapy was
provided to selected patients (refer to the Results section). Overall,
survival (OS) and disease free interval (DFI) curves were constructed
using the Kaplan-Meier method and significant differences were
analyzed with log-rank test.
RESULTS
The clinical-pathological data of the patients are summarized in
table 1. We analyzed 22 patients; 10 (45.45%) were men and twelve
(54.55%) were women. The average age of all patients at the time of
diagnosis was 52.3 years (range: 16-82 years). The mean follow-up
time was 43.5 months (range: 2-218 months). All lesions were unilateral and had caused extensive damage (extension to ocular globe).
Of the 22 patients, 72.72% had a previous history of melanosis. Fifteen
lesions (68.1%) involved the bulbar conjunctiva, and seven lesions
(31.9%) the palpebral conjunctiva. The limbus, fornix, and caruncle
were involved in 9 (40.9%), 8 (36.36%), and 5 (22.72%) cases, respectively. The mean tumor size was 20.4 mm (range: 3-70 mm). Alkaline
phosphatase levels were elevated in 10 (45.45%) cases.
All patients had a diagnosis of melanoma confirmed by histology.
One patient (4.54%) had bone infiltration. At clinical presentation, 6
patients (27.27%) were staged as T1, 12 patients (54.55%) as T3, and
4 patients (18.18%) as T4. One patient (4.54%) had metastatic disease
at the time of diagnosis. The overall survival curves regarding T classification are shown in figure 1. One case (4.54%) had positive lymph
nodes at presentation. The OS curve corresponding to the N factor is
depicted in figure 2 (p=0.004).
Eight (36.36%) patients underwent orbital exenteration, 2 (9.06%)
had enucleation, 5 (22.72%) had wide excision of the lesion followed by radiotherapy, 2 (9.06%) had orbital exenteration with neck
dissection, and the remaining 5 patients (22.72%) were considered
adequately treated only with wide excision.
Eight (36.36%) patients received adjuvant treatment. Four patients (18.18%) received chemo-radiotherapy, 2 patients (9.09%)
received chemotherapy alone, and 2 patients (9.09%) received only
radiotherapy. Disease-free survival at 5 years was 50% and overall
survival rates at 5 and 10 years were 51 and 37%, respectively (Figures 3 and 4). The chemotherapy treatment supplied was based
on carmustine, dacarbazine, and cisplatin, in the case of metastatic
melanoma (two patients). The radiotherapy regimen consisted on
hypo-fractionated stereotactic photon radiotherapy with 70 to 50 Gy
delivered in five fractions in 7 days.
DISCUSSION
The incidence of conjunctival melanoma is low, with an estimated rate of 0.2 to 0.5 per million in the Caucasian population(8).
However, in recent years a significant increase in the number of cases
of conjunctival melanoma has been reported in males with the inci-
Table 1. Clinical characteristics of twenty-two melanomas of the conjunctiva
Case
Sex
Age
Follow up
Survival (months)
Treatment
Metastasis
Outcome
01
Female
16
002
002
OE + ND
Yes, nodal
DOD
02
Male
53
030
258
E + CT
No
DOD
DOD
03
Female
42
036
060
WE + CTRT
No
04
Male
65
020
152
WE + CT
No
DFD
05
Male
47
032
060
WE + ND
No
DOD
06
Female
73
050
001
OE
No
AWD
07
Male
27
258
032
OE
No
DOD
DOD
08
Female
85
020
005
OE + ND
No
09
Male
55
066
017
OE + RT
No
AFD
10
Female
85
010
015
WE*
No
DOD
11
Male
53
040
007
WE*
No
AFD
12
Female
29
005
030
E
No
DOD
13
Male
70
020
012
WE*
No
DFD
14
Female
50
032
007
OE + RT
No
AWD
15
Male
65
050
010
WE*
No
DOD
16
Female
42
045
008
WE*
Yes, bone
DOD
17
Female
56
030
009
OE
No
DOD
18
Male
57
068
008
WE + CTRT
No
DOD
19
Male
60
061
030
OE
No
AFD
20
Female
52
024
024
OE + CTRT
No
AWD
21
Female
40
034
058
OE
No
AFD
22
Female
30
025
063
WE + CTRT
No
AFD
CC= cribriform carcinoma; TNM= tumor, node metastasis staging; AWD= alive with disease; DOD= dead of disease; AFD= alive free of disease; OE= orbital exenteration; E= enucleation;
WE= wide excision; ND= neck dissection; CTRT= chemoradiotherapy. CT= chemotherapy. RT= radiotherapy.
(*) Performed out of our institution.
156
Arq Bras Oftalmol. 2014;77(3):155-8
Salcedo-Hernández RA, et al.
Figure 1. Disease free survival according to Kaplan-Meier. The mean follow up time was
122 months. The 5-years disease free survival was 51%.
Figure 3. Survival by T stage, according to Kaplan-Meier. Tumors in advanced T stage show
the worse prognosis. For T3 tumors, the 5-years survival is 40% and 0% for T4 tumors.
Figure 2. Overall survival according to Kaplan-Meier. The 5-years overall survival was 50%
and the 10-years overall survival was 37%. The mean follow up time was 107 months.
Figure 4. Survival by the N stage, according to Kaplan-Meier. Tumors without nodal
metastasis showed a 5-year survival of 53%, but tumors with nodal metastasis.
dence of conjunctival melanoma remaining unchanged in females(8).
In the present study, we report a male to female ratio of 1:1.2 (45.8%
males and 54.17% females). The age of presentation of conjunctival
melanoma is usually in the fifth decade and it is only exceptionally
observed in patients under 20 years of age, data which are in agreement with our results, with only one patient presented being under
20 years old(9,10).
These tumors may arise de novo or from a pre-existing nevus, or
more frequently from a PAM with proportions highly variable among
different studies. Approximately 50% to 75% originate from areas
of PAM, 4% to 26% from conjunctival nevi and 18% to 39% arise de
novo(8-11). We found that 18 patients (75%) had a previous history of
melanosis. The most common presentation of conjunctival melanoma is a raised, irregular, unilateral pigmented area, brownish-black
in color and most often without other associated symptoms. The
presence of prominent and complex blood vessels is frequent(10). In
our study, all lesions were unilateral, and unlike the most common
symptoms, they included a foreign body sensation and pain in the
affected eye. Fifteen lesions (68.18%) involved the bulbar conjunctiva
and seven lesions (31.81%) involved the palpebral conjunctiva. These
data are in agreement with previous reports(8-10).
The standard management of conjunctival melanomas is wide
sur­gical excision, after which cryotherapy is applied to the normal
residual margins of resection(11). Patients treated initially with tumor
excision alone had a statistically higher recurrence rate than those
treated initially with excision and supplemental cryotherapy(12,13).
Surgical treatment of conjunctival melanoma has evolved to more
conservative procedures. In the past, conjunctival melanoma implied
an orbital exenteration(13).
Prognosis of conjunctival melanoma depends on several factors
previously reported in the literature: thickness >4 mm is associated
with a mortality rate 3.8 times higher than tumors measuring <1 mm
thick(8,10). Lesions located on the palpebral or fornix conjunctiva have
a poorer prognosis with a mortality rate 2.2 times higher than those
located in the bulbar conjunctiva or in the limbus. Conjunctival melanoma of mixed cellular type has three times higher mortality than
melanoma of fusiform cells(14). Lymphatic invasion is associated with
four times higher mortality rate. Amelanotic lesions demonstrate the
most aggressive course and neither age nor gender is significant to
the prognosis(10). According to our results, the prognosis was unfavorable because of the characteristics of the tumor, which showed an
average tumor size of 20.4 mm (range: 3-70 mm), with 68.1% of them
located in the extra-bulbar conjunctiva.
Arq Bras Oftalmol. 2014;77(3):155-8
157
Conjunctival melanoma: survival analysis in twenty-two Mexican patients
As well as other treatment modalities such as cryotherapy, surgical techniques for management of this tumor have evolved slowly,
being performed mainly at oncology centers(9). In conjunctival melanoma, relatively narrow margins are obtained to preserve visual
func­tion. Orbital exenteration (removal of eyelids, eye, membranes,
mucous membranes and orbital content) is reserved for patients with
massive invasive melanomas and for tumors that originate in unfavorable sites (palpebral or fornix conjunctiva). This is mostly because the
palpebral conjunctiva is closely attached to the tarsus by numerous
septal connections and a minor surgical procedure would not give
adequate margins. However, this procedure has not been shown to
increase overall survival of these patients(14). In our study, 8 (36.36%)
patients underwent orbital exenteration, 2 (9.06%) had enucleation,
5 (22.72%) had wide excision of the lesion followed by radiotherapy,
2 (9.06%) had orbital exenteration with neck dissection, and the
re­­maining 5 patients (22.72%) were considered adequately treated
only with wide excision. Eight (36.36%) patients received adjuvant
treat­ment. Treatment with exenteration was indicated by the size
and extent of the melanoma because these tumors were larger than
those reported in the literature.
Our results show that 6 patients had a T1 tumor. All of them were
treated with wide excision with no adjuvant treatment, and showed
no recurrence after a long term survival. In figure 1, as well, the prog­
nostic significance of the T classification of the tumor is demonstrated, which has been pointed out previously(15). These findings raise
the case against the indiscriminate use of orbital exenteration, which
could be reserved for T4 and selected T3 cases, since no real improvement in survival is obtained with this procedure. However, recently,
other studies have found greater significance for multi-focality and
status of surgical margins, which may require surgery that is more
extensive and/or radiotherapy to achieve local control(16). Therefore,
our results show that the use of chemotherapy alone or combined
with radiotherapy appears to give a survival benefit to our patients
(not extensively analyzed because of the small number of patients
of our series) and it helps to plan the surgical treatment with a less
invasive approach.
It is estimated that ~50% of patients present recurrence at 10 years(14).
A recent review set a survival rate at 5 and 10 years of ~85% and
70%, respectively(17). Overall mortality reported in different studies is
~25%(10). In this study, 18% of patients developed late cervical metastases, pre-auricular and sub-mandibular lymph nodes involvement
in descending order. This is due mainly to the fact that lymphatic
channels exist in all parts of the stroma of the conjunctiva and these
nodes mainly drain these sites(18). Of the total patient pool, 18.18%
died because of melanoma metastases.
In this study, the disease-free survival at 5 years was 51% and
overall survival at 5 and 10 years was 50% and 37%, respectively. This
is lower than reported in the literature because the tumor characteris­
tics in our study had an unfavorable prognosis. While the primary
treatment of eyelid and conjunctival tumors is frequently surgical,
se­­veral forms of ophthalmic radiation therapy have also been used to
treat these malignancies. The goal of radiation therapy is to eradicate
the tumor burden in a manner that maintains visual function and
preserves surrounding sensitive ocular tissues. Ophthalmic radiation
may be used as a curative therapy, as adjuvant treatment following
surgical excision, or as palliative therapy for advanced cases of eyelid and conjunctival tumors(18). Some reports have mentioned that
radiation therapy has not proved useful and generally results in the
loss of the eye as a complication(17-19). However, in our experience and
in the experience of others(18-20), the use of adjuvant therapy is being
increased due the greater prevalence of limited (organ preservative)
resections, with little, but useful, increase in survival and local control.
158
Arq Bras Oftalmol. 2014;77(3):155-8
CONCLUSION
Conjunctival melanomas are rare lesions showing an aggressive
local behavior. They most frequently originate from a primary acquired
melanosis. Any pigmented lesion in the conjunctiva in adults should
be evaluated properly in a way as to rule out melanoma. The most
common location is the bulbar conjunctiva. Surgery remains the cor­­­
nerstone of treatment, and in our study, we found some benefit from
adjuvant therapy, and its usage could determine a less aggressive
surgery. Five- and 10-year survival is reported as 85% and 70%, respectively in tumors staged as T1-T2. This figure decreases to 30% in
tumors classified in higher stages.
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Original Article
Static cyclotorsion measurements using the Schwind Amaris laser
Medições da ciclotorção estática usando o laser Schwind Amaris
Daoud C. Fahd1, Elyse Jabbour1, Charbel D. Fahed1
Abstract
RESUMO
Purpose: To assess the reliability and reproducibility of static cyclotorsion
correction (SCC) measurements made using the Schwind Amaris Excimer laser
in patients undergoing LASIK or PRK, and compare the outcomes of treating
astigmatism with and without SCC.
Methods: Eighty eyes of 40 patients were included in this study. All eyes underwent 2 or 3 sets of five measurements: before and after speculum placement,
and after flap-lift (in LASIK cases). We assessed the reproducibility, accuracy, and
the percentage of “no catch” measurements. The astigmatism was calculated pre-and
3-months-postoperatively by vector analysis.
Results: The mean age of the patients was 23.67 ± 4.19 years. Preoperative spherical
equivalent and astigmatism were -2.56 ± 2.86 D and +1.36 ± 0.98 D, respectively.
The mean measurement time was 15.1 seconds per measurement. The percentages
of “no catch” were: 63.8%, 14.9%, and 26.9%; pre-speculum, post-speculum, and
post flap-lift, respectively. Cyclotorsion of ≥±2° was seen in 41.25% and 66% of
the cases before and after the flap-lift, respectively. Significant cyclotorsion (≥±5°)
was seen in 12.50% and 18% of the eyes pre and post flap-lift. The mean as­­­­tigma­
tism dropped from +1.53 D@1° to +0.34D@3° when SCC was used and from
+1.86D@1° to +0.23D@7° when SCC was not used. No statistical difference was
noticed between the groups (p>0.05) in the postoperative residual astigmatism.
A postoperative astigmatism of ≥1 D was seen in 10% and 20% of eyes with and
without SCC, respectively (p<0.01).
Conclusion: Although not always feasible, the SCC measurement is a simple and
useful tool. Postoperative astigmatism showed less variability when SCC was used.
Objetivo: Avaliar a confiabilidade e reprodutibilidade da correção da medida de
ciclotorção estática (SCC), realizada com o excimer laser Schwind Amaris em pacientes
submetidos a LASIK ou PRK, e comparar os resultados do tratamento de astigmatismo
com e sem SCC.
Método: Oitenta olhos (40 pacientes). Todos os olhos foram submetidos a 2 ou 3 séries
de 5 medições: antes e após a colocação do espéculo, e depois do levantamento do flap
(nos casos de LASIK). Foram avaliadas a reprodutibilidade, a precisão e a porcentagem
de medições “não obtidas”. O astigmatismo foi avaliado no pré-operatório e aos 3
meses de pós-operatório, por meio de análise vetorial.
Resultados: A idade foi 23,67 ± 4,19 anos. O equivalente esférico e o astigmatismo
pré-operatórios foram -2,56 ± 2,86 D, e 1,36 ± 0,98 D, respectivamente. O tempo de
medição médio foi 15,1 segundos por medição; as porcentagens de medidas “não
obtidas” foram: 63,8%, 14,9% e 26,9%; pré, pós-espéculo, e pós-levantamento do flap,
respectivamente. Ciclotorção ≥±2° foi observada em 41,25% e 66 % dos casos pré e
pós-levantamento do flap. Ciclotorção significativa (≥±5°) foi observada em 12,50%
e 18% pré e pós-levantamento do flap. A média do astigmatismo diminuiu de 1,53D @ 1°
para 0,34D @ 3° quando SCC foi usado e de 1,86D @ 1° a 0,23D @7° quando SCC não
foi usado. O astigmatismo residual pós-operatório não foi estatisticamente diferente
entre os grupos (p>0,05). O astigmatismo pós-operatório ≥1D foi observado em 10% e
20 % dos olhos com e sem SCC, respectivamente (p<0,01).
Conclusão: A medição do SCC é fácil e útil, apesar de nem sempre ser possível nem
viável. O astigmatismo pós-operatório apresentou menor variabilidade quando a
SCC foi usada.
Keywords: Astigmatism/physiopathology; Astigmatism/surgery; Torsion abnormality; Keratomileusis, laser in situ; Posture; Photorefractive keratectomy/methods;
Visual acuity
Descritores: Astigmatismo/fisiopatologia; Astigmatismo/cirurgia; Anormalidade
torcional; Ceratomileuse assistida por excimer laser in situ; Postura; Ceratectomia
fo­­torrefrativa/métodos; Acuidade visual
INTRODUCTION
Excimer laser ablation is an effective method for correcting errors
of refraction either by surface treatment or by applying laser under
a corneal flap. Postoperative results depend on proper centration
of the ablation profile on the cornea. Customized excimer laser correction may enable individualized higher-order aberration correction(1).
However, centration and compensation for cyclotorsion are crucial
in these cases. Many patients were noted to have a cyclotorsion
of their eyes when shifting from erect to supine position, with one
study reporting as much as 96% of eyes having cyclotorsion(2) and a
different study reporting an amount as high as 9.5°(3). Compensation
for the cyclotorsion is particularly important in irregular corneas
undergoing topography-guided ablation, in eyes with a significant
cy­lindrical component, or when a wavefront-guided treatment is
de­sired. Not all laser platforms are able to automatically correct for
the cyclotorsion(4,5). The Schwind Excimer Laser Platform takes eye
movements into account and compensates before and during the
excimer treatment.
Previous reports have described the effect of centration and
cyclotorsion correction on postoperative cylinder and uncorrected
visual acuity (UDVA) in eyes with spherocylindrical errors of refraction(1,2,6,7). Here we report the efficacy, reliability, and reproducibility
of Static Cyclotorsion Correction (SCC) measurement using the
Schwind Amaris excimer laser in eyes undergoing LASIK or t-PRK
refractive surgery. We also report the time taken for cyclotorsion
measurements and compare the results of treating astigmatism with
and without SCC.
Submitted for publication: January 10, 2014
Accepted for publication: March 31, 2014
Funding: No specific financial support was available for this study.
Study conducted at Ophthalmic Consultants of Beirut, Jal El Dib, Lebanon.
1
Ophthalmic Consultants of Beirut, Jal El Dib, Lebanon.
http://dx.doi.org/10.5935/0004-2749.20140041
Disclosure of potential conflicts of interest: None of the authors have any potential conflicts of
interest to disclose.
Corresponding author: Charbel D. Fahed. Chairman Department of Ophthalmology, Lebanese
American University - Ophthalmic Consultants of Beirut - 20/20 Bldg, 1st floor - Jal-El-Dib, Metn,
Lebanon - E-mail: [email protected]
Arq Bras Oftalmol. 2014;77(3):159-63
159
Static cyclotorsion measurements using the Schwind Amaris laser
METHODS
This is a prospective study conducted on 80 eyes of 40 patients
operated in the Ophthalmic Consultants of Beirut, Jal el Dib, Lebanon
between the months of May and July of the year 2012. The study was
approved by the institutional review board and the ethics committee
of the Ophthalmic Consultants of Beirut. This study adhered to the
Declarations of Helsinki.
Preoperative testing
Patients wearing soft contact lens were asked to remove their
lenses for at least two weeks prior to performing the topography. Patients wearing hard contact lens were not included in this study. The
preoperative screening consisted of a complete ophthalmic workup,
including UDVA, corrected distance visual acuity (CDVA), manifest
re­­­fraction, ocular motility, and a full slit lamp examination, which
in­­­­­c­­luded a dilated fundus examination. Patients also underwent a
cor­neal wavefront analysis using the Keratron Scout Optikon 2000
Cor­­­­­­neal Wavefront Analyzer (Optikon 2000 S.p.A., Rome, Italy), an
ocular wavefront measurement using the Ocular Wavefront Analyzer
(Schwind Eye-Tech Solutions, GmbH, Kleinostheim, Germany), and a
Placido-Scheimpflug topography using the Orbscan IIZ (Bausch and
Lomb, Rochester, NY). Images used for comparisons of SCC were
obtained using the Keratron analyzer. For imaging, the patient was
asked to sit erect and the head was adjusted to be straight. The head
was positioned such that the vertical axis of the nose was perpendicular to the chin rest. The patient was also asked to look at the fixation
light positioned at the center of the machine with their eyes open.
No speculum or digital lid opening was performed. An experienced
optometrist made all measurements. At least 3 measurements were
made, which were used for assessing the reproducibility using a reproducibility curve. Only the best measurements were used in later
analyses. Pupil centroid shift was recorded and the laser system was
compensated for only when the shift was >0.2 mm in magnitude.
All the details of the study including the surgical procedures were
explained to the patients in detail. An oral informed consent for
measurements and surgery was obtained prior to making the mea­
surements.
Surgical technique and measurements
All procedures were performed by one surgeon (SF) at the same
surgical center using a single excimer laser (Schwind Amaris 500
Ex­cimer laser, Schwind Eye-Tech Solutions, GmbH, Kleinostheim,
Ger­­­many). Both eyes were operated using the same settings. Patients
were given 5 mg of diazepam (Valium®) orally 30-40 minutes before
the start of the surgery. One drop of propacaine (Novocain®) and
one drop of ofloxacin (Oflox®, Allergan) were applied to both eyes on
three occasions, each separated by 2 minute-intervals. The patients
were asked to lay flat on the laser table and measurements were first
made on the right eye. The fellow eye was occluded. Before each
measurement, the patient was asked to look at the blinking fixation
light and the head was adjusted to eliminate any possible head tilt,
with the vertical axis of the nose aligning with the sagittal plane of the
body. Care was taken to ensure that the shoulders were lying equally
flat on the table. The centration lights of the laser were used on the
glabella to ensure that the head was properly positioned (Figure 1,
additional video showing the effect of head rotation on the centration lights can be seen online). The eyes were scrubbed and draped. A
closed-loop speculum with suction was used. The amount of SCC and
the number of “no-catch” trials were recorded before the speculum
was placed, after the speculum was placed, and after the flap was
lifted (in LASIK eyes). When performing t-PRK (30 eyes, 37.5%), a third
set of measurements was not taken and the laser was directly applied
to the virgin cornea.
The cornea of the eyes that were to undergo LASIK (50 eyes,
62.5%) was marked and washed with BSS. The suction ring was
applied and maintained until the pressure on the console reached
160
Arq Bras Oftalmol. 2014;77(3):159-63
Figure 1. Adjustment of head positioning using the centration lights of the
excimer laser on the glabella. A) Patient position on the excimer laser table:
shoulders lying flat on the bed and head facing straight at the fixation light. The
axis of the nose is aligned with the sagittal axis of the body. Three line-lights
are brought into focus and proper superposition as in C). When the chin is
tilted excessively down or up, the lights shows pattern B) or D), respectively.
a value between 600 and 630 mmHg. The flap was done using the
Schwind pendular microkeratome with hinges placed superiorly.
The flap was reflected superiorly along its hinge. Patient position
was examined and adjusted as described earlier, and a third set of
5-SCC measurements was recorded. Following this, laser ablation
was applied. Intraoperative Dynamic Cyclotorsion Control (DCC) was
used in all cases.
All patients received the routine postoperative treatment regimen and follow-up, including steroid, artificial tears, and antibiotic
drops for the first week, a steroid taper for one month, and artificial
tears for at least 3 months(8). Astigmatism (manifest and cycloplegic
cy­­­­linder) was measured preoperatively and at 3 months postoperatively. We assessed the postoperative astigmatism and the effect of
SCC compensation in the eyes that underwent LASIK.
Variables assessed and statistical analysis
We noted the number of times when SCC could not be measured
(percentage “no catch”). The percentage of registration was calculated as, (Eyes in which measurements were successful/Total number of
eyes) x 100%. We recorded the amount of cyclotorsion and subcatego­
rized SCC into those with a negative value (counter-clockwise) and
those with a positive value (clockwise). Time taken for completing
the measurement was also recorded from the moment the “measure”
button was pressed on the screen to the time the result was displayed
on the screen.
Reproducibility, as indicated by the standard deviation and the
accuracy of the measurements were compared. Astigmatism analysis was performed using the polar method of vector analysis(9) with
cycloplegic cylinder values compared. The paired Student t-test was
used for statistical analysis. A p-value less than 0.05 was considered
statistically significant.
RESULTS
Demographics
This study included 80 eyes of 40 patients with mild to moderate
errors of refraction. Thirty eyes (37.5%) underwent t-PRK, and 50 eyes
Fahd DC, et al.
(62.5%) underwent LASIK. The mean age of patients was 23.67 ± 4.19
years. Of the 40 patients, 21 were males (52.5%). The mean preopera­
tive sphere was -3.06 ± 2.82 D (-7.25 D to +4.25 D) with a preoperative
cylinder of +1.36 ± 0.98 D (+0.25 D to +3.00 D). The mean preoperative spherical equivalent (SE) was -2.56 ± 2.86 D. All eyes had a
preoperative CDVA equal to or better than 20/20.
Ability to measure SCC
We were unable to measure SCC in 30 eyes (37.5%) before the
spe­­culum was placed, in 7 eyes (8.8%) after the speculum was inserted, and in 6 eyes (12.0% eyes that underwent LASIK) after the
flap was lifted. In 2 eyes (4.0%) that were to undergo LASIK, the SCC
measurement was not successful after lifting the flap (no-catch in 5
con­­secutive measurements). However, the measurement could be
made before and after the speculum placement.
The percentage of registration was 62.5% pre-speculum, 91.2%
after placing the speculum, and 88.0% after lifting the flap. The per­­
centage of “no catch” in the total number of measurements was 63.8%,
14.9%, and 26.9% pre-and post-speculum placement, and post-flap
lift, respectively.
The mean time taken per SCC measurement was 15.1 ± 2.7 se­
conds (range was 9.0 to 25.0 seconds). The mean time taken for 5
consecutive measurements was 3.6 ± 0.7 minutes (range was 2.0 to
5.5 minutes).
The mean standard deviation between the 5 successive measurements was 2.33° before speculum placement, 1.83° after speculum
placement, and 1.96° after flap lift.
The effect of the flap lift on SCC measurement
In the eyes that had a counterclockwise rotation, the mean SCC was
-3.2° before lifting the flap and -2.8° after lifting the flap (p=0.138),
whereas in the eyes that had a clockwise rotation, the mean SCC
was +4.9° before the flap was lifted and +2.0° after lifting the flap
(p=0.203).
Before lifting the flap, 34 measurements (10.3%) showed an SCC
of 0°, 151 measurements (45.8%) showed >±2° SCC, and 88 mea­­­
surements (26.7%) had an SCC of >±5°. After averaging the 5 mea­
surements for each eye, 4 eyes (5.0%) showed no cyclotorsion, 33
eyes (41.2%) had a cyclotorsion of >±2°, and 10 eyes (12.5%) had a
cyclotorsion of >±5°.
After the flap was lifted, 15 measurements (9.4%) showed an
SCC of 0°, 71 measurements (44.4%) showed >±2° SCC, and 25 mea­­
su­rements (15.6%) showed an SCC of >±5°. After averaging the 5
measurements for each eye, 3 eyes (6.0%) showed no cyclotorsion,
33 eyes (66.0%) had a cyclotorsion of >±2°, and 9 eyes (18.0%) had
a cyclotorsion of >±5°. Figure 3 shows the Bland-Altman plot of the
difference between the measurements made before and after lifting
the flap. The difference was statistically significant and was more pronounced when SCC was >2°. Figure 4 shows the Bland-Altman plot
of the difference in the measurements made before the speculum
The effect of the speculum on SCC measurement
In the eyes with a counter-clockwise rotation, the mean SCC was
-4.3° and -3.2° pre-, and post-speculum, respectively (p=0.304), whereas
in the eyes with a clockwise rotation, the mean SCC was +4.3° and
+4.9° pre-, and post-speculum, respectively (p=0.706).
Before placing the speculum, 11 measurements showed an SCC
of 0° (3.3%), 79 measurements (23.6%) showed an SCC of >±2°, and
36 measurements (10.8%) had an SCC of >±5°. After averaging the
5 measurements for each eye, 6 eyes (15.0%) were found to have no
cyclotorsion, 35 eyes (43.8%) had a cyclotorsion of >±2°, and 14 eyes
(17.5%) had a cyclotorsion of >±5°.
After placing the speculum, 34 measurements showed an SCC
of 0° (10.3%), 151 measurements (45.8%) showed an SCC of >±2°,
and 88 measurements (26.7%) showed >±5° SCC. After averaging
the 5 measurements for each eye, 4 eyes (5.0%) had no cyclotorsion,
33 eyes (41.2%) had a cyclotorsion of >±2°, and 10 eyes (12.5%) had
a cyclotorsion >±5°. Table 1 shows the distribution of SCC measurements based on the amount of cyclotorsion. Figure 2 shows the effect
of the speculum on the SCC measurements. The Bland-Altman plot
shows the difference between measurements made before and after
inserting the speculum. The difference was statistically significant
and was more pronounced when SCC was >2°.
Figure 2. Bland-Altman plot of mean static cyclotorsion correction (SCC) measurements
pre-speculum placement versus the difference in the mean SCC measurements pre- and
post-speculum placement.
Table 1. Distribution of static cyclotorsion correction (SCC) measurements
based on the amount measured, at each time-point
Amount
Time-point
0 ➡ |2|°
Pre-speculum
33.87%
Post-speculum
46.15%
Post-flap lift
38.30%
Pre-Speculum
37.30%
Post-Speculum
22.12%
Post-Flap Lift
38.40%
Pre-Speculum
29.00%
Post-Speculum
31.73%
Post-Flap Lift
22.30%
|2.01| ➡ |5|°
>±5.01°
%
Figure 3. Bland-Altman plot of mean static cyclotorsion correction (SCC) measurements
pre-flap lift versus the difference in the mean SCC measurements pre-and post-flap lift.
Arq Bras Oftalmol. 2014;77(3):159-63
161
Static cyclotorsion measurements using the Schwind Amaris laser
Figure 4. Bland-Altman plot of mean static cyclotorsion correction (SCC) measurements
pre-speculum placement versus the difference in the mean SCC measurements pre-specu­
lum placement and post-flap lift.
placement and after lifting the flap in the eyes that underwent LASIK
surgery. There was no statistical significance between the first and the
last set of measurements.
Study of astigmatism correction
Among the eyes that had a cylinder between +1.00 D and +2.00 D
(40 eyes), those in which SCC measurement was successful (20 eyes)
were compared to 20 matched eyes that underwent LASIK in which
SCC measurement was not possible. The eyes in which SCC measurement was successful had a preoperative cylinder of +1.53 D@1° as
com­pared to a value of +1.86 D@-1° when SCC was not used (p=0.865).
After 3 months of surgery, the mean cylinder became +0.34 D@3° in
the eyes where SCC was used and +0.23 D@7° in the eyes where SCC
was not used (p=0.611). Both preoperative and postoperative cylinders did not show any statistically significant differences between the
groups (p>0.05). Postoperatively, 10% of the eyes had a cylinder ≥1D
when SCC was used and 20% when SCC was not used (p<0.001).
DISCUSSION
The SCC measurement on the Schwind Custom Ablation Manager (CAM) platform is based on an algorithm that registers landmarks
and patterns on the iris and limbus. These landmarks taken from
the topography image are recognized by the cameras of the laser
system. The resultant angular difference between the images is recor­
ded as the SCC. In the Schwind Amaris Excimer laser platform, the
measurement starts from the center of the iris and rotates spirally,
recognizing and registering points on the iris as it rotates. To the best
of our knowledge, this is the first study that assessed the accuracy
and reliability of SCC measurements made using the Schwind CAM
platform. The ablation profile is adjusted to compensate the measured cyclotorsion.
Cyclotorsion can be due to many causes: i) positional (the eyes
cyclorotate when the patient assumes a supine position), ii) secondary
to head tilt (thus assuring a correct position on the laser bed is crucial),
iii) unmasking of a cyclophoria (patients had a motility assessment
preo­­peratively) following monocular occlusion(6,7), or iv) secondary to
distortion of the globe by the speculum. Compensating for the in­­
duced cyclotorsion as a result of assuming a supine position leads to
better results of astigmatism correction(10-12). Although cylinder values
of >1 D were not common, we found that this difference was neither
sta­­tistically nor clinically significant in postoperative cylinder.
It has been reported that the percentage of eyes with “no catch”
varies between 5 to 10%(10,13,14). We found that the percentage of “no
catch” dropped when the speculum was placed. This was expected
162
Arq Bras Oftalmol. 2014;77(3):159-63
since more of the limbus will be exposed when a lid-speculum is
placed and blinking is abolished. SCC registration after lifting the flap
diminished because the image of the iris is less recognizable due to
the stromal dryness.
The mean standard deviation between the 5 successive measurements was 2.3° before speculum placement, 1.8° after speculum
placement, and 2.0° after the flap was lifted. Many practitioners
opt to measure SCC only once before deciding whether or not to
compensate for the SCC while operating. The Schwind Excimer laser
software does not store repeated measurements and only allows
re-measurements if the surgeon suspects the SCC value. Therefore,
it is not possible to have an average of multiple consecutive measurements or to revert to a previously determined value. Additionally,
although we rehydrated all corneas initially and after the second set
of measurements, the measurement time was long, leading to increa­
sed corneal desiccation. The time taken for the SCC measurement
could be shortened by the use of a Sirius Schwind (Schwind Eye-Tech
Solutions, GmbH, Kleinostheim, Germany) instrument (discussion with
company representative).
The variation between the measurements likely originated from
various factors-the ocular surface dries out easily when the eye is left
open by the speculum (since blinking is suppressed) and the time
taken for repeated measurements is relatively long. Additionally, many
of the eyes were found to “wiggle and jiggle” before stabilizing.
If the laser system stored data from successive measurements,
the surgeon will be able to verify the reproducibility and calculate a
weighted average that can be used for customization. Additionally,
faster measurements would lead to less corneal dryness and increase
the yield of measurements. For custom treatments this becomes a
necessity, particularly since rotational malposition can be high(15).
One limitation of this study is that the follow-up was done at
3 months postoperatively. A second limitation is that the precise
assessment of the “wiggle and jiggle” that some patients experience
during the course of the procedure was not possible since the laser
system was not equipped for the continuous video-monitoring of
the eye movement.
CONCLUSION
Although the SCC measurement is a simple and straightforward
ma­­neuver, the measurement is not always possible. There was no
statistically significant difference between the measurements made
pre-and post-speculum placement, and post-flap lift. When the cylinder
was significant, the residual astigmatism correction was better when
SCC was used.
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Surg. 2011;37(3):574-81.
12. Prakash G, Agarwal A, Kumar DA, Jacob S, Agarwal A, Maity A. Surface ablation with
iris recognition and dynamic rotational eye tracking-based tissue saving treatment
with the Technolas 217z excimer laser. J Refract Surg. 2011;27(3):223-31.
13. Arba-Mosquera S, Arbelaez MC. Three-month clinical outcomes with static and dynamic cyclotorsion correction using the SCHWIND AMARIS. Cornea. 2011;30(9):951-7.
14. Aslanides IM, Toliou G, Padroni S, Arba Mosquera S, Kolli S. The effect of static cyclo­torsion
compensation on refractive and visual outcomes using the Schwind Amaris laser
platform for the correction of high astigmatism. Cont Lens Anterior Eye. 2011;34(3):114-20.
15. Swami AU, Steinert RF, Osborne WE, White AA. Rotational malposition during laser in
situ keratomileusis. Am J Ophthalmol. 2002;133(4):561-2.
I Simpósio de Atualização em
Oftalmologia do CEROF/UFG
21 e 22 de novembro de 2014
Sede do Conselho Regional de Medicina de Goiás
Goiânia - GO
Informações:
Tels.: (62) 3928-1416 / 9614-7922
E-mail: [email protected]
Arq Bras Oftalmol. 2014;77(3):159-63
163
Original Article
Is the cost the primary barrier for cataract surgery in Paraguay?
A taxa para a cirurgia é a principal barreira para a adesão à cirurgia de catarata no Paraguai?
Harumi G. Burga1, Celeste N. Hinds1, Van C. Lansingh1,2, Margarita Samudio3, Susan Lewallen4,5, Paul Courtright4,5, Rainald Duerksen1, Pablo Cibils1,
Manuel Zegarra1
ABSTRACT
RESUMO
Purpose: To determine if the cost was the main barrier to undergo cataract sur­
gery in Paraguay.
Methods: We conducted a cohort study with patients screened in the 2011 Rapid
Assessment of Avoidable Blindness (RAAB) who had reported that the cost was
the main barrier to undergo cataract surgery in Paraguay. All patients with operable cataract from the RAAB study and with registered telephone numbers were
interviewed by telephone and were offered free surgery services. The patients
who did not come for surgery were re-interviewed by telephone to analyze the
reasons for not undergoing the operation.
Results: Out of 122 patients identified in the RAAB study with barriers for cataract
surgery, 69 (56.6%) reported that the surgical fee was the main barrier; 52 (75.4%)
of them had their telephone numbers registered. Thirty-six (69.2%) patients did not
reside in the metropolitan area of Asunción. Six patients (12%), all from Asunción,
agreed to undergo free surgery. Forty-six patients did not agree the free surgery
mainly due to the costs associated with their transportation (n=31, 67%) and the
travel costs of their companion (n=6, 13%).
Conclusion: Surgery fee alone was not the major contributing factor for not un­
dergoing cataract surgery. Place of residence and other indirect out-of-pocket
expenses, such as transportation and companion-related costs appear to be more
relevant. While further investigation is needed to assess if reducing the cost of
transport will improve the uptake, the findings in this study suggest that a surgical
package with all costs should be offered to patients of cataract surgical programs
to increase cataract surgical coverage in Paraguay.
Objetivo: Determinar se a taxa de cirurgia é a principal barreira para a adesão à
cirurgia de catarata no Paraguai.
Métodos: Foi realizado um estudo de coorte com pacientes identificados na Avaliação
Rápida da Cegueira Evitável (RAAB) de 2011, que haviam informado ser a taxa para
a cirurgia a principal barreira para se submeter à cirurgia de catarata no Paraguai.
Todos os pacientes com catarata operável a partir do estudo RAAB, cujos números de
telefone foram registrados, foram entrevistados por telefone e foi oferecida a cirurgia
gratuitamente. Aqueles pacientes que não compareceram para a cirurgia foram então
re-entrevistados por telefone para confirmar as suas razões para não fazer a cirurgia.
Resultados: Das 122 pessoas identificadas no estudo RAAB com barreiras para a cirurgia de catarata, 69 (56,6%) relataram a taxa cirúrgica como a principal barreira para
a cirurgia; 52 (75,4%) destes indivíduos tiveram seus números de telefone registrados.
Trinta e seis (69,2%) pacientes não residiam na área metropolitana de Assunção. Seis
pacientes (12%) aceitaram se submeter à cirurgia gratuita, todos eles de Assunção. Dos
46 pacientes que não aceitaram a cirurgia gratuita, as duas principais razões para o
não comparecimento foi o custo de transporte (n=31, 67%) e os custos de viagem de
seu companheiro (n=6, 13%).
Conclusão: A taxa de cirurgia de catarata per se não foi a barreira principal. Local de
residência e outras despesas pessoais indiretas, como transporte e custos relacionados
à companhia parecem ser mais relevantes. Embora mais estudos sejam necessários
para avaliar se a redução do custo do transporte vai melhorar a adesão, os resultados
sugerem que um pacote cirúrgico que inclua todos os custos deve ser oferecido aos
pacientes dos programas de cirurgia de catarata a fim de aumentar a cobertura da
cirurgia de catarata no Paraguai.
Keywords: Cataract extraction/statistics and numerical data; Costs and cost analysis;
Health services accessibility; Paraguay
Descritores: Extração de catarata/estatística & dados numéricos; Custos e análise
de custos; Acesso aos serviços de saúde; Paraguai
INTRODUCTION
The World Health Organization (WHO) recently estimated that over
280 million of the global population is visually impaired and 39 million
of them are blind. Eighty-two percent of the blind and 65% of the
visually impaired are aged 50 and above(1). In Americas, approximately
3.2 million people are blind and 26.6 million people are visually impaired(2).
Cataract is responsible for 33% of the visual impairment worldwide and is the single most important cause of blindness affecting 51%
of the global population. Surveys in Latin America and the Caribbean
show that cataract is the leading cause of blindness and visual impairment, with 47%-87% of individuals bilaterally blinded(3,4).
The cataract surgical rate (CSR), the number of cataract operations
performed per year per million population, though is often associated
with the socio-economic development of the country, this is not
always true, especially in countries such as India and China(5-7). Across
Latin America, the CSR ranges from approximately 900-6,000, with
an average of 2,672(8).
Despite significant developments in the region, unless the regional CSR increases considerably, the VISION 2020 goal of eliminating
avoidable vision loss by cataract will not be met. In developed countries in the region,the visual impairment due to cataract is not a major
issue; however, for developing countries in the region increasing
CSRs remains a challenge due to several factors such as affordability,
place of residence, and difficult-to-reach communities with poor
access to information and services(5). Surgical fees are often reported
as barrier to undergo cataract surgery(9). However, some studies have
suggested that fear of surgery and a low perceived need for better
Submitted for publication: January 20, 2014
Accepted for publication: May 1, 2014
Funding: No specific financial support was available for this study.
Study conducted at Rapid Assessment of Avoidable Blindness (RAAB).
Fundación Visión, Asunción, Paraguay.
IAPB/VISION 2020 Latina America Regional Office.
National University of Asunción, Asunción, Paraguay.
4
Kilimanjaro Centre for Community Ophthalmology, Moshi, Tanzania.
5
Kilimanjaro Centre for Community Ophthalmology, Division of Ophthalmology, University of Cape
Town, Cape Town, South Africa.
1
2
Disclosure of potential conflicts of interest: None of the authors have any potential conflicts of
interest to disclose.
Corresponding author: Harumi G Burga. Quartier Las Marías 5-108. San Lorenzo - Paraguay E-mail: [email protected]
3
164
Arq Bras Oftalmol. 2014;77(3):164-7
http://dx.doi.org/10.5935/0004-2749.20140042
Burga HG, et al.
sight contribute more significantly. Even when free surgical services
are offered, there can be a lack of demand and low utilization(9-11).
In 2011, a Rapid Assessment of Avoidable Blindness (RAAB) survey
was conducted in Paraguay to follow up the RAACS (Rapid Assessment
of Cataract Surgical Services) survey conducted in 2000. The RAAB
survey showed that cataract was the main cause of blindness (43.8%)
and severe visual impairment (40.5%). The results of the study indicated an impressive reduction in the prevalence of blindness from 3.0%
to 1.1% among the people of age 50 years and above; cataract surgical coverage (at<6/60) increased from 36% to 78% and good quality
outcomes of cataract surgeries increased from 64% to 90%(12,13). These
results suggest that cataract is now better managed in Paraguay.
We sought to determine if the fee is the main barrier to undertake
cataract surgery in Paraguay.
METHODS
In October and November, 2011, a Rapid Assessment of Avoidable
Blindness (RAAB) national survey was undertaken in Paraguay(12). The
RAAB study was conducted by five third year ophthalmology residents, supervised by a senior ophthalmologist. All patients identified
in the RAAB with a visual acuity (VA) <6/18 attributed to cataract
in one or both eyes and judged to have an operable cataract. The
pa­tients, who reported that surgical fee was the main barrier to
undergo cataract surgery, were selected for the study. Patients with
incomplete forms, (n=13) and those who refused to respond to the
questionnaire (n=4) were excluded from the study.
All patients were contacted by phone by a trained social worker.
The questionnaire was designed to investigate if the fee for cataract
surgery was a barrier to undergo the surgery. Questions were asked
to reconfirm demographic data, the indication of cataract surgery,
and the issues regarding fees. As part of the study protocol, the social
worker then offered the patient cataract surgery free of charge. The
free surgeries were to be conducted during the cataract surgical campaign in Fundación Vision’s central clinic located in Asunción, Paraguay
and were scheduled to take place within the next two weeks following
the interview. Transportation costs to and from their residence and
accommodation were not provided with the free cataract surgery.
One week after the end of the surgical campaign the patients
who did not attend the free surgery were contacted and re-interviewed by telephone to establish the reasons for failure to attend.
An open ended quasi-structured questionnaire was used to solicit
the responses.
We first analyzed the differences between the people with and
without phone numbers. We next determined the proportion of
tho­se who took advantage of the free surgery service (and factors
associated with acceptance). Finally, we assessed the reasons to opt
out of the free surgery service. Comparisons were made based on sex,
age, province, and pre-operative VA. Data were entered in an Excel 6.0
spreadsheet and subsequently analyzed by SPSS 11.5 (Chicago, IL) for
Windows. Descriptive statistics for socio-demographic characteristics
and causes of nonattendance to cataract surgery nominal variables
were expressed as percentage.
The study was approved by the Investigation and the Medical
Ethics Committee of Fundación Vision, and was performed in accordance with the ethical standards laid down in the 1964 Declaration
of Helsinki. All patients signed a consent form prior to their inclusion
in the RAAB.
RESULTS
From the RAAB survey, among the 2,862 persons studied, 54 people had a bilateral cataract surgery and 75 people had undergone
unilateral cataract surgery. For this study, 122 people had operable
cataract with presenting vision of <6/18 in one or both eyes and qualified the study parameters. The study population included 4 people
who underwent a cataract surgery in one eye and visually impairing
cataract in the other eye. Among the 122 people, 69 (56.6%) reported
that the fee for surgery was the main barrier to undergo cataract
surgery. Other reasons included, fear (n=22), lack of desire to have
surgery (n=9), difficulty accessing surgical facilities (n=7), and other
reasons (n=15). Of the 69 people, 52 (75.4%) had a valid registered
telephone number. Of these, 37 (63.45) had unilateral cataract with
normal vision or vision loss due to other conditions such as refractive
error in the other eye. People with registered phone numbers were
slightly younger than those without phone numbers (Table 1).
After the phone interviews surgical campaign was conducted for
two weeks and offered free cataract surgery to the patients; only 6
out of the 52 people enrolled in the study (12%) attended the clinic
in Asunción for surgery and all were from the metropolitan area of
Asunción (Table 2).
The people who did not take advantage of the free cataract surgery were contacted by telephone after one week after the surgical
campaign. While 31 people (67%) had reported that the cost of transportation was the reason for not coming for the surgery, 6 people
(13%) reported that the cost of transportation of their companion
was the reason. Nine people (20%) mentioned other causes such as
difficulty traveling, other medical conditions, or poor weather conditions. Although the numbers are small, uptake was highest among
those who underwent a previous cataract surgery (50% uptake),
followed by those who had bilateral cataracts, (3/19) and finally those
with unilateral cataract (1/28).
Telephone number registered (n=52)
N (%)
No telephone number (n=17)
N (%)
Odds ratio (95% CI)
p value
71.6 ± 11.0
78.8 ± 8.9
p=0.02
Males
22 (42.3)
09 (52.9)
0.65 (0.22-1.96)
Females
30 (57.7)
08 (47.1)
p=0.62
Metropolitan
16 (30.8)
05 (29.4)
1.07 (0.32-3.53)
Outside metro
36 (69.2)
12 (70.6)
p=0.84
6/18
32 (61.5)
10 (58.8)
1.0 (reference)
<6/18 to 6/60
13 (25.0)
04 (23.5)
1.02 (0.27-3.83)
<6/60 to 3/60
04 (07.7)
01 (05.9)
0.73 (0.07-3.21)
<3/60
03 (05.7)
02 (11.7)
Patient characteristics
Average age (SD)
Sex
Residence
Visual acuity of eye to be operated
*= odds ratio includes <6/60 to 3/60 and <3/60.
Arq Bras Oftalmol. 2014;77(3):164-7
165
Is the cost the primary barrier for cataract surgery in Paraguay?
Table 2. Characteristics of people with cataract who attended the free cataract program
Attended free cataract surgery n=6
N (%)
Did not attend free cataract surgery n=46
N (%)
Odds ratio (95% CI)
p value
Females
4 (13.8)
25 (086.2)
1.68 (0.28-10.10)
Males
2 (09.0)
21 (091.0)
p=0.89
0 (00.0)
09 (100.0)
1.0 (reference)
Characteristic
Sex
Age*
50-59 years
60-69 years
1 (11.1)
08 (088.9)
2.22 (0.17-28.86)
70-79 years
3 (12.0)
22 (088.0)
1.74 (0.17-17.59)
80-89 years
2 (40.0)
03 (060.0)
7.50 (0.59-95.38)
≥90 years
0 (00.0)
04 (100.0)
2.00 (0.10-39.08)
69.8 (±11.1)
72.0 (±11.0)
p=0.22
Metropolitan
6 (37.5)
10 (062.5)
23.55 (2.61-212.67)
Outside metro
0 (00.0)
36 (100.0)
p=0.001
2 (33.3)
30 (065.2)
1.0 (reference)
Average age (SD)
Residence*
Visual acuity of eye to be operated
6/18+
<6/18 to 6/60
3 (50.0)
10 (021.7)
4.50 (0.66-30.91)
<6/60 to 3/60
1 (16.6)
03 (006.5)
2.50 (0.19-32.20)**
<3/60
0 (00.0)
03 (006.5)
6/18+
4 (66.6)
11 (023.9)
1.0 (reference)
<6/18 to 6/60
2 (33.3)
21 (045.6)
0.26 (0.04-1.66)
<6/60 to 3/60
0 (00.0)
08 (017.3)
0.16 (0.02-1.56)**
<3/60
0 (00.0)
06 (013.0)
No cataract surgery received
(unilateral cataract)
1 (16.6)
28 (060.8)
(reference)
Cataract surgery in one eye (cataract
causing vision loss in the second eye)
2 (33.3)
02 (004.3)
28.0 (1.71-458.8) p=0.04
No cataract surgery received
(bilateral cataract)
3 (50.0)
16 (034.7)
5.25 (0.50-54.78) p=0.33
Visual acuity in the better eye*
Previous cataract surgery
*= note in cases with 0 is one or more cells, 1 has been added to each cell to calculate an estimated odds ratio and 95% CI; **= odds ratio includes <6/60 to 3/60 and <3/60.
DISCUSSION
In most cases one can infer that free surgery would provide increa­
se access to patients who would not otherwise consider it; however,
there are always other complex factors involved in the decision to
undergo cataract surgery(14,15).
Lack of awareness, poor quality service, cost of surgery and cultural beliefs, distance to service, lack of escort, and fear are some of major barriers between cataract patients and service providers resulting
in a low uptake in the presence of adequate service availability(15,16).
There were slightly more women in our study compared to men;
however, this reflects the underlying prevalence of cataract in the
population. The average age of people accepting the surgery was
slightly younger than those not accepting the surgery, consistent
with studies in other settings(17).
The most important factor toward acceptance was residence;
while one in three cataract patients living in Asunción accepted surgery, none of those living outside of Asunción traveled to the capital
for surgery.
Some studies reported that the surgical fee is the single most important barrier to cataract surgery uptake(18, 19). If surgical fee is above
the affordable limits of the individual or family, this can be a significant
barrier. However, it should be recognized that families make financial
decisions regarding surgery based upon the total anticipated costs
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Arq Bras Oftalmol. 2014;77(3):164-7
associated with the surgery. Besides the surgical fee, these costs
include additional medications, transport to and from the surgical
facility, food at the surgical facility, transport and accommodation
expenses of the escort, and loss of income during the surgery and
recovery(6,19-21).
In our setting the offer to waive the fee for the surgery (approximately PGY1, 500,000 /US$334) (not including transportation, accommodation or medication) resulted in a low uptake (12%), only comprising
those living in the same metropolitan area as the surgical facility.
Further only one-third of the population living in the city accepted
the surgery.
Our results are consistent with findings from Kenya, Bangladesh,
and the Philippines(22), where free cataract surgery was offered and
only 30% of cases attended. In Nepal, where both transportation and
free surgery were offered, the utilization rate was still below 60%(23).
Similarly, in Tanzania when surgery and transportation services were
offered to those reporting the surgical fee as the primary barrier
to surgery, only a small proportion had accepted(14). In the Tanzanian
setting it was recognized that reporting “too poor to pay” was a convenient response that did not actually reflect reality. While our findings
are similar to the Tanzanian study, since free transport was not offered
in Paraguay it cannot be claimed that offer of free transport would
increase the uptake of surgery. The average cost of transportation
Burga HG, et al.
from the most rural areas of Paraguay to Asunción and back via public
transport (bus) is approximately PGY 80,000/US$20, while accommodation per night per person in moderate lodgings costs about
PGY100,000/US$25. Fundación Vision offers lodging at its central at
a cost of PGY 50,000 for both the patient and the companion. Free
transport offer to many of these patients may not result in a significant uptake of cataract surgery.
Some studies have highlighted the link between acceptance and
lack of information or awareness of the disease and its treatment(6,22).
However, it should be noted that in our setting, all the people with cataract enrolled in the study were provided information twice: during
the RAAB survey and during the phone interviews. Thus, it is unlikely
that lack of information is a contributing factor in the decision to not
to seek surgery.
While visual needs differ from person to person it may be surmised that people with the most reduced vision would more likely opt
for surgery. Evidence in other settings suggests just the opposite. In
the Tanzanian setting people with better pre-operative vision were
more likely to come for surgery. The more elderly and visually disabled did not seek surgery or were not supported by the family to seek
surgery(24). None of the 14 people, 3 from the metropolitan area, with a
best eye vision of <20/200 accepted surgery, similar to the Tanzanian
setting. People with unilateral cataract may not seek care if only one
eye is affected; however, once having had the surgery, it appears
that patients are keen to have the second eye operated. Perceptions
of vision needs can change with a successful operation(14,25). Studies
have noted that patients who had undergone a cataract surgery in
one eye with a good post-operative vision were more inclined to
accept surgery for the second eye as compared with those with poor
outcomes, highlighting the impact of postoperative visual acuity on
decision making(6,25).
There are several aspects of this study which limit interpretations
of findings. Although the study was nationwide, the number of study
participants was limited, making it difficult to assess factors associated with uptake. Few of our patients were blind per WHO definition
from cataract. Further, while participants who did not have a telephone number did not differ significantly with regard to age, sex, and
visual acuity of those with a telephone number. It is likely that those
without a telephone are poorer. The two weeks of free surgery campaign time may be too short for people to adequately prepare and
travel for the surgery. As noted above, we cannot infer with certainty
from our findings that transport is the primary barrier to accept the
surgery among this group. By offering free transport and assessing
the uptake we can further understand the contribution of transport
to undertake the surgery.
In Latin America there is a large gap between the target CSRs to operate on all eyes with VA<6/18 with the regional CSR being 1,425(15,26,27).
Resent analysis in 2012 show that the current CSR in the Latin American region at 2,672 per million with Paraguay at 1,539 indicating that
lot needs to be done to address the multiple factors influencing the
uptake of cataract surgery(5,8).
Our findings suggest that the direct fee for surgery is not the important contributing factor in cataract surgery services in Paraguay.
Similar to Ethiopia, indirect costs such as transportation, accommodation for both the patient and his/her companion, and medication
may play a more significant role in service uptake even if surgery fee
is completely waived(28).
Future work in Paraguay may need to focus on assisting ophthalmologists to work in rural areas of the country as well as conducting
more outreach in which surgeries are done in distant surgical facilities. Programmes should consider “packaging” transportation to and
from the clinics, accommodation, and medicines to reduce indirect
costs. The use of low cost mobile clinical and surgical services may
also be an additional approach to improve access to cataract surgical
services. That being said, further investigation is needed to clarify if
free transportation improves the uptake.
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Arq Bras Oftalmol. 2014;77(3):164-7
167
Original Article
Expression of TNF-α and IL-6 cytokines in the choroid and sclera of
hypercholesterolemic rabbits
Expressão das citocinas TNF-α and IL-6 na coroide e esclera de coelhos hipercolesterolêmicos
Rogil José de Almeida Torres1, Andrea Luchini2, Lucas Younes Barberini1, Leonardo Precoma3,Caroline Luzia de Almeida Torres4,
Robson Antonio de Almeida Torres4, Lucia de Noronha1, Bruna Olandoski Erbano5, Antonio Marcelo Barbante Casella6, Dalton Bertolim Precoma1
ABSTRACT
RESUMO
Purpose: This study aimed to evaluate the expression of the inflammatory cy­
tokines TNF-α and IL-6 in the sclera and choroid of hypercholesterolemic rabbits.
Method: Twenty-one New Zealand male albino rabbits were divided into two
groups: NG and HG. The NG group was fed a standard rabbit diet and the HG group
was fed a cholesterol-enriched diet (1%). The serum total cholesterol, triglyceride,
HDL cholesterol, and fasting blood glucose levels were determined at the beginning
of the experiment and on the day of euthanasia. Euthanasia of animals in the NG
and HG groups was performed at the end of the 4th and 8th week, respectively.
The eyes were analyzed immunohistochemically using TNF-α and IL-6 antibodies.
Results: At the time of euthanasia, the HG group showed a significant increase in
total cholesterol and triglyceride when compared with the NG group (p<0.001).
When compared with the NG group, there was a significant increase in the
expression of TNF-α (p<0.001) and IL-6 (p=0.002) in the choroid and sclera of
animals in the HG group.
Conclusion: This study demonstrates that the hypercholesterolemic diet induces
expression of TNF-α and IL-6 in the choroid and sclera of rabbits.
Objetivo: Avaliar a expressão das citocinas inflamatórias TNF-α e IL-6 na esclera e
coroide de coelhos hipercolesterolêmicos.
Método: Coelhos New Zealand foram organizados em dois grupos: GN recebeu
ração padrão para coelhos; GH recebeu dieta rica em colesterol a 1%. Foi realizada
a dosagem sérica de colesterol total, triglicerídeos, HDL colesterol, glicemia de jejum
no início do experimento e no momento da eutanásia. Ao final da 4 a semana para
o GN e 8a semana para o GH foi realizada a eutanásia dos animais. Os olhos foram
submetidos à análise imuno-histoquímica com os anticorpos TNF-α e IL-6.
Resultados: O GH manifestou significativo aumento do colesterol total e triglicerídeos
em relação ao GN (p<0,001). Houve significativo aumento da expressão da TNF-α
(p<0,001) e da IL-6 (p=0,002) na coroide e esclera dos animais do GH em relação ao GN.
Conclusão: Este estudo demonstra que a dieta hipercolesterolêmica induz ao aumento
da expressão das citocinas TNF-α e IL-6 na coroide e esclera de coelhos.
Keywords: Cholesterol; Macrophages; Cytokines; Tumor necrosis factor; Interleukin-6; Choroid; Sclera; Macular degeneration
Descritores: Colesterol; Macrófagos; Citocinas; Fator de necrose tumoral; Interleucina-6; Coroide; Esclera; Degeneração macular
INTRODUCTION
The inflammation, as an inducer of diseases, is no longer exclusively associated with autoimmune and infectious diseases. Convincing experimental evidence and many histopathological findings
support the current view of inflammation as a critical regulator in
Age-Related Macular Degeneration (AMD)(1,2). Macrophages, retinal
pigment epithelial (RPE) cells, and endothelial cells (EC) play an im­­
portant role in the pathogenesis of ocular inflammation and the
co­­nsequent formation of subretinal neovascular membrane (CNV).
These cells secrete various inflammatory, growth, and angiogenic
factors as well as pro-inflammatory cytokines, which contribute to
the development of wet AMD(3-5). The role of growth factors, such as
vascular endothelial growth factor (VEGF), on the formation of CNV
has been identified. However, the influence and the mechanism of
action of the inflammatory cytokines on the development of exudative AMD are poorly understood. It has been reported that signaling
events initiated by cytokines trigger the inflammatory reaction and
contribute to the development of CNV(6).
The tumor necrosis factor alpha (TNF-α) is a low-molecular weight
protein, primarily produced by activated macrophages. TNF-α pro­­
motes VEGF signaling by promoting its production(7) and by modulating the expression of its receptors(8). It has been reported that
TNF-α regulates cell survival and cell death through Tnfrsf1a and Tnfrsf1b
receptor. Activation of Tnfrsf1a receptors induces inflammation, inhibits
endothelial cell migration and apoptosis(9), which may inhibit CNV. The
Tnfrsf1b receptors regulate lymphocyte proliferation(10) and promote
endothelial cell activation, migration, and survival(11). It has been
reported that Tnfrsf1b promotes CNV(12). Studies have de­­­­­monstrated
that therapeutic targeting of TNF-α may provide benefits from CNV(12-15).
TNF-α stimulates the production of Interleukin 6 (IL-6)(16), a multifunctional cytokine that acts on a number of tissues and cell types(17). IL-6
is an important mediator of the inflammatory and immune responses(18), and regulates VEGF expression(19).
Submitted for publication: November 19, 2013
Accepted for publication: March 20, 2014
Funding: No specific financial support was available for this study.
Study conducted at Pontifícia Universidade Católica do Paraná, Curitiba, Paraná, Brazil.
Pontifícia Universidade Católica do Paraná, Curitiba, Paraná, Brazil.
Centro Oftalmológico de Curitiba, Curitiba, Paraná, Brazil.
Medical Clinicat the Hospital Angelina Caron, Campina Grande do Sul, Paraná, Brazil.
4
Universidade Positivo, Curitiba, Paraná, Brazil.
5
Universidade Evangélica, Curitiba, Paraná, Brazil.
6
Universidade Estadual de Londrina, Londrina, Paraná, Brazil.
1
2
3
168
Arq Bras Oftalmol. 2014;77(3):168-72
Disclosure of potential conflicts of interest: None of the authors have any potential conflicts of
interest to disclose.
Corresponding author: Rogil Jose de Almeida Torres. Rua Emiliano Perneta, 390 - Conj. 1.407 Curitiba (PR) - 80420-080 - Brazil - E-mail: [email protected]
Project Number 240/080. CEUA - Pontifícia Universidade Católica do Paraná.
CEUA Authorization Registration: 678- 2nd version.
Authorization Date: 08/24/2012.
http://dx.doi.org/10.5935/0004-2749.20140043
Torres RJA, et al.
These cytokines play direct and/or indirect roles in the development of AMD. However, few reliable experimental models exist that
simulate the development of macular degenerative diseases.
The objective of this study was to evaluate the expression of the
inflammatory cytokines TNF-α and IL-6 in the choroid and sclera of
hypercholesterolemic rabbits.
METHODS
The protocol for this study was approved by the Animal Experimentation Ethics Committee of the Pontifícia Universidade Católica
do Paraná (PUC-PR) and complies with the guidelines established by
the Declaration of Helsinki and the Association for Research in Vision
and Ophthalmology (ARVO).
Experiment environment
The procedures described in this study were performed at the
Surgical Technique Laboratory at PUC-PR and at the Study Center of
the Angelina Caron Hospital (HAC). The animals were housed in the
bioterium (macro environment) under 12h:12h light-dark cycles with
air changes and between 19 and 23ºC room temperature. Animals
were fed water ad libitum and were allowed free access to species
standard diet Nuvital® (Nuvital, Colombo, Brazil).
Animals and experimental methods
Twenty-one New Zealand male albino rabbits (Oryctolaguscuni­
cullus) of an average age of 110 days and an average weight of 2.770 g
were selected from the Central Bioterium of the Pontifícia Universidade Católica do Paraná. The animals were divided into 2 groups:
group 1, the normal diet group (NG) with 8 rabbits, and group 2, the
hypercholesterolemic group (HG) with 13 rabbits. The NG was fed
the rabbit standard diet from Nuvital® Lab (Nuvital, Colombo, Brazil)
and was euthanized after 4 weeks. The HG group was fed with the
standard rabbit diet from Nuvital® Lab (Nuvital, Colombo, Brazil),
supplemented with 1% cholesterol. The daily amount of diet per
animal was 600 g. The animals in the HG group were euthanized at
the end of the eighth week.
Each rabbit underwent measurements of serum total cholesterol,
triglycerides, HDL cholesterol, and fasting glucose at the start of the
experiment and at the time of euthanasia. Animals were euthanized
by intravenous administration of 5 mL pentobarbital. The eyes were
removed and immediately placed in 4% paraformaldehyde (Merck,
Darmstadt, Germany) in 0.1 M phosphate buffer (pH 7.4) for 4h for
immunohistochemical analyses.
Tissue preparation and immunohistochemical analysis
After fixation, the samples were evaluated under a microscope.
A coronal section at the level of the optic nerve was performed and
the ocular globe was divided into two equal halves. The lower half
was stored for future studies. The upper half underwent dehydration, diaphanization, and was embedded in paraffin using a Leica® TP
1020 Automatic Tissue Processor (Leica, Wetzlar, Germany). A Leica®
EG1160 paraffin embedding device was used for paraffin embedding.
A Leica® RM2145 Microtome was used to prepare 5-micron-thick
sections for histology. The sections were placed on glass slides smea­
red with albumin, stained with hematoxylin-eosin, and mounted on
24x900-mm coverslips using the Entellan Mounting Media (Merck,
Darmstadt, Germany).
The sections were deparaffinized, rehydrated, and the endogenous peroxidases were blocked. The sections were then washed with
deionized water and incubated in a moist chamber at 95ºC for 20
min for antigen retrieval. Following this, the endogenous peroxidases
were blocked again. The slices were stained with rabbit primary monoclonal antibody against TNF-α (Imuny Biotechnology, Campinas,
Brazil) at a dilution of 1:200 and with rabbit primary monoclonal
antibody against IL-6 (Imuny Biotechnology, Campinas, Brazil) at a
dilution of 1:50. The slices were incubated with a secondary antibody,
Envision® System labeled polymer-HRP anti-mouse (DakoCytomation, Carpinteria, CA, USA), at room temperature for 30 min. The
sections were incubated for 3 to 5 min with freshly prepared DAB
substrate (DakoCytomation, Carpinteria, CA, USA). The slides were
then counterstained with Mayer hematoxylin and mounted.
Positive and negative controls were used in all evaluations, and
the slides were initially analyzed by a masked observer. Positive and
negative staining detected for TNF-α and IL-6 were recorded. The
immunopositive areas showed a brownish color and were studied
using color morphometry. For this purpose, images of 3 consecutive
fields close to the optic nerve head were captured with the help of a
Bx50 Olympus microscope fitted with a 40x objective and equipped
with a Sony Model DXC-107A camera. The program Image Pro Plus
was used to select and color the immunopositive areas and measure
the immunoreactive areas. The data obtained were compiled in a Microsoft Excel spreadsheet (Redmond, WA) for statistical analysis. The
sum total of all immunopositive areas in each of the 3 fields studied
represented the variable immunoreactive area.
Statistical analysis
The t-test was used for the comparison of quantitative variables
between the groups. The Mann-Whitney nonparametric test was
also used when appropriate. The normality was evaluated with the
Shapiro-Wilk test. p<0.05 indicated statistical significance. Statistica v.
8.0 was used for data processing.
RESULTS
Comparison of variables between NG and HG groups:
fasting glucose, total cholesterol, HDL, and triglycerides
The total cholesterol, triglycerides, HDL cholesterol, and the fas­­
ting glucose in the NG group at the time of euthanasia were si­­milar
to those at the start of the experiment. However, in the HG group,
the total cholesterol at the time of euthanasia was significantly
higher than that of at the start of the experiment. At the start of the
experiment, the mean of the total cholesterol in both the groups
was approximately 41.3 mg/dL. However, by the end of the experiment, the total serum cholesterol in the HG group had increased by
2146.8 mg/dL (p<0.001). HG group also showed significant variation
in serum triglyceride levels. At the start of the experiment, the serum
triglyceride concentration was approximately 46.5 mg/dL in both
the groups, whereas at the time of euthanasia, the serum triglyceride
concentration was 168.5 mg/dL (p=0.001) in HG group. Fasting glucose
and HDL cholesterol levels did not vary significantly in NG or HG
group during the experiment.
Comparison of TNF-α immunoreactivities of the NG and
HG groups
The animals in the HG group showed a significant increase in
TNF-α expression in the sclera and choroid when compared to the
animals in the NG group (p<0.001) (Table 1). This was characterized
by the predominance of a brownish hue of these structures (Figure 1B).
The sclera and the choroid in the NG group showed a bluish color
and a thinner structure compared with the HG group, revealing low
immunoreactivity of these structures in NG group to the TNF-α antibody (Figure 1A).
Comparison of IL-6 immunoreactivities of the NG and
HG group
Compared with the NG group, the sclera and choroid of the HG
group showed a significant increase in IL-6 expression (p=0.002)
(Table 2), characterized by the predominance of the brownish hue
of these structures (Figure 2B). The sclera and choroid of the animals
Arq Bras Oftalmol. 2014;77(3):168-72
169
Expression of TNF-α and IL-6 cytokines in the choroid and sclera of hypercholesterolemic rabbits
in the NG group showed a thinner structure and a predominant
bluish color than those of the animals in the HG group, revealing low
immunoreactivity of these structures in NG group to IL-6 antibody
(Figure 2A).
The critical role of VEGF in angiogenesis is well documented.
Ho­­­­wever, it has been demonstrated that inflammatory reaction, cha­­
racterized by the presence of macrophages and inflammatory cyto­­
kines, also induces the anomalous formation of blood vessels(22). That
inflammation mediates neovascularization in AMD is supported by
studies that suggested depletion of macrophages can reduce the
laser-induced CNV(23).
In the present study, rabbits were fed with cholesterol enriched
diet to evaluate the expression of the TNF-α and IL-6 in the choroid­
scle­ral complex. It has been reported that cholesterol-enriched diet
induces hypoxia of the retinal tissue(24), increase in the macrophage
concentration in the choroid and sclera(24-25), as well as increase in
DISCUSSION
Angiogenesis, the formation of new blood vessels from pre-existing
endothelium, is an important event during vascular development,
wound healing, and organ regeneration. Angiogenesis and neovascularization during tumor growth, diabetic retinopathy, rheumatoid
arthritis, and AMD produce detrimental effects(20,21).
Table 1. Total area of the choroidscleral complex immunoreactive to TNF-α
Variable
Immunoreactive area
Group
N
Mean
Median
Min
Max
Standard
deviation
HG
13
60317.2
51130.9
24613.5
105314.6
28857.7
NG
08
07134.2
06686.2
01635.9
22214.6
6626.0
p*value
<0.001
*= Student’s t-test for independente samples, p<0.05.
NG= normal diet group; HG= cholesterol-enriched diet group.
A
B
C= choroid; S= sclera; magnification = 400x.
Figure 1. Immunoreactivity of choroid and sclera to TNF-α antibody. A) Choroid-scleral
complex of normal diet group. Predominance of the bluish hue indicates low immu­
noreactivity to TNF-α antibody. Thin choroid and sclera. B) Choroid-sclera complex of
hypercholesterolemic group. Predominance of a brownish hue indicates high immu­
noreactivity to TNF-α antibody. Thick choroid and sclera. reactivity to TNF-α antibody.
Thick choroid and sclera.
Table 2. Total área of the choroidscleral complex immunoreactive to IL-6
Variable
Immunoreactive area
Group
N
Mean
Median
Min
Max
Standard
deviation
HG
13
5301.0
5138.0
1963.0
9551.0
2590.0
NG
08
2427.0
2427.0
0987.0
3968.0
0893.0
*= Student’s t-test for independente samples, p<0.05.
NG= normal diet group; HG= cholesterol-enriched diet group.
A
B
C= choroid; S= sclera; magnification = 400x.
Figure 2. Immunoreactivity of choroid and sclera to IL-6 antibody. A) Choroid and sclera
of normal diet group. Predominance of the bluish hue indicates low immunoreactivity
to IL-6 antibody. Thin choroid and sclera. B) Choroid and sclera of hypercholesterolemic
group. Predominance of a brownish hue indicates high immunoreactivity to IL-6 antibody.
Thick choroid and sclera.
170
Arq Bras Oftalmol. 2014;77(3):168-72
p* value
0.002
Torres RJA, et al.
VEGF expression in these structures(25). Therefore, the significant
increase in the TNF-α expression observed in the choroid and sclera
of the animals in the HG group was likely due to hypoxia, as well as
an increase in the macrophage concentration(26). TNF-α is a multifunctional cytokine. TNF-α receptors are expressed in the retina,
including the Muller and the RPE cells, as well as in the choroid(6,13-14).
The TNF-α secreted by macrophages(22), observed in a large numbers
in this experimental model(24-26), triggers the production of VEGF
through Tnfrsf1b receptor by the RPE cells(6). TNF-α also stimulates
monocyte adhesion and upregulates the granulocyte-macrophage
colony-stimulating factor(27). Additionally, TNF induces EC migration
and tube formation in the absence of proangiogenic factors, suggesting that TNF can directly activate signaling pathways for epithelial
cell migration(27), thereby contributing directly to CNV formation.
Indeed, TNF has been considered a therapeutic target in exudative
AMD. Although the inhibition of TNF-α leads to the reduction in CNV
size and leakage in experimental models(13), clinical research studies
have shown inconsistent results(16,28).
It has also been demonstrated that TNF-α stimulates the production
of IL-6(16), an important marker of inflammation. RPE and inflammatory cells produce IL-6 in response to stimulation(5,16,29). In the present
study, a significant increase in the IL-6 expression was observed in the
choroid and sclera of the rabbits in the HG group. Besides TNF-α(16),
the macrophages and the hypoxia may have contributed to the
increased IL-6 expression(19,24). It has been demonstrated that the
in­­duction of IL-6 by hypoxia may induce VEGF expression, leading
to angiogenesis. Therefore, IL-6 is regarded as indirect angiogenic
factor(19). Further, it has been shown that the inhibition of the IL-6
expression by the pharmacologic blockade of its receptors or by the
genetic ablation of this cytokine suppresses laser-induced CNV(29).
The IL-6 receptor neutralization led to significant inhibition of the in
vivo and in vitro expression of monocyte chemotactic protein, intercellular adhesion molecule-1, and vascular endothelial growth factor,
and reduced macrophage infiltration into CNV(29). Consistent with
these reports, a population study concluded that IL-6 represents a
risk factor for CNV due to high levels in the plasma of AMD patients(30).
These findings suggest the possibility of using IL-6 receptor blockade
as a therapeutic strategy to suppress CNV associated with age-related
macular degeneration.
We used rabbits for this research. The advantages of using rabbits
over other animals include increased availability, low costs (when
compared with transgenic mice lacking receptors for LDL cholesterol
or apolipoprotein E), and a better genetic characterization(31). Additionally, the hypercholesterolemic diet rapidly induces endothelial
dysfunction and a response similar to atherogenesis, making it a
good model for cardiovascular diseases(32). Further, the normal serum
cholesterol levels in rabbits range from 25 to 60 mg%, whereas in
humans this variation is between 100 and 200 mg%. Therefore, the
metabolic system of rabbits may readily be overloaded with a simple
daily hypercholesterolemic diet, making the experiments more feasible and reproducible(32). Indeed, the total serum cholesterol level in
HG group increased from 41.3 mg/dL at the start of the experiment
to approximately 2146.8 mg/dL at the time of euthanasia.
Several studies have been performed on rabbits to demonstrate
that a cholesterol-enriched diet causes abnormalities in their sclera,
choroid, and retina. This include the administration of 0.5% cho­­
lesterol-enriched diet for at least six months(33,34). In this study, the
administered dosage of cholesterol was higher than that used in
other studies (1% cholesterol), which enabled the authors to obtain
immunohistochemical alterations of the choroid-sclera complex
during a period of eight weeks. This demonstrated that alterations in
the ocular walls as well as the arteries(32) could be brought about in
a shorter period, thus offering opportunities for more experiments
and reducing the costs. The NG group underwent euthanasia after 4
weeks. This short period has been proven to be sufficient to demonstrate that the serum total cholesterol, triglycerides, HDL cholesterol,
and fasting glucose level remained stable and did not interfere with
the immunohistochemical analysis of the choroid and sclera. The
decision to euthanize rabbits of the NG group after 4 weeks was made
based on the results of earlier studies(24,35).
We have demonstrated that cholesterol-enriched diet induces an
increase in macrophage concentration in the choroid-sclera com­­plex,
causing thickness of these structures(24,25,35). The diet also induced hypoxia of the retinal tissue, leading to neuronal damage(35). Therefore,
the hypercholesterolemic model used in the present study incorporates the increased macrophage concentration and hypoxia, the two
conditions that induce TNF-α and IL-6 expression(19,22,24).
CONCLUSION
In this study, we used immunohistochemistry to analyze the ex­­­
pression of TNF-α and IL-6 in the sclera and choroid of hypercholesterolemic rabbits. Although Western blotting is a more sensitive
method for the detection of these factors, it requires the use of
fresh or frozen tissue. Since the ocular globes were fixed in paraformaldehyde and embedded in paraffin, we were unable to use the
Western blotting technique.
Due to their role in mediating the intraocular inflammatory reaction,
VEGF-like functions, and their hypoxia-induced expression, TNF-α and
IL-6 have been considered as therapeutic targets in AMD. Our experimental model may help understand the development of AMD.
ACKNOWLEGMENTS
We thank Dr. Márcia Olandoski for assisting with the statistical
analy­sis of data.
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29. Izumi-Nagai K, Nagai N, Ozawa Y, Mihara M, Ohsugi Y, Kurihara T, et al. Interleukin-6 re­
ceptor-mediated activation of signal transducer and activator of transcription-3 (STAT3)
promotes choroidal neovascularization. Am J Pathol. 2007;170(6):2149-58.
30. Seddon JM, George S, Rosner B, Rifai N. Progression of age-related macular degeneration:
prospective assessment of C-reactive protein, interleukin 6, and other cardiovascular bio­­
markers. Arch Ophthalmol. 2005;123(6):774-82.
31. Kantor B, Ashai K, Holmes DR, Schwartz RS. The experimental animal models for assessing treatment of restenosis. Cardiovasc Radiation Med. 1999;1(1):48-54.
32. Sun YP, Lu NC, Parmley YWW, Hollenbeck CB. Effects of cholesterol diets on vascular
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33. Salazar JJ, Ramírez AI, de Hoz R, Rojas B, Ruiz E, Tejerina T, et al. Alterations in the choroid in hypercholesterolemic rabbits: reversibility after normalization of cholesterol
levels. Exp Eye Res. 2007;84(3):412-22.
34. Triviño A, Ramírez AI, Salazar JJ, de Hoz R, Rojas B, Padilla E, et al. A cholesterol-enriched
diet induces ultrastructural changes in retinal and macroglial rabbit cells. Exp Eye Res.
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VII Congresso Baiano de Oftalmologia
10 e 11 de outubro de 2014
Hotel Sheraton
Salvador - BA
Informações:
Site: www.sofba.com..br
172
Arq Bras Oftalmol. 2014;77(3):168-72
Original Article
Efficacy of a lutein-based dye (PhacodyneTM) for visualizing anterior capsulorhexis
during cataract surgery by phacoemulsification
Eficácia de corante à base de luteína (PhacodyneTM) para observação da capsulorrexis anterior em
cirurgia de facoemulsificação
Lucas Monferrari Monteiro Vianna1, Marcos J. Cohen1, Cristina Muccioli1, Acácio Lima1, Diogo Sousa-Martins1, Maurício Maia1, Rubens Belfort Jr.1
ABSTRACT
RESUMO
Purpose: To evaluate the efficacy and safety of a novel lutein-based dye for the
anterior capsulorhexis during phacoemulsification in cataract surgery in humans.
Methods: Twenty-five eyes from 25 patients were operated by 25 different
sur­­geons who performed continuous circular capsulorhexis (CCC) guided by a
lutein-based dye (Phacodyne™) during cataract surgery by phacoemulsification.
A questionnaire assessed the surgeon’s opinion regarding the efficacy of the dye.
Follow-up examinations were performed at 1, 7, and 30 days post-surgery. Eyes
were evaluated by full ophthalmic examination, corneal topography/pachymetry,
and corneal endothelial cell count.
Results: As revealed by the answers to the questionnaire, the dye facilitated the
CCC procedure in all eyes. Baseline nuclear cataract classification (according to
the Lens Opacities Classification System III; LOCS III) was 3.24 (± 1.12). Preoperative
BCVA (logMAR) was 0.89 ± 0.59 and improved to 0.23 ± 0.22 on day 30 after surgery.
The intraocular pressure (IOP) remained stable and the inflammatory reaction
subsided in all cases within the first 7 days after surgery. The pre-operative values
of corneal pachymetry and IOP were similar to those found on follow-up day 30.
Loss in endothelial cell number was similar to earlier reports.
Conclusion: Phacodyne™ was efficient when used for anterior capsulorhexis du­­ring
cataract surgery by phacoemulsification and showed no signs of toxicity or side
effects during the 30-day follow-up period.
Objetivos: Avaliar a eficácia e eficiência de um novo corante à base de luteína para
coloração da cápsula anterior durante cirurgia de facoemulsificação em humanos.
Métodos: Vinte e cinco olhos de 25 pacientes foram operados por 25 cirurgiões
di­­­­­­ferentes que realizaram capsulorrexis circular contínua e facoemulsificação após
coloração da cápsula anterior com corante à base de luteína. Um questionário ava­­liou
a opinião dos cirurgiões sobre a eficácia do corante. Exames pós-operatórios foram
realizados nos dias 1, 7 e 30 por meio de exame oftalmológico completo, topografia/
paquimetria e contagem de células endoteliais.
Resultados: De acordo com o questionário aplicado, o corante facilitou a cirurgia em
todos os olhos. A classificação da catarata de acordo com o LOCS III foi de 3,24 ± 1,12.
A acuidade visual pré-operatória com melhor correção foi de 0,89 ± 0,59 (logMAR),
passando a 0,23 ± 0,22 no pós-operatório. A pressão intraocular (PIO) permaneceu
estável e houve reação de câmara leve que desapareceu em todos os casos durante os
primeiros 7 dias de pós-operatório. Não houve significância estatística comparando
a paquimetria e PIO pré e pós-operatórios.
Conclusão: O novo corante se mostrou eficiente e sem sinais de toxicidade ou efeitos
adversos, após 30 dias, quando usado para auxiliar a cirurgia de facoemulsificação.
Keywords: Cataract extraction; Lutein; Phacoemulsification; Capsulorhexis; Lenses,
intraocular
Descritores: Extração de catarata/métodos; Luteína; Facoemulsificação; Capsulorrexe;
Lentes intraoculares
INTRODUCTION
The continuous circular capsulotomy (CCC) of the anterior lens
capsule is a critical step in the modern cataract surgery performed by
phacoemulsification, which offers advantage for the implantation of
intraocular lens correctly into the capsular bag(1). Good visualization
of the anterior capsule flap is needed when performing the CCC,
particularly in the absence of a red reflex(2-4). Since the lack of a red
reflex results in technical difficulties(2-4), a correct CCC is useful when
a more aggressive manipulation of the capsular bag is required(3). In
such clinical conditions, the improvement of the anterior capsule
visualization can also be of great value for surgeons, particularly for
those who are learning the surgical technique(4). Additionally, the
surgical procedure of staining the anterior capsule during CCC in
pediatric cataract extraction is useful since the anterior capsule of
these eyes is thin and elastic(5).
Since the first use of fluorescein for improving the visualization
during capsulorhexis in 1993(6), alternative techniques and a variety
of dyes have been used for anterior capsule staining during cataract
surgery(4). Although indocyanine green, trypan blue, sodium fluorescein, crystal violet, and gentian violet have been shown to be useful
Submitted for publication: February 6, 2014
Accepted for publication: March 29, 2014
Funding: This study has been conducted under grants from Kemin Industries Inc.
Study conducted at Departamento de Oftalmologia, Universidade Federal de São Paulo (UNIFESP),
São Paulo, SP, Brazil.
1
Departamento de Oftalmologia, Universidade Federal de São Paulo (UNIFESP), São Paulo, SP,
Brazil.
Disclosure of potential conflicts of interest: Diogo Sousa-Martins is an employee of Kemin Industries
Inc. Acacio Lima is the owner of Ophthalmo’s and received personal fees from Kemin Industries Inc.
Kemin Industries Inc. has supported the Department of Ophthalmology through Research Grants.
Diogo Sousa-Martins, Rubens Belfort Jr., Acácio Lima and Maurício Maia and Kemin Industries
Inc. hold patent related to the use of lutein or combinations thereof with synthetic dyes for staining
the anterior capsule (patent pending US 20120251458 and Publications WO 2012135432).
Corresponding author: Lucas Monferrari Monteiro Vianna. Rua Botucatu, 821 - São Paulo (SP) 04023-900 - Brazil - E-mail: [email protected]
Registered at clinicaltrials.org (NCT01627977) and approved by UNIFESP IRB (2146/11)
http://dx.doi.org/10.5935/0004-2749.20140044
Arq Bras Oftalmol. 2014;77(3):173-7
173
Efficacy of a lutein-based dye (Phacodyne TM) for visualizing anterior capsulorhexis during cataract surgery by phacoemulsification
for facilitating the CCC maneuver, only the trypan blue 0.06% - Vision
blue™ (Dorc, Netherlands) has been approved by the FDA for use in
cataract surgery(7,8).
New dyes that enhance the visualization of ocular tissues during
surgery have recently emerged(9-11). Lutein and zeaxanthin are two
major components of the macular pigment and are the only carote­
noids found in the macula and lens of humans. The antioxidant properties of the dyes and the ability to filter blue light facilitated their
use during the CCC procedure(12,13).
It has been reported that the green 1% solution of soluble lutein
and zeaxanthin-based dye combined with 0.04% trypan blue (Phacodyne™, Kemin, USA) is a useful intraocular dye for staining the an­­terior
capsule, enhancing the CCC procedure in human cadaveric eyes(11). Its
safety profile has been evaluated by clinical, histological, and electroretinographic methods after intravitreal injections into rabbit eyes(14).
The objective of this study was to evaluate the feasibility and safety
of application of a novel dye comprising 1% soluble lutein-zeaxanthin
together with 0.04% trypan blue (Phacodyne™, Kemin, USA) to improve
the anterior capsulorhexis during the phacoemulsification surgery in
human eyes.
METHODS
Preparation of the dye
The method of preparation described below is valid for lutein/
zeaxanthin regardless of the chemical form, purity, crystallization, or
degree of esterification (patent office application #61/468,838).
The initial steps of this study were the development of a water-soluble solution, characterization of the absorbance of the lutein/
zeaxanthin solution using the Aquamate device (Thermo Spectronic,
Cambridge, UK), and the identification of the color of the chromophoric groups. The physicochemical parameters were tested for the
optimum pH, osmolarity/osmolality, and concentration. Solubility in
water and polyvinyl alcohol was tested, the ultraviolet spectra were
recoded, and the blends showing different colors within the visible
spectrum were analyzed.
The method of preparation of the dye included dissolution, agitation, sterilization, and filtration. First, the components were dissolved
in balanced saline solution (BSS) or any other solution compatible
with the components of the formula that provided stability, suitable
pH, and osmolarity acceptable for ocular use. Sterilization using wet
heat was achieved by autoclaving at 121ºC. The final dye solution
contained 1% soluble lutein/zeaxanthin and 0.04% trypan blue (osmolarity, 280 mOsm; density, 1.05; pH, 7.00). Aliquots of 1 mL were
prepared, stored at room temperature, and were used within 30 days.
ocular surgeries in the eye studied, pregnancy, glaucoma, a past or
present intraocular infection, and any other ocular condition detected
during the pre-operative examination that could limit or affect the
postoperative results were excluded. The minimum follow-up period
was 30 days.
Physical evaluation and ocular examinations
All patients underwent a full ophthalmologic examination at the
start of the study and postoperatively (days 1, 7, and 30). This included evaluation of the best-corrected visual acuity (BCVA) that was
measured using the Snellen Charts and converted to logMAR,
mea­­­­surement of the intraocular pressure (IOP) using the Goldmann
tonometer, and slit-lamp evaluation. Complementary exams such
as fundoscopy, pachymetry, and specular microscopy (CSO, Firenze,
Italy) were also performed at the same time points. Baseline cataracts
were graded according to the “Lens Opacities Classification System III”
(LOCS III)(15). Anterior chamber reaction was graded according to SUN
Working Group(16).
Surgical procedures
The phacoemulsification was performed by 25 different experienced cataract surgeons. The first step consisted of making a 2.75-mm
clear corneal incision, filling the anterior chamber with Phacodyne™
(Kemin, USA), washing after 30 seconds with balanced salt solution,
and filling the anterior chamber with viscoelastic. The anterior continuous circular capsulorhexis (CCC) (Figure 1) was performed using
an Utrata forceps. This was followed by hydrodissection and hydrodelineation using approximately 0.1 mL BSS. Phacoemulsification was
performed using the Infinity Vision System™ (Alcon, USA). Following
this, the lens cortex was aspirated and a foldable intraocular lens was
inserted through the 2.75-mm corneal incision (Figure 2). At the end
of the surgical procedure, the viscoelastic substance was aspirated
and no sutures were placed at the corneal incision. Moxifloxacyn and
dexamethasone association - Vigadexa™ (Alcon, USA) eye drops were
used during the immediate post-operative period.
Figure 1. Dark green color of the dye.
Study design
This was a prospective, consecutive, non-randomized, interven­
tional study of 25 eyes of 25 patients performed by 25 different
sur­­geons. The study was registered at clinicaltrials.gov under the no
NCT01627977. The study was approved by the Ethics Committee of
the Federal University of São Paulo and was conducted according to
the Research Guidelines of the Association of Research in Vision and
Ophthalmology, adhering to the Declaration of Helsinki. All patients
were informed of the benefits and risks of the surgical procedure as
well as the nature and possible consequences of the new dye tested.
This study was conducted after receiving informed consent from all
participants.
Eyes were submitted to phacoemulsification at the Ophthalmo­
logy Department of Hospital São Paulo, Universidade Federal de São
Paulo, Brazil, with PhacodyneTM (Kemin, USA) assisting the CCC technique
and the hydrophilic foldable IOL implantation.
Inclusion and exclusion criteria
Patients over 50 years of age with indication for cataract surgery
in one eye were included in the study. Patients with any previous
174
Arq Bras Oftalmol. 2014;77(3):173-7
Figure 2. Anterior capsule staining with the solution containing 0.3% lutein/
zeaxanthin and 0.04% trypan blue, facilitating the CCC procedure.
Vianna LMM, et al.
Follow-up
All eyes received 0.5% moxifloxacin eye drops 4 times daily for 7
days and 0.1% dexamethasone as part of a regressive regimen. No hypotensive eye drops were prescribed. The eyes underwent an ophthalmologic examination at days 1, 7, and 30 by expert ophthalmologists.
Questionnaires
Surgeons’ evaluation of the use of PhacodyneTM (Kemin, USA) for
the CCC procedure was reported using a questionnaire.
There were no significant differences between the results of preand post-operative fundus biomicroscopy.
Questionnaires
The questionnaires showed that surgeons considered Phacodyne™
to be efficient for staining the anterior capsule and that the staining
facilitated the CCC procedure in all eyes (Table 1).
Nuclear cataract classification (according to LOCS III) was 3.24 ± 1.12
and changed from 2 to 6 in both groups. Preoperative BCVA (logMAR)
was 0.89 ± 0.59 and improved to 0.23 ± 0.22 at day 30 after the
surgery. The intraocular pressure (IOP) remained stable and similar
to the pre-operative measurements during the post-operative visits
(p=0.004) (Figure 3). A mild inflammatory reaction (grade 0.5+ according to SUN Working Group)(16) at the anterior chamber was observed
within the first 7 days (Figure 4).
The pre-operative corneal pachymetry average was 538.8 ± 40.0
and that on post-operative follow-up day 30 was 542.5 ± 39.8 (Figure 5).
The preoperative endothelial cell count average was 2573.5 ± 235.9 and
that on postoperative follow-up day 30 was 2311.36 ± 490.7 (Figure 6).
DISCUSSION
A previous study showed that a solution containing 1% soluble
lutein-zeaxanthin and 0.04% Brilliant Blue G efficiently stained the
anterior capsule and facilitated the CCC in cadaveric eyes(11). Additio­
nally, clinical, histological, and electroretinographic evaluations per­
formed after the intravitreal injection of the dye in rabbit eyes showed
no signs of toxicity,(14) indicating the enhanced safety in case of
accidental leak of the dye into the vitreous. Based on these reported
we decided to evaluate the application of s the new dye for cataract
surgery in humans.
Based on the nuclear cataract classification, LOCS III, the eyes
enrolled in this study showed varying grades of cataract from 2 to 6,
demonstrating that advanced cases of hypermature cataract were
also present(6). The surgeons classified the visualization of the anterior
capsule with the dye as “good” and considered it as a useful tool for
cataract surgery (Table 1). The green colored dye (Figure 1) stained
the anterior capsule of the lens, which facilitated the CCC procedure
in all cases, including the hypermature cataracts.
The surgeons observed that in 4 eyes, the cornea, the incision, or
iris were stained by the dye. Residual dye was found only in 2 eyes
at the end of the surgical procedure (Table 1). The dye was not seen
in any eye on the first postoperative day. A mild anterior chamber
reaction of grade 0.5+ (according to SUN Working Group)(16) was
observed during the first week after surgery (Figure 4). These results
were similar to those of earlier clinical studies, where trypan blue
was used during phacoemulsification to aid the CCC procedure or
when a dye was not used.(3,4,17-19) In agreement with other reports, the
IOP remained stable and similar to the pre-operative measurements
during the post-operative period (Figure 3)(20).
The pre-operative BCVA (logMAR) was 0.89 ± 0.59 and improved
to 0.23 ± 0.22 at day 30 after surgery, clearly showing that there was
an improvement in BCVA from 20/160 to approximately 20/32 in
Figure 3. Intraocular pressure (mmHg).
Figure 5. Corneal pachymetry (µm).
Figure 4. Post-operative anterior chamber reaction (+).
Figure 6. Endothelial cell count (/mm2).
Statistical methods
All data were presented as the mean and standard deviation for
quantitative variables, and absolute (n) and relative (%) values for qua­
litative variables. The prevalence of intense staining of the anterior
lens capsule was defined. The confidence interval was set at 95%.
RESULTS
Intraoperative findings
The lutein-based dye produced a green solution (Figure 1) that
stained the anterior capsule and facilitated the CCC procedure (Figure 2). The phacoemulsification followed by IOL implantation was
performed as traditionally reported by cataract surgeons. No sutures
were necessary.
Physical evaluation and ocular examinations at baseline and
follow-up
Arq Bras Oftalmol. 2014;77(3):173-7
175
Efficacy of a lutein-based dye (Phacodyne TM) for visualizing anterior capsulorhexis during cataract surgery by phacoemulsification
Table 1. Questionnaire returned by surgeons showing the effectiveness of the dye
Surgeons questionnaire response
How often do the surgeon use dyes in cataract surgery?
Which dye does the surgeon use?
How was the visualization of the anterior capsule with Phacodyne?
How was the degree of staining of the anterior lens capsule by the dye?
Did it color any other ocular tissues?
What is the surgeon’s opinion about the usefulness of the dye?
Is the color of the dye suitable for dying the anterior lens capsule?
Were there any signs of the dye at the end of the surgery?
majority of the eyes. No signs of toxicity were observed during the
30-day follow-up period(21).
Corneal pachymetric changes were observed soon after the surgical procedure and peaked at one week during the follow-up. The
values returned to the baseline levels on the 30th postoperative day.
The pre-operative corneal pachymetry average was 538.8 ± 40.0 and
the post-operative value was 542.5 ± 39.8 (Figure 5), demonstrating
that anatomical changes of the cornea were temporary and reversible within the first 30 days after the surgery(21,22).
The baseline endothelial cell count average was 2573.5 ± 235.9
and that post-operatively was 2311.36 ± 490.7 (Figure 6), showing
an average decrease of 10.18% in the first month after the surgery.
Similar endothelial cell loss during phacoemulsification procedures
has been reported by others(21,22).
Pre-and post-operative fundus biomicroscopy evaluations showed
no significant differences. Pre-and post-operative macular thickness
measurements are needed to assess the effect on the retina.
To our knowledge, this is the first study that used a lutein-based
dye (PhacodyneTM) for visualizing anterior capsulorhexis during cataract surgery by phacoemulsification. However, our study had limitations. This include, the small sample size, the absence of a control
group, the large number of surgeons (that may affect the outcomes,
although it is suitable for analyzing the efficacy), and the limited
follow up period of 30 days. The goal of this study using lutein and
zea­xanthin combined with trypan blue was to evaluate the safety
and efficacy of the dye for CCC. Further studies are warranted to evaluate the effectiveness of the new dye and its advantages over those
that are currently being used. We hypothesize that use of lutein and
176
Arq Bras Oftalmol. 2014;77(3):173-7
%
Never
00
000%
Rarely
08
032%
Frequently
13
052%
Always
04
016%
Trypan blue
25
100%
Indocyanine green
00
000%
Others
00
000%
Good
25
100%
Bad
00
000%
Nothing
00
000%
Adequate
20
080%
Intense
05
020%
No
21
084%
Yes
04
016%
Conjunctiva
00
000%
Iris
01
004%
Posterior capsule
00
000%
Incision
02
008%
Cornea
01
004%
Good
25
100%
Bad
00
000%
Yes
25
100%
No
00
000%
No
23
092%
Yes
02
008%
Incision
02
008%
p
p<0.001
p<0.001
p<0.001
p<0.001
zeaxanthin in combination with trypan blue may have two favorable
effects: 1) The lower concentration of trypan blue (that can also be
tested in more reduced concentrations in future studies(23)), and 2)
the antioxidant effect of lutein and zeaxanthin molecules that may
quench the singlet oxygen generated by the exposure of trypan blue
to light. Additionally, since lutein is a natural product, the manufacturing costs could be reduced. The use of lutein and zeaxanthin without
trypan blue will be investigated in future studies.
CONCLUSION
The newly formulated lutein-based dye facilitated the CCC during
phacoemulsification procedures and showed a good safety profile.
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VIII Congresso Brasileiro de Uveítes
29 a 31 de janeiro de 2015
Wetiga Hotel Natureza
Bonito - MS
Informações:
Cenacon
Tel.: (17) 3214-5900
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Arq Bras Oftalmol. 2014;77(3):173-7
177
Original Article
Ophthalmologic findings in hepatitis C patients treated with pegylated interferon α-2b
and ribavirin
Achados oftalmológicos nos pacientes portadores de hepatite C em tratamento com
interferon peguilado α-2b e ribavirina
Fernando José de Novelli1, André Przysiezny1, Evandro Luis Rosa1, Raquel Francine Liermann Garcia2, Mário Junqueira Nóbrega1
ABSTRACT
RESUMO
Purpose: To identify the effect of pegylated interferon α-2b and ribavirin treatment
in the ocular fundus examination, visual acuity, and visual field.
Methods: Prospective observational study was performed at the Hepatology Clinic
of São José Regional Hospital and at the Vitreoretinal Department at the Sadalla
Amin Ghanem Eye Hospital in patients with chronic hepatitis C before and during
treatment with pegylated interferon α-2b together with ribavirin.
Results: Six (37.5%) of 16 patients developed retinopathy during the treatment,
two of which (12.5%) presented retinal hemorrhage, and four patients (6 eyes)
presented cotton-wool spots (25%) that regressed during the treatment. One
patient (6.25%) presented transient decrease in visual acuity during the treatment
and recovered spontaneously without specific therapy.
Conclusion: Recommended treatment methods for hepatitis C may cause transient
retinopathy, commonly without any damage to visual function in most patients.
Although ocular involvement is rare, follow-up with an ophthalmologist is recommended during the course of the hepatitis C medication.
Objetivo: Identificar possíveis mudanças no exame de fundo de olho após o início do
tratamento, bem como alterações na acuidade visual e campo visual.
Métodos: Estudo observacional prospectivo realizado na Clínica de Hepatologia do
Hospital Regional de São José e no Departamento de Vítreo e Retina do Hospital de
Olhos Sadalla Amin Ghanem, em pacientes com hepatite C crônica antes e durante
o tratamento com interferon peguilado α-2b associado à ribavirina.
Resultados: Six (37,5%) dos 16 participantes desenvolveram retinopatia durante o
tratamento, dois dos quais (12,5%) apresentaram hemorragia retiniana unilateral, e
quatro pacientes com exsudatos algodonosos (25%), seis olhos, que regrediu du­rante
o tratamento. Um participante (6,25%) apresentou diminuição transitória da acuidade
visual durante o tratamento com recuperação espontaneamente sem tratamento
específico.
Conclusão: O tratamento recomendado para a hepatite C pode estar associado com
o desenvolvimento de retinopatia transitória, geralmente sem dano à função visual na
maioria dos pacientes. Embora o envolvimento ocular seja raro, o acompanhamento
com o médico oftalmologista é recomendado durante todo o uso da medicação.
Keywords: Antiviral agents/adverse effects; Hepatitis C, chronic/drug therapy;
Interferon-alpha/adverse effects; Retinal diseases/chemically induced; Ribavirin/
adverse effects
Descritores: Agentes antivirais/efeitos adversos; Hepatite C crônica/quimioterapia;
Interferon-alfa/efeitos adversos; Doenças retinianas/quimicamente induzido; Ribavirina/efeitos adversos
INTRODUCTION
The hepatitis C virus infection is a severe disease that can beco­
me chronic and progress to hepatic decompensation, cirrhosis, and
in 20% of the cases to hepatocellular carcinoma(1). Around 3% of
the world’s population (170 million people) is estimated to be the
chronic carrier of the hepatitis C virus(2). In Brazil, prevalence of this
disease ranges from 0.9% to 1.9%, proportionate to the population
of each state(3).
The current FDA approved and recommended treatment for
he­­­patitis C is the interpheron-alpha monotherapy, which includes
pegylated interferon α-2b or along with ribavirin. Interferon is an
immunomodulatory compound with direct antiviral and antiproliferative properties; it has been used as a therapeutic for hepatitis C, B,
and D, cancer, and multiple sclerosis. In vitro, interferon alpha inhibits
viral replication(4). Ribavirin is an immunomodulatory compound that
inhibits viral DNA and RNA. When used alone it has no affect on hepatitis C viral replication(5). However, when combined with interferon,
viral and biochemical response is sustained, when compared to the
stand-alone use of interferon alpha(6). The treatment duration of 24
to 48 weeks has been recommended(6).
The use of interferon as the treatment for hepatitis C in patients
might lead to systemic changes, such as myalgia, fever, erythema,
weakness, loss of appetite, anemia, and thrombocytopenia(1). Ribavirin has a fewer side effects among which hemolytic anemia being
the most frequent one(7). Studies have reported an association of
these compounds with optic neuropathy(7), retinopathy(8-14), subconjunctival hemorrhage(8), cystoid macular edema(15), and retinal and
choroidal perfusion deficiency(16).
The objective of this study is to identify possible alterations in
ocular fundus examination upon start of the treatment, as well as to
analyze the changes in visual acuity and visual field.
Submitted for publication: May 29, 2013
Accepted for publication: March 16, 2014
Funding: No specific financial support was available for this study.
Study conducted at Hepatology Clinic of São José Regional Hospital and at the Vitreoretinal Department
at the Sadalla Amin Ghanem Eye Hospital.
1
2
Sadalla Amin Ghanem Eye Hospital.
City Program of Viral Hepatitis Control, Joinville, SC, Brazil.
178
Arq Bras Oftalmol. 2014;77(3):178-81
METHODS
This was a prospective observational study performed at the
Hepatology Clinic of the São José Regional Hospital and at the Vitreo­
retinal Department at the Sadalla Amin Ghanem Eye Hospital. The
study was conducted in the patients with chronic hepatitis C immediately commencing a standard 48-week treatment regimen of pegylated interferon α-2b (1.5 mcg/kg/week) subcutaneous injections
Disclosure of potential conflicts of interest: None of the authors have any potential conflicts of
interest to disclose.
Corresponding author: Fernando José de Novelli. Joinville - SC - 89216-222 - Brazil
E-mail: [email protected]
http://dx.doi.org/10.5935/0004-2749.20140045
Novelli FJ, et al.
and ribavirin twice daily dosage of 800 mg. The study was approved
by the Ethics Board under number 196824. All patients signed the
informed consent form.
All the patients were interviewed regarding systemic diseases
and were evaluated with the following ophthalmologic evaluation
items before starting the treatment, after one month and quarterly
up to twelve months. Examination consisted of best corrected visual
acuity (subjective refraction); biomicroscopy; intraocular pressure (Goldmann applanation tonometry); retinal mapping with indirect ophthal­
moscope (using a 20D lens); direct and consensual pupillary light reflex
test; visual field analysis with automated perimetry (Humphrey Field
Analyzer II 750i, HFA 750i), with 24-2 SITA-standard strategy (Swedish
Interactive Threshold Algorithm). Patients with concomitant diabetes
mellitus underwent to fluorescein angiography exam (Topcon, TRC-50IX
system, IMAGEnet 2000, intravenous 2.5 ml of 20% sodium fluorescein solution) before starting the treatment, after one month, and
once in three months for up to twelve months. The glycosylated he­
moglobin dosage was monitored in the same periods.
Patients with the following characteristics were excluded: age
below 18 years; diabetic retinopathy with changes in retinal per­fusion
at fluorescein angiography exam on initial evaluation or un­controlled
clinical diabetes upon follow-up (such as glycosylated hemoglobinHbA1c over 8%) retinopathy; central or brain retinal vein occlusion; systemic arterial hypertension with retinopathy upon initial
evalua­tion, or uncontrolled clinical systemic arterial hypertension upon
follow-up during the existence of retinopathy; other type of retinal
vas­­­­cu­lopathy arising due to non-infectious (Behçet’s disease, Wege­­
ner granu­­­lomatosis, systemic lupus erythematous, polyarthritis no­­­­­­dosa,
Crohn’s disease, sarcoidosis, multiple sclerosis), infectious (syphilis,
Lyme’s disease, toxoplasmosis, toxocariasis, tuberculosis, herpes, mo­­­
nonucleosis, leptospirosis), and ocular concomitant diseases (Birdshot
chorioretinopathy, pars planitis, Eales disease, IRVAN syndrome, mul­­
tifocal choroiditis).
RESULTS
Nineteen patients, 7 females and 12 males of 21 to 65 years of age
were enrolled in the study (mean, 46 years). The duration of follow-up
varied from 4 to 48 weeks. Three patients missed the follow up after
first examination and were excluded. Out of sixteen patients two
were followed up to one month (12.5%), three patients for 3 to 6
months (18.75%), three patients for 6 to 9 months (18.75%), and eight
from 9 to 12 months (50%). One patient was followed for 24 months.
Average follow-up time was 8.18 months.
Retinopathy developed in six patients (37.5%) and among these
two patients (12.5%) showed unilateral retinal hemorrhage presenting
with a small and isolated hemorrhage; cotton-wool spots characterized by small, isolated whitish spots, not associated with changes in
visual function (Figure 1) were observed in four patients (25%) or six
eyes (18.75%).
Out of 16 patients, a group of patients were diagnosed with the
following systemic diseases: HIV, 1 (6.25%); diabetes, 3 (18.75%); 3 pa­
tients had known treated hypertension (18.75%); and liver failure, 1
(6.25%). After the beginning of treatment, 66.6% of the patients developed diabetic retinopathy and the same occurred with hypertensive
patients. Of the total of detected retinopathy, hypertension accounted
for 33.3%. The same was true for patients with diabetes.
These patients were instructed to continue systemic treatment
with an ophthalmologic evaluation every two months and return
if any ophthalmologic signal was detected. All patients adequately
completed the treatment without any interruption due to the severi­
ty of ophthalmic associated findings.
Upon completion of the treatment and terminating the medication
the patients showed no signs of retinopathy or visual damage (Figure 2).
One of the patient, patient number 6 presented bilateral decrease
of visual acuity during the treatment (6.25% of patients), associated
with cotton wool spots on the right eye. However, this condition
was not connected with that pegylated interferon α-2b and ribavirin
treatment as the condition persisted even in absence of the medication. The patient recovered after one year of interruption of the
treatment (Table 1). In the initial tests, patient also showed bilateral
nonspecific disturbances on peripheral visual field at 30-2 strategy,
without disc edema and not compatible with retinal manifestation
on the right eye.
No color vision damage was found in any patient throughout the
systemic treatment.
DISCUSSION
Physiopathology of retinopathy has not been clearly understood.
Guyer et al.(11) suggested that immune-complex deposition and leucocyte infiltration in the retinal vasculature would lead to ischemic
episodes. Earlier studies(17,18) have shown that the increase in plasma
complement levels and plasma aggregation would facilitate capillary
infarction, thus explaining the ischemic alterations of retinopathy.
Although treatment with pegylated interferon α-2b associated
with ribavirin might lead to ocular side effects, the associated use
seems to bring a few side effects(19). Irritability and eye discomfort are
most commonly reported due to the drug-induced conjunctivitis as
the drug is secreted along with tear(20).
The incidence of retinopathy related to pegylated interferon α-2b
has been widely reported in the literature. In a systematic review
from Raza et al.(21), the overall incidence of retinopathy during the
treatment was around 27%. In a prospective study Vujosevic et al.(22)
reported 30% of retinopathy in 97 patients. In another prospective
Figure 1. Color (upper) and red-free retinograph (below) of both eyes of patient 1 at
6-month follow-up treatment for hepatitis C, presenting with multiple cotton-wool
spots without associated hemorrhage, smaller in the superior papillomacular bundle
area and bigger in the inferior one.
Figure 2. Color retinography of both eyes of patient 1 showing no retinal lesions at one
year follow-up.
Arq Bras Oftalmol. 2014;77(3):178-81
179
Ophthalmologic findings in hepatitis C patients treated with pegylated interferon α-2b and ribavirin
Table 1. Profile of patients that underwent follow-up during the treatment for hepatitis C
BCVA* before treatment BCVA* last query
Age (years)
Associated disease
Ocular changes
Time of detection of ocular changes
Right
Left
Right
Left
01
21
-
Bilateral cotton wool spots
month 6
1.0
1.0
1.0
1.0
02
62
Hypertension
Bilateral cotton wool spots
month 3
1.0
1.0
1.0
1.0
03
42
-
-
-
1.0
1.0
1.0
1.0
04
47
Diabetes
Retinal hemorrhage in OS
week 3
1.0
1.0
1.0
1.0
05
47
-
-
-
1.0
1.0
1.0
1.0
06
58
-
Cotton wool spots in OD
month 5
1.0
1.0
1.0
1.0
07
44
Diabetes and hypertension
Retinal hemorrhage in OS
month 6
1.0
0.5
1.0
0.5
08
33
-
-
-
1.0
1.0
1.0
1.0
09
46
-
-
-
1.0
1.0
1.0
1.0
10
51
Diabetes and hypertension
-
-
0.9
0.9
1.0
0.9
11
40
-
-
-
1.0
1.0
1.0
1.0
12
44
HIV**
-
-
1.0
1.0
1.0
1.0
13
36
-
-
-
1.0
1.0
1.0
1.0
14
54
-
-
-
1.0
1.0
1.0
1.0
15
42
-
Left eye cotton wool spots
month 7
1.0
1.0
1.0
1.0
16
44
Liver failure
-
-
1.0
1.0
1.0
1.0
*BCVA= best corrected visual acuity; **HIV= human immunodeficiency virus.
study, Kim et al.(23) evaluated 32 patients (64 eyes) and 11 of them
developed retinopathy (34.4%). Cotton-wool spots were found in
six patients, both eyes (18.7%); retinal hemorrhages in four (12.5%),
both eyes. Panetta et al.(24) reported in a retrospective study a very
low incidence (3.8%) of retinopathy among 183 patients with chronic hepatitis C treated with pegylated interferon α-2b and ribavirin.
However, only symptomatic patients were included in this study.
It is likely that the incidence of retinopathy could be under re­­
presented. The cotton-wool spots were transient, often asymptomatic with no visual acuity, so it is possible that they were not always
detected, especially when the patients missed or were irregular with
the follow-up. Most patients showed full resolution without visual
sequelae.
Schulman et al.(25) showed among 42 patients (7%) treated with
interferon and ribavirin, three patients had be stopped the treatment
due to retinopathy (two) and disc edema (one) with low visual acuity.
The patients regressed spontaneously after stopping the treatment,
without sequelae.
Nagaoka et al.(26) suggested endothelial dysfunction as a cause
of interferon-associated retinopathy, with increased manifestation
within 2 weeks of treatment initiation. Schulman et al.(25) reported
a 67% chance of development of retinopathy among hypertensive
patients. Similar to the findings of Vujosevic et al.(22) that reported a
frequency of 68% Kim et al.(23) also claimed hypertension to be a risk
factor for retinopathy.
CONCLUSION
In our study, we diagnosed retinopathy in a considerable number
of cases, but most patients showed no changes in visual acuity and
quality. Only one patient showed a transient visual loss without loss
of term impairing of the visual function. We conclude that according
to our study and in agreement with studies published in literature, the
treatment for hepatitis C with pegylated interferon α-2b associated
with ribavirin although can cause retinal changes, usually do not lead
to damages to visual function, and has a transitional character with
complete anatomical and functional recovery. Although ocular involvement is rare, follow-up with an ophthalmologist is recommended
throughout the course of the medication, especially if symptoms are
detected.
180
Arq Bras Oftalmol. 2014;77(3):178-81
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Ophthalmol. 1995;113(8):1041-4.
8. Hayasaka S, Fujii M, Yamamoto Y, et al. Retinopathy and subconjunctival haemorrhage in patients with chronic viral hepatitis receiving interferon alfa. Br J Ophthalmol.
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9. Kadayifcilar S, Boyacioglu S, Kart H, et al. Ocular complications with high-dose interferon alpha in chronic active hepatitis. Eye (Lond). 1999;13(Pt 2):241-6.
10.Hayasaka S, Nagaki Y, Matsumoto M, Sato S. Interferon associated retinopathy. Br J
Ophthal­mol. 1998;82(3):323-5.
11.Guyer DR, Tiedeman J, Yannuzzi LA, et al. Interferon-associated retinopathy. Arch
Ophthalmol. 1993;111(3):350-6.
12. Esmaeli B, Koller C, Papadopoulos N, Romaguera J. Interferon-induced retinopathy in
asymptomatic cancer patients. Ophthalmology. 2001;108(5):858-60.
13.Hejny C, Sternberg P Jr, Lawson DH, et al. Retinopathy associated with high-dose
interferon alfa-2b therapy. Am J Ophthalmol. 2001;131(6):782-7.
14. Jain K, Lam WC, Waheeb S, et al. Retinopathy in chronic hepatitis C patients during
interferon treatment with ribavirin. Br J Ophthalmol. 2001;85(10):1171-3.
15.Tokai R, Ikeda T, Miyaura T, Sato K. Interferon-associated retinopathy and cystoid
macular edema. Arch Ophthalmol. 2001;119(7):1077-9.
16.Hoerauf H, Schmidt-Erfurth U, Asiyo-Vogel M, Laqua H. Combined choroidal and
retinal ischemia during interferon therapy: indocyanine green angiographic and
microperimetric findings. Arch Ophthalmol. 2000;118(4):580-2.
17.Sugano S, Suzuki T, Watanabe M. Retinal complications and plasma C5a levels during
interferon alpha therapy for chronic hepatitis C. Am J Gastroenterol. 1998;93(12):2441-4.
18.Sugano S, Yanagimoto M, Suzuki T. Retinal complications with elevated circulating
plasma C5a associated with interferon-alpha therapy for chronic active hepatitis C.
Am J Gastroenterol. 1994;89(11):2054-6.
19. Schalm SW, Hansen BE, Chemello L, et al. Ribavirin enhances the efficacy but not the
adverse effects of interferon in chronic hepatitis C. Meta-analysis of individual patient
data from European centers. J Hepatol. 1997;26(5):961-6.
20. Fraunfelder FT, Fraunfelder FW, Chambers WA. Clinical ocular toxicology. Philadelphia,
PA: Saunders. 2008;212-4.
21. Raza A, Mittal S, Sood GK. Interferon-Associated Retinopathy During the Treatment
of Chronic Hepatitis C. J Viral Hepat. 2013;20(9):593-9.
Novelli FJ, et al.
22. Vujosevic S, Tempesta D, Noventa F, Midena E, Sebastiani G. Pegylated interferon-associated
retinopathy is frequent in hepatitis C virus patients with hypertension and justifies
ophthal­mologic screening. Hepatology. 2012;56(2):455-63.
23. Kim ET, Kim LH, Lee JI, Chin HS. Retinopathy in hepatitis C patients due to combination therapy with pegylated interferon and ribavirin. Jpn J Ophthalmol. 2009;53(6):
598-602.
24. Panetta JD, Gilani N. Interferon-induced retinopathy and its risk in patients with dia-
betes and hypertension undergoing treatment for chronic hepatitis C virus infection.
Aliment Pharmacol Ther. 2009;30(6):597-602.
25. Schulman JA, Liang C, Kooragayala LM, King J. Posterior segment complication in patients
with Hepatitis C treated with interferon and ribavirin. Ophthalmology. 2003;110(2):437-42.
26.Nagaoka T, Sato E, Takahashi A, Yokohama S, Yoshida A. Retinal circulatory changes associated with interferon-induced retinopathy in patients with hepatitis C. Invest Ophthal­mol
Vis Sci. 2007;48(1):368-75.
17o Congresso de Oftalmologia USP
16o Congresso de Auxiliar
de Oftalmologia USP
28 e 29 de novembro de 2014
Centro de Convenções Rebouças
São Paulo - SP
Informações:
Tels.: (11) 5084-9174 / 5082-3030
E-mail: [email protected]
Site: www.oftalmologiausp.com.br
Arq Bras Oftalmol. 2014;77(3):178-81
181
Case Report
Severe scleral dellen as an early complication of pterygium excision with
simple conjunctival closure and review of the literature
“Dellen” escleral grave como complicação precoce de excisão de pterígio com fechamento conjuntival
simples e revisão da literatura
Jose Javier Garcia-Medina1,2,3, Mónica del-Rio-Vellosillo4, Vicente Zanon-Moreno3,5, Amanda Ortiz-Gomariz1, Manuela Morcillo-Guardiola1,
Maria Dolores Pinazo-Duran3,6
ABSTRACT
RESUMO
We describe a patient with acute scleral dellen (SD) after pterygium excision
with simple conjunctival closure. In addition, we present a PUBMED review on
the medical literature on early SD after pterygium surgery. This case describes a
45-year-old man who presented with severe SD, 7 days after pterygium surgery
with minimal cauterization of episcleral vessels and simple conjunctival closure.
No other adjunctive therapy was used intraoperatively. The patient refused
conjunctival flap coverage of the lesion. Therefore, medical treatment consisted
of antibiotic ointment, patching, and daily follow-up. After 7 days, the patching
was changed for intensive ocular lubrication. Five weeks later, the surrounding
conjunctiva had completely covered the affected sclera. To the best of our
knowledge, this is the first report of early SD following pterygium excision and
simple conjunctival closure with no other adjunctive therapy. When performing
pterygium excision with conjunctival coverage of the sclera, a close follow-up
is recommended to rule out wound dehiscence and SD, even when surgical
wound closure is considered to prevent SD. If this complication is detected, the
treatment can be conservative.
Descrevemos um paciente com “dellen” escleral agudo (SD) após excisão de pterígio
com fechamento conjuntival simples. Uma revisão adicional da literatura médica
sobre SD precoce após a cirurgia de pterígio também é realizada. Este caso descreve
um homem de 45 anos de idade, que apresentou SD grave, sete dias após a cirurgia
de pterígio com cauterização mínima de vasos episclerais e fechamento conjuntival
simples. Nenhuma outra terapia adjuvante foi utilizada no intraoperatório. O paciente recusou-se à cobertura de retalho conjuntival da lesão. Portanto, o tratamento
médico consistiu em pomada antibiótica, oclusão e acompanhamento diário. Após
sete dias, a oclusão foi mudada para a lubrificação ocular intensiva. Cinco semanas
após, a conjuntiva cobriu completamente a esclera afetada. Ao melhor de nosso
conhecimento, este é o primeiro relato de SD precoce após a excisão do pterígio e
fechamento conjuntival simples com nenhuma outra terapia adjuvante. Ao realizar
a excisão do pterígio com cobertura conjuntival da esclera, um acompanhamento
frequente é recomendado para descartar a deiscência da ferida e SD. Se esta complicação for detectada, o tratamento pode ser conservador.
Keywords: Pterygium/surgery; Gentamicins; Scleral diseases/etiology; Case
reports
Descritores: Pterígio/cirurgia; Gentamicinas; Doenças da esclera/etiologia; Relatos
de casos
INTRODUCTION
CASE REPORT
A 45-year-old bricklayer with a primary pterygium on the nasal
side of his right eye underwent surgical excision with minimal cauterization of episcleral vessels and simple conjunctival closure with
two stitches (7/0 silk). The procedure was carried out under topical
and subconjunctival anesthesia (lidocaine 2% and epinephrine
1/200.000). No adjunctive therapy was used intraoperatively. Dexamethasone (0.5 mg/g) and chloramphenicol (10 mg/g) ointment
were applied and the eye was patched. His medical and ocular histories were unremarkable. The day following surgery, the outcome
looked favorable; there was a nasal corneal epithelial defect and the
edges of the conjunctival incision were in close apposition with no
signs of infection or excessive inflammation. Topical steroids, antibiotics, and artificial tears were prescribed.
Several surgical techniques are available for treating pterygium,
such as bare sclera, simple conjunctival closure, sliding conjunctival
flaps, and conjunctival autografts. Adjunctive therapies, such as
pos­­­­toperative beta radiation or thiotepa drops and intraoperative
mitomycin C, can be used to prevent the recurrence of pterygium(1).
Severe scleral dellen (SD) is a rare complication during the early
postoperative period following pterygium surgery. The few reports
describing this condition are all related to the bare sclera technique
without adjunctive therapy(2,3) or with intraoperative mitomycin C(4,5)
or beta radiation(6). However, we are unaware of any report of SD asso­
ciated with pterygium excision followed by minimal cauterization of
episcleral vessels and simple conjunctival closure.
Submitted for publication: August 2, 2013
Accepted for publication: December 17, 2013
Study conducted at Department of Ophthalmology, General University Hospital Reina Sofia, Murcia
Spain.
Department of Ophthalmology, General University Hospital Reina Sofia, Murcia, Spain.
Department of Ophthalmology and Optometry, School of Medicine, University of Murcia, Spain.
3
Ophthalmology Research Unit “Santiago Grisolia”, Valencia, Spain.
4
Department of Anesthesia, University Hospital La Arrixaca, Murcia, Spain.
5
Department of Preventive Medicine & Public Health, School of Medicine, University of Valencia,
Valencia, Spain.
6
Department of Ophthalmology, School of Medicine, University of Valencia, Valencia, Spain.
1
2
182
Arq Bras Oftalmol. 2014;77(3):182-4
Funding: No specific financial support was available for this study.
Disclosure of potential conflicts of interest: None of the authors have any potential conflicts of
interest to disclose.
Corresponding author: Jose Javier García-Medina. Department of Ophthalmology. General University Hospital Reina Sofia. Avenida Intendente Jorge Palacios, 1 - 30003 Murcia, Spain
E-mail: [email protected]
http://dx.doi.org/10.5935/0004-2749.20140046
Garcia-Medina JJ, et al.
One week later, the patient arrived at the emergency department
complaining of moderate pain and a black dot in his right eye. His
best corrected visual acuity was 10/10 and intraocular pressure was
15 mmHg. Slit lamp examination revealed severe scleral thinning
reaching the choroid (Figure 1). The conjunctival sutures were no longer in place. The anterior chamber was deep with no Tyndall effect,
whereas the pupils were isocoric and normoreactive. The fundus
showed transparent media with no other abnormal findings. The
patient refused improper eye handling, therapeutic failure, or going
back to work in a dusty environment. Reconstructive surgery through
a conjunctival flap was offered, but the patient refused; therefore, a
conservative medical treatment was prescribed that included gentamicin antibiotic ointment (3 mg/g), patching for 7 days, and daily
outpatient monitoring, which was followed by intensive ocular lubrication (carmellose 10 mg/mL every hour) for 6 weeks. Within a few
weeks, the conjunctival defect was replaced by granulation tissue,
and later with a flap of adjacent conjunctiva. The photographic series
illustrates the patient’s evolution (Figures 2 and 3).
After solving the case, the patient was referred to internal medicine to rule out collagen or infectious disease. Medical history, physical
examination, and laboratory test (blood count, biochemistry, rheumatoid factor, autoantibody screening, infectious serology, and Mantoux) revealed no infectious or autoimmune inflammatory disease.
Figure 1. Initial appearance of the scleral dellen reaching the choroid.
DISCUSSION
As seen above, several surgical techniques can be used to treat
pterygium. The bare sclera technique includes excision of the pte­­
ry­­gium, which leaves the conjunctival defect to heal by sclera epithelization from the surrounding conjunctiva. Exposing the sclera
contributes to drying, and therefore is a risk factor for thinning. All
severe scleral thinning cases during the early postoperative period
seem to be associated with the bare sclera technique. In our case,
however, we used the primary excision technique with simple conjunctival closure (Table 1).
The fact that no stitches were found at about 1 week post-surgery
suggests improper eye handling by the patient, excessively lax
stitches, or a combination of both. The dehiscence of the wound,
possibly resulting in exposure of the underlying sclera and edema,
and raised conjunctiva edges, may have caused a discontinuity of the
tear film leading to exacerbated local dehydration. In their publication, Chen and Noonan(2) attributed SD after pterygium surgery with
the bare sclera technique to raised granulation tissue edges, which
developed in the conjunctiva margin of exposed sclera.
Whereas the growth of blood vessels in the wound bed is considered to contribute to pterygium recurrence, some authors have
recommended cauterization of episcleral vessels, especially at the
limbus. However, it appears that coagulation of the episcleral vessels,
which do not bleed, neither avoids recurrences nor contributes to
accomplishing better esthetic results during pterygium surgery
(personal communication of Lawrence W. Hirst). The cauterization
applied to our patient was performed carefully and only with the
purpose of avoiding bleeding during surgery. Nonetheless, this factor
has to be considered in the etiology of scleral perforation as it may
Figure 2. The sclera dellen on day 3 (top) and on day 7 (bottom) from its onset.
Figure 3. The sclera dellen on day 12 (top) and on day 38 (bottom) from its onset.
Arq Bras Oftalmol. 2014;77(3):182-4
183
Severe scleral dellen as an early complication of pterygium excision with simple conjunctival closure and review of the literature
Table 1. Summary of published cases of early scleral dellen after pterygium surgery
Reference
Surgical
technique
Cauterization
of episcleral
vessels
Intraoperative
adjunctive
therapy
Topical
corticosteroids
after surgery
Onset of signs/
symptoms
(from surgery)
Treatment
Chen and Noonan(2)
Bare sclera
Minimal
None
Yes
14 days
Conjunctival flap
Mitra et al.(3)
Bare sclera
Unknown
None
Yes
7 days
Antibiotic and artificial tears
Tsai et al.(4)
Bare sclera
Unknown
Mitomycin C
Yes
8 days
Artificial tears
Safianik et al.(5)
Bare sclera
Unknown
Mitomycin C
Unknown
21 days
Conjunctival flap
Bare sclera
Unknown
Beta-radiation
Unknown
2 days
Patching
Simple conjunctival
closure
Minimal
None
Yes
7 days
Patching, antibiotic, and
artificial tears
Hicks et al.(6)
Garcia-Medina et al.
(present case)
cause local ischemia. In the cases reported in the literature, whether
episcleral vessel cauterization was used or its duration is unclear.(2-6)
Subconjunctival anesthesia containing a vasoconstrictor agent (epinephrine) also may have been a contributory factor for local ischemia
in the present case.
Topical corticosteroids enhance collagenases and inhibit collagen synthesis, which may have also contributed to SD formation, as proposed by Mitra et al.(3). Therefore, they should be removed immediately.
The conjunctival flap graft has been used successfully to manage
these complications(2,5). As the patient refused this surgical procedure, we had the opportunity to assess the evolution of scleral erosion
with medical treatment. We found that eye patching, antibiotic coverage, and intensive lubrication combined are sufficient for healing
this com­­­­plication. Conservative treatment has also been proved to be
successful in the cases that other authors have presented(3,4,6).
In conclusion, we can state that pterygium excision with primary
conjunctival closure and cauterization of episcleral vessels may result
184
Arq Bras Oftalmol. 2014;77(3):182-4
in severe SD, even in patients with no history of risk, as was the case
presented here. Conservative treatment may be appropriate to manage this rare complication.
REFERENCES
1. Hirst LW. The treatment of pterygium. Surv Ophthalmol. 2003;48(2):145-80.
2.Chen S, Noonan C. Scleral dellen complicating primary pterygium excision. Eye.
2000;14(Pt 1):100-1.
3. Mitra S, Ganesh A, Shenoy R. Scleral dellen complicating primary pterygium excision.
Eye. 2000;14 (Pt 6):924-5.
4. Tsai YY, Lin JM, Shy JD. Acute scleral thinning after pterygium excision with intraope­
rative mitomycin C: a case report of scleral dellen after bare sclera technique and
re­­­view of the literature. Cornea. 2002;21(2):227-9.
5. Safianik B, Ben-Zion I, Garzozi HJ. Serious corneoscleral complications after pterygium
excision with mitomycin C. Br J Ophthalmol. 2002;86(3):357-8.
6.Hicks RR, Irvine AR, Spencer WH, Yuhasz Z. Scleral dellen. Arch Ophthalmol. 1975;
93(1):88-9.
Case Report
Transient spectral domain optical coherence tomography findings in classic mewds:
a case report
Alterações transitórias evidenciadas na tomografia de coerência óptica de domíno espectral em
quadro clássico de mewds: relato de caso
Luciana Castro Lavigne1, David Leonardo Cruvinel Isaac2, José Osório Duarte Júnior1, Marcos Pereira de Ávila2
ABSTRACT
RESUMO
The purpose of this study was to describe a patient with multiple evanescent
white dot syndrome (MEWDS) who presented with classic retinal findings and
transient changes in outer retinal anatomy. A 20-year-old man presented with mild
blurred vision in the left eye, reporting flu-like symptoms 1 week before the visual
symptoms started. Fundus examination of the left eye revealed foveal granularity
and multiple scattered spots deep to the retina in the posterior pole. Fluorescein
angiography and indocyanine green angiography showed typical MEWDS findings.
Spectral Domain Optical Coherence Tomography has shown transient changes
in outer retinal anatomy with disappearance of inner segment-outer segment
junction and mild attenuation of external limiting membrane. Six months later,
Spectral Domain Optical Coherence Tomography has shown complete resolution
with recovery of normal outer retinal aspect.
O propósito deste estudo é descrever o caso de um paciente com síndrome dos múltiplos
pontos brancos evanescentes (MEWDS), apresentando achados retinianos clássicos
e alterações transitórias na anatomia retiniana externa. Paciente do sexo masculino,
20 anos de idade, apresentando embaçamento visual no olho esquerdo, relatando
sintomas gripais uma semana antes do início dos sintomas visuais. Fundoscopia do
olho esquerdo revelou granularidade foveal, múltiplos pontos brancos retinianos no
polo posterior. A angiografia fluoresceínica e a indocianinografia verde evidenciaram
achados típicos de MEWDS. A tomografia de coerência óptica de domínio espectral
evidenciou alterações transitórias na anatomia retiniana externa como desaparecimento da junção dos segmentos interno-externo dos fotorreceptores e leve atenuação
da membrana limitante externa. Após 6 meses, a tomografia de coerência óptica
mostrou completa resolução com recuperação total da anatomia retiniana externa.
Keywords: Retinal diseases/diagnosis; Syndrome/diagnosis; Tomography, optical
coherence; Case reports
Descritores: Doenças retinianas/diagnóstico; Síndrome/diagnóstico; Tomografia de
coerência óptica; Relatos de casos
INTRODUCTION
Multiple evanescent white dot syndrome (MEWDS) is a benign
self-healing disease with an unknown etiology that was first described in 1984 by Jampol et al. It is a retinal pigment epithelial (RPE) and
choroidal inflammatory condition that predominantly affects young
to middle-aged women, is unilateral in 80% of cases, and causes
visual loss of variable degrees(1-5).
Associated clinical features include flu-like prodrome, blurred disc
margins, blind spot enlargement, and temporal scotomata(2,5). Fundoscopy typically reveals multiple, 100-200 µm yellow-white outer retina
dots in posterior pole and mid-periphery as well as a unique foveal
granularity(1,2,4-7).
Fluorescein angiography (FA) typical aspect comprises early foveal
granular hyperfluorescence, early hyperfluorescence, and late staining
of the white dots in a wreath-like pattern and disc capillary leakage.
Indocyanine green angiography (ICGA) shows numerous hypofluorescent nummular lesions that are evident in the late phase and predominant in the mid-periphery and around the optic disc(2,4,7).
Here, we report a case of MEWDS notable for its classic retinal appea­
rance, foveal granularity, and transient disruption of the macular
photoreceptor of the inner segment-outer segment (IS-OS) junction.
After six months of follow up, the patient presented full visual recovery and re-established a normal foveal aspect on Spectral Domain
Optical Coherence Tomography (SD-OCT).
CASE REPORT
A 20-year-old man presented for an ophthalmologic evaluation
with a 2-day history of blurred vision in his left eye and flu-like
symptoms that began 1 week before the visual symptoms started.
His best-corrected visual acuity was 20/20 (OD) and 20/40 (OS); in­­­­­­
traocular pressure was 15 mmHg in OU. Anterior biomicroscopy was
normal in OU. Fundus examination was normal in OD, and OS revealed multiple 100-500 µm yellow-white dots deep to the retina in the
posterior pole and mid-periphery, foveal granularity, and blurred disc
margins (Figure 1).
Automated perimetry showed a blind spot enlargement in the
affected eye. FA had shown earlier hyperfluorescent lesions in the
posterior pole and mid-periphery, with late staining of the white dots
in a wreath-like pattern and late staining in the optic nerve (Figure 2).
The corresponding ICGA demonstrated numerous hypofluorescent
areas predominantly in the mid-periphery and around the optic disc.
These hypofluorescent areas were mild and in an early angiographic
phase, but became more clearly delineated in the late phase (Figure 2).
SD-OCT showed mild attenuation of the external limiting membrane, a transient disruption of the macular photoreceptor IS-OS
junction, increased RPE reflectivity and enhanced signal penetration
into the underlying choroid (Figure 3). The patient was diagnosed
with MEWDS and observation without treatment was suggested.
The patient was lost at follow-up, but returned 24 weeks later after
Submitted for publication: September 17, 2013
Accepted for publication: January 27, 2014
Funding: No specific financial support was available for this study.
Study conducted at Universidade Federal de Goiás, GO, Brazil.
1
Setor de Retina e Vítreo, Universidade Federal de Goiás (UFG), Goiânia, GO, Brazil.
Universidade Federal de Goiás (UFG), Goiânia, GO, Brazil.
2
http://dx.doi.org/10.5935/0004-2749.20140047
Disclosure of potential conflicts of interest: None of the authors have any potential conflicts of
interest to disclose.
Corresponding author: Luciana Castro Lavigne. Rua S-4, 237 - Qd S19 - Lot 20/24 - Apto. 1.308 - Setor
Bela Vista - Goiânia (GO) - 74823-450 - Brazil - E -mail: [email protected]
Arq Bras Oftalmol. 2014;77(3):185-7
185
Transient spectral domain optical coherence tomography findings in classic mewds: a case report
A
B
Figure 1. A) Retinography demonstrating normal foveal aspect in the right eye. B) Retinography demonstrating foveal granularity
in the left eye.
A
B
C
D
Figure 2. Multiple evanescent white dot syndrome lesions. A) Fluorescein angiography demonstrating early hyperfluorescent lesions.
B) Fluorescein angiography, in late stage, demonstrating staining of the white dots in a wreath-like pattern and disc capillary leakage.
C) Indocyanine green angiography, in the early phase, showing discrete hypofluorescent nummular lesions. D) Indocyanine green
angiography (late phase) showing numerous clearly delineated hypofluorescent nummular lesions.
contacting the authors. He claimed that he had not attended the
visits because he had visual recovery within one month. His BCVA
was 20/20 OU. Fundus examination in the OD was normal, and the
OS revealed mild foveal granularity and RPE hyperpigmentation
surrounding the optic disc. Color and red-free fundus photography
showed the retinal white dots disappeared. SD-OCT indicated the
IS-OS disruption resolved with reestablishment of outer retina OCT
anatomy (Figure 3).
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Arq Bras Oftalmol. 2014;77(3):185-7
DISCUSSION
MEWDS is an acute, usually unilateral retinopathy that predominantly affects macular and mid-periphery regions of young women,
causing mild to moderate visual loss. Characteristic symptoms include photopsia, and a viral prodrome is reported in 50% of the cases.
In this case report, the patient was a young male who had unilateral
visual loss. He had flu-like symptoms 1 week before the initial evalua­
tion, and did not present with photopsia(1,2).
Lavigne LC, et al.
A
B
Figure 3. A) Spectral Domain Optical Coherence Tomography (SD-OCT) demonstrating mild attenua­
tion of the external limiting membrane, disruption of the macular photoreceptor inner segment-outer
segment (IS-OS) junction, and increased RPE reflectivity. B) SD-OCT demonstrating resolution of IS-OS
disruption with reestablishment of outer retina OCT anatomy.
In the present case, FA demonstrated typical early hyperfluorescence with late RPE staining, corresponding to hypofluorescent areas
in the late phase of ICGA(1,5). These hypofluorescent areas showed
moderately reflective focal lesions in the outer photoreceptor layer,
where the macular photoreceptor IS-OS junction was disrupted by
SD-OCT, which is associated with foveal granularity. Possibly, the
foveal granularity is the most specific characteristic of MEWDS(1,4,8,9).
Considering the clinical and angiographic pattern, and through
electrophysiological evidence, previous studies have suggested that
the white dot lesions in MEWDS are situated in the RPE and outer retina. Electrophysiology analysis has revealed an electro-oculographic
reduction in the light-dark ratio, and an electroretinographic alteration of the a-wave and early receptor potential(6,8).
Ophthalmologic studies have advocated the hypothesis that
injury to the RPE is the early pathologic event in MEWDS. FA showed
characteristic early hyperfluorescent lesions that were observed as
window defects. It was suggested the primary site of MEWDS is on
the RPE(2,6). With the clinical use of ICGA, MEWDS has become known
as a choroidopathy, suggesting that the cause of the photoreceptors
and RPE dysfunction is associated to decreased perfusion of the
choriocapillaris(4-6,10). This supposition is based on their angiographic
pattern that demonstrated hypofluorescent lesions on ICGA that may
appear even in normal areas on FA and funduscopy(6).
In the case reported here, the FA pattern demonstrated characte­
ristic early hyperfluorescence and late staining, which appeared to be
due to RPE changes; however, the ICGA showed numerous hypofluo­
rescent areas mainly in the mid-periphery. These hypofluorescent
areas are mild in initial angiographic phases and become more
evi­­­­­­­­dently delineated in the late phase, which appears to slightly
outnumber those observed on FA, suggesting that MEWDS involves
both RPE and choriocapillay(2,8).
In this case ICGA was not crucial to diagnosis, because of other
classic findings, but it was useful to confirm diagnosis and also in differential diagnosis with other white dot syndromes. Acute posterior
multifocal placoid pigment epitheliopathy (APMPPE) has been con-
sidered an important differential diagnosis. FA patterns in APMPPE
show early hypofluorescence, but become hyperfluorescent later in
the study. In ICGA, lesions present as early to late hypofluorescence.
MEWDS has been considered the first known disease involving
electrophysiological damage of photoreceptor outer segments with
complete return to normal conditions(8). We report a case of MEWDS
notable for both its classic retinal appearance, confirmed by automated perimetry, FA, ICGA, and SD-OCT exams. SD-OCT has showed
disruption of the IS-OS junction. The patient was observed with no
medical intervention, and had a favorable recovery of visual function
and macular photoreceptor IS-OS junction in SD-OCT. This is consistent with previous report and OCT findings about the disease.
REFERENCES
1. Hua R, Chen K, Liu LM, Liu NN, Chen L, Teng WP. Multi-modality imaging on multiple
evanescent white dot syndrome - A Spectralis Study. Int J Ophthalmol. 2012;5(5):644-7.
2.Kuznetcova T, Jeannin B, Herbort CP. A case of overlapping choriocapillaritis syn­
dromes: multimodal imaging appraisal. J Ophthalmic Vis Res. 2012;7(1):67-75.
3.Abu-Yaghi NE, Hartono SP, Hodge DO, Pulido JS, Bakri SJ. White dot syndromes: a
20-year study of incidence, clinical features, and outcomes. Ocul Immunol Inflamm.
2011;19(6):426-30.
4.Nguyen MH, Witkin AJ, Reichel E, Ko TH, Fujimoto JG, Schuman JS, Duker JS. Microstructural abnormalities in MEWDS demonstrated by ultrahigh resolution optical
coherence tomography. Retina. 2007;27(4):414-8.
5.Vianna RNG, Socci D, Nehemy MB, Deschênes J, Burnier MN Jr. The white dot syn­
dromes. Arq Bras Oftalmol. 2007;70(3):554-62.
6. Penha FM, Navajas EV, Bom Aggio F, Rodrigues EB, Farah ME. Fundus autofluorescence
in multiple evanescent white dot syndrome. Case Rep Ophthalmol Med. 2011;807565.
7.Slusher MM, Weaver RG. Multiple Evanescent White Dot Syndrome. Retina. 1988;
8(2):132-5.
8. Silva RA, Albini TA, Flynn HW Jr. Multiple evanescent white dot syndromes. J Ophthalmic Inflamm Infect. 2012;2(2):109-11.
9. Saito M, Barbazetto IA, Spaide RF. Intravitreal cellular infiltrate imaged as punctate spots
by spectral-domain optical coherence tomography in eyes with posterior segment
in­­flammatory disease. Retina. 2013;33(3):559-65.
10.Papadia M, Herbort CP. Idiopathic choroidal neovascularisation as the inaugural sign of
mul­­tiple evanescent white dot syndrome. Middle East Afr J Ophthalmol. 2010;17(3):270-4.
Arq Bras Oftalmol. 2014;77(3):185-7
187
Case Report
Susac syndrome: diverse clinical findings and treatment
Síndrome de Susac: achados clínicos diversos e tratamento
Ricardo Canto Bardal1, Emmerson Badaro2, Jayme Arana3, Fabio Alves3, Eduardo Cunha de Souza2, Pedro Paulo Bonomo2, Ezequiel Portella3,
Mauricio Maia2
ABSTRACT
RESUMO
We report a case of a 19-year-old woman presenting bilateral neurosensorial hearing loss, mental abnormalities, and loss of visual field in the left eye. Visual acuity
was 20/20 in OD and 20/25 in OS. Patient was examined systemically. Audiometry
showed sensorineural hearing loss in both ears. The magnetic resonance imaging
(MRI) of brain revealed multiple small lesions in the white matter in both cerebral
hemispheres and at the corpus callosum. Fundoscopy showed bilateral normal optic
disc and sheathing of the arterioles in the middle periphery of OD. Retinal edema
and cotton-wool spots were observed. Fluorescein angiography showed bilateral
peripheral occlusive arterial vasculopathy. The patient was diagnosed with Susac
syndrome and treated with quetiapine fumarate, flunitrazepam, and prednisone,
which resulted in stabile outcome. This case shows that a high index of suspicion
leading to early recognition and treatment is important to avoid irreversible damage.
Relatamos o caso de uma mulher de 19 anos apresentando perda auditiva neu­
rossensorial bilateral, anormalidades mentais e perda de campo visual no olho
es­­­­­querdo. A acuidade visual era 20/20 em OD e 20/25 em OE. Paciente foi sistematicamente investigada, audiometria mostrou perda auditiva neurossensorial nos dois
ouvidos e ressonância magnética nuclear (RNM) cerebral mostrou múltiplas pequenas
lesões na substância branca em ambos os hemisférios cerebrais e no corpo caloso. A
fundoscopia mostrou disco óptico normal bilateral, e embainhamento das arteríolas
na média periferia do olho direito. Edema de retina e exsudatos algodonosos foram
vistos. Angiofluoresceinografia mostrou vasculopatia arterial obstrutiva periférica
bilateral. A paciente foi diagnosticada com síndrome Susac e tratada com fumarato
de quetiapina, flunitrazepam e prednisona resultando em estabilização do quadro.
Este caso mostra que um alto índice de suspeita levando ao reconhecimento precoce
e tratamento é importante para evitar o diagnóstico tardio.
Keywords: Susac syndrome; Retinal artery occlusion; Hearing loss; Corpus callosum;
Fluorescein angiography; Humans; Female; Adult; Case reports
Descritores: Síndrome de Susac; Oclusão da artéria retiniana; Perda auditiva; Cor­­­po
caloso; Angiofluoresceinografia; Humano; Femino; Adulto; Relatos de casos
INTRODUCTION
Susac syndrome (SS), also known as retinal-cerebral-cochlear di­­
sea­se, although rare, needs to be considered as a differential diagnosis
when unexplained visual field or visual acuity loss is detected in a
patient. The triad of clinical symptoms that may not all be present at
initial stages include diffuse encephalopathy, branch retinal artery
occlusion, and sensorineural hearing loss(1).
The etiology and pathogenesis of SS are not clearly understood.
Autoimmune processes leading to the damage and inflammation-re­
lated occlusion of the microvessels in the brain, retina, and inner ear
may play a causal role(2). Electroencephalogram, audiometry, fluorescein angiography (FA), and magnetic resonance imaging (MRI) of the
brain sensitively detects the lesions(3).
Retinal abnormalities may have different clinical features. When
arteriolar abnormalities are observed close to the central vision,
symptoms of visual loss are more evident and the diagnosis may be
faster. However, most cases have peripheral arteriolar micro-occlusive
events, resulting in late ophthalmologic evaluation(4).
Multifocal arteriolar wall hyperfluorescence and peripheral branch
artery occlusion can occur in normal-appearing fundus. Gass plaques
(GP), which are yellow-white deposits seen at the mid segments of
the arteriole, are a helpful finding for the diagnosis(5). If an initial FA
is normal, it should be repeated at intervals during the early course
of definite or suspected SS. FA abnormalities serve as a valuable bio­
marker, and serial FA may be useful in monitoring the effect of the
treatment(1).
The natural history and outcomes of SS are not fully understood.
The disease may be active for several months and the time to remission can be long(4). After remission it results in various cognitive and
functional damages. However, serious loss of vision is not observed in
the majority of the patients.
The objectives of this study were to report a case of SS, its clinical
manifestations, and to discuss the variability in clinical findings as
well as management.
Submitted for publication: December 2, 2013
Accepted for publication: December 6, 2013
Funding: No specific financial support was available for this study.
Study conducted at Department of Ophthalmology, Hospital Evangélico, Curitiba, PR and Department
of Ophthalmology, Universidade Federal de São Paulo, São Paulo, SP, Brazil.
Department of Ophthalmology, Hospital Evangélico, Curitiba, PR, Brazil.
Department of Ophthalmology, Universidade Federal de São Paulo, São Paulo, SP, Brazil.
3
Paraná Eye Hospital, Curitiba, PR, Brazil.
1
RESULTS
A 19-year-old female was referred by a neurologist because of
visual field loss in the left eye that lasted for 10 days. Three months
earlier, the patient was examined for neurological abnormalities
associated with bilateral hearing loss and underwent audiometry,
impedance testing, brain MRI, and laboratory evaluations. The audiometry showed severe sensorineural hearing loss in the right ear
and moderate sensorineural hearing loss in the left ear. The brain MRI
showed multiple small lesions in the white matter in both cerebral
hemispheres and at the corpus callosum (Figure 1). The total com-
Disclosure of potential conflicts of interest: None of the authors have any potential conflicts of
interest to disclose.
Corresponding author: Mauricio Maia. Rua Otto Ribeiro, 901 - Assis (SP) - 19840-050 - Brazil E-mail: [email protected]
2
188
Arq Bras Oftalmol. 2014;77(3):188-90
http://dx.doi.org/10.5935/0004-2749.20140048
Bardal RC, et al.
plement, complement 3 and 4, antinuclear factor, thyroid-stimulating
hormone, and T4 thyroid level were normal.
Ophthalmologic examination showed best corrected visual
acuity (BCVA) of 20/20 in OD and 20/25 in OS. Fundoscopy showed
bilateral normal optic disc and sheathing of the arterioles in the
middle periphery of OD. Retinal edema was seen in the temporal
inferior quadrant and at the mid-peripheral temporal superior region
associated with cotton-wool spots and sheathing of the arterioles
nasally in the left eye.
FA showed bilateral normal choroidal perfusion­-arterial nonperfusion at the peripheral superior and nasal inferior areas in right eye
(OD) and in late phase temporal and inferiorly in left eye (OS), suggesting
bilateral peripheral occlusive arterial vasculopathy, which was more
evident in the left eye. Unusual leakage pattern of arterial wall in the
temporal inferior area, but not located in the arterial occlusion area
was noted in the right eye (Figure 2).
The clinical findings and the exclusion of other diseases resulted
in the diagnosis of SS. Quetiapine fumarate (100 mg/day), flunitra-
Figure 1. Brain MRI showing multiple small lesions at the corpus callosum.
A
B
C
D
Figure 2. FA images of both eyes of patient 2 shows microarterial nonperfusion in the peripheral retina. A) Microarterial occlusion in
the peripheral retina temporosuperiorly in the left eye. B) A similar image of the peripheral retina temporally in the left eye shows a
clearer image of the nonperfused arterioles. C) Unusual leakage pattern of arterial wall hyperfluorescence in the temporal inferior area
not located in the arterial occlusion area. D) FA of the right eye shows important nonperfusion of the arterioles in the temporosuperior
quadrant of the retina.
Arq Bras Oftalmol. 2014;77(3):188-90
189
Susac syndrome: diverse clinical findings and treatment
zepam (0.5 mg/day), and prednisone (40 mg/day) were prescribed.
Photocoagulation was applied to the ischemic areas to prevent re­
tinal neovascularization.
DISCUSSION
Susac syndrome has an unknown etiology and is associated with
varying outcomes(2,4,6). If not suspected of having the syndrome, the
diagnosis may be delayed. Once the diagnosis is made, close neurologic, otorhinolaryngologic, and ophthalmologic follow-up examinations are very important(3) since the damage could be irreversible.
A specific routine for the management of this disease has not
been described and approaches can be didactically divided into
two strategies, namely the management of complications and the
prevention of recurrences. The complications must be evaluated
and treated according to the preference of the ophthalmologist to
reestablish function. ASA, anticoagulants, steroids, immunosuppressors,
and immunoglobulins have been shown to be effective for the prevention of recurrence(6-8).
We observed no neovascularization in the peripheral retina and
a BCVA of 20/20 in the case.
The current study was limited by the retrospective design, the
di­­versity of the therapeutic approaches, and the difficulties in evaluating the efficacy of treatment. However, the results of our study,
which analyzed the diversity in systemic manifestations from early
symptoms are important due to the low disease prevalence.
Susac syndrome is considered as a rare disease. A high index of
sus­­­picion, which could lead to early recognition and treatment is important to avoid late diagnosis and to minimize the risk for persistent
impairment. Prospective studies analyzing the effectiveness of the
proposed treatments are critical for the establishment of therapeutic
approaches for each clinical finding.
REFERENCES
1. Rennebohm R, Susac JO, Egan RA, Daroff RB. Susac’s Syndrome-update. J Neurol Sci.
2010;299(1-2):86-91.
2. Susac JO, Egan RA, Rennebohm RM, Lubow M. Susac syndrome: 1975-2005 microangiopathy/autoimmune endotheliopathy. J Neurol Sci. 2007;257(1-2):270-2.
3.Dorr J, Jarius S, Wildemann B, Ringelstein EB, Schwindt W, Deppe M, et al. [Susac
syndrome: an interdisciplinary challenge]. Nervenarzt. 2011;82(10):1250-63. Epub
2011/04/12. Susac-Syndrom: Eine interdisziplinare Herausforderung.
4.Milbratz GH, Marquardt FA, Guimaraes Neto HP, Marquardt DA, Souza ES. Retinal
vasculitis in Susac syndrome: case report. Arq Bras Oftalmol. 2009;72(3):397-9. Epub
2009/08/12.
5. Egan RA, Ha Nguyen T, Gass JD, Rizzo JF, 3rd, Tivnan J, Susac JO. Retinal arterial wall
plaques in Susac syndrome. Am J Ophthalmol. 2003;135(4):483-6. Epub 2003/03/26.
6. Rennebohm RM, Susac JO. Treatment of Susac syndrome. J Neurol Sci. 2007;257(1-2):
215-20.
7. Naacke H, Heron E, Bourcier T, Borderie V, Laroche L. [A new case of Susac syndrome
and a review of the literature]. J Fr Ophtalmol. 2003;26(3):284-9. French.
8. Coppeto JR, Currie JN, Monteiro ML, Lessell S. A syndrome of arterial-occlusive retinopathy and encephalopathy. Am J Ophthalmol. 1984;98(2):189-202.
XXV Congresso Cearense de Oftalmologia
13 a 15 de novembro de 2014
Hotel Oásis Atlântico
Fortaleza - CE
Informações:
Tel.: (85) 3264-9404
E-mail: [email protected]
190
Arq Bras Oftalmol. 2014;77(3):188-90
Case Report
Intrastromal crosslinking in post-LASIK ectasia
“Crosslinking” intraestromal em ectasia pós-LASIK
Bernardo Kaplan Moscovici1, Mauro Campos1
ABSTRACT
RESUMO
We describe a case of early post-LASIK ectasia detected in the first 6 months after
surgery. The patient was treated by means of intrastromal corneal crosslinking under
the flap, without de-epithelialization, which resulted in a positive outcome. At the
time of writing, 2 years after the procedure, the patient remained free of progression.
Descrevemos um caso de ectasia de córnea precoce após cirurgia de LASIK, detectado no
primeiro semestre pós-operatório. Nós optamos tratar este paciente com “crosslinking”
embaixo do “flap”, sem desepitelização com bons resultados. A paciente permaneceu
sem progressão da ectasia até o momento atual, dois anos após o procedimento.
Keywords: Astigmatism; Refractive surgical procedures; Keratomileusis, laser in
situ; Corneal wavefront aberrations; Cross-linking reagent; Corneal stroma; Postoperative complications; Humans; Female; Adult; Case reports
Descritores: Astigmatismo; Procedimentos cirúrgicos refrativos; Ceratomileuse
assistida por excimer laser in situ; Aberrações de frente de onda da córnea; Reagentes
para ligações cruzadas; Substância própria; Complicações pós-operatórias; Humanos;
Feminino; Adulto; Relatos de casos
INTRODUCTION
A 28-year-old female was referred to the Universidade Federal de
São Paulo (UNIFESP), Department of Refractive Surgery in 2010 for
refractive surgery. Her refraction was -3.25 D -0.75 D 160° (OD) and
-3.25 D -0.75 D 180° (OS). Corneal topography revealed an asymmetry
of less than 0.5 diopters in the left eye (Figure 1). Corneal thickness
of right eye was 590 µm and the left eye was 591 µm. We performed
wavefront-guided laser-assisted in situ keratomileusis (LASIK) surgery
in both the eyes using a Moria M2 microkeratome and LADARVision
excimer laser with an ablation depth of 63.8 µm in the right eye and
70.5 µm in the left eye. There were no immediate postoperative com­­
plications and the uncorrected visual acuity was 20/20 bilaterally.
Four months after the procedure, the patient returned with a
complaint of decreased visual quality in the right eye. Visual acuity
was 20/25 uncorrected and 20/20 with -0.25 D -0.50 D 15° lenses. A
comparison of corneal topography findings between postoperative
months 1 and 4 (Figure 2) showed inferior corneal steepening (>1
diopter) in the right eye and a diffuse increase in corneal curvature
(<1 diopter) in the left eye. Corneal optical coherence tomography
(OCT, Figure 3) showed an abnormally thick flap (200-220 µm),
whereas aberrometry showed a high RMS (0.84) and an increase in
the negative vertical coma. As the patient was scheduled to leave the
country within a week for her doctoral studies in Barcelona, we chose
to perform under-the-flap intrastromal corneal crosslinking.
Operative technique
The flap was partially lifted with a corneal spatula so as to enable
separation of the stroma above and under the flap, but without lifting
the entire flap (Figure 4). A 0.1% riboflavin solution was injected into
the stroma at 15-minute intervals for 30 minutes. Crosslinking was
Submitted for publication: August 12, 2013
Accepted for publication: December 6, 2013
Study conducted at Department of Ophthalmology, Refractive Surgery Service, Universidade Federal
de São Paulo.
1
Department of Ophthalmology, Refractive Surgery Service, Universidade Federal de São Paulo
(UNIFESP), São Paulo, SP, Brazil.
http://dx.doi.org/10.5935/0004-2749.20140049
performed by standard technique by irradiating with 365 nm UV-A
light of intensity 3.0 mW/cm2.
Following surgery, the patient was prescribed with a 3-week
course of low-dose corticosteroids (topical fluorometholone), a
1-week course of a fourth-generation quinolone (topical gatifloxacin), and artificial tears for every 6 hours. Three days after the procedure, the uncorrected visual acuity in the treated eye was 20/25, with the
typical corneal haze commonly observed in the early postoperative
period of crosslinking in the flap area. The patient traveled as originally scheduled with instructions for eye care and under guidance to
seek ophthalmologic evaluation in Barcelona.
RESULTS
The patient returned to our service for 1-year follow-up and was
asymptomatic. The visual acuity was 20/20 in both eyes (OD: -0.75 D cyl
180°, OS: -0.25 D cyl 140°), and corneal topography showed absence
of disease progression bilaterally.
DISCUSSION
Post-LASIK corneal ectasia is a non-inflammatory process that
results in deformation of the cornea along with thinning and biomechanical weakening(1-10).
Crosslinking is the gold-standard treatment for progressive
corneal ectasia. However, it is often difficult to convince post-LASIK
patients with early-stage ectasia to undergo this procedure because
of slow and painful recovery periods(1-6).
Some researchers have focused on preventing corneal de-epi­
thelialization so as to achieve efficient and recovery from corneal
Funding: No specific financial support was available for this study.
Disclosure of potential conflicts of interest: None of the authors have any potential conflicts of
interest to disclose.
Corresponding author: Bernardo Kaplan Moscovici. Rua Apiacás 600/84 - São Paulo - (SP) 05017-020 - Brazil - E-mail: [email protected]
Arq Bras Oftalmol. 2014;77(3):191-2
191
Intrastromal crosslinking in post-LASIK ectasia
Figure 3. Postoperative optical coherence tomography of the cornea measuring the
LASIK flap, showing an abnormally thick flap.
Figure 4. Illustration of the new technique: The flap was partially elevated with a corneal
spatula to enable separation of the stroma above and under the flap, but without lifting
the entire flap. A 0.1% riboflavin solution was injected into the stroma at 15-minute
intervals for 30 minutes and after the crosslinking was performed.
Figure 1. Preoperative corneal topography showing an asymmetry
of less than 0.5 diopters in the left eye.
crosslinking. In one such study, femtosecond laser was used to create
a pocket, and riboflavin was administered for only 2 minutes before
UV-A irradiation(6). We propose a new technique in which riboflavin
is injected under the flap. As a preexisting flap is used, no decrease
in biomechanical power of the cornea should occur. The only disadvantage of this technique over the usual procedure is the possibility
of epithelial ingrowth, which can be easily avoided if the procedure
is performed with care.
Double-blind, randomized, case-control studies are required to
provide more reliable data, but this procedure appears simple, safe,
and effective technique for management of post-LASIK ectasia.
REFERENCES
Figure 2. Differential corneal topography between first and fourth month postoperative,
showing a steepening in both eyes, more evident in the right eye.
192
Arq Bras Oftalmol. 2014;77(3):191-2
1.Brenner LF, Alió JL, Vega-Estrada A, Baviera J, Beltrán J, Cobo-Soriano R. Indications
for intrastromal corneal ring segments in ectasia after laser in situ keratomileusis. J
Cataract Refract Surg. 2012;38(12):2117-24.
2.Sakhtar S, Kirat O, Alkatan HT, Almubrad T. Stromal alteration in post-lasik ectasia
córnea. Acta Ophthalmologica. 2012:90 Suppl.:S249.
3. Peinado TF, Pinero DP, López IA, Alió, JL. Correlation of both corneal surfaces in corneal ectasia after myopic LASIK. Optom Vis Sci. 2011;88(4):E539-42.
4. Gaster RN, Cnedo ALC, Rabinowits YS. Corneal collagen cross-linking for keratoconus
and Post-LASIK ectasia. Int Ophthalmol Clin. 2013 Winter;53(1):79-90.
5.Kanellopoulos AJ, Collagen Cross-linking in Early Keratoconus with riboflavin in a
femtosecond laser-created pocket: initial clinical results. J Refract Surg. 2009;25(11):
1034-7.
6. Randleman JB, Trattler WB, Stulting RD. Validation of the Ectasia Risk Score System for
Preoperative Laser In Situ keratomileusis screening. Am J Ophthalmol. 2008;145(5):
813-8.
7. Spadea L, Cantera E, Cortes M, Conocchia NE, Stewart CW. Corneal ectasia after myopic laser in situ keratomileusis: a long-term study. Clin Ophthalmol. 2012;6:1801-13 .
8. Poli M, Cornut PL, Balmitgere T, Aptel F, Janin H, Burillon C. Prospective study of corneal
collagen cross-linking efficacy and tolerance in the treatment of keratoconus and
corneal ectasia: 3-year results. Cornea. 2013;32(5):583-90.
9.Coskunvensen E, Jankov MR 2nd, Hafezi F, Atun S, Arslan E, Kymionis GD. Effect of
treatment sequence in combined intrastromal corneal rings and corneal collagen
crosslinking for keratoconus. J Cataract Refract Surg. 2009;35(12):2084-91.
10.Kiliç A, Kamburoglu G, Akinci A. Riboflavin injection into the corneal channel for
combined collagen crosslinking and intrastromal corneal ring segment implantation.
J Cataract Refract Surg. 2012;38(5):878-83. Comment in: J Cataract Refract Surg. 2012;
38(10):1878-9; J Cataract Refract Surg. 2012;38(10):1879-80.
Review Article
Is dry eye an environmental disease?
O olho seco é uma doença relacionada a exposição ambiental?
Monica Alves1, Priscila Novaes2, Monica de Andrade Morraye3, Peter Sol Reinach1, Eduardo Melani Rocha1
Abstract
RESUMO
Previous studies have revealed that eye contact with either air pollutants or adverse
indoor and/or outdoor environmental conditions can affect tear film composition
and ocular surface components. These effects are mediated by selective binding
of the environmental agents to ocular surface membrane receptors, leading to
activation of pro inflammatory signaling pathways. The aim of the current review
was to examine the published evidence associated with environmental factors and
ocular surface disease and dry eye. Specifically, the reader will appreciate why it is
possible to refer to them as mediators of Environmental Dry Eye Disease (EDED),
a singular clinical entity inside DED context, directly caused by pollutants and/
or adverse climatic conditions. The indicators and clinical findings are described
along with EDE differential diagnosis in its acute and the chronic phases. Based
on strong existing evidence of clinical reports and epidemiological observations
regarding DED and environmental factors we conclude that there is a straight
cause-and-effect relationship between ambient stresses and DED. International
standards and web-based tools are described for monitoring worldwide environmental conditions referring localities and populations susceptible to EDED.
This information is beneficial to health providers to pinpoint the individuals and
predisposed groups afflicted with DED. Such insights may not only improve the
understanding and treatment of DED but also help to identify the contributing
factors and lower the frequency and progression of EDED.
Diversos estudos têm demostrado que o contato ocular com poluentes ambientais
afeta a composição do filme lacrimal e de estruturas da superfície ocular. Tais efeitos
são mediados pela ligação de agentes ambientais com receptores na superfície ocular,
levando a ativação de mediadores pró inflamatórios. Esta revisão propõe uma avaliação
das evidências publicadas, que associam fatores ambientais as doenças de superfície
ocular e ao olho seco. O leitor compreenderá que é possível inferir olho seco ambiental
como uma entidade singular dentro do contexto da doença olho seco, diretamente
causado pela exposição a poluentes e/ou condições climáticas adversas. Serão descritos
os indicadores e achados clínicos, assim como o diagnóstico diferencial das fases aguda
e crônica. A avaliação de relatos clínicos e observações epidemiológicas demonstra
uma forte associação entre olho seco e fatores ambientais. O conhecimento sobre
parâmetros internacionais e ferramentas de monitorização das condições ambientais
no mundo, permite identificar localidades e populações mais suceptívies ao olho
seco ambiental e pode auxiliar na identificação de indivíduos acometidos e grupos
predispostos. E desta forma, melhorar o entendimento e tratamento dessa condição,
diminuir os fatores associados, sua frequência e progressão.
Keywords: Dry eye syndromes; Lacrimal apparatus diseases; Environmental illness;
Environmental pollutants/adverse effects
Descritores: Síndromes do olho seco; Doenças do aparelho lacrimal; Doença ambiental; Poluentes ambientais/efeitos adversos.
Introduction
Epidemiological studies have indicated increasing incidence of
dry eye disease (DED) in the worldwide population(1-3). This common ocular condition has multiple causes, which are not entirely
understood. The emerging awareness that environmental factors
can contribute to DED is supported by some recent studies and
reflects diffe­rences in cultural traditions and exposure to unfavorable working conditions. In these groups, the impact of environmental
factors in DED demands further characterization to develop strategies
to reduce its incidence(4,5). Due to the apparent relationship between
the aforementioned environmental influences and DED, this disease
can be better defined by delineating Environmental Dry Eye Disease
(EDED) as a clinical subtype of DED.
We summarize herein our current understanding of environmental
causes for DED. However, this review does not deal with some other
relevant exogenous factors, such as usage of drugs and alcohol as
their effects were recently well addressed(6,7). In addition, we omitted
the effect of nutritional factors on DED, which due to its extension and
complexity deserves an entire review.
EDED is not only an association between environmental condi­
tions and well-defined ocular surface inflammatory conditions, it
is considered as a clinical subtype of DED (Table 1). In EDED cases,
the inflammatory conditions and ocular discomfort are followed
by changes in tear film composition volume and osmolarity, which
may persist even after the individuals are no longer exposed to the
related environmental factors. In one example of EDED, following an
environmental accidence the symptoms persisted for two years(8-10).
EDED is strongly influenced by one or more environmental factor.
Additionally, improper diagnosis of toxic keratoconjunctivitis, solar
keratitis, allergic keratoconjunctivitis or some other types of ocular
surface disease can contribute to EDED. These conditions show similar symptoms and environmental factors on the existing condition
further leading to EDED. It is likely that some overlap exists among
the mediators of these diseases. This review focuses on some unique
environmental factors distinctive of EDED (Figure 1).
EDED gained relevance based on the recognition that environmental factors can be deleterious to human health and contributes
to DED(11,12). The impact of the environment in the pathophysiology
Submitted for publication: April 15, 2014
Accepted for publication: June 4, 2014
Funding: No specific financial support was available for this study.
Study conducted at Departamento de Oftalmologia, Otorrinolaringologia e Cirurgia de Cabeça e
Pescoço Universidade de São Paulo - Ribeirão Preto (USP-RP).
Universidade de São Paulo, Ribeirão Preto, SP, Brazil
Universidade de São Paulo, São Paulo, SP, Brazil
3
Universidade de Franca, Franca, SP, Brazil
1
2
http://dx.doi.org/10.5935/0004-2749.20140050
Disclosure of potential conflicts of interest: None of the authors have any potential conflicts of
interest to disclose.
Corresponding author: Monica Alves. Department of Ophthalmology, Otorhinolaryngology and Head
& Neck Surgery. Faculty of Medicine of Ribeirão Preto, University of São Paulo. Av. Bandeirantes,
3.900 - CEP 14049-900 - Ribeirão Preto, SP, Brazil - E-mail: [email protected]
Arq Bras Oftalmol. 2014;77(3):193-200
193
Is dry eye an environmental disease?
Table 1. Differential diagnosis of Environmental Dry Eye Disease
Disease
Causes
Clinical features
Solar keratitis (19)
UV exposure
Keratosis of exposed skin, burning sensation, redness, punctate keratitis
Allergic keratoconjunctivitis(10)(20)
Allergy
History of allergy, redness, itching, swelling
Floppy eyelid syndrome(21)
Rubbery, redundant upper tarsus
Lid eversion with minimal pressure. Redness, papillary conjunctivitis
Corneal hiperalgesia(22)
Up regulated nocioreception triggered by
corneal damage
Disparity between signs and symptoms, corneal sensory deficit and
decreased sensory nerve population
Ligneous conjunctivitis(23)
Impaired mucosal wound healing and fibrosis due
to plasminogen deficiency
Chronic membranous conjunctivitis triggered by local trauma
Mucous fishing syndrome(24)
Excess of mucous manipulation
Secretion, redness, and foreign body sensation along with
signs of epithelial trauma due to discharge of mucus
Pseudopemphigoid(25)
History of topical drug exposure.
Redness, tearing, itching, and progressive fibrosis of conjunctiva
Chronic blepharitis(26)
Dysfunction of lipid production and secretion
and epithelial metaplasia
Lid erythema, greasy crusting secretion. Redness and irritation of the eye
Seborrhea in other sites of the body
Stevens-Johnsons Syndrome(27)
Autoimmune disease triggered by drug or
microorganism
Acute: systemic epithelial bullous swelling. Chronic: ocular surface fibrosis,
corneal vascularization, and recurrent epithelial defect
Toxic keratoconjunctivitis(28)
Toxic agent traumatic, iatrogenic or factitious
contact with ocular surface
Variable, depending on agent and time. Commonly, acute epithelial swelling,
redness, and tearing
of DED has been studied and confirmed in animal models of human
DED(13-15).
As indicated, a healthy and pain-free ocular surface depends on
identifying and eliminating factors that cause ambient humidity,
airflow and purity, and temperature to intolerable levels. Such an
undertaking is needed to preserve tear film qualities commensurate
with ocular surface health. This is essential to sustain sufficient corneal
refractive power, visual acuity, and ocular comfort(5,16,17).
A desiccating environment can lead to increase in tear film evaporation and/or decline in its turn over and clearance. These initial
events lead to exposure of the ocular surface to hazardous environmental elements that trigger or exacerbate EDED symptoms. Clinical
findings have shown that increased numbers of people are affected
by EDED because of exposure to environmental factors (Figure 2).
Our purpose herein is to provide a critical appraisal of the clinical
and epidemiological evidence indicating that DED is influenced
by environmental factors. Secondly, we delineate EDED as a single
clinical entity with a unique set of symptoms and clinical findings
different from that of either DED or other diseases, such as Sjögren’s
syndrome, diabetes mellitus or drug induced, allergic conjunctivitis,
toxic or irritative conjunctivitis, and actinic keratitis. Moreover, we will
describe standard tools used to monitor environmental conditions
and discuss their relevance in EDED epidemiological studies. This
review enables the health care providers and researchers to identify
the environmental risk factors associated with the development and
progression of EDED. This initiative intends to help future studies to
improve our understanding and care for this possibly common and
complex disease.
Environmental Dry Eye Disease (EDED) can be considered a cli­­
nical entity that qualifies the definition of DED(18). The most relevant
causal factor is environmental exposure, such as pollutants and/or
adver­se climate. On the other hand, causative factors related to systemic di­seases (endocrine, metabolic, nutritional, autoimmune, genetic,
viral or neurologic), anti-cholinergic, adrenergic or other drug-related
side effects are considered as exclusion factors to maintain EDED as a
distinct disease entity within the DED envelope.
EDED differential diagnosis comprises the entities shown in table 1.
Possible non-environmental factors or undiagnosed causes of
DED were also considered as differential (for example a suspected
Sjögren’s syndrome was not investigated to fulfill the criteria). From
this perspective, diseases that were labeled as “pollution keratoconjuncitivitis,” “computer vision syndrome,” and other environmentally
related encounters, due to DED clinical presentation would be defi194
Arq Bras Oftalmol. 2014;77(3):193-200
Figure 1. Illustration of conditions whose signs and symptoms may overlap with envi­
ronmental dry eye disease clinical presentation.
Figure 2. Environmental factors that influence tear film and ocular surface indoors and
outdoors (air borne particles, air flow, temperature, ultraviolet rays).
Alves M, et al.
ned as EDED(29-31). Patients can be afflicted with EDED due to exposure to a variety of environmental stresses. Conditions that elicit this
disease are patient dependent(32,33). To establish a minimal normative
classification for research and clinical purposes and therapeutic mea­
sures, the following environmental factor categories are included:
Indoors: closed ambient like office settings, such as variations in
airflow, humidity, time in front of computer and other video displays,
and exposure to toxic elements (for example offices, health care facilities, poorly ventilated confinements such as subway stations and
other employment areas).
Outdoors: exposure to open areas with extreme temperatures,
gases and/or air suspended particles in the desiccating wind, intense
UV exposure, agricultural usage of state of the art technology and
mechanization, petrochemical industries, urban traffic, and other
polluted environments.
Although the clinical signs of EDED can be similar among individuals exposed to either indoor or outdoor environmental factors, the
detection preventive, and therapeutic methods are specific for each
of these different settings. Additionally, the combined exposure to
indoor and outdoor factors is also plausible.
Since the 1960’s, exposures to environmental factors such as air
pollution had been correlated with ocular surface irritation, resulting in
symptoms of hyperemia, swelling, tearing, and dry eye sensation(34).
EDED patients present a broad range of symptoms, the most
common being sorrow eyes and visual fatigue. The scores obtained
from structured questionnaires have been used for the analysis. One
of them is the Ocular Symptom Disease Index (OSDI), which evaluates
DED severity rather than EDED(35-37). In order to correlate ocular surface related DED signs with environmental activities, an interesting
activity log for DED was recently developed and tested in patients.
However, individual differences in pain perception or exposure to
environmental hazards in DED initiation were not evaluated(5).
EDED is distinguishable from aforementioned, because it is chronic
and is associated with environmental factors. Such clinical findings
are identifiable by the clinician/researcher investigating the disease.
EDED identification stems from controlled observations about pollution-induced ocular alterations, such as blinking rate, tear film break
up time (TFBUT), and corneal epithelia damage(38,39).
Tear film instability is a consistent finding in studies that showed
an association between air pollution and ocular surface damage(37,40-42).
Such an effect compromises the corneal epithelial barrier function
resulting in corneal and conjunctival epithelial chronic injury and
in­flammation.
A recent study has described a possible early adaptive response to
air pollution in which increased levels of air pollution reduce tear film
osmolarity and conjunctival goblet cell density(8,37). This negative correlation is indicative of EDED whereby increase in air pollution and/or
desiccation are thought to have an early reactive phase followed by a
chronic adaptive/metaplastic phase. Clinical findings can help to identify the contributions of exposure time to EDED progression (Table 2).
Table 2. Clinical findings in early and chronic phases of Environmental
Dry Eye Disease, compared with non-exposed individuals(8,37,41)
Clinical findings
Early reactive phase
Chronic adaptive phase
Variable
Low
Tear film osmolarity
Lower
Higher
Hyperemia
Present
Present
MGD
Present
Present
High
Low
Symptoms
Schirmer test
TFBUT
Lower
Lower
Vital staining
Normal
Altered
Higher number
Lower number
Conjunctival Goblet cells
On the other hand, it is possible that other clinical signs may be associated with the disease, complicating a definitive diagnosis. For example,
larger lid opening, lower mucous production, slower blinking rate,
and reduced tear film clearance. Such symptoms may be found in
different individuals afflicted with different degrees of EDED severity
even if they are exposed to the same adverse environmental factors.
Future studies are needed to characterize and weigh the individual
contributions of commonly observed environmental factors to EDED
progression.
Epidemiology of dry eye related to environmental factors
Outdoor EDED risk factors include exhaust emissions from automobiles and industrial facilities common in densely populated cities(43,44).
Furthermore, occupational hazards related to large-scale agriculture
and sugar cane processing can lead to exposure to gases, particulate
matter, UV exposure, and altered microbiota(45,46).
On the other hand, indoor environmental conditions involving low
humidity, excessive use of video display units (VDU), and high levels
of CO2 can be equally threatening to ocular surface health(4,47-49).
Case-control studies confirm the cause-effect relationship between
the indoor or outdoor environmental conditions and the irritant
symptoms in exposed individuals(49,50). Also, the individual risk factors
are similar to those in other populations afflicted with other types of
DED(51). They include aging, females, allergic or autoimmune conditions, and usage of contact lenses(4,48,52-55).
Part of the confusion that persists about EDED recognition is
because individuals exposed to high air pollution levels are often at
greater risk of developing allergies and present more symptoms(55).
Moreover, there is also an association between increase in air pollution and autoimmune diseases, such as rheumatoid arthritis and
systemic lupus erythematous(56-58). There is also speculation about the
existence of an “urban allergy syndrome” (Table 3)(59). Such individuals
have a higher incidence of ocular surface inflammation and DED.
Although the acceptable levels of pollutants are established by
national and world agencies (see below), the cut-off limits of the most
harmful pollutants and environmental risk factors to the ocular surface capable to induce EDED are unknown. If more than one factor is
involved, depending upon their characteristics they may interact at
lower threshold values and induce EDED. Accordingly, the detrimental effects of environmental toxic agents on EDED epidemiology are
not entirely understood(43,44,60-62).
The impact of urban pollution and environmental toxins on the
ocular surface has been evaluated in a few case-control studies. These
studies reported a high incidence of ocular discomfort, tear film instability, and ocular surface changes among individuals lived in highly
polluted cities of the world (Table 4).
Two studies in New Delhi compared the groups of individuals living
inside and outside the metropolitan area(63). A higher frequency of EDED
findings with TFBUT <10 seconds, Schirmer Test (ST) <10 mm, and low
lysozyme levels in tears were reported among the individuals living
within the metropolitan area. The decline in these values correlate
with increase in pollutant levels in the metropolitan area compared
with the rural area. Another study on 500 volunteers documented
Table 3. Individual and environmental risk factors for Environmental
Dry Eye Disease (EDED)
Risk factors for EDED
Individual
Age, female gender, contact lens usage, lengthy exposure to the
hazards (video display, air conditioning), allergies, eye make up,
blinking frequency
Environmental Humidity, temperature, high levels of pollutants (particulate matter,
CO2, NO2, elemental carbon), regions with heavy automobile
transport, pollutant industrial activity, subway stations
Arq Bras Oftalmol. 2014;77(3):193-200
195
Is dry eye an environmental disease?
Table 4. Effects of pollution on ocular surface: summary of epidemiological studies
Author
Year
Study design
Local
n
Endpoints
Conclusions
Versura(44)
1999
Case-control
Italy
200
Schirmer
Ferning
BUT
Impression cytology
Inflammation
Abnormal values of BUT 32%,
Schirmer 40%, and Ferning 45%.
Abnormal impression cytology:
odds ratio 2.66 (IC95% 1.42-5.02)
Inflammation: odds ratio 2.27
(IC95% 1.14-2.16)
Gupta(63)
2002
Case- control
New Delhi, India
400
BUT
Schirmer
Lysozyme activity
BUT (odds ratio: 5.63, IC 95% 2.76-11.46)
Saxena(43)
2003
Case-control
New Delhi, India
500
Symptoms
Lysozyme
Rose bengal
BUT
Schirmer
Positive correlation with symptoms
BUT and Schirmer were lower in
study group
No difference in lysozyme
and rose bengal
Novaes(8)
2007
Case-control
Sao Paulo, Brazil
029
Impression cytology
Increased goblet cells density in
individuals exposed to higher levels of NO2
Novaes(41)
2010
Series of cases
Sao Paulo, Brazil
055
Symptoms
BUT
Schirmer
Positive correlation with symptoms
Higher incidence of MGD, BUT weak
correlation and Schirmer, no correlation
with levels of NO2
Malerbi(64)
2012
Series of cases
Sao Paulo, Brazil
Meibomian gland evaluation
Increased incidence of blepharitis in
high levels of NO2
a greater frequency of lower ST values and TFBUT values in hospital
workers more exposed to traffic derived air pollution(43).
In Italy, patients who presented to an ophthalmological emergency unit with “eye discomfort,” reduced ST values and tear film
instability were evaluated during the periods of acute rise in air pollution levels, summer and winter. Road traffic, heating system usage,
and photochemical smog levels were reported as the main causes
of their symptoms. Subjective symptoms were ocular irritation, such
as heavy or tired eyes, foreign body sensation, burning, stinging, and
photophobia. Also, impression cytology findings in six areas of bulbar
and tarsal conjunctiva were altered in 69% of the subjects-49%
presented an early loss of goblet cells, 15% showed a total loss of
goblet cells without keratinization, and 5% had a total loss of goblet
cells with mild keratinization. Women showed higher frequency of
symptoms that include ST<10 mm, and higher impression cytology
score. In those subjects who lived in more polluted areas (urbanized
compared to rural areas), impression cytology documented a greater
frequency of keratinization and higher numbers of inflammatory cells
(mainly mononuclear cells) in conjunctival scraping scores(44).
Exposure to NO2, traffic derived air pollutant, and ocular surface
changes were studied in volunteers in Sao Paulo, Brazil, the largest
city in Latin America, and compared with individuals from a countryside area. The individuals living in Sao Paulo showed high levels of NO2
exposure and displayed goblet cell hyperplasia as a result of the chronic insult(8). The same research group analyzed 55 cases of NO2 exposure and found that there is a dose-response relationship between
incidence of symptoms and higher prevalence of meibomian gland
dysfunction. However, there was a weak negative association with
TFBUT and no correlation with ST values(41). Recently another study
demonstrated that exposure to high levels of air pollutants canlead
to eyelid margin alterations(64). The series of studies on the effects of
air pollution on EDED in Brazil were innovative. The pollutant levels
were individually measured with portable filter paper for a period of
time rather than using broad environmental indices. Together, these
findings suggest that life in large and polluted cities cause increased
exposure of risk factors toward EDED.
Ultraviolet (UV) radiation is a common risk factor to ocular surface health for unprotected outdoor workers. For instance, climatic
droplet keratopathy has been described and correlated with UV
exposure(65). Excess exposure to UV has been considered to result in
196
Arq Bras Oftalmol. 2014;77(3):193-200
acute tear film instability and induce transitory EDED, however, the
reports are contradictory. Not enough evidence is currently available
to indicate UV is a risk factor for EDED(66-68). On the other hand, it has
been well established that UV is one of the major risk factors in pterygium, a degenerative condition of the ocular surface resulting tear
film instability. However, a cause and effect relationship still needs to
be determined(69,70).
A large-scale study in Indonesia had shown that agricultural work
is not a risk factor for EDED. Type of agricultural activities, amount, and
time of exposures, climatic, chemical, and other environmental conditions need to be controlled in future studies to better understand
their contributions as possible risk factors. Such an assessment entails
delineating involvement of pesticides, fire, and UV irradiation(70).
Indoor environmental contamination also has adverse health
effects. The factors are lumped together into a group of signs and
symptoms named the “Sick Building Syndrome” (SBS). In the last few
decades the symptoms were described in workers in poorly venti­
lated office buildings. SBS includes non-specific ocular, nose and
throat irritation, headache, and respiratory symptoms. Emission of
the volatile organic compounds (VOCs) from the synthetic materials
used in homes and offices together with other micro environmental
variables such as temperature, humidity, lighting and airborne substances can also contribute to EDED. They can cause ocular symptoms,
tear film instability, and alterations in ocular surface characteristics
of EDED(40,62,71-74). In 1992, Norn described that “sick building” workers
have “pollution keratoconjunctivitis” with decline in BUT values and
epithelial alterations detected by lissamine green staining(31).
The broad ranges of environmental factors in office ambience
associated with the demanding video display unit disrupt ocular surface homeostasis(4,30). In epidemiologic and clinical studies it is important to consider the weight of confounding or summing factors such
as allergic conjunctivitis, certain oral medications, BAK preservative
eye drops, eye make up, blinking frequency, and contact lens wear.
The prevalence of indoor EDED can be estimated based on ocular discomfort complaints by office building workers. Based on the
studies performed using questionnaires, it ranges from 5%-40%(62,75).
This large range may be due to the design of questionnaire, types of
reported symptoms, inclusion of confounding variables that include
contact lens wear, medications, and differences in recall periods. For
instance, in 56 European buildings across 9 countries, 39% of the
individuals showed the mean prevalence of dry eye symptoms(76).
Alves M, et al.
The anterior ocular surface forms a mucosal interface with large area
continuously exposed to the environment. Comfort, proper visual
acuity, and cellular maintenance are guaranteed by complex and
harmonic interactions of epithelial cells and accessory glands and
tear film compounds. Since the anterior ocular surface is the most
densely innervated area of the body(77), it is very sensitive to irritants
and adverse environmental conditions (Figure 3).
Receptor-induced events that mediate signaling pathway of inflammatory responses resulting EDED symptoms such as decline in
tear volume and altered composition are not completely understood.
The following questions are need to be answered: to what extent
the ocular surface discriminates different types of hazards? What
makes the transition between an early/reactive phase to a chronic/
adaptive phase?
Environmental injury might induce increasing expression of cy­
to­­kines, growth factors and other molecules that mediate specific
signaling pathways, and corneal inflammatory and allergic response.
During acute and chronic phases, specific cell types, inflammatory
mediators, and neurotransmitters are involved(78). Such responses
vary depending on the nature and intensity of the stimulus and some
mediators have been pointed as major contributors in the process of
ocular surface damage related to environmental factors. Members
of the transient receptor potential (TRP) channel superfamily, which
include subfamilies in corneal epithelial and keratocytes, respond to
environmental irritants inducing afferent impulses to the central nervous system(79). Chemical burns in mice induce a specific TRP vanilloid
type 1 (TRPV1) channel deregulated inflammatory responses leading
to corneal melt and opacification(80). The injury-induced inflammatory
and opacification responses resulting from TRPV1 activation were
attributed to the up regulation of pro inflammatory and chemo
attractive cytokines. TRPV1-induces downstream events by eliciting
time dependent stimulation of the mitogen activated protein kinase (MAPK) cascade in epithelial cells and stromal fibroblasts(79,81).
Corneal epithelial wound is also accompanied by increased release
of mitogens such as, epidermal growth factor (EGF), which induces
cell proliferation and migration through activation of a TRP channel
in the canonical subfamily identified as TRPC4 and MAPK signaling
pathway(82-85).
Flow cytometry analysis of the tear fluid collected from the individuals with atopic keratoconjunctivitis after a conjunctival allergen
provocation test presented higher levels of interferon-gamma, IL-6,
and a borderline increase in IL-10 after 48 hours. There was a significant difference between provoked and unprovoked eye for the same
cytokines: IL-6, IFNγ, and IL-10(86). We speculate that individuals exposed to air pollution or other hazardous stimuli can elicit the similar
inflammatory cascade during acute phase and lead to EDED clinical
presentation, similar to other ocular surface inflammatory diseases,
such as AKC(78).
Goblet cell hyperplasia results from exposure to high levels of air
pollution in the urban population(8). This is due to chronic exposure
to air pollution by human nasal and respiratory mucosal surfaces
that are considerably similar to conjunctiva(84,87-89). However, studies
in mice exposed to a desiccating environment showed the opposite
response. The differences between the human and mouse may be
explained by species-specific responses, complexity of the trigger
(humans are frequently exposed to combined factors, such as pollutants and adverse climate), and/or observations collected at different
time-points in the disease progression of both the species.
In vitro models are useful to simulate hazardous conditions and
assess their effects on the ocular surface at the molecular level. In this regard, the observation that particulate pollutants disrupt meibomian
gland lipid structure and consequently the tear film organization
was reproduced using benzalkonium chloride (BAK) and quartz particles(90). This study suggested that BAK affects the surface activity of
meibomian lipids and quartz particles adsorbed to meibomian lipids,
by removing them from the air/water interface. The authors proposed that a similar mechanism accounts for the effect of particulate
pollutants on the tear film lipid layer(90).
The possibility of measuring specific effects of air pollutants and
exposure to other environmental hazards on ocular surface integrity
and health will identify the individuals with pathologic correlations
to EDED. A recently described method is proven to be useful for this
purpose. It comprises a filter paper in a small chamber attached to
a belt or other piece of clothing (Figure 4). Air pollutants deposited
on filters after different times were eluted and measured(41). In this
direction, a better understanding of EDED inducing factors and
underlying mechanisms can be achieved. Such insights will help the
development of more efficient preventive and therapeutic strategies.
Environment monitoring tools
The environment is being polluted by industrial waste, automo­
bile and truck exhaust fumes, burning of coal and fossil fuels as well
as chemical manufacturing. Air pollution can even come from small-­
scale every day indoor activities, such as dry cleaning, degrea­sing,
and painting. These activities accumulate gases and particles that
come incontact with our mucosal tissues, especially the anterior
ocular surface.
There is an increasing demand for environmental health indicators capable of measuring the amount of chemical, climatic, and
physical hazards. Since 1987, World Health Organization (WHO) published guidelines for air quality are reviewed periodically(91,92). Similar
guidelines, some with differences in items monitored or cut-off levels
are provided by the Environmental Protection Agency (EPA) from the
USA and other national or continental agencies (Table 5).
Among outdoor environmental parameters, climatic variables in­­
cluding temperature, atmospheric precipitation, humidity and UV ra­
diation, and air pollutants including particulate matter (PM), CO2, NO2, O3
and SO2 were correlated with ocular and systemic diseases(92-94). As mentioned above, the indoor pollutants are same as the more commonly
monitored climatic parameters and they include include pollen, tobacco
Figure 3. Illustrative steps of pathophysiological mechanisms in the acute phase of EDED at the cellular level.
Arq Bras Oftalmol. 2014;77(3):193-200
197
Is dry eye an environmental disease?
A
B
C
D
Figure 4. A) Double passive NO2 sampler containing a cellulose filter (Energetica, Rio de Janeiro, Brazil) impregnated
with an absorbent solution of 2% triethanolamine, 0.05% o-methoxyphenol, and 0.025% sodium metabisulfite inside a
small plastic tube with one of its extremities open to ambient air. The nitrite produced during sampling is determined
colorimetrically by reacting the with sulfanilamide and 8-anilino-1-naphthalene-sulfonic acid (ANSA) and monitoring
the absorption at 550 nm wavelength; B) Superior view of the NO2 sampler; C) Portable gravimetric impactor with
a flow rate of 1.8 L/min. Air is aspirated into the impactor by a pump, PM is retained by a filter, and the particles in
suspension in the air are measured gravimetrically; D) Portable sampler carried in a small bag by a research subject.
Table 5. Websites of agencies that provide guidelines and databases related to the environmental parameters in different regions of the world
Agency
Website
Country/area
European Space Agency
http://www.earthobservations.org/geoss_cl_ph.shtml
Global
United Nation Economic Commission for Europe
http://www.unece.org/env/europe/monitoring/iandr_en.html
Global
World Health Organization
http://www.who.int/ipcs/publications/ehc/ehc_numerical/en/index.html
Global
Environmental Protection Agency
http://www.epa.gov/oaqps001/montring.html
Health Canada
http://www.hc-sc.gc.ca/ewh-semt/air/in/res-in/index-eng.php
Instituto Nacional de Metereologia do Brasil
http://www.inmet.gov.br/portal/
Companhia Ambiental do Estado de São Paulo
http://www.cetesb.sp.gov.br/
Ministry of the Environment Government of Japan
http://www.env.go.jp/en/
Ministry of Environmental Protection
http://english.mep.gov.cn/
Department of Sustainability, Environment, Water, Population
and Communities
http://www.environment.gov.au/
Environment Agency
http://www.environment-agency.gov.uk/
smoke elements, mold, pesticides, carbon monoxide, formaldehyde, and
lead among others(95).
Those indicators are also monitored by national and international
health and/or environmental agencies. They are then applied in health
analysis studies to correlate diseases with epidemiology, governmental policy directives, and economic studies(12,96,97).
This approach supports analysis of the health status of individuals
or groups exposed to the above-indicated environmental risk factors.
The results guide public health policies and preventive care(94,98-100).
They also help comparing environmental hazards in different areas
or countries to promote actions that may reduce their effects(101).
The information collected by the international or governmental agencies are available for public consulting(102). These agencies
work together to adopt similar measurement standards, units, and
me­­­­­thods, and make the data available to the public through web
databases and annual publications(91).
Data on air quality or climate could be used to correlate with clinical observations of incidences of EDED in different cities or regions.
However, the daily range of pollutants, hazardous agents, confounding factors, and individual variable time-exposure to any of the studied agents can be too large to precisely identify agents responsible
for higher EDED incidence in a certain area. These limitations may
make it difficult to draw meaningful conclusions. To avoid that, study
designs are required to include homogeneous groups with similar
habits and comparable exposure times. One report had described that
chil­­­dren living close to three petrochemical companies in Nigeria
have te­­­­­traethyl lead and black carbon tear film(29). Similar studies are
necessary to identify the specific pollutants responsible for a cause
and effect relationship between an environmental factor and EDED.
198
Arq Bras Oftalmol. 2014;77(3):193-200
USA
Canada
Brazil
São Paulo State, Brazil
Japan
China
Australia
United Kingdom
Conclusions
For several years, environmental factors have been known to be
associated with DED. A more extensive and detailed analysis of the
association between environmental factors and DED suggest that
EDED as a DED subtype will aid efforts to pinpoint different factors
responsible for this disease. To this end, we propose that combined
clinical and laboratory studies can help identify different environmental factors that induce EDED. At this point, we were able to
summarize evidence supporting the association of specific environmental hazards such as pollutants and adverse outdoor and indoor
environmental factors with EDED.
DED clinical findings and symptoms resulting from environmental factor mediated anterior ocular surface receptor activation induce
pro inflammatory cytokines, chemo attractant expression, and elaboration of extracellular stromal matrix due to increases in myofibroblast
expression. These mechanisms induce tear film instability, stromal
immune cell infiltration, and disruption of lacrimal gland mediated
tear film volume and composition. Constant exposure to environmental factors may allow the clinician to distinguish between acute
and a chronic phase of the disease.
Environmental data monitoring and safety limits obtained from international or governmental agencies may help clinicians to associate
DED disease stages with environmental factor exposure. Researchers
may be aided in identifying relevant stress to apply to their different
model systems to pinpoint the mechanisms mediating responses
underlying EDED.
Unfortunately, except for using protective equipment to counter
specific hazardous environmental agent stresses, EDED treatment is
limited to the same medications and interventions available for other
Alves M, et al.
types of DED.(103) Given this limitation, it remains important to promote
novel investigative interventions to treat or minimize EDED damage.
Acknowledgement
This study was supported by grants from the following Brazilian
governmental agencies: “Fundação de Amparo a Pesquisa do Estado
de São Paulo” (FAPESP), “Conselho Nacional de Desenvolvimento
Científico e Tecnológico” (CNPq), “Fundação de Apoio ao Ensino, Pesquisa e Assistência do Hospital das Clinicas da Faculdade de Medicina
de Ribeirão Preto da Universidade de São Paulo” (FAEPA), and “Núcleo
de Apoio a Pesquisa - Fisiopatologia e Terapêutica Ocular (NAP-FTO)
da Universidade de São Paulo.”
The authors would like to acknowledge Maria Helena Andrade
and Andre Torricelli for their contribution to this study.
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Letters to the Editor
Bilateral acute depigmentation of the iris
(BADI): first reported case in Brazil
Dear Editor,
We have read with considerable interest the article entitled “Bilateral acute depigmentation of the iris (BADI): first reported case in
Brazil”, by Maestrini et al.(1). The authors describe a patient who was
diagnosed as having BADI, which has attracted a lot of attention
among ophthalmologists in recent years. We would like to thank the
authors for reporting on this interesting case, and we want to contribute further by making the following three points.
Bilateral acute iris transillumination (BAIT) and BADI are both re­­­­­­
latively new clinical entities and share some important features: an
acute onset of severe photophobia and red eyes after a flu-like syndrome, pigment dispersion into the anterior chamber, and exclusive
involvement of the iris. However, in patients who have BAIT the pigment discharge is from the iris pigment epithelium, whereas for those
with BADI, the pigment discharge comes from the iris stroma. This
leads to iris transillumination defects and mydriatic/atonic pupilla in
patients with BAIT, but not in those who have BADI.
First, the authors report that there are two clinical sub-types of
BADI. The first sub-type has a more benign course, a lower incidence
of increased intraocular pressure (IOP), and reversibility of the iris
changes without transillumination defects or pupil distortion. The
second sub-type, BAIT, has diffuse iris transillumination and mydriatic/
atonic pupilla or distorted pupil, occasional posterior synechiae, and increased IOP(1). Indeed, the first sub-type mentioned by the authors reflects the characteristic clinical features of the BADI (2), and the second
sub-type, referred to in the study as BAIT, shares some properties with
BADI but has differentiating characteristic features(3). In addition, BAIT
was first described by Tugal-Tutkun et al. as being a probable distinct
entity(3), and several publications have subsequently reported it as
being a distinct entity from the BADI(4,5). It is not clear, therefore,
whether BAIT is a sub-type of the BADI. It appears to be a different
entity or an expanded spectrum of BADI, which makes it incorrect to
describe BAIT as a sub-type of BADI.
In addition, Maestrini et al.(1) report that both conditions have a
self-limited course and a good prognosis. However, BAIT cases may
present with severe IOP rise, which is sometimes resistant to medical
treatment and necessitates trabeculectomy surgery as in our case
report(5). Therefore, clinicians should be aware of a severe IOP rise in
patients with BAIT during their follow-up.
Finally, although the exact etiopathogenesis of BAIT remains unclear, several publications have reported a relationship between BAIT
and systemic use of moxifloxacin(4), upper respiratory tract in­­­­fections(3),
and a toxic effect following a fumigation therapy(5). Maestrini et al.(1)
reported the cause of BADI may be a viral etiology considering empirical antiviral therapy has provided some clinical improvement by
reducing pigment dispersion into the anterior chamber. However,
these authors should have taken an aqueous sample for viral analysis
in order to conclude such a relationship. Therefore, further study is
needed to include the aqueous tap for local antibody production
against the virus, or to demonstrate the viral DNA to clarify the viral
etiology in patients with BAIT.
Saban Gonul1, Banu Bozkurt1
1
Selcuk University Faculty of Medicine, Department of Ophthalmology, Konya, Turkey.
Funding: No specific financial support was available for this study.
Disclosure of potential conflicts of interest: None of the authors have any potential conflicts of
interest to disclose.
Corresponding author: Saban Gonul. Selcuk University Faculty of Medicine, Department of Ophthalmology, Konya, Turkey - E-mail: [email protected]
Submitted for publication: April 28, 2014
Accepted for publication: May 1, 2014
http://dx.doi.org/10.5935/0004-2749.20140051
REFERENCES
1. Maestrini HA, Maestrini AA, Machado Dde O, Santos DV, Almeida HG. Bilateral acute
depigmentation of the iris (BADI): first reported case in Brazil. Arq Bras Oftalmol. 2013;
76(1):42-4.
2. Tugal-Tutkun I, Araz B, Taskapili M, Akova YA, Yalniz-Akkaya Z, Berker N, et al. Bilateral
acute depigmentation of the iris: report of 26 new cases and four-year follow-up of
two patients. Ophthalmology. 2009;116(8):1552-7.
3. Tugal-Tutkun I, Onal S, Garip A, Taskapili M, Kazokoglu H, Kadayifcilar S, et al. Bilateral
acute iris transillumination. Arch Ophthalmol. 2011;129(10):1312-19.
4.Morshedi RG, Bettis DI, Moshirfar M, Vitale AT. Bilateral acute iris transillumination
following systemic moxifloxacin for respiratory illness: report of two cases and review
of the literature. Ocul Immunol Inflamm. 2012;20(4):266-72.
5.Gonul S, Bozkurt B, Okudan S, Tugal-Tutkun I. Bilateral acute iris transillumination
following a fumigation therapy: a village-based traditional method for the treatment
of ophthalmomyiasis. Cutan Ocul Toxicol. 2014 Mar 31. [Epub ahead of print]. doi:
10.3109/15569527.2014.886589
Reply
Dear Editor,
We were happy to receive the letter from Dr. Saban Gonul, who
resides in Turkey, concerning our article titled ‘‘Bilateral acute depigmentation of the iris (BADI): first reported case in Brazil”. The vast
majority of BADI and bilateral acute iris transillumination (BAIT) cases
have occurred in Turkey; therefore, it is very important to listen to
researchers experienced with this fascinating new clinical entity.
Dr. Gonul suggests that it would be incorrect to describe BAIT as
a subtype of BADI. However, both are new clinical entities that share
many important features, such as an acute onset of severe bilateral
photophobia and red eyes, pigment discharge in the anterior chamber, heavy pigment deposition in the trabecular meshwork, and a
marked symptom relief with topical corticosteroids. In addition, both
are more common in women, and in many cases, it occurs after a
flu-like illness and many patients have histories of previous antibiotic
use, particularly moxifloxacin. It is not yet clear if they are distinct
entities or subtypes of the same disease. The fact that both share so
many features gives strong support to the idea that they are subtypes
of the same disease. Tugal-Tutkun et al. (2011) published the first and
most important study on BAIT, with 26 cases(1). In their conclusion, the
authors state very clearly that BAIT might be a new entity or might
represent an expanded spectrum of BADI. This question has not yet
been answered and further research is needed to clarify this point.
Indeed BAIT is more severe than BADI, as we pointed out in our
paper. BADI has a more benign course, a shorter duration of pigment
discharge, a lower incidence of elevated intraocular pressure (IOP)
that is only transient, and sometimes reversible iris changes. BAIT is
frequently associated with an early, severely elevated IOP, and the iris
changes are usually irreversible. A few cases of BAIT might need a
trabeculectomy to control an intractably elevated IOP. In Tugal-Tutkun et
al. (2011), 2 of 26 patients needed a bilateral trabeculectomy(1). Although
both BADI and BAIT are self-limited, we agree with Dr. Gonul that
clinicians should be aware of the possibility of a severe, intractable
elevation in IOP and a longer duration of disease in cases of BAIT.
Finally, the exact etiopathogenesis of BADI and BAIT remain un­
clear. All previous studies(1-3) have entertained the viral hypothesis.
The fact that many cases of BADI and BAIT occur after a flu-like illness
or upper respiratory tract infection, with or without the use of antibiotics, suggests a relationship with some kind of infection, viral or not.
In the first paper on BADI, Tugal-Tutkun et al. (2006) suggested that
it represents a new entity or an unusual presentation of herpetic eye
disease(2). In Tugal-Tutkun et al. (2009)(3), viral serology was performed
in 10 of 26 cases of BADI, and all 10 had IgG antibodies against cytomegalovirus (CMV). Consequently, the authors proposed that BADI
be considered part of an expanded spectrum of CMV-related ocular
Arq Bras Oftalmol. 2014;77(3):201-2
201
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diseases. Five patients in that series had histories of recurrent fever
blisters. In Tugal-Tutkun et al. (2011)(1), 83% of BAIT patients tested
were seropositive for IgG antibodies against herpes simplex virus
type 1 and 75% were positive for Epstein-Barr virus IgG antibodies. All
patients tested for anti-varicella zoster virus and CMV were found to
have IgG antibodies. The authors hypothesized that BAIT represents
a condition triggered by a viral infection. In Weffers Bettink-Remeijer
et al. (2009)(4), the herpetic genome was positive in the aqueous tap
of one patient with BAIT. Furthermore, BAIT shares some features of
viral herpetic iridocyclitis, in which ischemic necrosis of the iris results
in iris atrophy, distortion of the pupil, and transillumination defects. In
our study, a herpetic etiology cannot be ruled out because we did not
have access to the analysis of intraocular specimens. We decided not
to perform an anterior chamber tap to try polymerase chain reaction
(PCR) for herpes viruses because PCR of aqueous humor is rather
insensitive in the absence of posterior segment involvement(5). A
biopsy of the iris or cornea obtained during a trabeculectomy might
be more elucidative. We preferred to institute empirical treatment
with valacyclovir, which resulted in marked clinical improvement.
Obviously, this is not proof of a viral etiology, but it is certainly sugges­
tive. In conclusion, the etiopathogenesis of BADI remains to be eluci-
202
Arq Bras Oftalmol. 2014;77(3):201-2
dated, and we still have more questions than answers regarding this
interesting and challenging new disease.
Heloisa Andrade Maestrini
Department of Glaucoma, Oculare Centro de Oftalmologia, Belo Horizonte, MG, Brazil.
Corresponding author: Heloisa Andrade Maestrini. Rua Maranhão, 65 - Belo Horizonte (MG) 30150-330 - Brazil - E-mail: [email protected]
REFERENCES
1.Tugal-Tutkun I, Onal S, Garip A, Taskapili M, Kazokoglu H, Kadayifcilar S, et al. Bilateral
acute iris transillumination. Arch Ophthalmol. 2011;129(10):1312-9.
2. Tugal-Tutkun I, Urgancioglu M. Bilateral acute depigmentation of the iris. Graefes Arch
Clin Exp Ophthalmol. 2006;244(6):742-6.
3. Tugal-Tutkun I, Araz B, Taskapili M, Akova YA, Yalniz-Akkaya Z, Berker N, et al. Bilateral
acute depigmentation of the iris: report of 26 new cases and four-year follow-up of
two patients. Ophthalmology. 2009;116(8):1552-7, 1557 e1.
4. Wefers Bettink-Remeijer M, Brouwers K, van Langenhove L, De Waard PW, Missotten
TO, Martinez Ciriano JP, et al. Uveitis-like syndrome and iris transillumination after the
use of oral moxifloxacin. Eye (Lond). 2009;23(12):2260-2.
5. Matos K, Muccioli C, Belfort Junior R, Rizzo LV. Correlation between clinical diagnosis
and PCR analysis of serum, aqueous, and vitreous samples in patients with inflamma­
tory eye disease. Arq Bras Oftalmol. 2007;70(1):109-14.
Letters to the Editor
Refractive error in school children in
Campinas, Brazil
Erros refrativos em escolares de Campinas, Brasil
Dear Editor,
Refractive errors such as myopia, astigmatism, and hyperopia are
common ocular conditions that have been identified as concerns for
public health and economy. The World Health Organization’s “Vision
2020: The Right to Sight” initiative included the correction of refractive errors as one of the target areas to eliminate avoidable causes of
visual impairment. Uncorrected refractive error is the most common
cause of visual impairment in school-age children in both industrialised and developing countries(1).
The following report describes the prevalence of refractive error
(myopia, hyperopia, and astigmatism) in school children in Campinas,
Brazil.
This cross-sectional study was conducted in 2012. According to
2010 census(2), the population of Campinas, Brazil was approximately
1 million. Of these, 180,560 were within the age limits of the study
and 126,392 (70%) of them attended public schools. Four groups
of children, from the 1st (5-7 years-old), 5th (9-11 years-old), 9th (13-15
years-old), and 12th (16-18 years-old) levels of the Brazilian educational
system, a total 1,100, were randomly selected from different public
schools. The study has complete approval from the University of
Campinas Research Ethics Committee. The research adhered to the
prin­­ciples of the Declaration of Helsinki.
The protocol for data collection included measurement of logMAR
monocular distance, best-corrected visual acuity, and cycloplegic
autorefraction (1% cyclopentolate hydrochloride) using cycloplegic
autorefraction (autorefractor model AR-8900; Topcon Corporation,
Tokyo, Japan). The measurements were obtained after adding 1 drop
of a topical anesthetic eye drop (proxymetacaine hydrochloride)
in both eyes and waiting 2 minutes to achieve ocular surface
anes­thesia followed by addition of 2 drops of 1% cyclopentolate
hydrochloride 10 minutes apart in each eye. Cycloplegic dilation
was performed by an ophthalmic technologist. Five readings were
recorded and the representative value, determined by the instrument, was used for further analysis. The representative value from
the autorefractor was used to calculate spherical equivalent refraction (SER=sphere + cylinder/2). Myopia was defined as SER ≤ -0.50 D,
hyperopia as SER ≥ +2.00 D, refractive astigmatism as cylinder ≥ 1.00 D
if -0.50 > SER < +2.00, and emetropia as -0.50 > SER < +2.00 with
cylinder < 1.00 D(3). All statistical analyses were carried out using
PSPP software.
Among the 1,100 students invited to participate in the study,
pa­­rental consent was obtained from 778 (70.7%). 440 (56.5%) were
female. Table 1 describes the age and visual acuity of the par­­­­ticipants.
Table 2 describes the distribution according to the refrac­­­tive errors.
The current paper presents a population-based data describing the prevalence of cycloplegic measures of refractive errors of
students in Campinas, Brazil. There was a preponderance of emmetropes (75.1%), and the prevalence of myopia was only 2.8% among
the children of age group 5-7 years. Among the 16-18 years old age
group, the prevalence of myopia increased sevenfold (19.3%). Similar
findings in young children have been reported by other studies(3). By
contrast, the prevalence of myopia in 7-years-old children in Singapore is 28%(4). One Brazilian study presented different results, but it was
not possible to compare, as the protocols in our study are different
from their study(5).
One limitation of this study was the use of SER to classify myopia,
which can result in over-estimation of prevalence in populations with
significant levels of astigmatism. Despite this aspect, SER has been
used to facilitate comparisons with other epidemiological studies of
refractive error. Another limitation is that due to the limited data available for Brazil (a large and multi-ethnic country), it is unclear whether
the prevalence of refractive errors in Campinas is representative of
the Brazilian population as a whole.
Rodrigo Pessoa Cavalcanti Lira1, Italo Fernandes do Espírito
Santo2, Gustavo Lima do Valle Astur2, Diana Maziero2, Thais Helena
Moreira Passos2, Carlos Eduardo Leite Arieta1
Table 1. Distribution of students according to age and visual acuity
School level
Mean
SD
Min
Max
Female
Male
01st
06.17
0.67
05
07
06.19
06.15
05th
09.82
0.52
09
11
09.77
09.88
09th
14.03
0.56
13
15
13.99
14.09
12th
17.28
0.58
16
18
17.32
17.22
Total
11.45
4.04
05
18
11.61
11.24
Best-corrected visual acuity
01
st
85.08
6.34
38.00
88.00
86.56
86.49
(ETDRS letters)
05th
85.60
6.07
38.00
88.00
86.02
86.22
Right eye
09th
84.72
7.63
38.00
88.00
84.35
85.31
12th
84.91
7.20
38.00
88.00
85.25
85.19
Total
85.47
6.73
38.00
88.00
85.13
85.91
Age (years)
P=0.410
Table 2. Distribution of students according to refractive errors
School level
Myopia
Hyperopia Astigmatism
st
05
15
5th
17
18
9th
21
08
1
12
th
Total
http://dx.doi.org/10.5935/0004-2749.20140052
Emmetropia
Total
P
025
136
181
<0.001
036
195
266
027
111
167
32
02
036
094
164
75
43
124
536
778
Arq Bras Oftalmol. 2014;77(3):203-4
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Study conducted at Universidade Estadual de Campinas (UNICAMP), Campinas, SP - Brazil.
REFERENCES
Department of Ophthalmologic, Universidade Estadual de Campinas (UNICAMP), Campinas,
SP - Brazil.
2
Universidade Estadual de Campinas (UNICAMP), Campinas, SP - Brazil.
1. Resnikoff S, Pararajasegaram R. Blindness prevention programmes: past, present, and
future. Bull World Health Organ. 2001;79(3):222-6.
2.IBGE. São Paulo Campinas Censo Demográfico 2010: Resultados da Amostra Educação. [cited 2013 Oct 13]. Available at: http://cidades.ibge.gov.br/xtras/temas.
php?lang=&codmun= 350950&idtema=105&search=sao-paulo|campinas|cen­sodemografico-2010:-re­sultados-da-amostra-educacao
3.Gilbert CE, Ellwein LB. Refractive Error Study in Children Study Group. Prevalence
and causes of functional low vision in school-age children: results from standardized population surveys in Asia, Africa, and Latin America. Invest Ophthalmol Vis Sci.
2008;49(3):877-81.
4. Saw SM, Zhang MZ, Hong RZ, Fu ZF, Pang MH, Tan DT. Near-work activity, night-lights,
and myopia in the Singapore-China study. Arch Ophthalmol. 2002;120(5):620-7.
5.Garcia CA, Oréfice F, Nobre GF, Souza D de B, Rocha ML, Vianna RN. Prevalence of
refractive errors in students in Northeastern Brazil. Arq Bras Oftalmol. 2005;68(3):321-5.
1
Funding: This study was supported by FAPESP 2011/21773-2; FAPESP 2011/19835-0; FAPESP
2011/09514-1.
Disclosure of potential conflicts of interest: None of the authors have any potential conflicts of
interest to disclose.
Corresponding author: Rodrigo Pessoa Cavalcanti Lira. Rua Irma Maria David, 200/1.302 - Recife PE - 52061-070 - Brazil - E-mail: [email protected]
Project number and institution responsible for the approval of the Research Ethics Committee:
UNICAMP 933/2011 - CAAE 0842.0.146.000-11
Submitted for publication: October 14, 2013
Accepted for publication: June 9, 2014
204
Arq Bras Oftalmol. 2014;77(3):203-4
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Editorials are contributed by invitation and should be related to
to­pics of current interest, preferentially related to articles published
in the same issue of ABO (title, maximum of 1,000 words, 2 figures or
tables, and 10 references).
Original Articles
Original articles present complete experiments with results that
have never been published before (title, structured abstract, maximum of 3,000 words, 7 figures or tables, and 30 references). The evaluation of the manuscripts will be based on the following priorities:
Review articles follow the editorial line and are accepted only by
invitation from the editor. Suggestions of topics for review articles
should be sent directly to the editor, but manuscripts cannot be sent
without an invitation (title, unstructured abstract, maximum of 4,000
words, 8 figures or tables, and 100 references).
Editorial Process
Manuscripts will only be considered for publication if they meet
all the journal’s requirements. The editorial office will inform the
authors if their manuscript fails to meet such requirements. Upon
notification, the corresponding author will have 30 days to make the
necessary changes in the manuscript. If the deadline is not met, the
manuscript will be excluded from the editorial process.
The manuscripts submitted to ABO are initially evaluated by the
editors to check for content compliance with the editorial line of
the journal. After this assessment, all manuscripts are sent for peer
review. The anonymity of reviewers is preserved throughout the
whole process. However, the authors of manuscripts do not remain
anonymous.
After the initial editorial evaluation, the reviewers’ comments can
be sent to the authors to guide the changes to be implemented in
the text. After implementing the changes suggested by the revie­
wers, the revised manuscript should be resubmitted along with a
letter (which is sent as a supplementary document) with specific
in­­­dications of all changes made to the manuscript or the reasons
why the suggested changes were not made. Manuscripts that are
resubmitted without a letter will be withheld until the editorial office
receives the letter. The deadline to submit the new version of the ma-
Arq Bras Oftalmol. 2014;77(3):205-8
205
nuscript is 30 days after the authors are informed of the need to make
changes in their manuscript. Manuscripts will be excluded from the
process if authors fail to meet this deadline. The ultimate publication
will be based on the final approval of the editors.
Manuscripts submitted to ABO should not be simultaneously
considered for publication by other journals. In addition, total or partial publication or translation for publication in another language of
the manuscripts submitted to ABO should not be considered without
the permission of the editors of ABO.
Authorship
The criteria for authorship of manuscripts in medical journals are
well established. Individuals who have contributed in a concrete way
during the following three phases of manuscript preparation should
be considered authors:
I. Conception and design, acquisition of data, or analysis and
interpretation of data.
II. Draft or critical revision of the article for important intellectual
content.
III. Final approval of the version to be published.
The authors of manuscripts submitted to ABO should make sure
that all authors meet the criteria mentioned above and that all per­­
sons who meet these criteria are listed. Individuals who hold head­
ship positions cannot be considered authors of manuscripts based
only on their positions. ABO does not accept the participation of
honorary authors.
The corresponding author should complete and submit the Author Contribution Statement as a supplementary document.
Guidelines for Excellent Research
It is recommended that authors follow the appropriate guideline
bellow before submitting your work:
• CONSORT (Controlled and randomized clinical trials)
• STARD (Diagnostic instruments or techniques)
• PRISMA (Systematic reviews and meta-analyses)
• STROBE (Observational studies)
Manuscript Preparation
Manuscripts should only be submitted online using the appropriate interface of ABO. The following guidelines were based on the
format suggested by the International Committee of Medical Journal
Editors (ICMJE) and published in the document: Uniform Requirements for Manuscripts Submitted to Biomedical Journals.
Only the manuscripts complying with these guidelines will be
considered for analysis.
The text should be sent as a digital file. Only the following formats
are accepted: .doc or .rtf. The text should be typed double-spaced,
in 12 point font. The pages should be numbered in Arabic numerals,
starting each section on a new page.
The sections should be presented according to the following sequence: Title page (as a separate document); Abstract and Keywords;
Introduction; Methods; Results; Discussion; Acknowledgements (if
any); References; Tables (optional) and Figures (optional) including
legends.
1. Title Page. It should contain: a) title (no more than 135 characters
with spaces); b) running title to be used as a page heading (no more
than 60 characters with spaces); c) authors’ names as they should
appear in print; d) each author’s affiliation* (city, state, country and,
if applicable, department, school, university); e) corresponding
author’s, name, address, phone number, and email; f ) sources of fi206
Arq Bras Oftalmol. 2014;77(3):205-8
nancial support (if any); g) project number and institution responsible
for the approval of the Research Ethics Committee; h) statement of
conflicts of interests of all authors; i) clinical trial registration number
on a public trials registry.
* Professional or academic degrees, as well as job position will not
be published.
Approval of the Institutional Review Board (IRB). All retrospective, cross-sectional, or prospective studies involving primary data
collection or clinical and surgical reports should include the project
number and name of the institution that provided the approval of the
IRB on the title page. Studies involving humans should be compliant
with the Declaration of Helsinki, whereas studies involving animals
should be in accordance with the principles suggested by the Association for Research in Vision and Ophthalmology (ARVO).
As a supplementary document, the corresponding author should
send the IRB approval or its report stating that the evaluation of the
project by the Committee is not necessary. The author cannot decide
on the need for evaluation by the Research Ethics Committee.
Statement of Conflicts of Interest. The title page should contain
the statement of conflicts of interest of all authors (even if there is no
conflict of interest). For more information about potential conflicts of
interest, refer to: World Association of Medical Editors: Conflict of
interest in peer-reviewed medical journals.
All authors should send the Form for Disclosure of Potential Conflicts of Interest as supplementary documents.
Clinical Trials. All Clinical Trials shall include on the title page the
registration number in an international registry that allows free access to trial information (examples: U.S. National Institutes of Health,
Australian and New Zealand Clinical Trials Registry, International
Standard Randomised Controlled Trial Number - ISRCTN, University
Hospital Medical Information Network Clinical Trials Registry - UMIN
CTR, Nederlands Trial Register).
2. Abstract and Keywords. Structured abstract (Objective, Methods, Results, Conclusions) with no more than 300 words. Unstructured
abstract with no more than 150 words. Five keywords in English
listed by the National Library of Medicine (MeSH - Medical Subject
Headings).
3. Abstract and Keywords in Portuguese. Structured abstract
(Objective, Methods, Results, Conclusions) with no more than 300
words. Unstructured abstract with no more than 150 words. Five
keywords in Portuguese listed by BIREME (DeCS - Descritores em
Ciências da Saúde). Portuguese translation may be provided by ABO
at publication.
4. Introduction, Methods, Results, and Discussion. Citations
in the text should be numbered sequentially in superscript Arabic
numerals and in parentheses. The names of the authors should not
be cited in the text.
5. Acknowledgements. This section should include the colla­
boration of people, groups or institutions that deserve to be acknowledged but do not meet the criteria for authorship. Statisticians
and medical editors may meet the criteria for authorship and, in this
case, should be acknowledged as authors. When they do not meet
the criteria for authorship, they should be mentioned in this section.
Writers who are not identified in the manuscript cannot be accepted
as authors; therefore, professional writers should be acknowledged
in this section.
6. References. Citations (references) of authors in the text should
be numbered sequentially in the same order as they are cited and
identified using superscript Arabic numerals. References should
be in accordance with the format suggested by the International
Committee of Medical Journal Editors (ICMJE), based on the examples below.
Supplemental files can have the following extensions: JPG, BMP, TIF,
GIF, EPS, PSD, WMF, EMF or PDF.
The titles of the journals should be abbreviated according to the
style provided by the List of Journal Indexed in Index Medicus of the
National Library of Medicine.
9. Abbreviations and Acronyms. Abbreviations and acronyms
should be preceded by the spelled-out abbreviation on first mention
and in the legends of tables and figures (even if they have been previously mentioned in the text). Titles and abstracts should not contain
abbreviations and acronyms.
The names of all authors should be cited for references with up to
six authors. For studies with seven or more authors, cite only the first
six authors followed by et al.
Examples of references:
Journal Articles
Costa VP, Vasconcellos JP, Comegno PEC, José NK. O uso da mitomi­cina
C em cirurgia combinada. Arq Bras Oftalmol. 1999;62(5):577-80.
Books
Bicas HEA. Oftalmologia: fundamentos. São Paulo: Contexto; 1991.
Book Chapters
Gómez de Liaño F, Gómez de Liaño P, Gómez de Liaño R. Exploración
del niño estrábico. In: Horta-Barbosa P, editor. Estrabismo. Rio de
Janeiro: Cultura Médica; 1997. p. 47-72.
Annals
Höfling-Lima AL, Belfort R Jr. Infecção herpética do recém-nascido.
In: IV Congresso Brasileiro de Prevenção da Cegueira; 1980 Jul 28-30,
Belo Horizonte, Brasil. Anais. Belo Horizonte; 1980. v.2. p. 205-12.
Dissertations
Schor P. Idealização, desenho, construção e teste de um ceratômetro
cirúrgico quantitativo [dissertation]. São Paulo: Universidade Federal
de São Paulo; 1997.
Electronic Documents
Monteiro MLR, Scapolan HB. Constrição campimétrica causada por
vigabatrin. Arq Bras Oftalmol. [online journal]. 2000 [cited 2005
Jan 31]; 63(5): [about 4 p.]. Available at:http://www.scielo.br/scielo.
php?script=sci_arttext&pid=S0004-27492000000500012&lng=pt&
nrm=iso
7. Tables. Tables should be numbered sequentially using Arabic numerals in the order they are mentioned in the text. All tables should
have a title and a heading for all columns. Their format should be
simple, with no vertical lines or color in the background. All abbreviations (even if previously defined in the text) and sta­tistical tests
should be explained below the table. The bibliographical source of
the table should also be informed when the table is extracted from
another study.
Do not include tables in the main document of the manuscript, they
should be uploaded as supplementary documents
8. Figures (graphs, photos, illustrations, charts). Figures should
be numbered sequentially using Arabic numerals in the order they
are mentioned in the text. ABO will publish the figures in black
and white at no cost to the authors. Manuscripts with color figures
will be published only after the authors pay a publication fee of
R$ 500.00 per manuscript.
Graphs should preferably be in shades of gray, on a white background
and without three-dimensional or depth effects. Instead of using pie
charts, the data should be included in tables or described in the text.
Photos and illustrations should have a minimum resolution of
300 DPI for the size of the publication (about 2,500 x 3,300 pixels for
a full page). The quality of the images is considered in the evaluation
of the manuscript.
The main document should contain all figure legends, typed dou­blespaced and numbered using Arabic numerals.
Do not include figures in the main document of the manuscript; they
should be uploaded as supplementary documents.
10. Units of Measurement: Values of physical quantities should be
used in accordance with the standards of the International System
of Units.
11. Language. Texts should be clear to be considered appropriate
for publication in a scientific journal. Use short sentences, written in
a direct and active voice. Foreign words should be in italics. Therapeutic agents should be mentioned by their generic names with the
following information in parentheses: trade name, manufacturer’s
name, city, state and country of origin. All instruments or apparatus
should be mentioned including their trade name, manufacturer’s
name, city, state and country of origin. The superscript symbol of
trademark ® or™ should be used in all names of instruments or trade
names of drugs. Whenever there are doubts about style, terminology,
units of measurement and related issues, refer to the AMA Manual of
Style 10th edition.
12. Original Documents. Corresponding authors should keep the
original documents and the letter of approval from the Research
Ethics Committee for studies involving humans or animals, the consent form signed by all patients involved, the statement of agreement
with the full content of the study signed by all authors and the statement of conflict of interest of all authors, as well as the records of the
data collected for the study results.
13. Corrections and Retractions. Errors may be noted in published
manuscripts that require the publication of a correction. However,
some errors pointed out by any reader may invalidate the results
or the authorship of a manuscript. If substantial doubt arises about
the honesty or integrity of a submitted manuscript, it is the editor’s
responsibility to exclude the possibility of fraud. In these situations,
the editor will inform the institutions involved and the funding agencies about the suspicion and wait for their final decision. If there is
confirmation of a fraudulent publication in ABO, the editor will act in
compliance with the protocols suggested by the International Committee of Medical Journal Editors (ICMJE) and by the Committee on
Publication Ethics (COPE).
Checklist
Before submitting their manuscript, authors should make sure
that all the following items are available:
□ Manuscript prepared in accordance with the instructions to
authors.
□ Maximum number of words, tables, figures, and references
according to the type of manuscript.
□ Title page including the clinical trial registration number is not
included in the main document
□ No figures and tables are included in the main document of
the manuscript.
□ All figures and tables were uploaded separately as supplementary documents.
□ Author Contribution Statement completed and saved as a
digital file to be sent as a supplementary document.
□ Form for Disclosure of Potential Conflicts of Interest of all
authors completed and saved as digital files to be sent as
supplementary documents.
□ Digital version of the report provided by the Institutional Review Board containing the approval of the project to be sent
as a supplementary document.
Arq Bras Oftalmol. 2014;77(3):205-8
207
List of WEBSITES
Authorship Principles according to the ICMJE
http://www.icmje.org/recommendations/browse/roles-andresponsibilities/defining-the-role-of-authors-and-contributors.html
Authors’ Participation Form
http://www.cbo.com.br/site/files/Formulario Contribuicao dos
Autores.pdf
CONSORT (Consolidated Standards of Reporting Trials)
http://www.consort-statement.org/consort-statement/
STARD (Standards for the Reporting of Diagnostic accuracy studies)
http://www.stard-statement.org/
PRISMA (Preferred Reporting Items for Systematic Reviews and
Meta-Analyses)
http://www.prisma-statement.org/index.htm
Form for Disclosure of Potential Conflicts of Interest
http://www.icmje.org/coi_disclosure.pdf
U.S. National Institutes of Health
http://www.clinicaltrials.gov
Australian and New Zealand Clinical Trials Registry
http://www.anzctr.org.au
International Standard Randomised Controlled Trial Number ISRCTN
http://isrctn.org/
University Hospital Medical Information Network Clinical Trials
Registry - UMIN CTR
http://www.umin.ac.jp/ctr/index.htm
Nederlands Trial Register
http://www.trialregister.nl/trialreg/index.asp
STROBE (Strengthening the Reporting of Observational studies
in Epidemiology)
http://www.strobe-statement.org/
MeSH - Medical Subject Headings
http://www.ncbi.nlm.nih.gov/sites/entrez?db=mesh&term=
Online interface for submission of manuscripts to ABO
http://www.scielo.br/ABO
DeCS - Health Sciences Keywords in Portuguese
http://decs.bvs.br/
International Committee of Medical Journal Editors (ICMJE)
http://www.icmje.org/
Format suggested by the International Committee of Medical
Journal Editors (ICMJE)
http://www.nlm.nih.gov/bsd/uniform_requirements.html
Uniform requirements for manuscripts submitted to biomedical
journals
http://www.nlm.nih.gov/bsd/uniform_requirements.html
List of Journal Indexed in Index Medicus
http://www.ncbi.nlm.nih.gov/journals
Declaration of Helsinki
http://www.wma.net/en/30publications/10policies/b3/index.html
AMA Manual of Style 10th edition
http://www.amamanualofstyle.com/
Principles of the Association for Research in Vision and Ophthalmology (ARVO)
http://www.arvo.org/About_ARVO/Policies/Statement_for_the_
Use_of_Animals_in_Ophthalmic_and_Visual_Research/
Protocols of the International Committee of Medical Journal
Editors (ICMJE)
http://www.icmje.org/recommendations/browse/publishing-andeditorial-issues/scientific-misconduct-expressions-of-concern-andretraction.html
World Association of Medical Editors: Conflict of interest in peer-­
reviewed medical journals
http://www.wame.org/about/wame-editorial-on-coi
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Chief Executive Officer: Fernando Steven Ullmann;
Commercial Director: Helen Suzana Perlmann; Art Director: Elza Rudolf;
Publishing, Printing and CTP: Ipsis Gráfica e Editora S.A.
Frequency of publication: Bimonthly; Circulation: 7.500 copies
208
Arq Bras Oftalmol. 2014;77(3):205-8
Protocols of the Committee on Publication Ethics (COPE)
http://publicationethics.org/resources/flowcharts
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