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Objective: Biallelic RPE65 pathogenic variants may cause Leber congenital amaurosis (LCA). Voretigene neparvovec-rzyl (VN, Luxturna) is the only approved subretinal gene therapy that demonstrated benefit and safety. The eligibility criteria are vague and variable between centres. This is the first comprehensive outcome report of RPE65-LCA patients with the World Health Organization blindness criteria vision treated with VN., Design: Multicentre retrospective case series., Participants: Patients meeting the treatment criteria for VN who had best-corrected visual acuity (BCVA) <20/400 or visual field (VF)-III4e isopter <10°., Methods: Patients were followed for a mean of 11.1 ± 4.7 months. Age, sex, BCVA, central retinal thickness (CRT), retinal atrophy, VF, full-field stimulus testing (FST), and subjective impressions were assessed., Results: Nine patients met the inclusion criteria (mean: BCVA 1.89 LogMAR, range: 1.4 - 2.7 LogMAR, mean age: 28.7-years-old, range: 17-59 years). Though VF area did not improve, FST improved in patients with better baseline FST (-8.83 dB vs -0.56 dB; p = 0.010), and better VF-V4e (7245 vs 341 o2 ; p < 0.001) and III4e (596.1 vs 24.8 o2 ; p = 0.011) area. VA improved in younger (20 vs 32 years; p = 0.011) patients with thinner CRT 1mm (155 vs 193 µm; p = 0.038). VF-V4e loss occurred in older (38 vs 19 years; p = 0.001) patients with worse baseline V4e area (1728 vs 8159 o2 ; p < 0.001). Subjective improvement in dim light navigation skills occurred in younger patients (20.3 vs 45.3 years; p < 0.001)., Conclusions: Blindness is not a contraindication to VN treatment for RPE65-LCA. Superior results correlated with greater baseline FST but not with CRT 1mm , provided that measurable outer retinal structures persist., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To report our long-term experience with the local toxicity profile and ocular motility changes after treatment of intraocular retinoblastoma with subtenon topotecan chemotherapy., Design: Cross-sectional study., Participants: Ten eyes in 8 patients with retinoblastoma treated with subtenon topotecan., Methods: We assessed potential complications in ocular motility in eyes with retinoblastoma treated with subtenon topotecan using forced duction testing under general anaesthesia. Eyes subsequently enucleated because of treatment failure were examined histologically., Results: Ten eyes in 8 patients with retinoblastoma treated with 1 to 4 injections of subtenon topotecan were examined repeatedly, with a mean follow-up period of 37 months. Ocular motility remained normal in all eyes by forced duction, with no observed persistent conjunctival congestion, abnormal ocular motility, or enophthalmos in retained eyes 3 years after last injection. Histopathologic examination of the 2 enucleated eyes did not reveal signs of orbital tissue necrosis or fibrosis., Conclusions: Unlike subtenon carboplatin, subtenon topotecan therapy is not associated with long-term toxicity affecting ocular muscles or orbital soft tissue. No effect on ocular motility was observed., (Copyright © 2013 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.)

Background: Patients who suffer from ocular genetic diseases have special needs in terms of diagnosis and management of rare entities, low-vision needs, genetic counselling, and psychosocial adjustments that are usually not addressed by an ophthalmologist alone. The Ocular Genetics Program (OGP) at the Hospital for Sick Children, Toronto, was established in 1994 to provide comprehensive, multidisciplinary care of patients with inherited eye disorders. We now assess the benefits of such a program and of integrating research into the care of patients., Methods: We report our experience in developing a multidisciplinary ocular genetics program and the results of a pilot patient satisfaction survey that involved 61 patients., Results: The OGP multidisciplinary aspects are described. Of the 61 patients surveyed, 98% stated that they were satisfied with the OGP; 93%-96% of patients were content with "one day of appointments", "understanding of eye problem", and "coordination of ancillary tests such as visual fields test, electrophysiology, and others"; and for 70%-86% of respondents "waiting time to get an appointment", "information received on current research", and "primary health care provider adequately informed" were satisfactory., Interpretation: The OGP is a unique service in Canada, which strives to provide the comprehensive care needed by ocular genetic patients. High patient satisfaction is an indicator of the success of this approach. Long waiting times for appointments and application of laboratory research in clinical care remain challenging.

Background: The purpose of this study was to describe our experience with the clinical effects of molecular genetic testing for retinitis pigmentosa (RP) and related retinal dystrophies., Methods: Chart review of 303 consecutive patients with retinal dystrophies was done when blood was sent for molecular genetic testing between 1993 and 2001. Phenotype information was retrieved for patients with identified mutations. The yield of positive and clinically useful results was assessed., Results: Participants comprised 35 patients with Leber congenital amaurosis, 18 with Usher syndrome, and 250 with isolated RP or other retinal dystrophies. Of these 303 participants, 203 (67%) received positive or negative results of molecular testing for an average of 2.7 genes. Positive results were available in 19 patients after an average time interval of 38+/-22 months (median 33 months, range 1-89 months). No results were received for 84 (28%) patients. In 16 (5%) cases, patients received partial results. Only 19 (6%) patients were found to have sequence changes in RHO, RDS, CRB1, or USH2A, 2 of which were thought to be disease-causing. Only 2 sequence changes were previously documented mutations, but several other novel changes were suspected to be disease-causing mutations also., Interpretation: Molecular testing was helpful only in the minority of cases, largely because of a lack of availability, as well as the complexity of the molecular genetics of RP. Improvements in funding, infrastructure, and molecular knowledge will be necessary to improve the transformation of molecular genetic testing into a clinically relevant bedside tool.

Case Report: We report a young girl who first presented with a unilateral total exudative retinal detachment diagnosed as Coats' disease. Eight years later, when she presented with classical retinal hemangioblastomas with reduced vision in the fellow eye, the diagnosis of von Hippel-Lindau (VHL) disease was confirmed., Comments: This case highlights the importance of considering the possibility of VHL in atypical cases of Coats' disease and unusual sporadic cases of unexplained unilateral exudative retinal detachment. The identification of VHL mutations and subsequent screening allows early diagnosis and treatment of asymptomatic retinal or central nervous system hemangioblastomas, as well as other malignancies associated with this syndrome.

Background: The myocilin gene is the first glaucoma gene to be associated with primary open-angle glaucoma (POAG). The hereditary subset of POAG and the role of the myocilin gene in our population are not clearly defined. Identification of cases of hereditary glaucoma and a better appreciation of the role of the myocilin gene may allow earlier diagnosis of the disease and optimize management of those at risk for glaucoma., Methods: Patients were recruited from university glaucoma practices in the Greater Toronto area from 1996 to 1998. Pedigree analysis and DNA banking were performed for each participant. Mutational analysis of the myocilin gene by means of single-strand conformation polymorphism analysis and direct sequencing was completed for 140 probands with POAG of diverse ethnic background., Results: A total of 103 patients (55.7%) had a family history of glaucoma. Disease-causing mutations of the myocilin gene were observed in 7 (5.0%) of the 140 probands, which accounted for 6.5% (5/77) of the familial cases. Most mutations were associated with familial disease, which implies a 50% risk of transmission of a high-risk factor for glaucoma., Interpretation: The hereditary subset of POAG is significant, and heritable glaucoma should always be suspected. In spite of the diversity of the ethnic background of our subjects, the observed prevalence of myocilin gene mutations was comparable to that previously reported, and such mutations do not appear to spare any ethnic group.