Predicting Progression of Untreated Macular Pucker Using Retinal Surface En Face Optical Coherence Tomography.

PURPOSE: To review visual outcomes in untreated premacular membrane (PMM) with macular pucker (MP) and evaluate novel predictors of progression. METHODS: In this retrospective observation study, we included 342 eyes with untreated PMM with MP between 2012 and 2015. PMMs were characterized by spectral-domain optical coherence tomography (SD-OCT) imaging based on foveal morphologies, number of retinal contraction centers, central subfield thickness (CST), inner segment ellipsoid band integrity, and photoreceptor deformation index. Additionally, the thickened retina portion was identified by en face OCT and processed digitally to calculate its area. Parameters were retrospectively analyzed using multiple regression analyses to identify associations with change in visual acuity (VA) between initial to final follow-up visit. RESULTS: In 468 eyes with untreated PMM, VA and CST did not change significantly during a mean observation period of 448 days (p = 0.52 and 0.35, respectively). Specifically, VA improved or stayed the same in 80% and worsened by 2 lines or more in 20% of eyes. The only consistent predictor of PMM progression was area of retinal thickening: for every 1 mm2 of retinal thickening at baseline, the odds of having worsened vision at follow-up increased by 6% (OR 1.0606, 95% CI 1.0031-1.1214, p = 0.0387). CONCLUSIONS: The majority of eyes with PMM and good visual function at baseline remain stable or spontaneously improve in VA and macular thickness. Area of retinal thickening as evaluated by en face OCT may be a novel predictor of vision loss in untreated PMM with MP.

Identification of novel mutations causing pediatric cataract in Bhutan, Cambodia, and Sri Lanka.

BACKGROUND: Pediatric cataract is an important cause of blindness and visual impairment in children. A large proportion of pediatric cataracts are inherited, and many genes have been described for this heterogeneous Mendelian disease. Surveys of schools for the blind in Bhutan, Cambodia, and Sri Lanka have identified many children with this condition and we aimed to identify the genetic causes of inherited cataract in these populations. METHODS: We screened, in parallel, 51 causative genes for inherited cataracts in 33 probands by Ampliseq enrichment and sequencing on an Ion Torrent PGM. Rare novel protein coding variants were assessed for segregation in family members, where possible, by Sanger sequencing. RESULTS: We identified 24 rare (frequency <1% in public databases) or novel protein coding variants in 12 probands and confirmed segregation of variants with disease in the extended family where possible. Of these, six are predicted to be the cause of disease in the patient, with four other variants also highly likely to be pathogenic. CONCLUSION: This study found that 20%-30% of patients in these countries have a mutation in a known cataract causing gene, which is considerably lower than the 60%-70% reported in Caucasian cohorts. This suggests that additional cataract genes remain to be discovered in this cohort of Asian pediatric cataract patients.

PAX6 molecular analysis and genotype-phenotype correlations in families with aniridia from Australasia and Southeast Asia.

Purpose: Aniridia is a congenital disorder caused by variants in the PAX6 gene. In this study, we assessed the involvement of PAX6 in patients with aniridia from Australasia and Southeast Asia. Methods: Twenty-nine individuals with aniridia from 18 families originating from Australia, New Caledonia, Cambodia, Sri Lanka, and Bhutan were included. The PAX6 gene was investigated for sequence variants and analyzed for deletions with multiplex ligation-dependent probe amplification. Results: We identified 11 sequence variants and six chromosomal deletions, including one in mosaic. Four deleterious sequence variants were novel: p.(Pro81HisfsTer12), p.(Gln274Ter), p.(Ile29Thr), and p.(Met1?). Ocular complications were associated with a progressive loss of visual function as shown by a visual acuity ≤ 1.00 logMAR reported in 65% of eyes. The prevalence of keratopathy was statistically significantly higher in the Australasian cohort (78.6%) compared with the Southeast Asian cohort (9.1%, p=0.002). Variants resulting in protein truncating codons displayed limited genotype-phenotype correlations compared with other variants. Conclusions: PAX6 variants and deletions were identified in 94% of patients with aniridia from Australasia and Southeast Asia. This study is the first report of aniridia and variations in PAX6 in individuals from Cambodia, Sri Lanka, Bhutan, and New Caledonia, and the largest cohort from Australia.

Causes of Severe Visual Impairment and Blindness: Comparative Data From Bhutanese and Laotian Schools for the Blind.

PURPOSE: To determine and compare the major causes of childhood blindness and severe visual impairment in Bhutan and Laos. DESIGN: Independent cross-sectional surveys. METHODS: This survey consists of 2 cross-sectional observational studies. The Bhutanese component was undertaken at the National Institute for Vision Impairment, the only dedicated school for the blind in Bhutan. The Laotian study was conducted at the National Ophthalmology Centre and Vientiane School for the Blind. Children younger than age 16 were invited to participate. A detailed history and examination were performed consistent with the World Health Organization Prevention of Blindness Eye Examination Record. RESULTS: Of the 53 children examined in both studies, 30 were from Bhutan and 23 were from Laos. Forty percent of Bhutanese and 87.1% of Laotian children assessed were blind, with 26.7% and 4.3%, respectively, being severely visually impaired. Congenital causes of blindness were the most common, representing 45% and 43.5% of the Bhutanese and Laotian children, respectively. Anatomically, the primary site of blinding pathology differed between the cohorts. In Bhutan, the lens comprised 25%, with whole globe at 20% and retina at 15%, but in Laos, whole globe and cornea equally contributed at 30.4%, followed by retina at 17.4%. There was an observable difference in the rates of blindness/severe visual impairment due to measles, with no cases observed in the Bhutanese children but 20.7% of the total pathologies in the Laotian children attributable to congenital measles infection. CONCLUSIONS: Consistent with other studies, there is a high rate of blinding disease, which may be prevented, treated, or ameliorated.

Management of diffuse ocular surface squamous neoplasia: efficacy and complications of topical chemotherapy.

BACKGROUND: Ocular surface squamous neoplasia (OSSN) characterized by diffuse conjunctival or corneal spread is much less common than localized conjunctival disease. However, it is an important subcategory of the disease because of the difficulty it poses to treatment. It is rarely amenable to simple excision, and a purely surgical approach usually necessitates ocular surface reconstruction. Primary treatment with topical chemotherapy is an alternative, but its efficacy for these lesions is not well understood. DESIGN: Retrospective case series. PARTICIPANTS: Thirty-eight eyes treated for diffuse OSSN, defined as a lesion extending over five or more limbal clock hours or by extensive central or paracentral corneal spread. METHODS: Treatment utilized either topical 5-FU 1% or mitomycin-C (MMC) 0.04%. MAIN OUTCOME MEASURES: (i) Disease remission; (ii) complications. RESULTS: Thirty-two patients were treated for a primary diffuse OSSN. Ten patients (31%) required further treatment for disease persistence or recurrence. Thirteen patients had previously undergone a single unsuccessful treatment course for diffuse OSSN. Administration of a second treatment course (whether MMC or 5FU) was successful in 46% (six) of patients. 5-FU 1% resulted in drug-related complications in seven of 12 cases, and included a single case of focal paracentral corneal stromal melt. MMC 0.04% resulted in transient drug related complications in 23 of 39 cases. CONCLUSION: Diffuse OSSN is often recalcitrant to initial treatment with either 5-FU 1% or MMC 0.04%, and a pragmatic and vigilant approach to this heterogenous disease is required. Compared to localized disease, diffuse disease often requires multiple treatment efforts.

Traumatic corneal endothelial rings from homemade explosives.

Traumatic corneal endothelial rings are remarkably rare ocular findings that may result from blast injury. We present a unique case of bilateral traumatic corneal endothelial rings secondary to blast injury from homemade explosives.

Homozygous mutations in PXDN cause congenital cataract, corneal opacity, and developmental glaucoma.

Anterior segment dysgenesis describes a group of heterogeneous developmental disorders that affect the anterior chamber of the eye and are associated with an increased risk of glaucoma. Here, we report homozygous mutations in peroxidasin (PXDN) in two consanguineous Pakistani families with congenital cataract-microcornea with mild to moderate corneal opacity and in a consanguineous Cambodian family with developmental glaucoma and severe corneal opacification. These results highlight the diverse ocular phenotypes caused by PXDN mutations, which are likely due to differences in genetic background and environmental factors. Peroxidasin is an extracellular matrix-associated protein with peroxidase catalytic activity, and we confirmed localization of the protein to the cornea and lens epithelial layers. Our findings imply that peroxidasin is essential for normal development of the anterior chamber of the eye, where it may have a structural role in supporting cornea and lens architecture as well as an enzymatic role as an antioxidant enzyme in protecting the lens, trabecular meshwork, and cornea against oxidative damage.

Adjuvant 5-fluorouracil in the treatment of localised ocular surface squamous neoplasia.

AIM: To report the outcome of treatment of localised non-invasive ocular surface squamous neoplasia (OSSN) where topical 5-fluorouracil (5-FU 1%) is used as an adjuvant to surgical excision. METHODS: The study was a prospective non-comparative interventional case series. 55 cases of primary localised OSSN and 10 cases of recurrent localised OSSN were treated with excision, cryotherapy and adjuvant 5-FU 1%. In all cases, irrespective of the involvement of surgical margins, a single cycle of 5-FU 1% was administered, four times a day for 2 weeks continuously. The main outcome measures were (1) recurrence and (2) complications related to adjuvant topical chemotherapy. Individuals were reviewed for a minimum of 12 months. RESULTS: There was a single case of recurrence (1.5%). 57% of patients had short-term complications secondary to 5-FU 1%, most frequently lid toxicity (49%), followed by superficial keratitis, epiphora and corneal epithelial defects. Four patients were unable to complete the course of 5-FU 1% because of local toxicity. CONCLUSIONS: The management of localised non-invasive OSSN with adjuvant 5-FU 1% was associated with a low rate of local recurrence. Although 5-FU 1% frequently results in short-term complications, most commonly lid toxicity, a full course is usually tolerated. Serious complications appear uncommon in the treatment of localised disease.

The differential diagnosis of localised amelanotic limbal lesions: a review of 162 consecutive excisions.

AIMS: To report the distribution of histopathological diagnoses in patients who underwent excision of localised limbal lesions that were clinically suspected to be squamous neoplasia (intra-epithelial neoplasia or squamous cell carcinoma). METHODS: 162 consecutive patients of a single ocular oncologist underwent an excisional biopsy between 1998 and 2009 for suspected squamous neoplasia. Histopathological reports were retrospectively reviewed. RESULTS: The population comprised 122 males and 40 females. The mean age was 63.4±15.8 (range: 27-90). 138 (85.2%) lesions were identified as intraepithelial neoplasia (CIN), of which 34 (21.0%) were CIN I, 32 (19.8%) were CIN II and 72 (44.4%) were CIN III or squamous cell carcinoma in situ. In seven (4.3%) cases, the lesion was invasive squamous cell carcinoma. In two (1.2%) cases, the lesion was amelanotic malignant melanoma. In 16 (9.9%) cases, histopathology revealed a benign entity including lesions described as squamous papilloma, solar elastosis and epithelial hyperplasia, keratosis or reactive atypia. CONCLUSIONS: In this population, for an experienced ocular oncologist, the misdiagnosis of localised limbal squamous neoplasia occurred in 10.5% of cases, with 5.5% of cases being malignant. This study highlights the importance of acquiring a clinical diagnosis before administering a topical chemotherapeutic agent.

Bilateral simultaneous acute angle closure glaucoma precipitated by non-prescription cold and flu medication.

We present a case of a 63-year-old woman who presented to an ED with bifrontal headache, nausea and vomiting and reduced visual acuity. Examination revealed bilateral elevated intraocular pressures, corneal haze, shallow anterior chambers and poorly reactive, mid-dilated pupils. Diagnosis was made of simultaneous bilateral acute angle closure glaucoma. A complete drug history revealed that she had been using an over-the-counter cold and flu remedy whose active ingredients included atropa belladonna, an herb with anticholinergic properties. It is likely that drug-induced dilatation of the individual's pupils precipitated this angle closure emergency. In the report we discuss the risk factors for angle closure glaucoma, and review the local and systemic drugs known to trigger this sight-threatening emergency.

Ocular neovascularization following central retinal artery occlusion: prevalence and timing of onset.

PURPOSE: Debate exists in the literature on the prevalence and etiology of neovascularization following central retinal artery occlusion (CRAO). The reported prevalence varies from 2.5% to 31.6%. We conducted a retrospective study to determine the prevalence of ocular neovascularization following acute CRAO in our institution. METHODS: A retrospective audit of consecutive patients with nonarteritic/thromboembolic CRAO presenting between 1997 and 2009 in a single tertiary teaching hospital. RESULTS: Thirty-three patients were identified as having nonarteritic CRAO, and of this cohort 6 patients (18.2%) developed ocular neovascularization. Neovascular glaucoma was present in 5 cases (15.2%); 2 of these presented through an emergency department with painful eyes, both at 16 weeks post CRAO. The other cases of neovascularization were detected on scheduled follow-ups. Mean time from retinal occlusive event to observed neovascularization was 8.5 weeks (range 2-16 weeks). One case of neovascularization was associated with hemodynamically significant ipsilateral carotid stenosis; no patient had proliferative diabetic retinopathy or other causes of neovascularization. CONCLUSIONS: The prevalence of neovascularization following acute CRAO in our population was 18.2% at an average of 8.5 weeks post CRAO. There was a temporal relationship between the 2 events and no other causes of neovascularization demonstrable in our cohort of patients. There is no consensus on the follow-up regimen post CRAO to detect ocular neovascularization complications. Our study suggests that neovascularization can occur early and regular follow-up especially in the first 4 months is important post CRAO.

Clinical characteristics and outcome of current standard management of central retinal artery occlusion.

BACKGROUND: To investigate the visual outcomes in acute central retinal artery occlusion (CRAO) with current standard therapy at two university teaching hospitals. METHODS: Retrospective analysis of two cohorts of CRAO patients from John Hopkins Hospital (JHH; USA), and Flinders Medical Centre (FMC; Australia), treated with current standard therapy. The outcome measures were visual acuity, and subsequent ocular and systemic ischaemic events. RESULTS: The mean follow-up period was 11.2 +/- 13.1 months in the JHH cohort and 35.4 +/- 34.9 months in the FMC cohort. The frequency distribution of vascular risk factors and the incidence of subsequent ischaemic events were similar for the patients from both institutions. All patients from JHH were treated as inpatients, whereas 79% of patients from FMC were treated as outpatients. More patients in the JHH cohort underwent paracentesis, ocular massage or were treated with intraocular hypotensive agents (76%) than in the FMC cohort (26%); however, there was no significant difference in visual outcome between the two cohorts (P = 0.114). CONCLUSION: Despite differences in management of CRAO between two institutions in different countries, visual outcomes were similar. This suggests a lack of efficacy of current standard treatment in acute CRAO.

Isolated unilateral abducens cranial nerve palsy: a rare presentation of pituitary apoplexy.

PURPOSE: To describe a rare presentation of pituitary apoplexy as unilateral abducens nerve palsy demonstrating the various presentations of the condition. METHODS: Case report. RESULTS: A 48-year-old man presented with isolated right abducens nerve palsy. Magnetic resonance imaging showed a large pituitary macroadenoma with evidence of recent bleed into the right cavernous sinus and surrounding the right internal carotid artery. CONCLUSIONS: Pituitary apoplexy may present subtly with an isolated sixth nerve palsy but the condition is critical and high index of suspicion needs to be governed.

Retinal vascular abnormalities in patients with cerebral amyloid angiopathy.

OBJECTIVE: To describe the ophthalmology findings in patients with cerebral amyloid angiopathy (CAA). METHODS: Data source and subjects: 7 consecutive patients admitted to a tertiary stroke unit with CAA-related hemorrhage, confirmed on magnetic resonance brain imaging gradient echo sequences by 2 independent neuroradiologists. DESIGN: case series. Measurements and data analysis: fundus colored photographs and fundus fluorescein angiography. RESULTS: All patients showed bilateral multiple dot and blot hemorrhages as well as multiple microaneurysms on fundus fluorescein angiography. CONCLUSION: Microaneurysms and dot and blot hemorrhages funduscopically mirror the histopathology of CAA. This case series is the first to describe retinal vessel changes in CAA and, if confirmed in larger population studies, has the potential to provide insights into the natural history of CAA.

Mitomycin-C as adjuvant therapy in the treatment of sebaceous gland carcinoma in high-risk locations.

PURPOSE: To report on the use of Mitomycin-C as adjuvant therapy to excision and cryotherapy in patients with sebaceous gland carcinoma (SGC) in high-risk locations. DESIGN: Retrospective, consecutive, case series. PARTICIPANTS: Three patients with SGC of the upper palpebral conjunctiva or caruncle, but without clinical pagetoid spread. METHODS: Following excision and double freeze-thaw cryotherapy, patients with histology demonstrating SGC of the ocular surface were treated with topical Mitomycin-C (0.04%). Follow-up was conducted over an average of 30 months (range: 24-37 months). MAIN OUTCOME MEASURES: Postoperative evidence of local recurrence, lymph node or distant organ metastasis. RESULTS: No patients had evidence of local recurrence or systemic disease. CONCLUSIONS: Wide surgical excision with cryotherapy is the basis of treatment of SGC without pagetoid spread. The use of Mitomycin-C as adjuvant therapy remains controversial, although there is some rationale for its use in high-risk situations.