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ARVO 2014 Annual Meeting Abstracts
479 Non-infectious Inflammation
Wednesday, May 07, 2014 3:45 PM–5:30 PM
Exhibit/Poster Hall SA Poster Session
Program #/Board # Range: 5295–5326/C0113–C0144
Organizing Section: Immunology/Microbiology
Program Number: 5295 Poster Board Number: C0113
Presentation Time: 3:45 PM–5:30 PM
Long-term results of dexamethasone intravitreal implant for
noninfectious uveitic macular edema
Zohar Habot-Wilner1, 2, Nir Sorkin1, 2, Dafna Goldenberg1, 2,
Michaella Goldstein1, 2. 1Ophthalmology, Tel-Aviv Medical Center,
Tel Aviv, Israel; 2Sackler Faculty of Medicine, Tel Aviv University,
Tel Aviv, Israel.
Purpose: To report the long-term outcome of the 0.7-mg
dexamethasone drug delivery system (DEX-DDS) intravitreal
injection for noninfectious uveitic macular edema.
Methods: Retrospective study of eyes with noninfectious uveitic
macular edema treated with DEX-DDS injection with at least 6
months follow-up time. Macular edema was diagnosed by clinical
examination, fluorescein angiography and Heidelberg Spectralis
spectral domain optical coherence tomography (SD-OCT).
Patients’ data were collected and included details of uveitis, ocular
inflammation, best corrected visual acuity (BCVA) and SD-OCT at
baseline and each visit during follow-up. Number of injections and
potential complications were recorded.
Results: 8 eyes (7 patients) were included. One eye with anterior
uveitis, six eyes with intermediate uveitis and one eye with
panuveitis. Mean follow-up time was 17 months. In 1 eye the
injection was given as adjunctive treatment. Macular edema resolved
in all eyes, 3.9 weeks (range, 1–6.9) post injection. The mean BCVA
improvement was 0.25 logMAR (p < 0.05), 3.9 weeks (range, 1–6.9)
post injection. Central point thickness improved from 612 ±143 m to
250 ±55 m (p < 0.05). Macular edema did not recur in 5 eyes after a
mean follow-up of 14.5 months. Macular edema relapsed in 3 eyes
(2 patients) after a mean time of 4.7 months (range, 3.6–6.3). These
patients had repeated injections; 1 patient had 2 injections and 1
patient had 4 injections with macular edema resolution. Two eyes
had intraocular pressure elevation which was well controlled under
topical treatment.
Conclusions: Intravitreal DEX-DDS injections resulted in macular
edema resolution and visual acuity improvement. Some eyes needed
repeated injections, but most eyes achieved long-term resolution. No
significant complications were noticed.
Commercial Relationships: Zohar Habot-Wilner, None; Nir
Sorkin, None; Dafna Goldenberg, None; Michaella Goldstein,
None
Program Number: 5296 Poster Board Number: C0114
Presentation Time: 3:45 PM–5:30 PM
Treatment with immunosuppressive therapy in patients with pars
planitis: experience of a reference center in Mexico
Juan Carlos Serna-Ojeda, Miguel Pedroza-Seres. Ophthalmology,
Institute of Ophthalmology “Conde de Valenciana”, Mexico City,
Mexico.
Purpose: To evaluate the clinical course of the patients with pars
planitis that received immunosuppressive drugs.
Methods: We retrospectively analyzed the data of 10 years from 374
patients with pars planitis in a large reference center in Mexico City
and included 49 patients (92 eyes)
Results: Median age at presentation was 8 years. 35 patients (71.4%)
were male and 43 patients (87.7%) had bilateral disease. The median
of the visual acuity at presentation was 20/60 (range 20/20 – light
perception). The main complaint was low visual acuity in 37 patients
(75.5%). The most common ocular manifestation was vitritis in
all the patients and the main ocular complication was cataract in
52.1%. Diverse immunosuppressive medications were used, mainly
methotrexate (69.4%) and azathioprine (63.3%) with 18 patients
requiring more than one drug. The main indications for starting
immunosuppressive therapy were lack of response to initial treatment
and advance disease at presentation. The results showed good
response with steroid reduction (69.3% of patients), visual acuity
improvement (51% of patients) and inflammatory disease reduction
(59.1% of patients). In 25 patients (51%) steroids were started
previous to immunosuppressors and in 24 (49%) at the same time
without significant difference in clinical improvement (p=0.210) or
visual outcome (p=0.498). Thirteen patients (26.5%) presented mild
adverse effects. Median follow up was 4 years. The median of the
final visual acuity was 20/40 (range 20/20 – no light perception).
Conclusions: Immunosuppressive therapy allows an adequate control
of inflammatory disease in pars planitis, with clinical and visual
improvement and steroid dose reduction.
Commercial Relationships: Juan Carlos Serna-Ojeda, None;
Miguel Pedroza-Seres, None
Program Number: 5297 Poster Board Number: C0115
Presentation Time: 3:45 PM–5:30 PM
CD4+CD25+FoxP3+ T regulatory cells in experimental
autoimmune anterior uveitis
Nalini S. Bora, Bharati Matta, Purushottam Jha, Puran S. Bora.
Ophthalmology, Jones Eye Institute-UAMS, Little Rock, AR.
Purpose: To explore the role of CD4+CD25+FoxP3+ T regulatory
cells (Tregs) in experimental autoimmune anterior uveitis (EAAU).
Methods: Male Lewis rats injected with melanin associated antigen
(MAA) were sacrificed at different time points and lymphocytes were
purified from the eyes. For the detection of Tregs, lymphocytes were
first surface stained with anti CD4-APC and anti CD25-PE. Cells
were then intra-cellularly stained with FITC labeled FoxP3 antibody.
The percentage of Tregs was determined by flow cytometry. Effect of
TGFβ2 on the proliferation of CD4+ T cells harvested from popliteal
lymph nodes (LNs) in response to MAA was determined by CFSE
cell proliferation assay. MAA sensitized Lewis rats were injected
with recombinant TGFβ2 intravenously via the tail vein at days 15,
16 and 17 post-immunization and days -1, 0 and 1 post-immunization
separately to study the effect of TGFβ2 on EAAU. Effect of Tregs
on on-going EAAU was investigated by adoptive transfer of Tregs
purified from LNs of rats tolerized against MAA.
Results: Our results demonstrate that the percentage of
CD4+CD25+FoxP3+ Tregs in the eye peaked during the resolution
of EAAU. TGFβ2 when injected at the onset of EAAU reduced
the severity and duration of the disease. EAAU failed to develop
in animals injected with TGFβ2 at the time of immunization.
Treatment with TGFβ2 in vitro inhibited the proliferation of CFSE
labeled CD4+T cells in response to MAA. Increased percentage of
CD4+CD25+FoxP3+ Tregs was noted in MAA-sensitized Lewis rats
injected intravenously with TGF-β2. Adoptive transfer of Tregs in the
rats with on-going EAAU resulted in sharp decline in disease activity
and early resolution of uveitis.
Conclusions: Our data demonstrate that Tregs induced by TGFβ2
inhibited the induction of EAAU. Furthermore, on-going EAAU was
suppressed by CD4+CD25+FoxP3+ Tregs. Together, results from
present investigation suggest that Tregs play an important role in this
model of anterior uveitis.
Commercial Relationships: Nalini S. Bora, None; Bharati Matta,
None; Purushottam Jha, None; Puran S. Bora, None
©2014, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2014 Annual Meeting Abstracts
Support: Pat and Willard Walker Eye Research Center, Jones Eye
Institute, University of Arkansas for Medical Sciences, Little Rock,
AR
Program Number: 5298 Poster Board Number: C0116
Presentation Time: 3:45 PM–5:30 PM
Subconjunctival Sirolimus in the Treatment of Autoimmune NonNecrotizing Anterior Scleritis: Results of a Pilot Clinical Trial
Nirali Bhatt, Monica D. Dalal, William R. Tucker, Robert B.
Nussenblatt, H Nida Sen. National Eye Institute/National Institutes of
Health, Washington, DC.
Purpose: Scleritis is a chronic, painful and potentially blinding
inflammatory disease. Sirolimus suppresses cytokine-driven T-cell
proliferation, inhibiting the activity of many growth factors relevant
to scleritis. This study investigates the safety, tolerability and efficacy
of subconjunctival sirolimus injections as a treatment for active,
autoimmune, non-necrotizing, anterior scleritis.
Methods: Five participants with active, autoimmune, non-necrotizing
anterior scleritis with scleral inflammatory grade of ≥1+ in at least
one quadrant with a history of flares were enrolled in this phase I/II,
single-center, open-label, non-randomized, prospective pilot study.
Patients received a baseline injection with the primary outcome
measure of at least a 2-step reduction or reduction to grade zero
scleral inflammation according to a standardized photographic
grading scale in the study eye by eight weeks. Secondary outcomes
included changes in visual acuity, ability to taper from their standard
immunosuppressive regimen, number of partients who experienced
a disease flare, and those requiring re-injection. Safety outcomes
include the number and severity of systemic and ocular toxicities,
adverse events, vision loss ≥ 15 ETDRS letters, and rise in intraocular
pressure. The study included six visits over four months with an
extension phase to one year.
Results: All patients (N=5, 100%) achieved at least a 2-step
reduction or reduction to grade zero inflammation in the study eye
by the Week 8 visit. Mean baseline visual acuity was 84.6 ETDRS
letters and 84.4 at the end of the study. None of the patients who
were previously on systemic immunosuppressive medications (N=4)
were successfully tapered off therapy during the study. Three out of
five patients (60%) experienced disease flares requiring re-injection.
No systemic toxicities were observed, and none of the patients
experienced a rise in intraocular pressure. Two patients (40%)
experienced a localized sterile inflammatory reaction at the site of the
subconjunctival injection which resolved without complication. One
of these patients withdrew from the study during the extension phase.
Conclusions: Subconjunctival sirolimus leads to a short-term
reduction in scleral inflammation, though relapses requiring reinjection do occur. A local sterile conjunctival inflammatory reaction
was an ocular side effect observed during this study.
Commercial Relationships: Nirali Bhatt, None; Monica D. Dalal,
None; William R. Tucker, None; Robert B. Nussenblatt, None; H
Nida Sen, None
Support: National Eye Institute Intramural Research Program
Clinical Trial: NCT01517074
Program Number: 5299 Poster Board Number: C0117
Presentation Time: 3:45 PM–5:30 PM
Long-term evaluation of non-infectious uveitic macular edema
treated with Ozurdex
Laura Pelegrin1, Marina Mesquida1, Victor Llorens1, Blanca Molins2,
Maite Sainz de la Maza1, Alfredo Adan Civera1. 1Institut Clínic
d’Oftalmologia, Hospital Clinic i Provincial de Barcelona, Barcelona,
Spain; 2Institut d’Investigacions Biomèdiques Agustí Pi i Sunyer,
IDIBAPS, Barcelona, Spain.
Purpose: To evaluate the long-term visual prognosis and
complications of patients who received intravitreal Ozurdex
injections for the treatment of non-infectious uveitic macular edema
(UME).
Methods: A retrospective study of 32 patients with UME refractory
to systemic and intraocular therapies were treated with intravitreal
dexamethasone. Vitrectomized (PPV) versus non vitrectomized
(non-PPV) patients were analyzed. The main variables analyzed
were the reduction in central retinal thickness (CRT), best corrected
visual acuity (BCVA) and intraocular pressure (IOP). Activity status
of uveitis and side effects were also assessed. Statistical analysis was
adjusted by the presence of vitrectomy, reinjection of dexamethasone
during follow-up and number of treatments for high IOP. These
estimations of effects were performed by means of Longitudinal
Linear model using the General Estimating Equation (GEE)
methodology to account for intra-subject correlations for visits with
the assumption of first degree dependence of correlation
Results: The median age of patients was 46,7 years (range, 18–61
years). The mean follow-up time was 38,5 months. The CRT (95%
confidence interval) was 571.9 microns (476.1–667.9) in non-PPV
patients and 509,63 (428,3; 590,9) in PPV patients at baseline, its
maximum decrease was at first month, 320,53 (266,09; 374,9) and
278,74 (224,6; 332,8) respectively which was maintained all over
the follow-up BCVA logMar improved from 0,912 (0,685; 1,139) at
baseline to 0,651 (0,428; 0,873) at 3 months in non-PPV patients and
from 0,875 (0,682; 1,067) to 0,522 (0,35; 0,694) in PPV patients. IOP
showed statistically differences of 3,82 mmHg (p=0,012) between
non-PPV and PPV patients from third to twelfth month 4,5 mmHg
(p=0,001)
In 22 eyes (50%), reinjection of the implant was performed at a mean
of 4.8 months. Ocular hypertension (50%), hypotony (7.1%), anterior
chamber displacement of the implant (4.7%), cataract surgery (7,1%)
and glaucoma, which required filtration surgery (4.7%), were the
most common adverse events.
Conclusions: Our results indicate that treatment with dexamethasone
intravitreal implant injection for uveitic macular edema has favorable
long-term safety profile. IOP shows statistically differences between
PPV and non-PPV patients
Commercial Relationships: Laura Pelegrin, None; Marina
Mesquida, None; Victor Llorens, None; Blanca Molins, None;
Maite Sainz de la Maza, None; Alfredo Adan Civera, None
Program Number: 5300 Poster Board Number: C0118
Presentation Time: 3:45 PM–5:30 PM
The Dublin Uveitis Evaluation Tool (DUET) – an algorithm for
earlier diagnosis of spondyloarthropathies by ophthalmologists in
acute anterior uveitis
Micheal O’Rourke1, Muhammad Haroon2, Pathma Ramasamy1,
Oliver FitzGerald2, Conor Murphy1. 1Department of Ophthalmology,
Royal College of Surgeons in Ireland, Royal Victoria Eye and Ear
Hospital, Dublin 2, Ireland; 2Rheumatology, St Vincent’s University
Hospital, Dublin 4, Ireland.
Purpose: The incidence of spondyloarthropathy (SpA) is 1%. Early
diagnosis is crucial as morbidity in SpA is related to duration of
the disease. Advanced disease is typified by joint fusion in the axial
skeleton but even early disease can impact greatly on quality of life.
The acutely painful red eye in anterior uveitis (AU) will prompt a
patient to seek medical attention more readily than lower back pain
of insidious onset. The first aim of this study was to establish the
incidence of previously undiagnosed SpA in patients presenting with
AU. The second aim was to formalize a referral algorithm for early
referral to a rheumatologist with the aim of earlier diagnosis and
treatment.
©2014, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2014 Annual Meeting Abstracts
Methods: 104 consecutive patients with non-infectious AU were
recruited prospectively. Other causes of AU and a known history of
SpA were excluded. All patients were subsequently screened by a
rheumatologist for the presence or absence of SpA. A detailed clinical
history was undertaken and the most significant features which may
identify patients with SpA were identified to generate a predictive
algorithm. This algorithm was subsequently validated in a further
cohort of 80 patients.
Results: A new diagnosis of SpA was made in 42 patients. Of
these, over 60% had previously attended their family doctor for
backache and the average duration of backache was 9.36 years
prior to diagnosis. HLA-B27 positivity and backache were the
most statistically relevant features with an odds ratio of 27 and
21 respectively. An algorithm consisting of the most significant
confounding clinic features of these patients advised that any patient
with AAU and back pain of onset under 45 years of age with duration
greater than 3 months should have HLA-B27 checked. If this is
positive then the patient should be referred. In addition to this, any
patient presenting with AAU with a personal history of psoriasis,
even in the absence of back pain should also be referred. This
algorithm has sensitivity of 95% and specificity of 98%. Validation
of this algorithm in a second cohort had comparable sensitivity and
specificity.
Conclusions: Close collaboration between ophthalmologists and
rheumatologists utilizing our algorithm will result in earlier treatment
intervention to improve disease outcome in SpA.
Commercial Relationships: Micheal O’Rourke, None;
Muhammad Haroon, None; Pathma Ramasamy, None; Oliver
FitzGerald, None; Conor Murphy, None
Program Number: 5301 Poster Board Number: C0119
Presentation Time: 3:45 PM–5:30 PM
Sustained-release dexamethasone intravitreal implant in juvenile
idiopathic arthritis-related uveitis
Francesco Pichi1, 2, Kimberly Baynes2, Paolo Nucci1, Careen Y.
Lowder2, Sunil K. Srivastava2. 1University Eye Clinic, San Giuseppe
Hospital, Milan, Italy; 2Cole Eye Institute, Cleveland Clinic
Foundation, Cleveland, OH.
Purpose: To present a series of patients with JIA uveitis treated with
dexamethasone implant (Ozurdex®).
Methods: Retrospective chart review.
Results: Seventeen eyes of 12 patients (10 girls, mean age 12.5±6.7
years) with JIA uveitis received intravitreal Ozurdex®. Mean
duration of: arthritis before starting treatment with Ozurdex was
49±35.6 (12-132) months; uveitis was 31±20.1 (12-72) months;
follow-up was 11.6±13.2 (2-24) months. One month after injection,
vision improved to 40.2±11 logMAR (p<0.001). Seven of 8 eyes that
received Ozurdex for persistent iritis had resolution by clinical exam.
Nine of 17 eyes had macular edema prior to injection with central
retinal thickness of 437.6±96.2 mm that decreased to 342.4±79.3 mm
(p<0.01) at one month. Twelve of 17 eyes received a second implant
at 7.5±3.1 months after first injection. One month after second
implant, iritis resolved in 11 eyes (91.6%), mean BCVA improved to
44.6±8.1 logMAR (p<0.01). Five of 12 eyes had macular edema at
second injection with central retinal thickness of 399.8±59.8 mm that
improved to 250.4±13.7 mm (p<0.01) in 4/5 eyes at one month. Five
eyes received a third Ozurdex iimplant 7±4.6 months after second
injection; of these 5 eyes, 4 had iritis and 1 had macular edema. One
eye received a fourth injection 3 months after the third for iritis.
Five of 17 eyes were pseudophakic prior to first injection. Of the
remaining 12, 8 (66.6%) developed worsening posterior subcapsular
cataract at a mean of 7.3±1.2 months after first implant. Three of
these 8 eyes required cataract surgery 10.7±4.8 months from initial
injection. Prior to Ozurdex injection, none of the 17 eyes was on
anti-glaucoma therapy. After the first injection, 1 eye required therapy
with maximum IOP of 25 mmHg. Mean IOP prior to first injection
was 15 mmHg; at 1 month, 25 and at 3 months, 23. In the 12 eyes
that received a second injection, mean IOP was 13.4±1.3 mmHg at
the time of injection, 14.6±0.8 at 1 month and 15.3±1.1 at 3 months.
None of the eyes receiving 3 or 4 injections developed IOP rises.
Conclusions: Our series suggests that Ozurdex can be effective in the
treatment of JIA-associated uveitis and macular edema with few side
effects.
Commercial Relationships: Francesco Pichi, None; Kimberly
Baynes, None; Paolo Nucci, None; Careen Y. Lowder, Clearside
(C), Santen (C); Sunil K. Srivastava, Allergan (F), Bausch and
Lomb (C)
Clinical Trial: 12-612
Program Number: 5302 Poster Board Number: C0120
Presentation Time: 3:45 PM–5:30 PM
Optic nerve and retinal features in uveitis associated with
juvenile systemic granulomatous disease (Blau’s syndrome)
Ester Carreno1, Catherine M. Guly1, Michael Chilov4, Annie
Hinchcliffe1, Juan I. Aróstegui2, Richard W. Lee1, Andrew D. Dick1,
Athimalaipet V. Ramanan3. 1Bristol Eye Hospital, Bristol, United
Kingdom; 2Hospital Clinic, Barcelona, Spain; 3Bristol Royal
Infirmary, Bristol, United Kingdom; 4Save Sight Institute, University
of Sydney, Sidney, ACT, Australia.
Purpose: Juvenile systemic granulomatous disease (JSGD),
also known as Blau’s syndrome, is a dominantly-inherited
autoinflammatory disorder associated with gain-of-function mutations
in the NOD2 gene. The aim of this study was to determine whether
patients with JSGD and uveitis have a specific ocular phenotype.
Methods: Case series of patients with uveitis and a confirmed NOD2
mutation. Clinical and imaging data were retrospectively collected
from patients attending to the Regional Ocular Inflammatory Service,
Bristol Eye Hospital. General demographic information, visual
acuity at the last visit, laterality of the uveitis, age at onset of clinical
symptoms, anatomical classification and course of the uveitis, clinical
phenotype, and specific NOD2 mutation were recorded for each
patient. All data were collected in a database designed in Microsoft®
Access®.
Results: Seventeen eyes, 9 patients (5 males; 4 females). Mean
age at the onset of symptoms was 15 months (range 1-84 months).
Mean visual acuity at the last visit was 0.48 logMAR. Eight patients
had bilateral uveitis. Anterior uveitis was present in five eyes,
intermediate uveitis in 2 eyes and there were 10 eyes with panuveitis
(which characteristically manifested in association with multifocal
choroiditis). Disc margins were blurred in 6 eyes; the colour of the
disc was pale in 6 eyes; the optic disc vessels were sheathed in 4
cases; peripapillary area was hypo/hyperpigmented in 13 eyes; 13
eyes showed nodular excrescences in the peripapillary area. The
heterozygous p.R334W NOD2 mutation was the most frequently
detected (n: 4 patients). The novel p.Q809K NOD2 mutation was
identified in one patient.
Conclusions: There are characteristic peripapillary changes in
patients with JSGD, which may assist early diagnosis and treatment.
This is the first report of p.Q809K NOD2 mutation causing JSGD.
Commercial Relationships: Ester Carreno, None; Catherine M.
Guly, None; Michael Chilov, None; Annie Hinchcliffe, None; Juan
I. Aróstegui, None; Richard W. Lee, None; Andrew D. Dick, None;
Athimalaipet V. Ramanan, None
©2014, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2014 Annual Meeting Abstracts
Program Number: 5303 Poster Board Number: C0121
Presentation Time: 3:45 PM–5:30 PM
Efficacy and safety of TNF-α inhibitors in non-infectious uveitis :
a multicenter retrospective study
Melanie Bidaut-Garnier1, 2, Hélène Vallet3, Pascal Seve4, Emmanuel
Heron5, Antoinette Perlat6, Nathalie Tieulie7, Laurent Perard8, Phuc
Lehoang2, 9, David Saadoun3, 9, Bahram Bodaghi2, 9. 1Ophthalmology,
University Hospital of Besancon, Besancon, France; 2Ophthalmology,
DHU ViewMaintain, Pitie Salpetriere Hospital, Paris, France;
3
Internal medicine, University Hospital of Pitié Salpêtrière, Paris,
France; 4Internal medecine, University Hospital of Lyon, Groupement
Hospitalier Nord, Croix-Rousse Hospital, Lyon, France; 5Internal
medecine, Quinze-Vingts National Ophthalmology Hospital, Paris,
France; 6Internal medicine, University Hospital of Rennes, Southern
Hospital, Rennes, France; 7Internal medecine, University Hospital of
Nice, Archet Hospital, Nice, France; 8Internal medicine, University
Hospital of Lyon, Groupe Hospitalier Edouard Herriot, Lyon, France;
9
Vision and Handicaps, ViewMaintain, University of Pierre et Marie
Curie, University Department of Hospital, Paris, France.
Purpose: TNF-α inhibitors have been used over the last few years
in noninfectious uveitis refractory to traditional immunosuppressive
agents, with promising results. Most autoimmune uveitis are
T-cell-mediated diseases, and TNF-α is one of the most important
amplifying factors in the genesis of the inflammatory reaction.
However, in the literature, TNF-α blockers have mostly been studied
in uncontrolled trials, or case-series with small effectives. The
purpose was to evaluate the efficacy and safety of anti TNF-α in a
larger effective of patients.
Methods: Evolution of noninfectious uveitis in patients treated
with anti TNF-α agents was retrospectively reviewed, for subjects
managed of between July 2001 and June 2013 in six French
Ophthalmology Departments. Ocular inflammation, visual acuity, and
number of relapses were the main criteria for efficacy.
Results: We included 136 patients. Uveitis was granulomatous
in 24%, bilateral in 85%, total in 63%, with retinal vascularitis in
32%, macular edema in 54% of cases. Conditions associated with
uveitis were Behçet’s disease (25%), juvenile idiopathic arthritis
(26%), spondyloarthropathy (11%), sarcoidosis (4%), Birdshot
retinochoroidopathy and Vogt Koyanagi Harada (15%), idiopathic
(19%). TNF-α inhibitors (infliximab, 57%, adalimumab, 40%,
etanercept, 3%) were introduced in patients who did not respond to
conventional immunosuppressors in 88% of cases. Median duration
of treatment was 18 months [8-33] with a median follow up of 27
months [8-53]. Complete or partial response was reported in 111
patients (n=118, 94%). Mean dosage of prednisone was significantly
reduced after 6 and 12 months of treatment (n=101 ; 15mg [6-47.5]
at introduction vs 10mg [8-15] at 6 months and 9mg [5-15] at 12
months; p<0.0001). Number of relapses was also significantly
reduced (n=74; 4 [3-5]; 0 [0-1]; p<0.0001). Side effects were
observed in 32 patients (n=130; 25%); they were severe in 3 cases (1
lymph node tuberculosis and 2 angioedema).
Conclusions: TNF-α inhibitors seem to be safe and effective in
reducing inflammation with further tapering of corticosteroids, in
severe cases of noninfectious uveitis.
Commercial Relationships: Melanie Bidaut-Garnier, None;
Hélène Vallet, None; Pascal Seve, None; Emmanuel Heron, None;
Antoinette Perlat, None; Nathalie Tieulie, None; Laurent Perard,
None; Phuc Lehoang, None; David Saadoun, None; Bahram
Bodaghi, None
Program Number: 5304 Poster Board Number: C0122
Presentation Time: 3:45 PM–5:30 PM
Behcet Disease in the United States: Ocular and Systemic
Manifestations
Didar Ucar, Monica D. Dalal, Austin Fox, William R. Tucker, Nirali
Bhatt, Robert B. Nussenblatt, H Nida Sen. National Eye Institute,
National Institutes of Health, Bethesda, MD.
Purpose: Behcet’s disease (BD) is uncommon in the United
States (US). Prior studies have indicated different characteristics
among different ethnic groups. The aim of this study is to describe
demographic and clinical features, ocular and systemic manifestations
in a US population with BD.
Methods: Electronic medical records of BD patients seen for ocular
screening as part of an interdisciplinary clinical study (systemic
cohort) and those seen as part of a natural history study for ocular
disease (ocular cohort) at the National Eye Institute between 1999
and 2011 were reviewed. Data collected included demographics,
clinical features, ocular and systemic manifestations. Patients were
also categorized based on ethnicity into two groups: Caucasians of
European descent (CEu) or Non-Caucasian or non-European descent
(NCEu). Results were also compared to previously published large
epidemiologic studies from different geographic regions.
Results: A total of 70 patients were identified. The mean age at
diagnosis was 27.8 years, 44 were female (63%), 52 were CEu
(74%), 32 (46%) were in the ocular cohort and 38 (54%) in the
systemic cohort. Female-to-male (F/M) ratio in the entire cohort was
1.7; 2.0 among CEu, 1.0 among NCEu patients. HLA B51 positivity
was 23% and 33% in the CEu and NCEu groups, respectively. Uveitis
was slightly more common among NCEu compared to CEu patients
(78% vs 67%), and posterior/panuveitis was the most common form
of uveitis in all groups (71%). F/M ratio was higher in the systemic
cohort (3.8) compared to ocular cohort whereas, HLA B51 positivity
was higher in the ocular cohort (31%). Anterior uveitis was the most
common anatomical location in the systemic cohort (53%) whereas
posterior/panuveitis was the most common in the ocular cohort
(88%). In terms of extraocular manifestations there was no significant
difference between the ethnic categories or systemic and ocular
cohorts. Compared to previous reports, F/M ratio in this study was
higher and HLAB51 prevalence was lower.
Conclusions: BD in the US appears to have different clinical
characteristics with more females affected and lower prevalence of
uveitis as well as a lower HLAB51 prevalence among Caucasians
of European descent. Posterior/panuveitis was the most common
anatomical location for uveitis in the entire cohort. Extraocular
manifestations were similar among different ethnic groups in the US
BD patients.
Commercial Relationships: Didar Ucar, None; Monica D. Dalal,
None; Austin Fox, None; William R. Tucker, None; Nirali Bhatt,
None; Robert B. Nussenblatt, None; H Nida Sen, None
Support: This study was supported by The National Eye Institute
Intramural Research Program. Dr Ucar received grant support from
The Scientific and Technological Research Council of Turkey
Program Number: 5305 Poster Board Number: C0123
Presentation Time: 3:45 PM–5:30 PM
Clinical and functional evaluation of experimental autoimmune
uveitis in B10.RIII mice: monophasic versus biphasic forms
Jun Chen1, 3, Haohua Qian2, Chi-Chao Chan3, Rachel R. Caspi3.
1
State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic
Center, Sun Yat-sen University, Guangzhou, China; 2Visual Function
Core, National Eye Institute, Bethesda, MD; 3Laboratory of
Immunology, National Eye Institute, Bethesda, MD.
©2014, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2014 Annual Meeting Abstracts
Purpose: Non-infectious uveitis in humans is an autoimmune
disease of the retina and uvea that leads to blindness. Its laboratory
equivalent is experimental autoimmune uveitis (EAU) induced in
susceptible rodents by immunization with retinal antigens. The
murine model of EAU has been particularly useful, permitting
to dissect basic mechanisms as well as serving as a template for
translational therapies. The B10.RIII mouse strain is the most
susceptible strain known. To characterize EAU in the B10.RIII strain,
we used multiple methodologies including non-invasive assessments
in comparison with histology for disease evaluation.
Methods: EAU was induced in B10.RIII mice by immunization
with IRBP161-180 in the absence of pertussis toxin. Disease was
evaluated longitudinally using non-invasive clinical assessments by
fundus examination and photography, optical coherence tomography
and functional evaluation by electroretinography (ERG), which were
then compared to histopathology.
Results: The EAU model in the B10.RIII strain had been thought
until now to only manifest an acute-monophasic pattern of disease.
Unlike previously reported, we found that IRBP-immunized EAU in
B10.RIII mice exhibited two distinct patterns of disease depending
on clinical scores developed after onset: (i) severe monophasic form
of EAU with diffuse/extensive destruction of the retina, followed
by a rapid retinal atrophy and loss of visual signal two weeks post
immunization, or (ii) lower grade of EAU with an initial acute phase,
followed by a prolonged chronic phase and partial recovery of the
ERG response, culminating in focal retinal degeneration and loss of
vision after 6-7 months.
Conclusions: We demonstrate for the first time that EAU model
in the B10.RIII strain can be either monophasic or biphasic, with
distinguishing features. These findings can affect the choice of
animal model of human uveitis as a platform to evaluate effects of
investigational therapeutic modalities.
Commercial Relationships: Jun Chen, None; Haohua Qian, None;
Chi-Chao Chan, None; Rachel R. Caspi, None
Support: NEI Intramural Research Program
Program Number: 5306 Poster Board Number: C0124
Presentation Time: 3:45 PM–5:30 PM
Characterization of Retinal Expression of Intercellular Adhesion
Molecule 1 (ICAM-1) During Experimental Autoimmune Uveitis
Deborah Lipski1, 2, Remi Dewispelaere1, 3, Ariane Frère3,
Laure E. Caspers3, Catherine Bruyns1, François Willermain1, 3.
1
Ophthalmology, IRIBHM, Brussels, Belgium; 2Ophthalmology,
Erasme Hospital, Brussels, Belgium; 3Ophthalmology, CHU SaintPierre, Brussels, Belgium.
Purpose: During inflammation, activated T cells producing proinflammatory cytokines induce the expression of adhesion molecules,
which allow for the recruitment of immune cells responsible for
tissue damage. Immunoglobulin superfamily members play a central
role in leukocyte adhesion to the blood-retinal barrier (BRB). We
have previously demonstrated that VCAM-1 is induced on BRB cells
during experimental autoimmune uveitis (EAU) in correlation with
the severity of the disease. Here, we investigate the retinal expression
of ICAM-1 in EAU and the expression of integrins VLA-4 and
LFA-1, respectively VCAM-1 and ICAM-1 ligands, on transferred
uveitogenic cells.
Methods: C57Bl/6 mice were immunized with interphotoreceptor
retinoid-binding protein (IRBP) peptide 1–20. After 12 days, T
cells were semi-purified from draining lymph nodes and spleens,
restimulated in vitro with IRBP1-20 for 2 days and injected to
C57Bl/6 mice. Before being adoptively transferred, T cells were
tested by flow cytometry for their expression of CD4, VLA-4 and
LFA-1. Fundoscopy was performed before euthanasia after 1, 2 or
3 weeks. Eyes were processed and ICAM-1 expression analyzed by
immunohistology. Co-labellings for GFAP and endoglin detection
were done to identify cells expressing ICAM-1.
Results: ICAM-1 is faintly present in naive eyes but its expression
develops in parallel to EAU, with an intensity and extension
correlated to disease severity. ICAM-1 expression is maximal at the
retinal pigment epithelium level but it also extends to the ciliary body,
the external limiting membrane, the inflammatory cells infiltrating the
retina and the vitreous and the vascular endothelial cells in vasculitis
lesions. VLA-4 and LFA-1 are expressed on both T and non T cells,
VLA-4 sparsely and LFA-1 ubiquitously.
Conclusions: This work provides the first full description of ICAM-1
expression in the retina during EAU and the first study of VLA-4
and LFA-1 membrane expression on uveitogenic cells. As previously
shown for VCAM-1, ICAM-1 expression develops simultaneously
with uveitis and correlates with the severity of the disease. However,
VCAM-1 and ICAM-1 have a distinct intraocular distribution.
VCAM-1 seems most strongly expressed on the internal BRB while
ICAM-1 predominates on the external BRB. ICAM-1 and VCAM-1
may thus represent differential entry pathways for inflammatory cells
during EAU.
Commercial Relationships: Deborah Lipski, None; Remi
Dewispelaere, None; Ariane Frère, None; Laure E. Caspers, None;
Catherine Bruyns, None; François Willermain, None
Program Number: 5307 Poster Board Number: C0125
Presentation Time: 3:45 PM–5:30 PM
Behavioural conditioning of immune response with cyclosporine
A in a model of experimental autoimmune uveitis (EAU)
mitigates Th1 immune response but antagonizes Th17 responses
Dirk Bauer1, Martin Busch1, Lena Bagnewski1, Maren Hennig1,
Hanna Bähler1, Manfred Schedlowski3, Solon Thanos2, Arnd
Heiligenhaus1. 1Ophtha-Lab, Department of Ophthalmology at St.
Franziskus Hospital, Münster, Germany; 2Institute of Experimental
Ophthalmology, Westfalian-Wilhelms-University of Münster,
Münster, Germany; 3Institute of Medical Psychology and Behavioral
Immunobiology, University Hospital Essen, Essen, Germany.
Purpose: To examine the influence of behavioural conditioning
with cyclosporine A (CsA) on the outcome of Th1/Th17 driven
experimental autoimmune uveoretinitis (EAU) in B10.RIII mice.
Methods: Animals were placed on a water deprivation regimen. On
day 10, the conditioning procedure started: Mice received a 0.2%
w/v saccharin solution as conditioned stimulus combined with CsA
(20 mg/kg) in six association trials with 72h intervals. For evocation,
conditioned mice were re-exposed to saccharin, whereas the shamconditioned group received water only. The evocation trials were
pursued until the end of the experiment.
After the third evocation trial (day 31), all animals were immunized
with hIRBPp161-180 peptide in CFA and a concomitant injection
of pertussis toxin. One hour after the last evocation (day 51, +1h)
the animals were sacrificed; eyes were collected for histology;
©2014, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2014 Annual Meeting Abstracts
splenocytes were cultured, and analyzed by ELISA for various
cytokines.
Results: Behavioural conditioned and evocated mice had no
improvement of EAU with respect to incidence and severity of
disease. ELISA analysis revealed that the Th1 response of mice
was reduced with a shift towards Th2 and Th17 cytokine profiles.
Adoptive transfer of antigen-specific splenocytes from conditioned
and evocated mice to healthy mice resulted in a decreased severity of
EAU as compared to the control group.
Conclusions: We conclude that conditioning of immune responses
with CsA mitigates Th1 but maintains Th17 autoimmune responses
and does not improve Th1/Th17 mediated EAU. Thus, behavioural
conditioning may regulate the immune mechanism of autoimmune
diseases.
Commercial Relationships: Dirk Bauer, None; Martin Busch,
None; Lena Bagnewski, None; Maren Hennig, None; Hanna
Bähler, None; Manfred Schedlowski, None; Solon Thanos, None;
Arnd Heiligenhaus, None
Support: DOG
Program Number: 5308 Poster Board Number: C0126
Presentation Time: 3:45 PM–5:30 PM
Use of dexamethasone implant for refractory CME secondary to
uveitis
Nikolaos Krassas, Natasha Spiteri, Nicholas Beare, Ian A. Pearce.
St Paul’s Eye Unit, Royal LIverpool University Hospital, Liverpool,
United Kingdom.
Purpose: To report effectiveness and safety of dexamethasone
implant (Ozurdex) in refractory uveitic cystoid macular edema
(CME) cases.
Methods: Retrospective case note review of consecutive cases
of CME in a tertiary uveitis referral service managed with 700μg
intravitreal dexamethasone implant. Patients with intraocular pressure
(IOP) greater than 25mmHg or who had a previous significant IOP
rise following peri- / intra-ocular steroid were not considered for this
treatment.
Results: Fourteen eyes of nine uveitis patients with refractory
CME were identified. All were on systemic immunosuppression
(diagnosis intermediate uveitis = 5, birdshot chorioretinopathy =
1, anterior uveitis with CME = 2, idiopathic non-occlusive retinal
vasculitis = 1). In all patients the CME had an unsatisfactory response
to peri- and/or intra-ocular triamcinolone; four patients were also
refractory to intravitreal methotrexate, and four patients to intravitreal
bevacizumab.
The mean age was 47.9 years, mean pre-operative central foveal
thickness (CFT) was 539μm and mean pre-operative LogMAR visual
acuity was 0.55. The mean change in CFT after a single intravitreal
dexamethasone implant was -280μm (SD = 172μm), mean change
in LogMAR visual acuity was -0.28 (SD = 0.23). Eight of 14 eyes
gained two lines of Snellen visual acuity after a single injection. Ten
eyes had repeat dexamethasone implants and the mean time to the
first repeat injection was 7.75 months (range 4.25 -16 months).
There were no cases of endophthalmitis and seven eyes had cataract
surgery following dexamethasone implant. The mean change in IOP
was +1.3 mmHg and none of the patients required any additional
IOP-lowering treatment or surgery following the intravitreal
dexamethasone implant.
Conclusions: In our tertiary uveitis service the introduction of the
intravitreal dexamethasone implant has had a substantial impact on
the management of refractory CME. The dexamethasone implant is
well tolerated, leads to significant reduction in CME and significant
visual improvement in 60% of complex uveitic cases with CME.
Our data suggests it remains effective for more than 6 months in the
majority of cases.
Commercial Relationships: Nikolaos Krassas, None; Natasha
Spiteri, None; Nicholas Beare, None; Ian A. Pearce, None
Program Number: 5309 Poster Board Number: C0127
Presentation Time: 3:45 PM–5:30 PM
Risk of Leaving the Workforce in Non-infectious Uveitis
Namita Tundia1, Martha Skup1, Rachael Sorg2, Dendy Macaulay2,
Jingdong Chao1, Parvez Mulani1, Jennifer E. Thorne3. 1AbbVie Inc.,
North Chicago, IL; 2Analysis Group, Inc., New York, NY; 3Johns
Hopkins School of Medicine, Baltimore, MD.
Purpose: Non-infectious uveitis (NIU) is a spectrum of diseases
characterized by intraocular inflammation of uvea that may cause
disabling visual impairment. We assessed risk of leaving the
workforce among privately insured US employees with non-anterior
NIU compared with matched controls.
Methods: Patients aged 18–64 with ≥2 occurrences of diagnoses
of non-anterior NIU (ICD-9: 360.12, 362.12, 362.18, 363.0x,
363.10-363.13, 363.15, 363.2x, 364.24) from 1/1/1998 to 3/31/2012
were identified in the OptumHealth claims database. Patients had
continuous eligibility for ≥6 months before their first non-anterior
NIU diagnosis (index date). Patients with non-anterior NIU (cases)
were matched 1:1 by age, sex, region, employment status, and
company to controls without a diagnosis of uveitis (infectious or noninfectious). Patients were actively employed on the index date and
were followed until loss of insurance eligibility or until age 65. Risks
of leaving the workforce (leave of absence, early retirement, shortterm disability, or long-term disability) were compared between cases
and controls using time-to-event Kaplan-Meier analysis and Cox
proportional hazard regressions adjusting for baseline characteristics.
Results: Cases and controls (N=776 each) were 61.9% male; mean
age was 44.7 years. In unadjusted Kaplan-Meier analyses, risk of
leaving the workforce was significantly higher in cases vs. controls
(P=.0069); risk among cases at 5- and 10-years was 31.3% and
43.9% while that among controls was 23.4% and 33.1%, respectively
(figure). Risks of leave of absence at 5- and 10-years were 14.9%
and 19.8% for cases vs. 10.5% and 12.9% for controls; risk of longterm disability at 5- and 10-year were 3.7% and 6.0% for cases vs.
1.2% and 2.8% for controls (all comparisons P<.05). Risk of early
retirement and short-term disability were also greater for NIU vs.
controls; however, differences in time to early retirement and time to
short-term disability were not statistically significant. Results were
supported by regression analysis; cases were significantly more likely
to leave the workforce over the course of follow-up vs. controls
(adjusted hazard ratio=1.27, 95% CI=1.01–1.59, P=.039).
Conclusions: Compared with matched controls, patients with NIU
were more likely to leave the workforce. Substantial burden due to
loss of workforce participation is associated with NIU.
©2014, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2014 Annual Meeting Abstracts
Risk of Leaving the Workforce
Commercial Relationships: Namita Tundia, AbbVie (E), AbbVie
(I); Martha Skup, AbbVie (E), AbbVie (I); Rachael Sorg, AbbVie
(F), Analysis Group (E); Dendy Macaulay, AbbVie (F), Analysis
Group (E); Jingdong Chao, AbbVie (E), AbbVie (I); Parvez
Mulani, AbbVie (E), AbbVie (I); Jennifer E. Thorne, AbbVie (C),
Allergan (F), Gilead (C), NEI (F), NIAID (F), RPB (F), The Wilmer
Eye Institute, Johns Hopkins School of Medicine (E), XOMA (C)
Support: Financial support for the study was provided by AbbVie.
AbbVie participated in the interpretation of the data, review, and
approval of the abstract. All authors contributed to the development
of the abstract and maintained control over the final content. Eric
Bertelsen, of Arbor Communications, Inc., provided medical writing
and editing services in the development of this abstract. Financial
support for these services was provided by AbbVie.
Program Number: 5310 Poster Board Number: C0128
Presentation Time: 3:45 PM–5:30 PM
INFLUENCE OF THE VITREOMACULAR INTERFACE
ON THE EFFICACY OF INTRAVITREAL THERAPY FOR
UVEITIS-ASSOCIATED CYSTOID MACULAR EDEMA
Radha Ram1, Marion R. Munk1, 3, Vikram J. Setlur2, Alfred
Rademaker4, Dachao Liu4, Ursula Schmidt-Erfurth3, Felix Chau2,
Debra A. Goldstein1. 1Ophthalmology, Northwestern University,
Chicago, IL; 2Ophthalmology, University of Illinois, Chicago, IL;
3
Ophthalmology, Medical University Vienna, Vienna, Austria;
4
Preventive Medicine, Northwestern University, Chicago, IL.
Purpose: To evaluate the effect of the vitreomacular interface on
treatment efficacy of intravitreal therapy of uveitis-associated cystoid
macular edema (CME)
Methods: Retrospective analysis of CME resolution, CME
recurrence rate, monthly course of visual acuity (VA), and central
retinal thickness (CRT) after therapeutic intravitreal injection with
respect to configuration of the vitreomacular interface (VMI) on
OCT. Non-parametric data were compared with Chi-Quadrat test.
Differences in distance VA and CRT were evaluated with one-way
ANOVA.
Results: 59 eyes of 55 patients (47.4±17.7years) were included. 29%
had anterior uveitis, 40% intermediate uveitis, 11% posterior uveitis
and 20% panuveitis. Mean CME duration was 33±31months. 66%
received Intravitreal triamcinolone acetonide, 5% methotrexate, 17%
dexamethasone bioerodible implant, and 12% bevacizumab. 39% had
posterior vitreous detachment (PVD), 46% vitreomacular adhesion
(VMA), 2% vitreomacular traction (VMT), and 13% posterior
vitreous attachment (PVA). 64% had epiretinal membranes, however
the presence of this confounding factor was equally distributed within
groups. 38% showed persistent CME after injection, and 22% had
CME relapse within the first 4 months and were retreated.
Improvement of vision did not differ among groups (p=0.98) at 1, 2,
and 3 months post-injection. The total central retinal thickness (CRT)
decrease also did not differ among groups (p=0.29). However, the
percentage of patients experiencing a ≥20% CRT-thickness decrease
differed according to vitreomacular interface group (p=0.027): 83%
of the PVD patients had a more than 20% CRT decrease, whereas
only 64% and 16% of the VMA and the PVA groups experienced a
more than 20% CRT decrease after intravitreal injection, respectively.
The percentage of patients showing persistent CME did not differ
among the groups (p=0.18), nor did the relapse rate (p=0.21) nor time
until CME relapse (p=0.18).
Conclusions: The configuration of the VMI seems to be a factor
contributing to treatment efficacy in uveitis-associated CME;
nevertheless the functional VA outcome parameters did not differ
according to VMI status. This is the first study showing an effect of
the VMI on treatment response in uveitis, but further studies with
larger patient populations are warranted to investigate this effect.
Commercial Relationships: Radha Ram, None; Marion R. Munk,
None; Vikram J. Setlur, None; Alfred Rademaker, None; Dachao
Liu, None; Ursula Schmidt-Erfurth, Alcon Labaratory Inc (F),
Bayer Health Care (F), Novartis (F); Felix Chau, None; Debra A.
Goldstein, None
Support: N/A
Program Number: 5311 Poster Board Number: C0129
Presentation Time: 3:45 PM–5:30 PM
Multimodal Imaging of lesions in Birdshot Chorioretinopathy
Allison R. Soneru1, Marion R. Munk1, Phoebe Lin2, Amani A. Fawzi1,
Debra A. Goldstein1. 1Ophthalmology, Northwestern Ophthalmology,
Chicago IL, IL; 2Ophthalmology, Oregon Health and Sciences
University, Portland, OR.
Purpose: To describe two different types of chorioretinal lesions in
birdshot chorioretinopathy using multimodal imaging techniques
Methods: Data was collected retrospectively on 34 eyes of 17
patients (15 women and 2 men) seen from 2008 to 2013 diagnosed
with Birdshot Chorioretinopathy (BSCR). Their lesions were imaged
using fundus photos, blue fundus autofluorescence (FAF) (488nm),
near infra-red (NIR)-FAF (788nm), Infrared, Red-free, Spectralis SDOCT and EDI-OCT.
Results: The patients’ ages ranged from 44 to 68 years (mean age
57.8). They were imaged over a period of time ranging between a
single visit and 5.5 years. All 17 of these patients presented clinically
with deep choroidal lesions, whereas a subset of five of these patients
(29%) also exhibited superficial, punched-out lesions compromising
the integrity of the outer retina and the retinal pigment epithelium
(RPE). These lesions were hypoautofluorescent in FAF and NIRFAF and hyperreflective in infrared and red-free. On SD-OCT the
superficial lesions demonstrated RPE-atrophy and disruption of the
ellipsoid band and the interdigitation zone with focal enhancement of
the choroidal signaling. The typical deep choroidal lesions, however,
©2014, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2014 Annual Meeting Abstracts
were not readily visible on any imaging techniques except fundus
photography, unless the overlying RPE atrophied. However, some
of the lesion corresponded to hyperreflective changes in the Sattler’s
layer and the choriocapillaris in EDI-OCT. Once there was associated
RPE-atrophy however, the deeper lesions were hypoautofluorescent,
the Red free showed corresponding subtle hyperreflectivity and the
SD-OCT revealed RPE atrophy and enhanced choroidal reflectivity
due to increased signal penetration.
Conclusions: Patients with BSCR may present with two different
lesion types (choroidal vs. outer retinal), a distinction never before
made in the literature. The two distinct lesions are best imaged by a
multimodal imaging approach. However, the clinicopathological and
prognostic correlates of the two lesions needs to be further evaluated.
Commercial Relationships: Allison R. Soneru, None; Marion R.
Munk, None; Phoebe Lin, None; Amani A. Fawzi, None; Debra A.
Goldstein, None
Support: Supported by an unrestricted grant from Research to
Prevent Blindness, New York, NY
Program Number: 5312 Poster Board Number: C0130
Presentation Time: 3:45 PM–5:30 PM
Ocular Manifestations in Patients with Psoriasis and Psoriatic
Arthritis.
Anton M. Kolomeyer1, Ashwinee Ragam2, Natasha V. Nayak1, Sergio
Schwartzman3, David S. Chu2, 4. 1Ophthalmology, UPMC, Pittsburgh,
PA; 2Ophthalmology and Visual Science, Rutgers, Newark, NJ;
3
Rheumatology, HSS, New York, NY; 4Ophthalmology, MERCI,
Palisades Park, NJ.
Purpose: To describe ocular findings in patients with Psoriasis and
Psoriatic arthritis.
Methods: Retrospective chart review of ocular manifestations in
patients with Psoriasis (n=3) and Psoriatic arthritis (n=4). Data was
collected on age, gender, ethnicity, length of follow-up, associated
autoimmune disease, ocular manifestations and surgeries, systemic
immunomodulating agents, ocular medications, and visual acuity
(VA).
Results: Seven patients (12 eyes) were included (mean ± SD
age, 53.1 ± 19.6 years; 57% female; 57% Caucasian; mean ±
SD follow-up, 57.4 ± 61.0 months). Five (71%) patients had an
associated systemic autoimmune disease (Rheumatoid arthritis
[n=3] and Sarcoidosis [n=2]). All seven patients were on systemic
immunomodulating agents (mean ± SD number, 2.1 ± 1.2; range,
1-4). Four (57%) patients required topical corticosteroid therapy
(mean ± SD number, 1.8 ± 1.0; range, 1-3). Mean initial and final
Snellen VA was 20/83 and 20/77, respectively. Ocular manifestations
included panuveitis (n=6 [50%]); scleritis (n=3 [25%]); keratitis,
corneal melt, inflammatory glaucoma, uveitic cataract, uveitic
papillitis, pigmentary retinopathy, and iritis (n=2 [17%] each); and
perforated ulcer, peripheral ulcerative keratitis, epiretinal membrane,
and phthisis (n=1 [8.3%] each). Two (29%) patients underwent
surgical procedures for these complications; one had a bilateral
cataract extraction-intraocular lens placement and a unilateral
glaucoma drainage implant, while another received a bilateral
conjunctival resection with glue or patch grafting.
Conclusions: The breadth and severity of ocular manifestations in
patients with Psoriasis and Psoriatic arthritis are underrecognized.
These involve the anterior and posterior segments, and require
systemic and topical therapy to control. Further studies are necessary
to characterize the long-term effects of ocular disease in patients with
Psoriasis and Psoriatic arthritis.
Commercial Relationships: Anton M. Kolomeyer, None;
Ashwinee Ragam, None; Natasha V. Nayak, None; Sergio
Schwartzman, Abbvie (C), Amgen (C), Genentech (C), Hospira (C),
Janssen (C), Pfizer (C), UCB (C); David S. Chu, Abbvie (F), Alcon
(R), Allergan (F), Bausch and Lomb (R), Genentech (F), Novartis (F),
Santen (F), Xoma (F)
Program Number: 5313 Poster Board Number: C0131
Presentation Time: 3:45 PM–5:30 PM
Electroretinographic Findings in Birdshot Chorioretinopathy:
Associations with Clinical Measures of Visual Function and with
Spectral-domain Optical Coherence Tomography
Christian Boeni, Alla Kukuyev, Leticia Dourado Alves, David Sarraf,
Ralph D. Levinson, Fei Yu, Steven Nusinowitz, Gary N. Holland.
Ophthalmology, Jules Stein Eye Institute, UCLA, Los Angeles, CA.
Purpose: To evaluate associations between full-field and pattern
electroretinographic (ffERG, pERG) responses, best-corrected visual
acuity (BCVA), central color vision, visual field (VF) sensitivity,
and structural abnormalities of the retina (assessed by SD-OCT) in
patients with birdshot chorioretinopathy (BCR).
Methods: In a cross-sectional study, 17 patients with BCR and 44
normal controls received a standardized evaluation, including ffERG
and pERG, which were recorded in accordance with standards set
forth by the International Society for Clinical Electrophysiology
of Vision. Abnormality was defined as a departure of >2SD from
normative values. Central color vision was assessed with the
Lanthony-D15 color test. VF mean deviation (MD) was determined
by Humphrey automated perimetry. Presence or absence of any
structural abnormality (e.g. disintegrity of ellipsoid layer, alteration
of retinal architecture, atrophy, or intraretinal cystoid edema) was
assessed on the macula volume scan by a masked reader.
Results: Response parameters of ffERG and pERG for the group as
a whole differed significantly from control data (all p values<0.05).
Regarding ffERG, 6 eyes (4 patients) had normal rod and cone
function (Group 1); 11 eyes (7 patients) had normal rod and abnormal
cone function (Group 2); 17 eyes (10 patients) had both abnormal
rod and cone function (Group 3). Selective loss of the b-wave
was observed infrequently. No eyes had abnormal rod and normal
cone response. There was a weak association between groups and
median BCVA (1.0, 0.8 and 0.5 for Groups 1, 2, and 3, respectively;
p=0.078). There were statistically significant differences between
Groups 1, 2 and 3 for the following factors: abnormal color vision
(17% [1/6], 64% [7/11], and 94% [16/17], p=0.001); median VF-MD
(-2.6dB, -6.8dB, and -13.0dB, p=0.022); abnormal SD-OCT findings
(33% [2/6], 82% [9/11], and 100% [17/17], p=0.001); and abnormal
pERG parameters (33% [2/6], 100% [11/11], and 88% [15/17],
p=0.003).
Conclusions: The ffERG phenotype is associated with certain
clinical measures of visual function (color, HVF) in people with
BCR. Measures dominated by central cones (pERG, HVF) can
detect dysfunction of vision even when ffERG response parameters
are within normal limits. In addition, SD-OCT may show localized
structural abnormalities in the absence of ffERG changes.
Commercial Relationships: Christian Boeni, None; Alla Kukuyev,
None; Leticia Dourado Alves, None; David Sarraf, Heidelberg (C),
Regeneron (F); Ralph D. Levinson, None; Fei Yu, None; Steven
Nusinowitz, None; Gary N. Holland, None
Program Number: 5314 Poster Board Number: C0132
Presentation Time: 3:45 PM–5:30 PM
Racial Differences in HLA-B27 Associated Anterior Uveitis
Mehrine Shaikh1, Alla Hynes2, Veena Raiji1. 1George Washington
University Hospital, Washington, DC; 2Eye Care Physicians and
Surgeons, PC, Winchester, VA.
©2014, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2014 Annual Meeting Abstracts
Purpose: To report our experience with HLA-B27 related Anterior
Uveitis in our Washington, DC based referral center and specifically
its distribution by race.
Methods: All patients with anterior uveitis between 2007-2009
were identified based on ICD-9 code search. Patients with HLA-B27
related disease were identified and data collected included age, sex,
race (based on patient self-identification), ocular exam findings,
number of recurrences, results of uveitis work-up, systemic comorbidities and therapies employed. Statistical analysis by race was
done using Chi-squared and Fisher’s exact test.
Results: 59 patients with HLA-B27 related anterior uveitis were
seen, 19 African Americans and 40 non-African American. The
average age at presentation of African American patients was
42.2 years and of non-African American patients was 42.4 years.
There were more females in the African American group (63%)
compared with the non-African American group (45%), although
this difference was not statistically significant. 47.4% of African
Americans and 52.5% of non-African Americans had an HLA-B27
associated systemic disease. Final log MAR visual acuity was
0.169 in African Americans and 0.058 in non-African Americans
(p=0.114). Additionally, we noted a trend toward more frequent
cystoid macular edema in our African American patients (10.5%)
compared with our non-African American patients (2.5%), however
this was not statistically significant (p-value 0.24). 58.0% of African
Americans and 7.5% of non-African Americans had hypopyon
(p<0.001). Only 26.3% of African American patients with HLA-B27
related anterior uveitis were diagnosed with the HLA-B27 antigen
prior to presentation to our clinic, requiring work-up and subsequent
diagnosis with HLA-B27 antigen positivity by our service in 73.7%
of African Americans compared with 23.5%% of non-African
American patients.
Conclusions: In our study both African American and non-African
Americans had associated HLA-B27 systemic disease at similar rates.
African Americans had a trend toward poorer visual outcomes and
were more likely to have hypopyon. This underlines the necessity
for casting a wide diagnostic net in patients with anterior uveitis
without attention to racial background. The relationship between the
HLA-B27 antigen and anterior uveitis varies amongst races and may
be changing due to the increasing heterogeneity of our population.
Commercial Relationships: Mehrine Shaikh, None; Alla Hynes,
None; Veena Raiji, None
Program Number: 5315 Poster Board Number: C0133
Presentation Time: 3:45 PM–5:30 PM
Peripapillary Atrophy in Chronic Vogt-Koyanagi-Harada Disease
Pooja Bhat, Anjali Parekh, Lana M. Rifkin, Debra A. Goldstein.
Department of Ophthalmology, Northwestern Memorial Hospital,
Feinberg School of Medicine, Chicago, IL.
Purpose: Vogt-Koyanagi-Harada disease (VKH) is characterized by
granulomatous panuveitis, exudative retinal detachment, papillitis
in the acute phase and sunset glow fundus, retinal pigment epithelial
migration, and atrophic chorioretinal lesions during the chronic
convalescent phase. The chronic phase may have peripapillary
atrophy (PPA) and neuroretinal rim (NRR) thinning. Patients with
VKH with greater choroidal thickness at presentation are at higher
risk of developing PPA (1). Most patients with non-glaucomatous
optic neuropathies do not exhibit NRR thinning, optic disc cupping
and PPA except for arteritic- anterior ischemic optic neuropathy
(A-AION) (2). The purpose of this study is to evaluate optic nerve
head changes in chronic VKH compared to glaucomatous optic
neuropathy.
Methods: Retrospective review of patients with chronic VKH,
including demographics, NRR status and PPA as assessed by disc
photos, and visual fields.
Results: 30 eyes of 15 patients were included. Mean age was 45
years (15-70), 11 were female. 4 were Hispanic, 2 African American,
and 9 Caucasian. 26 eyes revealed PPA. Of these 26 eyes, 15 had
NRR loss. PPA was not greater in areas of rim thinning. Visual fields
were available in 11 eyes with PPA. Only 5 had typical glaucomatous
field loss corresponding to NRR loss. The other 6 had field changes
inconsistent with NRR loss and cupping.
Conclusions: To date, NRR loss and PPA have been described only
in glaucomatous optic neuropathies and in A-AION. In this study,
87% of eyes with chronic VKH exhibited PPA. Of these eyes, only
57% exhibited significant NRR loss and >50% of eyes with PPA had
field changes that did not correspond to NRR loss. These findings
are important, as optic neuropathy in VKH may be secondary to
an inflammatory vascular event akin to A-AION, different from
mechanical and vascular mechanisms postulated in the pathogenesis
of glaucomatous optic neuropathy.
References
1. Nakayama M, Keino H, Okada AA, Watanabe T, Taki W, Inoue M,
Hirakata A Enhanced depth imaging optical coherence tomography
of the choroid in Vogt-Koyanagi-Harada disease. Retina 2012 NovDec;32 (10):2061-2069.
2. Hayreh SS, Jonas JB (2001) Optic disc morphology after arteritic
anterior ischemic optic neuropathy. Ophthalmology 108 (9):15861594.
Commercial Relationships: Pooja Bhat, None; Anjali Parekh,
None; Lana M. Rifkin, None; Debra A. Goldstein, None
Support: Research to Prevent Blindness, NY
Program Number: 5316 Poster Board Number: C0134
Presentation Time: 3:45 PM–5:30 PM
Clinic & Treatment of Tubulo-Interstitial Nephritis and Uveitis
Syndrome (TINU)
Tarek Bayyoud, Christoph M. Deuter, Bianka Sobolewska, Manfred
Zierhut. Ophthalmology, Eberhard-Karls-University, Tuebingen,
Germany.
Purpose: To study complications and therapy of patients with
Tubulointerstitial nephritis and uveitis (TINU) syndrome over a
prolonged period.
Methods: Retrospective observational study of 9 patients with
TINU-Sydrome. All patients had standardized clinical and
ophthalmological assessments. Diagnosis of TINU was confirmed
via beta-2 microglobuline determination in urine (n= 8) and/or renal
biopsy (n= 1).
Results: Nine patients (5 female and 4 male) with TINU-Syndrome
were followed up for a mean of 44.1 months (range 6-113 months).
The mean age at diagnosis was 16.7 years (range 9-43 years). The
anatomical diagnosis was bilateral anterior (5 patients), intermediate
(3 patients) and panuveitis (1 patient). Complications involved
were increased intraocular pressure due to a response to steroids (1
patient), development of optic disc edema (2 patients) and cystoid
macular edema (2 patients). The treatment consisted in a stepladder
approach beginning with local steroids (9 patients), systemic steroids
(7 patients), immunosuppression (2x MTX, 1x Mycophenolic acid
and 1x Mycophenolate mofetil) and anti-TNF alpha blocking agents
(adalimumab; 2 patients). The number of relapses ranged between
0 and 7 (mean 1.9; 0: n= 2, 1-3: n= 6, 7: n= 1). The response to the
final, adjusted regimen was quite acceptable and the patients could
have been kept in prolonged periods of remission.
Conclusions: In this study, analyzing the course of TINU patients
for a prolonged period, we found 3 of 9 patients with intermediate
©2014, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2014 Annual Meeting Abstracts
uveitis and also one patient with panuveitis. Topical and/ or
systemic corticosteroids were effective in 5 patients, while 4
received immunosuppression or biologicals. In our study TINU was
characterized by reduced responsiveness to corticosteroid therapy and
less by severe complications.
Commercial Relationships: Tarek Bayyoud, None; Christoph M.
Deuter, None; Bianka Sobolewska, None; Manfred Zierhut, None
Program Number: 5317 Poster Board Number: C0135
Presentation Time: 3:45 PM–5:30 PM
Epidemiological characteristics of Sympathetic Ophthalmia
PABLO J. GUZMAN-SALAS, Ethel B. Guinto-Arcos, Miguel
Pedroza-Seres. INSTITUTO DE OFTALMOLOGIA “CONDE DE
VALENCIANA“, Mexico City, Mexico.
Purpose: Report the number of patients with Sympathetic
Ophthalmia, attending a Uveitis Department in a period of time, and
analyze different epidemiological characteristics of this disease.
Methods: Retrospective case series study in one academic
tertiary care uveitis department with 20 patients with Sympathetic
Ophthalmia from 2007 to 2013. We reviewed medical records from
patients of Instituto de Oftalmologia “Conde de Valenciana“ in
Mexico. We collected information of: gender, age, symptoms, type
of event: trauma or surgery (type of surgery), time from event to
onset of symptoms, visual acuity in both eyes in their first and last
consultation, clinical findings, treatment received and progression of
inciting eye to ptisis bulbi.
Results: We analyzed 20 patients, with average age of 50±19.33
years, with 65% being males. With 50% trauma, 50% surgery
distribution regarding the initial event in the inciting eye. In surgery,
40% of patients had Phacoemulsification with intraocular lens
implantation, 25% had unspecified Retinopexy procedure, and 35%
got other surgical procedures. 60% of patients had a right inciting
eye. 100% of cases seek consultation because of decreased vision in
the sympathizing eye. Time between injury and onset of symptoms
had and average of 104.45±134.41 months. 75% of patients had
vision between no light perception and LogMAR 3 initially in the
inciting eye, with a final vision in 90% between no light perception
and LogMAR 3. Visual acuity in the sympathizing eye initially 50%
between LogMAR 0 and LogMAR 0.60; the other 50% between
LogMAR 0.70 and LogMAR 3. In the final visit, 60% had vision
between LogMAR 0 to LogMAR 0.30. Clinical findings were
variable, 100% patients showed mutton-fat keratic precipitates and
anterior chamber reaction, followed by vitreitis in 60% of cases.
20 patients received Prednisolone drops, an at least 45% of cases
received Methotrexate, Azathioprine or Cyclophosphamide.
Conclusions: This information helped us to better understand
epidemiological characteristics of Sympathetic Ophthalmia. We had
a predominant male population in their fifties, with equal distribution
of trauma versus surgery, that had bad visual acuities in the inciting
eye that tends to get worse, an a bad visual acuity that appears to get
better with time and treatment in the sympathized eye in most cases.
This is an important study because it is the first one to analyze a
series of cases with this disease in Mexico.
Commercial Relationships: PABLO J. GUZMAN-SALAS, None;
Ethel B. Guinto-Arcos, None; Miguel Pedroza-Seres, None
Purpose: To determine whether variations exist in the geographic
distribution of uveitis diagnoses seen at a regional referral center.
Methods: Retrospective review of cases seen between 2007 and
2009 inclusive at the University of Alabama at Birmingham, a
tertiary referral center. De-identified zip code data was matched with
diagnoses and anatomical categorization. Google Fusion Tables and
Batchgeo.com were used to construct geographic representations
of the distribution of uveitis diagnoses and anatomical disease
categories.
Results: 412 patients had clinical data and a matching zip code
available. Of these, 279 were female (68%), 178 were African
American (43%), 224 were Caucasian (54%), and the remainder
were Latino, Asian, or of mixed heritage. Anterior uveitis comprised
252 (61%) of cases, 40 were intermediate or anterior & intermediate
(9.7%), 47 were posterior uveitis (11%), and 73 (18%) were
panuveitis. The geographic distribution of anatomical category
varied by zip code, with the urban areas closest to the study center
having more anterior disease, while individuals from urban areas
more distant had a greater proportion of anatomical cases of other
than anterior disease (Figure 1). Idiopathic disease was the most
common “diagnosis” in all geographic areas, but the make up of other
diagnoses varied, though in no specific pattern (Figure 2).
Conclusions: The anatomical category of uveitis presenting to a
regional referral center appears to vary based on the distance from
the referral center the patient lives. Possible explanations for this are
that anterior disease may be considered milder and thus not worthy
of distant referral by the local treating physician; that patients with
anterior disease distant from the referral center may have more
difficulty in or be more resistant to travel; that ethnic clustering
of populations results in similar clustering of diagnoses; or that
geography, with its attendant variations in environmental exposure
and genetic makeup of it population, does result in a difference in
disease.
Program Number: 5318 Poster Board Number: C0136
Presentation Time: 3:45 PM–5:30 PM
Geographic Variations in Referrals to a Tertiary Uveitis Center in
the Southeast United States
Russell W. Read, Kinley Beck. Ophthalmology, University of
Alabama at Birmingham, Birmingham, AL.
©2014, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2014 Annual Meeting Abstracts
Geographic distribution of uveitis cases by anatomical category.
Legend, Red = Anterior, Blue = Panuveitis, Green = Posterior, Yellow
= Anterior and Intermediate, Purple = Intermediate.
Geographic distribution of associated diagnosis. Legend, Red =
Idiopathic, Blue = HLA-B27, Green = HZO, Yellow = Persistent
postoperative, Purple = Sarcoid, Light Blue = Juvenile arthritis.
Commercial Relationships: Russell W. Read, None; Kinley Beck,
None
Support: Research to Prevent Blindness; EyeSight Foundation of
Alabama, Matthews Family Foundation
Program Number: 5319 Poster Board Number: C0137
Presentation Time: 3:45 PM–5:30 PM
Ocular complications in juvenile idiopathic arthritis associated
uveitis patients on TNF inhibitor therapy
Ann-Marie Lobo1, Sepideh Faez1, Mindy Lo2, George N. Papaliodis1,
Danielle M. Ledoux3. 1Department of Ophthalmology, Harvard
Medical School, Massachusetts Eye and Ear Infirmary, Boston, MA;
2
Department of Rheumatology, Children’s Hospital, Boston, MA;
3
Department of Ophthalmology, Children’s Hospital, Boston, MA.
Purpose: Juvenile idiopathic arthritis (JIA) associated uveitis is
the most common cause of childhood uveitis and is associated
with significant ocular morbidity. Advances in therapy, including
tumor necrosis factor (TNF) alpha inhibitors, have improved visual
outcomes and control of ocular inflammation in severe JIA uveitis.
This study examines ocular complications and rate of development of
complications in patients treated with standard immunosuppressive
therapy and TNF inhibitor therapy.
Methods: A retrospective chart review of all patients diagnosed
with JIA uveitis in the Uveitis Service at Massachusetts Eye and
Ear Infirmary and the pediatric ophthalmology service at Children’s
©2014, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2014 Annual Meeting Abstracts
Hospital Boston between 2006 and 2012 was performed. Data from
baseline visit, visits at 6 months, 1, 2 and 3 years were obtained for
each patient. For patients on TNF inhibitor therapy, baseline visit was
defined as the visit prior to starting TNF inhibitor therapy or initial
visit (for patients already on TNF inhibitor therapy).Visual acuity,
medications, ocular complications, inflammation grade, and flares
since last visit were recorded. Inclusion criteria were: diagnosis of
JIA prior to age 16 with documented uveitis and follow up period
greater than 6 months.
Results: 46 patients (83 eyes) with JIA uveitis met the inclusion
criteria. 23 patients were on TNF inhibitor therapy and 23 were
on other systemic anti-inflammatory therapy. 74% of patients
were female and 75% were ANA positive. Median age at uveitis
presentation was 3 years in the TNF group and 4 in the non-TNF
group. At baseline visit, there was no significant difference in
complication rates between the TNF and non-TNF groups (p=0.53,
CI 0.45-4.67). The rate of development of any complication was
significantly higher in the TNF group at 0.12/person-year than
the non-TNF group at 0.03/person year (p=0.04). The rate of
development of cataract was significantly higher in the TNF group at
0.06/eye-year than the non-TNF group at 0.01/eye-year (p=0.04).
Conclusions: JIA uveitis patients with recalcitrant uveitis are often
treated with TNF inhibitors. Although these medications control
inflammation, patients on TNF inhibitors are still at higher risk for
developing ocular complications. Disease duration and severity of
inflammation may contribute to higher complication rates in these
patients.
Commercial Relationships: Ann-Marie Lobo, None; Sepideh
Faez, None; Mindy Lo, None; George N. Papaliodis, None;
Danielle M. Ledoux, None
Support: Lions Eye Research Fund
Program Number: 5320 Poster Board Number: C0138
Presentation Time: 3:45 PM–5:30 PM
Direct and Indirect Resource Use and Costs Associated With
Non-Infectious Non-Anterior Uveitis
Jennifer E. Thorne1, Namita Tundia2, Martha Skup2, Dendy
Macaulay3, Cindy Revol3, Jingdong Chao2, Parvez Mulani2,
Andrew D. Dick4. 1Ophthalmology, Johns Hopkins Wilmer Eye Inst,
Baltimore, MD; 2AbbVie Inc., North Chicago, IL; 3Analysis Group,
Inc., New York, NY; 4University of Bristol, Bristol, United Kingdom.
Purpose: Non-infectious uveitis (NIU) can cause visual impairment
and as a result may incur an extensive economic burden to society.
We assessed direct (medical service and prescription drug) and
indirect (work loss) resource use and costs of privately insured US
employees with non-anterior NIU and compared them to matched
controls.
Methods: Employees 18–64 years old with ≥2 visits for non-anterior
NIU (intermediate-, posterior- or pan-uveitis: ICD-9: 360.12, 362.12,
362.18, 363.0x, 363.10-13, 363.15, 363.2x, 364.24) from January
1, 1998 to March 31, 2012 were identified in the OptumHealth
claims database. Employees had continuous eligibility ≥6 months
before (baseline period) and 1 year after (study period) a randomly
selected non-anterior NIU diagnosis (index date). Non-anterior NIU
patients (cases) were matched 1:1 by sex, age, region and index date
to controls without a diagnosis of uveitis. Direct resource use and
costs associated with inpatient stays; emergency department (ED),
outpatient and ophthalmologist/optometrist visits; and prescription
drugs were calculated. Indirect resource use and costs associated with
work loss resulting from disability and medically-related absenteeism
also were calculated. All costs were adjusted to 2012 US dollars
(USD). Direct/indirect resource use and costs incurred during the
study period were compared between the 2 cohorts using Wilcoxon
signed-rank or McNemar tests. Multivariate regression assessed key
cost differences between cases and controls, adjusting for baseline
characteristics.
Results: 705 cases and 705 matched controls met the selection
criteria (mean age, 45 years; 62.6% men). Cases had a significantly
(P<0.05) higher number of mean visits compared to controls: ED
(0.4 vs 0.2) and outpatient (16.5 vs 7.6) visits during the study
period. Cases also used more prescription drugs (7.8 vs 4.1) and had
more mean disability (10.3 vs 4.6), medically related absenteeism
(8.5 vs 3.8), and total work loss days (18.7 vs 8.4) than controls (all
comparisons P<0.05). Total direct and indirect costs were higher
in cases than in controls, both in unadjusted (Figures 1 and 2) and
adjusted results.
Conclusions: Non-anterior NIU is associated with substantial direct
and indirect costs. More effective therapies may reduce this economic
burden.
Commercial Relationships: Jennifer E. Thorne, AbbVie (C),
Allergan (F), Gilead (C), NEI (F), NIAID (F), RPB (F), XOMA (C);
Namita Tundia, AbbVie (E), AbbVie (I); Martha Skup, AbbVie
(E), AbbVie (I); Dendy Macaulay, AbbVie (C), Analysis Group
(E); Cindy Revol, AbbVie (C), Analysis Group (E); Jingdong
Chao, AbbVie (E), AbbVie (I); Parvez Mulani, AbbVie (E),
AbbVie (I); Andrew D. Dick, University of Bristol and Institute of
Ophthalmology, UCL (E)
Support: Research to Prevent Blindness Sybil B. Harrington Special
Scholars Award
Program Number: 5321 Poster Board Number: C0139
Presentation Time: 3:45 PM–5:30 PM
Indocyanine Green Angiography (ICGA) for the Detection of
Disease Progression or Recurrence in Uveitis
William R. Tucker, Nirali Bhatt, Monica D. Dalal, Wendy M. Smith,
Dominic Obiyor, Robert B. Nussenblatt, H Nida Sen. National Eye
Institute, National Institutes of Health, Bethesda, MD.
Purpose: To report the longitudinal ICGA findings of non-infectious
uveitis patients enrolled in a clinical trial.
Methods: Patients with an established diagnosis of intermediate,
posterior or panuveitis entered a one-year prospective clinical trial.
Uveitis had to be clinically quiescent at entry on high dose steroid
therapy, which was then tapered to low dose with concomitant study
medication. Unless contraindicated ICGA was performed alongside
fluorescein angiogram (FA) at baseline and closure visits as well as
at 5 follow-up study visits. ICGA was run with a standard protocol
on a Heidelberg Spectralis and assessed for these recognized ICG
©2014, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2014 Annual Meeting Abstracts
characteristics of posterior uveitis; optic disc and early stromal
choroidal vessel hyperfluorescence, choroidal vasculitis and
hypofluorescent lesions during intermediate and late phases.
Results: Thirty-one patients were identified, 2 patients could not
receive ICGA due to allergy and were excluded from further analysis.
Female:male split was 20:9 with a mean age of 45 years (range 1964). Average uveitis duration was 67 months (range 3 -300).
Among the 29 patients, 24 had posterior or panuveitis [5 birdshot
chorioretinopathy (BCR), 5 Vogt-Koyanagi-Harada (VKH) disease,
10 sarcoidosis associated panuveitis, 4 idiopathic panuveitis] and 5
had intermediate uveitis (IU). All IU patients had normal baseline and
follow-up ICGA.
At baseline 24/24 posterior/panuveitis patients (100%) demonstrated
hypofluorescent dark lesions/spots but no other characteristic ICGA
findings. During steroid taper 20 of these 24 (83.3%) experienced
an inflammatory flare detected on either clinical examination or FA
while only 6 of the 24 (25.0%) (4 BCR, 1 VKH, 1 Sarcoid panuveitis)
demonstrated an increase in ICGA hypofluorescent lesions at the
time of flare. These changes were particularly dramatic in the BCR
patients.
Conclusions: Confirming its utility in initial diagnosis ICGA
demonstrated characteristic signs at baseline in the majority
of posterior/panuveitis patients. Only in a minority of patients
experiencing a clinically detectable disease flare over follow-up, did
these hypofluorescent ICGA spots increase in size or number. This
ICGA activity correlated with contemporaneous FA and clinical
findings so that no disease recurrence or progression was detected
with ICGA alone during this year long trial involving over 200 ICGA
procedures.
Commercial Relationships: William R. Tucker, None; Nirali
Bhatt, None; Monica D. Dalal, None; Wendy M. Smith, None;
Dominic Obiyor, None; Robert B. Nussenblatt, None; H Nida Sen,
None
Support: This study was supported by the National Eye Institute
Intramural Research Program
Clinical Trial: NCT01195948
Program Number: 5322 Poster Board Number: C0140
Presentation Time: 3:45 PM–5:30 PM
Findings in Multiple Sclerosis associated Uveitis
Friederike Mackensen1, Lena Hildebrandt1, Wyatt Messenger2,
Phoebe Lin2, 4, Eric B. Suhler2, 4, James T. Rosenbaum2, 3.
1
Ophthalmology, Interdisciplinary Uveitis Center, Heidelberg,
Germany; 2Ophthalmology, Casey Eye Institute, Portland, OR;
3
Ophthalmology, Legacy Devers Eye Institute, Portland, OR;
4
Ophthalmology, Portland VA medical center, Portland, OR.
Purpose: About 1% of patients with Multiple Sclerosis (MS) have
uveitis and about 10% of patients with intermediate uveitis have MS.
Uveitis subtypes associated with MS are variable and not restricted
to intermediate uveitis. We describe the largest reported series of
patients with uveitis in association with MS in order to characterize
the uveitis subtypes and to determine if a diagnosis of uveitis has
clinical implications in MS.
Methods: Retrospective chart review of patients with a diagnosis
of MS and uveitis identified in the electronic database of 2 uveitis
centers (Heidelberg, Germany and Portland, OR, USA).
Results: We identified 167 patients with MS and uveitis; charts
were available of 162. Among them 122 (75%) were female and
the mean age at first presentation for uveitis was 42 years (range 13
-70). Anatomic localization was anterior or anterior to intermediate
in 21 and 19 respectively, resulting in 22.5% anterior uveitis (AU).
Intermediate uveitis (IU) was seen in 109 (65%) of patients. There
were patients with scleritis, panuveitis and no location given (each
n=3) and 4 with posterior uveitis.
Information on the subtype of MS was available for 55 patients:
38 (69%) with relapsing remitting MS (RRMS), 12 (22%) with
secondary progressive MS (SPMS), 4 (7%) with primary progressive
MS (PPMS). Of the AU patients 9 had RRMS (81%), 2 SPMS (17%)
and 1 PPMS (8%), while among the IU patients 26 had RRMS
(68%), 9 SPMS (24%) and 3 PPMS (8%).
Conclusions: A relevant proportion of the patients had anterior
uveitis associated with MS instead of the more common intermediate
uveitis. We found no apparent correlation between uveitis subtype
and MS diagnosis. MS subtypes were of similar frequencies as
found in MS clinics. This database is roughly 5 times larger than any
previous report on this association and thus it should provide new
information on the clinical implications of the co-existence of uveitis
and MS.
Commercial Relationships: Friederike Mackensen, Merck Serono
(C); Lena Hildebrandt, None; Wyatt Messenger, None; Phoebe
Lin, None; Eric B. Suhler, None; James T. Rosenbaum, None
Program Number: 5323 Poster Board Number: C0141
Presentation Time: 3:45 PM–5:30 PM
Age-Related Macular Degeneration among Uveitis Patients
Austin Fox, Catherine A. Cukras, Nirali Bhatt, William R. Tucker,
Robert B. Nussenblatt, H Nida Sen. National Eye Institute, National
Institutes of Health, Bethesda, MD.
Purpose: To evaluate the prevalence of Age-Related Macular
Degeneration (AMD) among uveitis patients.
Methods: Patients with non-infectious uveitis 55 years or older seen
at NEI since 2004 were identified using EMR and photographic
databases. Color fundus photos, fundus autofluorescence, fluorescein
angiography, and optical coherence tomography were reviewed by
two separate examiners. Patients were classified as having “any
AMD” if they had large drusen or advanced AMD (geographic
atrophy (GA) or neovascular AMD (NV AMD)) in at least one
eye according to The Eye Diseases Prevalence Research Group’s
definition.
Results: 182 patients were identified, and 171 had gradable fundus
images. Forty-seven had anterior uveitis, 41 intermediate uveitis
and 83 posterior or panuveitis. Average age was 64.2±7.7 years,
66.1% were female, majority were non-Hispanic White (51.5%) and
38.6% were African American. AMD was identified in 9 of the 171
patients, and all cases were in the form of large drusen. Of these 9
patients, 4 had anterior uveitis, 3 intermediate uveitis and 2 posterior
or panuveitis. The total prevalence of “any AMD” was 5.26 per
100 individuals, which is less than the estimated overall prevalence
of “any AMD” or large drusen in the US for individuals ≥55 years
of age (12.8% and 10.0%, respectively; p=0.001 and 0.019).
Advanced AMD was present in 0 out of 171 patients which was also
significantly lower (0% vs 2.8%; p=0.008).
Conclusions: Patients with uveitis appear to be relatively spared
from AMD, especially from its advanced forms. It is not clear
whether this is due to underlying disease process or long-term antiinflammatory use among uveitis patients.
Commercial Relationships: Austin Fox, None; Catherine A.
Cukras, None; Nirali Bhatt, None; William R. Tucker, None;
Robert B. Nussenblatt, None; H Nida Sen, None
©2014, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2014 Annual Meeting Abstracts
Support: This study was supported by The National Eye Institute
Intramural Research Program and also made possible through the
National Institutes of Health (NIH) Medical Research Scholars
Program, a public-private partnership supported jointly by the NIH
and generous contributions to the Foundation for the NIH from
Pfizer Inc, The Doris Duke Charitable Foundation, The Alexandria
Real Estate Equities, Inc. and Mr. and Mrs. Joel S. Marcus, and the
Howard Hughes Medical Institute, as well as other private donors.
For a complete list, please visit the Foundation website at: http://fnih.
org/work/education-training-0/medical-research-scholars-program.
Program Number: 5324 Poster Board Number: C0142
Presentation Time: 3:45 PM–5:30 PM
Epidemiology and etiology on uveitis in a department of internal
medicine: a retrospective study on 441 patients
Andy LOCATELLI1, Shirine Mohamed2, Karine Angioi3.
1
Ophthalmology, CH Verdun, Verdun, France; 2Internal Medicine,
CHU Nancy, Vandoeuvre-les-nancy, France; 3Ophthalmology, CHU
Nancy, Vandoeuvre-les-nancy, France.
Purpose: A retrospective study on uveitis features on patients
referred to internal medicine for etiologic work-up.
Methods: All new patients with uveitis referred to internal medicine
for diagnostic work-up between 2005 and 2013 were retrospectively
reviewed. Patients with systemic disease in relation with their uveitis
were excluded. Patients with ophthalmic disease only (toxoplasmosis,
herpes simplex virus, Birdshot disease,…) were also excluded.
Demographic datas, uveitis localization and its features, etiology and
internist follow-up were collected for each patient.
Results: The study concerned 441 patients. It reveals 59% women,
85% with european origins, an average age of 45,9 years with 1.1
year average follow-up.
59% had unilateral uveitis. The most common was the anterior uveitis
(40.6%) followed by the panuveitis (35.8%), the posterior uveitis
(19,5%) and the intermediate uveitis (3,6%).An infectious cause
was found for 11,1 %, a non-infectious pathology for 32%. Uveitis
remains idiopathic for 56,9%.
Conclusions: Idiopathic uveitis percentage still high .A close
collaboration between the ophthalmologist and the internal physician
is essential for the care of uveitis
A prolonged follow-up of patients with repetitive etiologic checkup, if necessary, could increase the percentage of forms linked to a
systemic pathology.
Commercial Relationships: Andy LOCATELLI, None; Shirine
Mohamed, None; Karine Angioi, None
Program Number: 5325 Poster Board Number: C0143
Presentation Time: 3:45 PM–5:30 PM
Disease Activity of Adult Patients with a History of Juvenile
Idiopathic Arthritis Associated Uveitis
Yufei Tu1, Sergio Schwartzman3, David S. Chu2, 1. 1The Institute of
Ophthalmology and Visual Science, New Jersey Medical School,
Rutgers University, Newark, NJ; 2Metropolitan Eye Research and
Surgery Institute, Palisades Park, NJ; 3Hospital for Special Surgery,
Weill Cornell Medical College, New York, NY.
Purpose: To study whether uveitis activity subsides in patients with
history of uveitis associated with juvenile idiopathic arthritis (JIA) as
they become adults.
Methods: Retrospective chart review using the following criteria:
patients with history of JIA and noninfectious uveitis; at lease one
office visit at age equal or greater than 17 years.
Results: 20 subjects were identified. 19 of 20 (95%) patients were
female. Mean age at the final visit was 25.6 years (range, 17-43).
Bilateral uveitis represents 17 cases (85%). There were 10 anterior
uveitis (50%), 2 intermediate (10%), and 8 panuveitis (40%). 6
patients was inactive and medication-free (Group I) at the last visit
(6/20, 30%). Among the rest (Group A), of 14 patients (70%), 3
patients had active disease with immunomodulatory therapy (IMT)
or topical anti-inflammatory therapy and 11 patients (55%) were
inactive with IMT. Among patients in I, average best-corrected
logMAR visual acuity (BCVA) in the better eye was 0.07 at the
final visit. For group A, the average BCVA in the better eye was
0.16. Among those patients, biologics including adalimumab and
infliximab were used in 8 patients (8/14, 57%). Cataract (14, 70%)
and glaucoma (8, 40%) were the most common complications of
all patients. Among all patients, 8 (40%) had cataract surgery and 2
(10%) had glaucoma surgery.
Conclusions: Uveitis of most patients with history of JIA continues
to be active or requires treatment through early to middle adulthood.
Although the visual acuity among these patients is excellent, the need
for cataract surgery among them is common.
Commercial Relationships: Yufei Tu, None; Sergio Schwartzman,
Abbvie (C), Amgen (C), Discus (C), Genentech (C), Hospira (C),
Janssen (C), Pfizer (C), UCB (C); David S. Chu, Allergan (F),
Bausch and Lomb (R), Genentech (F), Novartis (F), Santen (F),
Xoma (F)
Program Number: 5326 Poster Board Number: C0144
Presentation Time: 3:45 PM–5:30 PM
Incidence and Risk Factors for Recurrent Uveitis after Longterm Treatment
Margot Lazow, Stephen Kim. Ophthalmology, Vanderbilt University
Medical Center, Nashville, TN.
Purpose: To determine the incidence and associated risk factors for
recurrent uveitis in patients with autoimmune chronic uveitis with at
least 12 months of inactive disease on immunosuppression followed
by elective cessation of treatment.
Methods: This was a retrospective cohort study. Records of 1,901
patients with ICD-9 codes for uveitis were reviewed, and 42 eyes of
23 patients (1.21%) met inclusion criteria. Patients were included if
they had non-infectious, autoimmune chronic uveitis diagnosed by
a fellowship-trained uveitis specialist, and were inactive for at least
12 months on immunosuppression before cessation of treatment,
with at least 6 months of follow-up. Subject characteristics, lab data,
and documented clinic visits were reviewed and recorded from the
Vanderbilt Medical Center’s electronic medical record. Descriptive
statistics including mean and standard deviation were calculated for
case characteristics, and the Fisher exact test was used to compare
categorical values between remission and recurrence eyes. Main
outcome measures were incidence of recurrent inflammation after
cessation of treatment and predisposing risk factors.
Results: Uveitis recurred in 15 of 42 eyes (35.7%). Eyes with
anterior uveitis were less likely to recur than eyes with intermediate,
pan, or posterior uveitis (RR: 0.18, p<0.05). The recurrence group
was more likely to have stopped immunosuppression at a younger age
(<25y/o) (p<0.05); average age of immunosuppression cessation was
29.1±19.1 for the recurrence eyes, vs. 42.2±21.4 for the remission
eyes. In addition, we noted two trends: females seemed more likely to
recur than males (p =0.11), and eyes that started immunosuppression
<1 year after disease onset seemed more likely to recur (vs. >1yr)
(p=0.11). Also, there was no significant difference in duration of
inactive disease on immunosuppression (before cessation) between
the two groups (18.0±3.9 vs. 19.0±6.3 months, p=0.58). Lastly, of
the eyes that recurred, 100% recurred within 12 months of stopping
immunosuppression, and 67% recurred within 6 months.
Conclusions: Uveitis recurred in approx. 1 of 3 eyes, and
100% of these recurrences occurred within 1 year of stopping
©2014, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2014 Annual Meeting Abstracts
immunosuppression. Risk characteristics for recurrence include nonanterior uveitis and stopping immunosuppression at a younger age.
Duration of inactive disease on immunosuppression before cessation
was not a significant factor.
Commercial Relationships: Margot Lazow, None; Stephen Kim,
None
Support: unrestricted grant from Research to Prevent Blindness
to the Vanderbilt University School of Medicine Department of
Ophthalmology and Visual Sciences
©2014, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].