BackgroundLeber congenital amaurosis (LCA) is the most severe form of inherited retinal visual impairment in children. So far, mutations in more than 20 genes have been known to cause LCA and among them, RPE65 is a suitable candidate for gene therapy. The mutational screenings of RPE65 and other LCA genes are requisite in support of emerging gene specific therapy for LCA. Therefore, we have carried out a comprehensive LCA genes screening using a combined approach of direct sequencing and DNA microarray based Asper chip analysis.Methodology/Principal FindingsThirty clinically diagnosed index LCA cases from Southern India were screened for coding and flanking intronic regions of RPE65 through direct sequencing. Among thirty, 25 cases excluded from RPE65 mutations were subjected to Asper chip analysis, testing 784 known pathogenic variations in 15 major LCA genes. In RPE65 screening, four different pathogenic variations including two novel (c.361insT & c.939T>A) and two known (c.394G>A & c.361delT) mutations were identified in five index cases. In the chip analysis, seven known pathogenic mutations were identified in six index cases, involving genes GUCY2D, RPGRIP1, AIPL1, CRX and IQCB1. Overall, 11 out of 30 LCA cases (36.6%) revealed pathogenic variations with the involvement of RPE65 (16.6%), GUCY2D (10%), RPGRIP1 (3.3%), AIPL1 (3.3%) and CRX & IQCB1 (3.3%).Conclusions/SignificanceOur study suggests that such combined screening approach is productive and cost-effective for mutation detection and can be applied in Indian LCA cohort for molecular diagnosis and genetic counselling.

This study reveals the range of ectodermal pathology in cases of SSPS that result from WNT10A mutations. Eyelid cysts provide a useful clinical clue to diagnosing SSPS which may be less rare than is currently appreciated.

In our study, rs1015213 (located in the intergenic region between PCMTD1 and ST18) was associated significantly with PAC/PACG, confirming prior reports of an association between this region and angle closure glaucoma. Further work with a larger sample size is necessary to confirm the importance of COL11A1 and PLEKHA7 in the pathogenesis of glaucoma.

Purpose To report the technical aspects, systemic, and ocular safety of a novel, low-cost, wide-field, infant retinal camera for use on premature infants. Methods The device, the “3nethra Neo” (Neo) is a 120° portable, contact, wide-field, unibody camera, with a CMOS sensor (2040 × 2040 resolution) and a warm light-emitting diode (LED) illumination source. The Neo was used to image 140 awake, preterm infants between postmenstrual age (PMA) of 28 to 37 weeks, undergoing retinopathy of prematurity (ROP) screening. Baseline, ‘during procedure', at 5 minutes, and for 60 minutes postprocedure, readings of oxygen saturation and heart rate were recorded. The device design, optics, illumination, and software specifications were compared with the RetCam 3. Results Study defined bradycardia (9 infants, 6.4%), tachycardia (3 infants, 2.1%), and hypoxia (2 infants, 1.4%) were observed but there were no clinically significant systemic changes that required intervention during or following any of the study time intervals. There was a transient increase in heart rate by 9.68 (7.53–11.83; P < 0.0001) and marginal decrease in oxygen saturation (−1.94 [−1.60 to −2.28], P < 0.0001), which started to return to baseline 5 minutes after the procedure. Transient redness was seen in two eyes (0.7%) of two infants. No other ocular adverse effects were observed. Conclusions The Neo is easy to use in preterm infants and being compact was readily portable. There were no significant ocular or systemic adverse effects, potentially allowing it to be a viable low-cost device for ROP screening in low resource settings. Translational Relevance The camera provides a safe and affordable alternative to image the retina of infants by using novel illumination and lens mechanics and has the potential of worldwide acceptance.

Stargardt disease (STGD) is the leading cause of juvenile macular degeneration associated with progressive central vision loss, photophobia, and colour vision abnormalities. In this study, we have described the clinical and genetic features of Stargardt patients from an Indian cohort. The next generation sequencing was carried out in five clinically confirmed unrelated patients and their family members using a gene panel comprising 184 retinal specific genes. Sequencing results were analyzed by read mapping and variant calling in genes of interest, followed by their verification and interpretation. Genetic analysis revealed ABCA4 mutations in all of the five unrelated patients. Among these, four patients were found with compound heterozygous mutations and another one had homozygous mutation. All the affected individuals showed signs and symptoms consistent with the disease phenotype. We report two novel ABCA4 mutations in Indian patients with STGD disease, which expands the existing spectrum of disease-causing variants and the understanding of phenotypic and genotypic correlations. Screening for causative mutations in patients with STGD using panel of targeted gene sequencing by NGS would be a cost effective tool, might be helpful in confirming the precise diagnosis, and contributes towards the genetic counselling of asymptomatic carriers and isolated patients.