Retinal dystrophy (RD) is a heterogeneous group of hereditary diseases caused by loss of photoreceptor function and contributes significantly to the etiology of blindness globally but especially in the industrialized world. The extreme locus and allelic heterogeneity of these disorders poses a major diagnostic challenge and often impedes the ability to provide a molecular diagnosis that can inform counseling and gene-specific treatment strategies. In a large cohort of nearly 150 RD families, we used genomic approaches in the form of autozygome-guided mutation analysis and exome sequencing to identify the likely causative genetic lesion in the majority of cases. Additionally, our study revealed six novel candidate disease genes (C21orf2, EMC1, KIAA1549, GPR125, ACBD5, and DTHD1), two of which (ACBD5 and DTHD1) were observed in the context of syndromic forms of RD that are described for the first time.

Bardet-Biedl syndrome (BBS) is an autosomal recessive ciliopathy with multisystem involvement. So far, 18 BBS genes have been identified and the majority of them are essential for the function of BBSome, a protein complex involved in transporting membrane proteins into and from cilia. Yet defects in the identified genes cannot account for all the BBS cases. The genetic heterogeneity of this disease poses significant challenge to the identification of additional BBS genes. In this study, we coupled human genetics with functional validation in zebrafish and identified IFT27 as a novel BBS gene (BBS19). This is the first time an intraflagellar transport (IFT) gene is implicated in the pathogenesis of BBS, highlighting the genetic complexity of this disease.

Diabetic retinopathy (DR) is a retinal disease which is one of the most severe complications occuring due to diabetes mellitus and is a major cause of blindness. Patients who have diabetes mellitus for number of years develop characteristic group of lesions in the retina which leads to Diabetic retinopathy. It is a multifactorial condition occuring due to complex cellular interactions between biochemical and metabolic abnormalities taking place in all retinal cells. Considerable research efforts in the past 20 years have suggested that the microvasculature of the retina responds to hyperglycemia through a number of biochemical changes, which includes polyol pathway, protein kinase C activation, upregulation of advanced glycation end products formation and renin angiotensin system activation. Various previous studies had suggest that interaction of these biochemical changes may cause a cascade of events, such as apoptosis, oxidative stress, inflammation and angiogenesis which can lead to the damage of a diabetic retina, causing DR. This highlights that oxidative stress, inflammation, angiogenesis-related factors triggers the occurrence of retinal complication in diabetes are highlighted.

Purpose To identify prognostic factors for outcome in children with Vogt-Koyanagi-Harada (VKH) disease. Methods All children 16 years and younger with acute uveitis associated with VKH disease treated between 1999 and 2006 were reviewed. Results Twenty-three children (46 eyes) were identified; 20 (87%) girls and three (13%) boys with a mean age at presentation of 12.572.4 years. Mean follow-up period was 48.6730.8 months. Visual acuity of 20/40 or better was achieved in 38 (82.6%) eyes. Eleven eyes developed at least one complication, including cataract in eight eyes, glaucoma in eight eyes, subretinal neovascular membranes in two eyes, and subretinal fibrosis in one eye. Disease recurred during follow-up in 18 eyes. Development of complications was negatively associated with final visual acuity of 20/20 (P ¼ 0.0317). Shorter interval between symptoms and treatment was a predictor of final visual acuity of 20/20 (odds ratio ¼ 10.4; 95% confidence interval ¼ 1.61-67.3). Recurrence of inflammation was significantly associated with development of complications (P ¼ 0.003), worse visual acuity (P ¼ 0.022) and presence of posterior synechiae of the iris at presentation (P ¼ 0.0083), longer interval between symptoms and treatment (P ¼ 0.013), initial treatment with intravenous corticosteroids (P ¼ 0.0012), and rapid tapering of corticosteroids (P ¼ 0.0063). Conclusion Visual prognosis of VKH in children is generally favourable. Clinical findings at presentation, development of complications, interval between symptoms and treatment, recurrence of inflammation, use of intravenous corticosteroids, and method of tapering of systemic corticosteroids were significant prognostic factors.

Clinical findings at presentation, duration and method of tapering of systemic corticosteroids, and development of extraocular manifestations are significantly associated with final visual acuity, development of ocular complications, and recurrent inflammation. The development of ocular complications was significantly associated with a worse final visual acuity.