Mutation profile of Bardet-Biedl syndrome patients from India: Implicative role of multiallelic rare variants and oligogenic inheritance pattern.

Bardet-Biedl syndrome (BBS), a rare primary form of ciliopathy, with heterogeneous clinical and genetic presentation is characterized by rod cone dystrophy, obesity, polydactyly, urogenital abnormalities, and cognitive impairment. Here, we delineate the genetic profile in a cohort of 108 BBS patients from India by targeted gene sequencing-based approach for a panel of ciliopathy (including BBS) and other inherited retinal disease genes. We report here a higher frequency of BBS10 and BBS1 gene variations. A different spectrum of variations including a putatively novel gene TSPOAP1, for BBS was identified. Increased percentage frequency of digenic variants (36%) in the disease cohort, role of modifiers in familial cases are some of the salient observations in this work. This study appends the knowledge of BBS genetics pertaining to patients from India. We observed a different molecular epidemiology of BBS patients in this study cohort compared to other reports, which emphasizes the need for molecular testing in affected patients.

Association of HERPUD1 genetic variant rs2217332 with age-related macular degeneration and polypoidal choroidal vasculopathy in an Indian cohort.

PURPOSE: Age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV) are sister diseases and have several similar clinical features and still have few genetic differences. The association of HERPUD1 (homocysteine inducible ER protein with ubiquitin like domain 1) gene variant rs2217332 with PCV is known; however, such association with AMD has not been reported in the Indian population. We analyzed the association of rs2217332 with PCV and AMD to identify the preferential association of this variant with these diseases. METHODS: This is a population-based case-control study consisting of 422 patients (129 AMD cases; 101 PCV cases, 192 healthy controls) recruited from the vitreoretinal clinic Sankara Nethralaya. The sample size for the study was calculated using appropriate power calculation methods. Genotype was determined using PCR-based Sanger sequencing. The SPSS V23.0 statistical package tool was used to calculate chi-square and ROC to determine the association of rs2217332 with control, AMD, and PCV. RESULTS: Here, we report for the first time the association of this genetic variant (rs2217332) with AMD and PCV in the Indian population. The case-control study shows a significant association of this SNP with PCV (P value = 0.002); however, this variant is not significantly associated with AMD (P value = 0.602). Comparison between AMD (as control) and PCV (as case) also showed significant association of the SNP with PCV (P value = 0.02). Minor allele A conferred to increase the risk of PCV. CONCLUSIONS: The study concludes that the genetic variant rs2217332 in HERPUD1 gene is highly significantly associated with PCV and not with AMD in Indian populations.

COMBINED HAMARTOMA OF THE RETINA AND RETINAL PIGMENT EPITHELIUM AT PEDIATRIC AGE: Surgical Versus Conservative Approach.

PURPOSE: To report outcomes of pediatric patients with combined hamartoma of the retina and the retina pigment epithelium followed up conservatively or after pars plana vitrectomy. METHODS: This retrospective multicenter study included 62 eyes of 59 pediatric patients with combined hamartoma of the retina and the retina pigment epithelium from 13 different international centers with an average age of 7.7 ± 4.7 (0.3-17) years at the time of the diagnosis and having undergone pars plana vitrectomy or followed conservatively. At baseline and each visit, visual acuity values, optical coherence tomography for features and central foveal thickness, and tumor location were noted. Lesions were called as Zone 1, if it involves the macular and peripapillary areas, and the others were called as Zone 2 lesions. RESULTS: Twenty-one eyes of 20 patients in the intervention group and 41 eyes of 39 patients in the conservative group were followed for a mean of 36.2 ± 40.4 (6-182) months. Best-corrected visual acuity improved in 11 (68.8%) of 16 eyes in the intervention group and 4 (12.9%) of 31 eyes in the conservative group ( P < 0.001). The mean central foveal thickness decreased from 602.0 ± 164.9 µ m to 451.2 ± 184.3 µ m in the intervention group, while it increased from 709.5 ± 344.2 µ m to 791.0 ± 452.1 µ m in Zone 1 eyes of the conservative group. Posterior location of tumor, irregular configuration of the foveal contour and ellipsoid Zone defect in optical coherence tomography, subretinal exudate and prominent vascular tortuosity were associated with poor visual acuity. CONCLUSION: Vitreoretinal surgery is safe and effective in improving vision and reducing retinal distortion in Zone 1 combined hamartoma of the retina and the retina pigment epithelium in children.

Zone-wise examination of optical coherence tomography features and their correspondence to multifocal electroretinography in eyes with nonproliferative diabetic retinopathy.

PURPOSE: To examine (1) the retinal structure by optical coherence tomography (OCT) and function by means of multifocal electroretinography (mfERG) in eyes with and without nonproliferative diabetic retinopathy (NPDR) (2) for correspondence between local retinal function and OCT zones with retinal lesions. METHODS: One hundred and thirty-two eligible participants (30 with nonproliferative DR (NPDR) and 102 with diabetes with no DR) underwent comprehensive ophthalmic examination, optical coherence tomography for retinal thickness measures, mfERG, and ultra-wide field fundus photography. OCT Early Treatment Diabetic Retinopathy Study (ETDRS) grid was overlaid on to mfERG plots. RESULTS: Those with NPDR had significantly thicker full retinal measures in the nine (ETDRS) zones compared to no DR. mfERG P1 latencies in rings 1-6 were significantly delayed, while the response densities in rings 4-6 were lower in the NPDR group. Significant negative correlation was noted between OCT thickness and mfERG P1 response densities in many ETDRS zones. Significant positive correlation was noted between P1 latencies and OCT thickness in a few zones. The combination of cystic spaces, microaneurysms, and hard exudates were present in all zones and were associated with a decrease in P1 response densities compared to no lesions. Reduced P1 response densities were associated with a sporadic delay in the mfERG latencies and vice versa. The number of lesions did not show correspondence to the mfERG measures. CONCLUSIONS: In eyes with NPDR, retinal function is differentially correlated with the DR lesions on OCT and can be assessed using multimodal imaging modalities.

Choroidal neovascularization in 111 eyes of children and adolescents.

PURPOSE: To describe the clinical features, management, and outcomes of choroidal neovascularization (CNV) in children less than 18 years of age. METHODS: This was a retrospective, case control study of 111 eyes of 96 patients. CNV was clinically diagnosed in all patients. Eyes were classified as those that were observed (Controls; Group 1) or those that had treatment (Cases; Group 2). CNV was categorized as regressed, persistent, or recurrent in order to evaluate the anatomical outcomes. RESULTS: Of 96 patients, 68(71%) were male. Mean presenting age was 11.4 ± 3.4 years (median = 11 years, range = 1-17 years). CNV was bilateral in 15(16%) patients. Of 111 eyes, 38 eyes had treatment (Cases) and 73 eyes did not (Natural history group or Controls). Subfoveal CNV was seen in majority of cases (59%). Most common etiology was post-inflammatory (38%), followed by trauma (16%). Eyes were classified as those that were observed (controls; Group 1) or those that had treatment (cases; Group 2). In group 1, spontaneous regression of CNV was seen in 26(36%) eyes and there was no recurrence in this group. In group 2 following treatment, 25(66%) of 38 eyes achieved complete regression at mean 4.9 months and was persistent in 5 eyes. CNV recurrence was seen in 10 eyes with the mean time to first recurrence being 9 months. At presentation, mean best-corrected visual acuity (BCVA) of eyes with subfoveal CNV was logMAR 0.99 that improved to logMAR 0.63 with treatment. Mean follow-up was 17 months. CONCLUSION: CNV results in significant visual decline in children; most commonly of post-inflammatory etiology. Treatment achieves high regression rates, albeit with limited visual improvement.

A prospective, interventional study comparing the outcomes of macular hole surgery in eyes randomized to C3F8, C2F6, or SF6 gas tamponade.

PURPOSE: Analysis of outcomes of macular hole (MH) surgery using 12% C3F8, 16% C2F6, or 18% SF6 as randomized gas tamponading agent. METHODS: This is a prospective, randomized, interventional study of 159 eyes with idiopathic MH undergoing 23/25G pars-plana vitrectomy with internal limiting membrane peeling and gas tamponade. Eyes were stratified into two groups: Group I (MH < 800 µ) and group II (MH > 800 µ) according to MH apical diameter. Eyes in group I were randomized to receive either 18% SF6, 16% C2F6, or 12% C3F8. Eyes in group II were randomized to either 16% C2F6 or 12% C3F8. Clinical details, MH parameters on optical coherence tomography, surgical details and complications were analyzed. Outcome measures were type of hole closure (I/II), best corrected visual acuity, intraocular pressure, and cataract progression. RESULTS: In Group I (n = 139), type 1 closure was achieved in 107 (77%) eyes. Type 1 closure rates in group I per gas tamponade were as follows: SF6 (70%), C2F6 (80%), C3F8 (78%) (p = 0.503, chi-square test for independence). There was no statistical difference in MH closure rates between SF6 and C2F6 (p = 0.134), SF6 and C3F8 (p = 0.186), and C2F6 and C3F8 (p = 0.373). In Group II (n = 20), type 1 closure was achieved in 12 (60%) eyes. Type 1 closure rates in group II per gas tamponade were as follows: C2F6 (75%), C3F8 (50%) (p = 0.132, Two proportion Z test). Mean follow-up after surgery was 2.66 ± 2.74 months. CONCLUSION: Given the similar outcomes of using 18% SF6, 16% C2F6, or 12% C3F8 in idiopathic macular hole surgery, the advantage of using a shorter acting tamponade translates into earlier recovery and rehabilitation.

Incidence, Risk Factors, and Outcomes of Retinal Detachment after Pediatric Cataract Surgery.

PURPOSE: To report the incidence of, and to estimate the long-term risk and predisposing factors and the surgical outcomes for, retinal detachment (RD) after pediatric cataract surgery. DESIGN: Retrospective consecutive interventional case series. PARTICIPANTS: During the study period 1996 to 2007 at a tertiary eye care institute, 481 eyes of 295 children aged below 16 years with no other ocular and systemic anomalies who underwent lensectomy, posterior capsulorrhexis, and anterior vitrectomy combined with primary intraocular lens implantation were included. The median follow-up was 66 months. METHODS: Kaplan-Meier estimates and Cox proportional hazard regression model were used for estimating cumulative risk and hazard ratio (HR), respectively. Difference between measured preoperative axial length and age-matched mean axial length (prior studies) was calculated, and was defined as age-adjusted axial length difference (ALD) (minus and plus denotes myopia and hypermetropia, respectively). MAIN OUTCOME MEASURES: Cumulative risk and potential risk factors for RD. RESULTS: Of the total, 12 eyes of 9 children developed RD after cataract surgery, with a median time of 70 months. The overall risk of RD was 5.5% at 10 years after cataract surgery. All 9 children were male. The multi-adjusted HR associated with increased risk of RD was 12.42 (95% confidence interval [CI], 2.91-53.01; P = 0.001) for eyes of children with intellectual disability and 21.93 (95% CI, 2.95-162.80; P = 0.003) for eyes of children with age-adjusted ALD < -1 mm (myopic). Retinal break associated with induction of posterior vitreous detachment was the most common (8 eyes) cause of RD. No surgical intervention was done in 2 eyes. Scleral buckle and vitrectomy combined with belt buckle were performed in 4 and 6 eyes, respectively. At final follow-up, 5 and 9 eyes had a visual acuity better than or equal to 6/18 and 6/60, respectively. CONCLUSIONS: A 5.5% risk for RD is estimated for the first 10 years after cataract surgery in children with no known ocular and systemic anomalies. The risk significantly increases in a male, myopic, and intellectual disabled child. We emphasize the need for regular and long-term follow-up after pediatric cataract surgery.

Artificial intelligence and hemodynamic studies in optical coherence tomography angiography for diabetic retinopathy evaluation: A review.

Diabetic retinopathy (DR) is a rapidly emerging retinal abnormality worldwide, which can cause significant vision loss by disrupting the vascular structure in the retina. Recently, optical coherence tomography angiography (OCTA) has emerged as an effective imaging tool for diagnosing and monitoring DR. OCTA produces high-quality 3-dimensional images and provides deeper visualization of retinal vessel capillaries and plexuses. The clinical relevance of OCTA in detecting, classifying, and planning therapeutic procedures for DR patients has been highlighted in various studies. Quantitative indicators obtained from OCTA, such as blood vessel segmentation of the retina, foveal avascular zone (FAZ) extraction, retinal blood vessel density, blood velocity, flow rate, capillary vessel pressure, and retinal oxygen extraction, have been identified as crucial hemodynamic features for screening DR using computer-aided systems in artificial intelligence (AI). AI has the potential to assist physicians and ophthalmologists in developing new treatment options. In this review, we explore how OCTA has impacted the future of DR screening and early diagnosis. It also focuses on how analysis methods have evolved over time in clinical trials. The future of OCTA imaging and its continued use in AI-assisted analysis is promising and will undoubtedly enhance the clinical management of DR.

Natural course of non-center-involving diabetic macular edema progression in patients under initial observation.

PURPOSE: We aim to report the natural course of non-center involving diabetic macular edema (NCIDME) progression to center involving diabetic macular edema (CIDME) and associated risk factors. METHODS: This is a multicenter retrospective comparative study. Data was collected from electronic medical records from 8 centers in India covering. We included patients with type 2 diabetes above 18 years of age with treatment-naïve NCIDME on OCT and best-corrected visual acuity at baseline of 6/12 or better who were under observation for NCIDME and had 2 years follow-up data. RESULTS: Out of 72 patients with NCIDME, 26.38% patients progressed to CI DME by 2 years, and the visit wise proportion was 11.11% at 6 months, 7% at 1st year and 8.3% at 2 years. The change in CST was statistically significant at 2 years in patients who developed CIDME, the mean difference was 137.73 ± 48.56 microns p = 0.045. Duration of diabetes mellitus > 10 years was the only risk factor for conversion to CIDME. CONCLUSION: A quarter of eyes with NCIDME developed CIDME and 15% progressed from NPDR to PDR by 2 years, highlighting the disease burden in these patients with NCIDME.

Rationale and protocol paper for the Asia Pacific Network for inherited eye diseases.

PURPOSE: There are major gaps in our knowledge of hereditary ocular conditions in the Asia-Pacific population, which comprises approximately 60% of the world's population. Therefore, a concerted regional effort is urgently needed to close this critical knowledge gap and apply precision medicine technology to improve the quality of lives of these patients in the Asia-Pacific region. DESIGN: Multi-national, multi-center collaborative network. METHODS: The Research Standing Committee of the Asia-Pacific Academy of Ophthalmology and the Asia-Pacific Society of Eye Genetics fostered this research collaboration, which brings together renowned institutions and experts for inherited eye diseases in the Asia-Pacific region. The immediate priority of the network will be inherited retinal diseases (IRDs), where there is a lack of detailed characterization of these conditions and in the number of established registries. RESULTS: The network comprises 55 members from 35 centers, spanning 12 countries and regions, including Australia, China, India, Indonesia, Japan, South Korea, Malaysia, Nepal, Philippines, Singapore, Taiwan, and Thailand. The steering committee comprises ophthalmologists with experience in consortia for eye diseases in the Asia-Pacific region, leading ophthalmologists and vision scientists in the field of IRDs internationally, and ophthalmic geneticists. CONCLUSIONS: The Asia Pacific Inherited Eye Disease (APIED) network aims to (1) improve genotyping capabilities and expertise to increase early and accurate genetic diagnosis of IRDs, (2) harmonise deep phenotyping practices and utilization of ontological terms, and (3) establish high-quality, multi-user, federated disease registries that will facilitate patient care, genetic counseling, and research of IRDs regionally and internationally.

DEVELOPMENT OF FOCAL CHOROIDAL EXCAVATION IN A CASE OF IDIOPATHIC CHOROIDAL NEOVASCULAR MEMBRANE.

PURPOSE: The purpose of this study was to demonstrate the evolution of focal choroidal excavation in a 17-year-old girl on treatment for a choroidal neovascular membrane over a 6-year follow-up. METHODS: Review of medical and imaging records of a 17-year-old girl who presented with a choroidal neovascular membrane in her left eye treated with multiple intravitreal antivascular endothelial growth factor injections over a period of 6 years. RESULTS: The patient developed recurrent episodes of subretinal hemorrhage that were treated with antivascular endothelial growth factor injections. Over the follow-up period, swept source optical coherence tomography through the lesion revealed progressive reduction in size of the choroidal neovascular membrane complex with the development of acquired focal choroidal excavation.

Examination under anesthesia: Preferred Practice.

Pediatric ocular examinations are often a challenge in the outpatient setting due to limited cooperation of the child. Hence an evaluation under anesthesia (EUA) or sedation is important for a holistic ophthalmic examination. It can be combined with short procedures, such as suture removal and corneal scrappings, both for diagnosis and for the management of several ophthalmic disorders. It can also be performed before planning a surgical intervention to record the baseline characters and formulate or refine a surgical plan. Every EUA must be used as a chance to perform a complete ophthalmic examination rather than perform a single task such as recording the intraocular pressure. This article aims to provide a protocol that can be followed for a complete EUA.

Association of OCT and OCT angiography measures with the development and worsening of diabetic retinopathy in type 2 diabetes.

OBJECTIVE: To assess if optical coherence tomography (OCT) and OCT angiography (OCTA) measures are associated with the development and worsening of diabetic retinopathy (DR) over four years. METHODS: 280 participants with type 2 diabetes underwent ultra-wide field fundus photography, OCT and OCTA. OCT-derived macular thickness measures, retinal nerve fibre layer and ganglion cell-inner plexiform layer thickness and OCTA-derived foveal avascular zone area, perimeter, circularity, vessel density (VD) and macular perfusion (MP) were examined in relation to the development and worsening of DR over four years. RESULTS: After four years, 206 eyes of 219 participants were eligible for analysis. 27 of the 161 eyes (16.7%) with no DR at baseline developed new DR, which was associated with a higher baseline HbA1c and longer diabetes duration. Of the 45 eyes with non-proliferative DR (NPDR) at baseline, 17 (37.7%) showed DR progression. Baseline VD (12.90 vs. 14.90 mm/mm2, p = 0.032) and MP (31.79% vs. 36.96%, p = 0.043) were significantly lower in progressors compared to non-progressors. Progression of DR was inversely related to VD ((hazard ratio [HR] = 0.825) and to MP (HR = 0.936). The area under the receiver operating characteristic curves for VD was AUC = 0.643, with 77.4% sensitivity and 41.8% specificity for a cut-off of 15.85 mm/mm2 and for MP it was AUC = 0.635, with 77.4% sensitivity and 25.5% specificity for a cut-off of 40.8%. CONCLUSIONS: OCTA metrics have utility in predicting progression rather than the development of DR in individuals with type 2 diabetes.

Inter-observer agreement in grading severity of diabetic retinopathy in wide-field fundus photographs.

OBJECTIVE: To examine the inter-observer agreement between two retina specialists in grading diabetic retinopathy (DR) severity in ultra-wide-field fundus photographs. METHODS: Two hundred and seventy patients with diabetes, who visited the vitreoretinal specialty at a tertiary eye care hospital, with or without DR underwent comprehensive ophthalmic examination, dilated retinal exam and Optos ultra-wide-field (UWF) retinal photography. Optos images were graded for DR severity based on the International Clinical Diabetic Retinopathy Disease Severity Scale by two retina specialists with same number of years of experience, masked to the clinical details of the participants. RESULTS: The two graders showed agreement in 229/270 images (84.8%) and disagreement in 41/270 images (15.2%). The unweighted kappa for agreement between graders was k = 0.715, SE = 0.037 and the weighted kappa was k = 0.838, SE = 0.022. No DR was identified in 170/270 (62.9%) patients, mild NPDR in 15/270 (5.6%) patients, moderate NPDR in 35/270 (12.9%) patients, severe NPDR in 4/270 (1.48%) patient and PDR in 5/270 (1.85%) patients by both graders. Disagreement was neither related to the learning curve of graders nor with the patient's age (p = 0.574), gender (p = 0.169), duration of diabetes (0.660) or the lens being phakic or pseudophakic (p = 0.171) on logistic regression. CONCLUSIONS: The impact of disagreement noted between observers in grading DR on UWF fundus photographs should be considered when utilizing UWF system in clinical studies.

Next-generation sequencing--based genetic testing and phenotype correlation in retinitis pigmentosa patients from India.

Purpose: Inherited retinal dystrophies (IRD) are a heterogeneous group of retinal diseases leading to progressive loss of photoreceptors through apoptosis. Retinitis pigmentosa (RP) is considered the most common form of IRD. Panel-based testing in RP has proven effective in identifying the causative genetic mutations in 70% and 80% of the patients. This is a retrospective, observational, single-center study of 107 RP patients who had undergone next-generation sequencing-based targeted gene panel testing for IRD genes. These patients were inspected for common phenotypic features to arrive at meaningful genotype-phenotype correlation. Methods: Patients underwent complete ophthalmic examination, and blood was collected from the proband for DNA extraction after documenting the pedigree. Targeted Next Generation Sequencing (NGS) was done by panel-based testing for IRD genes followed by co-segregation analysis wherever applicable. Results: Of the 107 patients, 72 patients had pathogenic mutations. The mean age of onset of symptoms was 14 ± 12 years (range: 5-55). Mean (Best Corrected Visual Acuity) BCVA was 6/48 (0.9 logMAR) (range 0.0-3.0). At presentation, over one-third of eyes had BCVA worse than 6/60 (<1 logMAR). Phenotype analysis with the gene defects showed overlapping features, such as peripheral well-defined chorioretinal atrophic patches in patients with CERKL, PROM1, and RPE65 gene mutations and large macular lesions in patients with RDH12 and CRX gene mutations, respectively. Nummular or clump-like pigmentation was noted in CRB1, TTC8, PDE6A, and PDE6B. Conclusion: NGS-based genetic testing can help clinicians to diagnose RP more accurately, and phenotypic correlations can also help in better patient counselling with respect to prognosis and guidance regarding ongoing newer gene-based therapies.

Retinal Displacement after Scleral Buckle versus Combined Buckle and Vitrectomy for Rhegmatogenous Retinal Detachment: ALIGN Scleral Buckle versus Pars Plana Vitrectomy with Scleral Buckle.

PURPOSE: To assess the risk of retinal displacement after scleral buckle (SB) versus pars plana vitrectomy with SB (PPV-SB). DESIGN: Multicenter prospective nonrandomized clinical trial. METHODS: The study took place at VitreoRetinal Surgery in Minneapolis, Minnesota, Sankara Nethralaya in Chennai, India, and St. Michael's Hospital in Toronto, Canada from July 2019 to February 2022. Patients who underwent successful SB or PPV-SB for fovea-involving rhegmatogenous retinal detachment with gradable postoperative fundus autofluorescence (FAF) imaging were included in the final analysis. Two masked graders assessed FAF images 3 months postoperatively. Metamorphopsia and aniseikonia were assessed with M-CHARTs and the New Aniseikonia Test, respectively. The primary outcome was the proportion of patients with retinal displacement detected with retinal vessel printings on FAF in SB versus PPV-SB. RESULTS: Ninety-one eyes were included in this study, of which 46.2% (42 of 91) had SB and 53.8% (49 of 91) underwent PPV-SB. Three months postoperatively, 16.7% (7 of 42) in the SB group and 38.8% (19 of 49) in the PPV-SB group had evidence of retinal displacement (difference = 22.1%; odds ratio = 3.2; 95% confidence interval [CI], 1.2-8.6; P = 0.02) on FAF. The statistical significance of this association increased after adjustment for extent of retinal detachment, baseline logarithm of the minimum angle of resolution, lens status, and sex in a multivariate regression analysis (P = 0.01). Retinal displacement was detected in 22.5% (6 of 27) of patients in the SB group with external subretinal fluid drainage and 6.7% (1 of 15) of patients without external drainage (difference = 15.8%; odds ratio = 4.0; 95% CI, 0.4-36.9; P = 0.19). Mean vertical metamorphopsia, horizontal metamorphopsia (MH), and aniseikonia were similar between patients in the SB and PPV-SB groups. There was a trend to worse MH in patients with retinal displacement versus those without retinal displacement (P = 0.067). CONCLUSIONS: Scleral buckle is associated with less retinal displacement compared with PPV-SB, indicating that traditional PPV techniques cause retinal displacement. There is a trend toward increased risk of retinal displacement in SB eyes that underwent external drainage compared with SB eyes without drainage, which is consistent with our understanding that the iatrogenic movement of subretinal fluid, such as that which occurs intraoperatively during external drainage with SB, may induce retinal stretch and displacement if the retina is then fixed in the stretched position. There was a trend to worse MH at 3 months in patients with retinal displacement. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Genetic testing in four Indian families with suspected Stickler syndrome.

Purpose: Stickler syndrome is associated with the development of rhegmatogenous retinal detachment (RRD), and often presents with ocular, auditory, skeletal, and orofacial abnormalities. Molecular analysis has proven effective in diagnosis, confirmation and classification of the disease. We aimed to describe the utility of next-generation sequencing (NGS) in genetic analysis of four Indian families with suspected Stickler syndrome. Methods: The index cases presented with retinal detachment with family history. Genetic analysis in the index case was performed by next-generation sequencing of inherited retinal degeneration genes, and validated by Sanger sequencing followed by co-segregation analysis in the other family members. Results: Twenty patients were included for the genetic analysis (15 males and 5 females from four families). Clinical details were available for 15 patients (30 eyes). Fourteen eyes (11 patients) developed RRD. In the 16 eyes without RRD, 8 underwent barrage laser to lattice degeneration and 8 were under observation. Disease segregating heterozygous mutations with pathogenic/likely pathogenic effect was identified in COL2A1 (c.4318-1G>A, c.141G>A, c.1221+1G>A for 3 families) and COL11A1 (c.1737+1 G>A for 1 family) gene. In addition to the mutation in the COL2A1 gene, a pathogenic heterozygous variant associated with risk for arrhythmogenic right ventricular cardiomyopathy (ARVC) was identified in one member. Conclusion: NGS testing confirmed the presence of the causative gene for Stickler syndrome in the index case followed by evaluation of family members and confirmation of genetic and ocular findings. We believe that this may be the first such report of families with RRD from India.

Optical Coherence Tomography-Based Prevalence of Diabetic Macular Edema and its Associated Risk Factors in Urban South India: A Population-Based Study.

BACKGROUND: To estimate the prevalence of optical coherence tomography (OCT)-defined diabetic macular oedema (DME) in urban South Indian population and to elucidate their associated risk factors. METHODS: Of 911 participants from the Sankara Nethralaya Diabetic Retinopathy and Molecular Genetics Study-II (SN-DREAMS-), 759 who underwent OCT were analysed. The participants underwent a comprehensive examination and retinal photography following a standard protocol for diabetic retinopathy (DR) grading. The subjects were categorized into centre-involving DME (CI-DME), non-centre involving DME (NCI-DME), and No-DME based on the mean retinal thickness at the central 1 mm, inner and outer ETDRS subfields. RESULTS: The prevalence of CI-DME and NCI-DME in the Chennai population was 3.03% (95% CI: 3.01-3.05) and 10.80% (95% CI: 10.7-11.02). NCI-DME was found to be higher by 9.5% (95% CI: 0.07-0.11) in the early stages of DR. A greater number of subjects with CI DME were aged >60 years and had diabetes mellitus (DM) for >10 years. The significant risk factors for NCI-DME are diastolic blood pressure, serum total cholesterol, serum triglyceride, insulin use and neuropathy (OR (95% CI): 0.97 (0.94-100), 1.00 (1.00-1.01), 0.99 (0.98-0.99), 2.32 (1.15-4.68) and 4.24 (1.22-14.69), respectively) and for CI DME are duration of diabetes, anaemia, neuropathy and insulin use (OR (95% CI): 2.49 (0.96-6.40), 3.41 (1.34-8.65), 10.58 (1.68-66.56) and 3.51 (1.12-10.95), respectively). CONCLUSIONS: The prevalence of NCI-DME was found to be higher than that of CI-DME in patients with DR.