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A PUBLICATION OF SINGAPORE NATIONAL EYE CENTRE AUGUST 2010 EDITION EDITORIAL MESSAGE 02 EDITORIAL TEAM 03 04 RIBOFLAVIN-UVA INDUCED COLLAGEN CROSS-LINKING TREATMENT FOR KERATOCONUS AND CORNEAL ECTASIA FINDINGS FROM THE STARS STUDY : STRABISMUS, AMBLYOPIA, AND REFRACTIVE ERROR IN SINGAPORE CHILDREN AGED 6-72 MONTHS OLD 06 EYELID MALPOSITIONS 10 ANSWERS TO PHOTOQUIZ 16 14 QUESTION TO PHOTOQUIZ 17 15 Created in September 2010 Editorial Message (Dr Aliza Jap) A 37 female Chinese National arrived in Singapore 6 months ago with her son who is studying in a local school. She came to see me with a complaint of having a sensation that her visual field was getting smaller in both eyes over the past month. She felt that her superior fields were shrinking. She had no medical history of note and there was no history of trauma. She was seeing 6/6 in both eyes. Her intraocular pressures were normal. There was no RAPD. Her ocular examination was normal with pink healthy discs and the retina was also normal in both eyes. Her colour vision was normal. Confrontation fields though did suggest bilateral superior field loss and and this was confirmed on Humphrey field testing. She elected to return to China for neuroimaging due to cost considerations. However her VDRL and TPA were positive. Subsequently an 18 year old boy came with a complaint of noticing an inferior field defect in the right eye for about one month. Again there was no trauma. He did not have any pain on eye movements , preceding flu or any medical history of note. He didn’t think the field defect had increased in size over the past one month. He was seeing 6/6 in both eyes. There was no RAPD and his ocular examination including intraocular pressures, fundal examination, colour vision and confrontation fields were normal. However in view of his very specific compliants Humphrey fields were performed and this confirmed the presence of a inferior arcuate field defect in the right eye. MRI of the anterior visual pathways showed a sellar mass possibly a craniopharyngioma. I wonder how many of my other less articulate patients who came with non specific blurring of vision, but were refracted to 6/6 and had normal ocular examinations had in fact also neurological abnormalities? Especially if they were young, and may possibly have other issues in their life to account for their symptoms such as stress or pre-enlistment anxiety? And I just sent them away with a prescription for artificial tears? It gets even more scary when you consider that the communication gap between health care providers and patients can only grow wider and that patient expectations are also increasing. I wonder if we will come to the point where we MRI all our patients as they register? | 02 EDITORIAL TEAM Editor-in-Chief Dr Ian Yeo Head, Training and Education Senior Consultant, Vitreo-Retinal Service, SNEC Editorial Board Dr Aliza Jap Head and Senior Consultant, CGH Eye Service Assoc Prof Seah Lay Leng Senior Consultant, Oculoplastic Service Dr Daniel Su Consultant, Glaucoma Service, SNEC Dr Loh Boon Kwang Associate Consultant, Vitreo-Retinal Service, SNEC Ms Chia Hui Yien Secretariat Ms Daphne Khoo Creative Designer, Corporate Communications | 03 Riboflavin-UVA Induced Collagen Cross-linking Treatment for Keratoconus and Corneal Ectaisa Presented by Dr Lim Li on 18 November 2009 Written by Dr Laurence Lim Keratoconus is a bilateral, progressive non-inflammatory corneal ectasia in which the cornea assumes a conical shape due to central thinning of the corneal stroma. The estimated incidence amongst Western populations is 1 in 2000, with a higher incidence rate in South Asians of up to 1 in 600 to 1 in 420. The condition is typically seen in young, economically active subjects. Visual rehabilitation in the early, less severe stages of the disease can usually be effected with non-invasive modalities like spectacles and rigid contact lenses, but surgery is ultimately required in approximately 20% of subjects at some point in the course of the disease. Although surgery in the form of lamellar or penetrating keratoplasty is usually associated with good outcomes, it is not without its complications and inconveniences. Riboflavin-ultraviolet-A (UVA) corneal collagen cross-linking (CXL) is a new technique that aims to arrest keratoconus progression, thereby obviating or delaying the need for surgery. Topically applied riboflavin is adsorbed to corneal stromal collagen fibres and activated by UVA light, with the formation of cross-links between collagen fibrils that confer greater corneal rigidity, and increased resistance to digestion by proteolytic enzymes like collagenase. The procedure is currently performed for cases with definite keratoconus progression, contact lens intolerance, good visual potential, and a minimum corneal thickness of 400 m. The last criterion is required to avoid endothelial toxicity from UVA irradiation, as the corneal stroma acts to shield the endothelium from UVA light. Subjects are asked to discontinue contact lens wear 3 days before surgery and to discontinue Vitamin C supplements 1 week before surgery. Pachymetry is performed to ensure a thickness >400 m before the epithelium is removed in several areas within a central 8-9mm zone. Riboflavin/Dextran solution is instilled as a viscous eyedrop every 2 minutes for 30 minutes, and corneal penetration is checked by noting homogenous yellow fluorescence in the anterior chamber at a slit-lamp before proceeding. UVA light is then focused on the cornea using the UV-X illumination system (IROC, Zurich, Switzerland) for 30 minutes with continued instillation of riboflavin solution every 2 minutes. Illumination intensity (3 mW/cm2) is checked with the included light meter prior to each treatment. Post-operatively, all subjects receive a topical antibiotic-steroid combination and a bandage contact lens. To date, data on the clinical outcomes with the procedure have come from a number of small, uncontrolled studies. In general, most studies have shown modest objective improvements in refractive error (up to 1-2D reduction) and keratometry (up to 2-3D reduction). A pilot study on 30 subjects led by Dr Lim Li at SNEC has shown similar outcomes, with no changes in visual acuity, keratometry or corneal thickness at 6 months. Corneal hysteresis, a new measure of corneal biomechanics, was also found to be unchanged following the procedure. | 04 Riboflavin-UVA Induced Collagen Cross-linking Treatment for Keratoconus and Corneal Ectaisa Presented by Dr Lim Li on 18 November 2009 Written by Dr Laurence Lim Confocal microscopy is an imaging modality that captures high resolution en-face images of the cornea in-vivo. Evaluation of the cornea with confocal microscopy after CXL has demonstrated more dramatic and definite changes. Changes that occur after CXL include increased density and regularity of the epithelial mosaic, increased subepithelial nerve plexus density, increased stromal reflectivity, hyperactivated hyperdense keratocyte nuclei (Figure 1, arrowhead) and spindle-shaped hyper-reflective bands which presumably represent the ‘cross-links’ (Figure 1, arrow). Figure 1: Confocal microscopy of the anterior corneal stroma after CXL. Figure 2: Deep stromal scar after CXL Figure 2: Deep stromal scar after CXL Initial clinical experience has suggested that the technique is safe. Stromal haze formation is the most frequently reported complication. In most reports, haze following CXL is relatively mild and transient, and usually occurs in eyes with advanced keratoconus. In our series at SNEC, however, 2 of the 30 cases developed dense, deep stromal scars following CXL for relatively mild keratoconus (Figure 2). Increased astigmatism was induced in one of these cases, although the best corrected visual acuity was fortunately unaffected. Confocal microscopy in these cases revealed an exaggerated fibrotic response with sheets of dense hyper-reflective tissue in the mid- to deep stroma (Figure 3). Riboflavin-UVA exposure typically causes keratocyte apoptosis in the early post-operative period, and we speculate that a sub-lethal effect in the deep stroma where the UVA irradiation dose is lower may lead instead to fibroblastic transformation and an aberrant scarring response. This would explain the delayed reaction seen, and, if proven to be so with subsequent study, may suggest that longer or higher intensity UVA irradiation is indicated. Key Learning Points: 1) 2) 3) Keratoconus is a progressive corneal ectasia. CXL may prevent keratoconus progression in early keratoconus. CXL is generally safe but may rarely be associated with stromal scarring. | 05 Findings from the STARS Study : Strabismus, Amblyopia, and Refractive Error in Singapore children aged 6-72 months old Presented by Dr Audrey Chia on 3 February 2010 Written by Dr Khor Wei Boon Introduction The STARS (Strabismus, Amblyopia, and Refractive Error in Singapore) study was a cross-sectional population study looking at the prevalence of strabismus, amblyopia and refractive error in young Chinese pre-school children1, 2. The study design was similar to the Multiethnic Pediatric Eye Disease Study (MEPEDS)3 and the Baltimore Pediatric Eye Disease Study (BPEDS)4, two large studies conducted in the United States, to allow for comparison with the STARS findings. Methods The study recruited Chinese children aged between 6 to 72 months, living in Housing Development Board estates in the South-West region of Singapore. Eligible children were invited to attend two study centres (one at the Singapore National Eye Centre, and the other at the Jurong Medical Centre) with written consent from parents or guardians to participate in the study. Children included in the study underwent the following tests: Visual acuity (VA), with or without glasses Stereoacuity tests in children aged 30 to 72 months Orthoptic assessment Anterior and posterior segment exam Cycloplegic autorefraction with a table-mounted autorefractor if possible or handheld autorefractor or streak retinoscopy Biometry Parents of these children were also asked to complete a detailed questionnaire on demographic details, pre-natal / peri-natal / postnatal history, as well as details on relevant family history. Results Of the 4126 eligible children, a total of 3009 children were examined (participation rate, 72.3%). There were no significant differences between participants and non-participants in terms of age or gender, although participants tended to stay closer to the study centres. There was also a slightly lower representation of children whose parents were from the lower education and income groups compared to the national average. | 06 Findings from the STARS Study : Strabismus, Amblyopia, and Refractive Error in Singapore children aged 6-72 months old Presented by Dr Audrey Chia on 3 Feb 2010 Written by Dr Khor Wei Boon Refractive Error In all, 2639 children (88%) had cycloplegic refraction, while 370 had non-cycloplegic refraction; the mean spherical equivalence was lower in the non-cycloplegic refraction (P<0.001). Conventionally, it is believed that children are more hyperopic at birth, and become more myopic with age. However, the STARS data revealed that there were more myopic children in the <36 months age group as compared to those children in the >36months age group; this finding was present even if only those children with cycloplegic refraction (n=2639) were analysed. In these 2639 cyclopleged children, the prevalence of myopia <-0.5D was 7.5%, prevalence of myopia < -2D was 1.1%, and the prevalence of hyperopia > +2 was 6.0%. Another surprising finding was that the prevalence of astigmatism appeared to higher in older children. For example, the prevalence of astigmatism (at least -1.5D) in the children aged 60 to 72 months was 11.3%, compared with only 3.6% in the children aged 12 to 23.9 months. In those aged above 36 months, the overall prevalence of astigmatism > -1.5D was 9.7%, and of astigmatism > -2D was 3.2%. This is contrary to the belief that astigmatism is high in infancy and decreases and stabilizes with age. The number of children with anisometropia was small, with rates of anisometropia >1D being only 2% in children aged between 36 and 72 months. Potentially amblyogenic refractive errors were seen in 131 children (4.3%), and included myopia < -6D (n=9), hyperopic > +4D (n=16), astigmatism > -2.5D (n=96) and anisometropia >1.5D (n=26). However, the prevalence of amblyopia was found to be much lower than these refractive errors would suggest. Amblyopia In adults, a generally accepted definition for amblyopia is that of a 2-line difference in vision between the two eyes, with vision worse than 6/12 in the eye with poorer vision, in the absence of any organic cause for the poor vision. However, there is no universally accepted definition for amblyopia in small children, especially given the difficulties with VA testing in pre-school children. With these considerations in mind, only children aged between 30 to 72 months (n=2015) were assessed for amblyopia in this STARS study. Even so, 333 (16.5%) were excluded because they could not complete the vision testing, and this ranged from 67% in children aged 30-35 months, to only 1% in those aged 60-72 months old. The definition of amblyopia used in the study was based on the MEPEDS definition for unilateral and bilateral amblyopia, which in general consisted of a visual acuity cutoff, and supporting past or present amblyogenic factor such as strabismus, refractive error, or some obstruction of the visual axis. | 07 Findings from the STARS Study : Strabismus, Amblyopia, and Refractive Error in Singapore children aged 6-72 months old Presented by Dr Audrey Chia on 3 February 2010 Written by Dr Khor Wei Boon Unilateral amblyopia was defined, as a 2-line difference in best VA, when <20/30 (logMAR 0.18) in the worse eye, and with amblyogenic factors such as past or present strabismus, anisometropia (>1.00 D difference in hyperopia, >3.00 D difference in myopia, or >1.50 D difference in astigmatism), and past or present obstruction of the visual axis. Bilateral amblyopia was defined as best VA in both eyes of <20/40 (logMAR 0.3) in children aged 48 to 72 months or <20/50 (logMAR 0.4) in children aged <48 months, in the presence of amblyogenic factors such as hyperopia > 4 D, myopia > -6.00 D, or astigmatism > 2.50 D, or past or present obstruction of the visual axis. In all, 48 children (2.8%) met the VA criteria for amblyopia, but 28 were not considered to have amblyopia because of the lack of amblyogenic risk factors; 19 (67%) had minimal refractive error and no past/present strabismus of visual obstruction and 9 children missed refractive error cutoffs by small margins. Only 20 children satisfied all the requirements, so that the amblyopia prevalence rate amongst Singaporean Chinese children aged 30-72 months was 1.15% (95%CI 1.21-1.25). Compared with children in the MEPEDS and BPEDS, this prevalence was less than that for Hispanic/Latino (2.6%,95%CI,1.8–3.4) but similar to that found in White (1.8%, 95% CI, 0.9–3.1) and African-American (0.8%, 95% CI, 0.3–1.6, in the MEPEDS, and 1.5%, 95% CI, 0.9–2.1, in the BPEDS) children. Although we found the prevalence of amblyopia to be much lower than the 3% that is usually quoted in other studies, this may be due in part to the much stricter criteria used in the MEPEDS study. Using the more liberal definitions suggested by the American Association of Pediatric Ophthalmology and Strabismus (AAPOS)5, our amblyopia prevalence would increase dramatically to 3.27%. Strabismus Strabismus was much easier to ascertain in the children of the STARS study, and orthoptic assessment was only not possible in 17 children. Strabismus was defined as any manifest tropia, and this was found in 24 children, giving an overall prevalence in children aged 6 – 72 months of 0.80% (95%CI 0.51-1.19). The ratio between exotropias (XT) and esotropias (ET) was 7:1; there were 12 intermittant XT, 7 constant XT, 3 constant ET, and one patient with a dissociated vertical deviation. The prevalence of strabismus was much lower than those found in the other racial groups (whites, blacks and Hispanics/latinos) of the MEPEDS and BPEDS studies, but closer to reports on strabismus in China and Japan. | 08 Findings from the STARS Study : Strabismus, Amblyopia, and Refractive Error in Singapore children aged 6-72 months old Presented by Dr Audrey Chia on 3 February 2010 Written by Dr Khor Wei Boon Conclusion In summary, the findings of the STARS study suggest that in young Singaporean Chinese children: - Children younger than 36 months may be more myopic and less astigmatic than previously believed. - Amblyopia prevalence was low (1.2%) and more likely associated with refractive error unlike in the West where strabismus was a more significant associative factor. - Strabismus prevalence of esotropia was very low (0.1%), but the prevalence of XT (0.7%) was also much lower compared with US-based studies. References 1. Dirani M, Chan YH, Gazzard G et al. Prevalence of refractive error in Singaporean Chinese children: the strabismus, amblyopia, and refractive error in young Singaporean Children (STARS) study. Invest Ophthalmol Vis Sci; 51(3): 1348-1355. 2. Chia A, Dirani M, Chan YH et al. Prevalence of amblyopia and strabismus in young singaporean chinese children. Invest Ophthalmol Vis Sci; 51(7): 3411-3417. 3. Varma R, Deneen J, Cotter S et al. The multi-ethnic pediatric eye disease study: design and methods. Ophthalmic Epidemiol 2006; 13(4): 253-262. 4. Friedman DS, Repka MX, Katz J et al. Prevalence of decreased visual acuity among preschool-aged children in an American urban population: the Baltimore Pediatric Eye Disease Study, methods, and results. Ophthalmology 2008; 115(10): 1786-1795, 1795 e1781-1784. 5. Eye examination and vision screening in infants, children, and young adults. American Academy of Pediatrics Committee on Practice and Ambulatory Medicine, Section on Ophthalmology. Pediatrics 1996; 98(1): 153-157. | 09 Eyelid Malpositions Presented by Dr Audrey Looi on 7 April 2010 Written by Dr Livia Teo There are 2 main malpositions of the eyelid: entropion and ectropion. ENTROPION Entropion refers to the inward rotation of the lid margin towards the globe. Differential diagnosis include epiblepharon, lid retraction e.g. in Grave’s disease, trichiasis and dystichiasis. In all the differentials, the lid margin position is always normal. Epiblepharon is a congenital lid anomaly whereby a fold of skin and orbicularis muscle over-rides the lid margin and pushes the lashes against the eye. In lid retraction, there is a relative posterior lamellar shortening resulting in malrotation of the lashes inwards in a pseudoepiblepharon manner. Trichiasis and dystichiasis refer to the misdirection or aberrant posterior lashes against the globe. Causes of entropion can be divided into 1) Congenital causes (e.g. tarsal kink syndrome) or 2) Acquired causes a) Involutional b) Cicatricial c) Spastic Congenital entropion is rare and it usually involves both lower lids. It is usually due to a maldeveloped distal lower lid retractor with dehiscence near the tarsal plate, hypertrophy of the marginal orbicularis or levator disinsertion in the upper lid. Lower lid entropion repair involves excision of the excess skin and orbicularis (3-6mm), lower lid retractor repair and excision of tarsal kink if present. Acquired causes Involution entropion is the commonest cause of acquired entropion locally. The mechanisms of this include vertical lid laxity (lid retractor dehiscence), horizontal lid laxity (medial and lateral canthal tendon laxity) overriding of the preseptal orbicularis over the pretarsal orbicularis, tarsal plate atrophy and enophthalmos (orbital fat atrophy). Management includes temporizing measures such as lid taping, lubricants, bandage contact lens, or everting sutures. Everting sutures can be done using a double-armed 6/0 vicryl suture passed from the inferior conjunctival fornix to the skin just below the lid margin. The aim is to shorten the lower lid retractors and transfer their pull to the upper border of the tarsal plate. Surgical repair would include lower lid retractor repair and horizontal lid tightening with a wedge resection or a lateral tarsal strip procedure. | 10 Answers to PhotoQuiz 16 | 14 Fig 1. Left optic disc pit with neurosensory detachment over macula Fig 2. Neurosensory detachment of macula with intra-retinal schisis Congenital optic disc pits have a rare occurrence of 1 in 11000 patients and is bilateral in 10-15% of cases. The affected disc is larger than the fellow eye. There is a 25% to 75% lifelong risk of developing serous macular detachments. The occurrence of macular detachment is most common between the ages of 20 and 40. Fenestrations in the diaphanous tissue overlying the optic pit has been documented. Traction from surrounding attached vitreous allows fluid to enter the intra and subretinal space via these fenestrations. Schisis-like separation of the inner retinal layers is thought to be the primary pathology with secondary development of neurosensory detachment after formation of the schisis cavity. The extent of detachment may be limited by the small amount of liquefied vitreous in these young patients. There is spontaneous resolution of the serous detachment in up to 25% of patients. Final vision of 6/60 or worse has been reported in 80% of patients over a 9-year follow up period. These patients can be observed if vision is reasonably good with no significant progression. In patients who progress, vitrectomy with complete surgical posterior vitreous detachment and gas tamponade achieves relief of vitreous traction on the small fenestrations overlying the pit and is associated with reasonably good anatomical and functional outcomes. Macular scleral buckling has also been tried. Other novel treatment options include vitrectomy with partial thickness fenetration of the retina immediately temporal to the pit as well as the use of autologous platelets as an adjunct to vitrectomy. Eyelid Malpositions Presented by Dr Audrey Looi on 7 April 2010 Written by Dr Livia Teo Mechanical ectropion requires excision of the causative lesion with care being taken to create as vertical a wound as possible so as to avoid subsequent cicatricial ectropion. Any horizontal lid laxity can also be addressed at the same time. Surgical correction in paralytic ectropion also involves the lateral tarsal strip procedure and Tse procedure +/- lower lid lengthening with auricular cartilage. Medial canthoplasty may be necessary as well. If lagophthalmos is a feature, lateral tarsorraphy or a gold weight implant procedure may be performed to reduce exposure keratopathy. EPIBLEPHARON Epiblepharon is a congenital anomaly due to a redundant horizontal skin- muscle fold that results in vertical orientation of the cilia. It is more commonly seen in the oriental population. The patient may present with chronic eye irritation, redness, tearing, mucoid discharge, frequent eye rubbing and blepharospasm. In the lower lid, this can be due to a congenital absence of retractor insertion into the skin and orbicularis or it can be due to insertion of the retractor being too near to the lid margin. Failure of the retractor muscle to bind skin and pretarsal orbicularis to the tarsal plate results in the horizontal skin- muscle fold seen clinically. However, retractor insertion onto the tarsal plate is intact. In the upper eyelid, a lower insertion of the levator aponeurosis to the anterior surface of the tarsal plate and deficiency of the fibres to skin and pretarsal orbicularis allows relative overriding of the latter over the lid margin. It usually resolves by the age of 3 years and can be managed initially with lubricants. Surgery can be performed for persistent cases. Methods of repair for the lower lid include the Hotz procedure, Quickert suture or anterior lamellar reduction and repositioning (Choo). Quickert suture involves passing a 4/0 chromic catgut suture through the full thickness of the lid just below the tarsus and tying it firmly on the skin. This creates a tissue adhesion between the anterior and posterior lamellar and reinforces the action of the retractors on the anterior lamella. Choo’s anterior lamellar reduction and repositioning includes the excision of excess skin and pretarsal orbicularis with placement of buried 7/0 vicryl sutures to reposition the anterior lamella. The skin incision is made 2-3 mm below the lower lid margin and a greater amount of skin is excised on the nasal half of the lower lid. The aim of this procedure is to debulk the pretarsal orbicularis. A similar approach can be taken for the upper lid. | 12 Eyelid Malpositions Presented by Dr Audrey Looi on 7 April 2010 Written by Dr Livia Teo Key Learning Points: 1. Entropion refers to the inward rotation of the lid margin towards the globe. Its causes can be divided as follows: - Congenital Acquired Involutional Cicatricial Spastic 2. Ectropion is the outward rotation of the eyelid margin. Its causes can be divided as follows: - Congenital causes (e.g. blepharophimosis syndrome) Acquired causes Involutional Cicatricial (burns) Mechanical Paralytic (e.g. 7th nerve palsy) 3. Management of both conditions includes identification and treatment of the underlying cause and mechanism as well as ensuring protection of the cornea. This can include temporizing measures such lid taping, lubricants, bandage contact lens, botox injections or everting sutures while more definitive management will require surgical intervention. | 13 Answers to PhotoQuiz 16 | 14 Fig 1. Left optic disc pit with neurosensory detachment over macula Fig 2. Neurosensory detachment of macula with intra-retinal schisis Congenital optic disc pits have a rare occurrence of 1 in 11000 patients and is bilateral in 10-15% of cases. The affected disc is larger than the fellow eye. There is a 25% to 75% lifelong risk of developing serous macular detachments. The occurrence of macular detachment is most common between the ages of 20 and 40. Fenestrations in the diaphanous tissue overlying the optic pit has been documented. Traction from surrounding attached vitreous allows fluid to enter the intra and subretinal space via these fenestrations. Schisis-like separation of the inner retinal layers is thought to be the primary pathology with secondary development of neurosensory detachment after formation of the schisis cavity. The extent of detachment may be limited by the small amount of liquefied vitreous in these young patients. There is spontaneous resolution of the serous detachment in up to 25% of patients. Final vision of 6/60 or worse has been reported in 80% of patients over a 9-year follow up period. These patients can be observed if vision is reasonably good with no significant progression. In patients who progress, vitrectomy with complete surgical posterior vitreous detachment and gas tamponade achieves relief of vitreous traction on the small fenestrations overlying the pit and is associated with reasonably good anatomical and functional outcomes. Macular scleral buckling has also been tried. Other novel treatment options include vitrectomy with partial thickness fenetration of the retina immediately temporal to the pit as well as the use of autologous platelets as an adjunct to vitrectomy. Question to PhotoQuiz 17 Figure 1 | 15 Figure 2 A 45-year-old gentleman, with a known history of high hypermetropia of 17 dioptres spherical equivalent, presented with a decrease in his right visual acuity for 5 months. The Snellen visual acuity for right and left eye were 6/120 and 6/21 respectively. Fundus photography (Figure 1) and fluorescein angiography (Figure 2) of the right eye were done. What is the diagnosis?