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.

Fractal analysis of the macular region in healthy eyes using swept-source optical coherence tomography angiography.

PURPOSE: This cross-sectional observational study evaluated the relationship between retinal vascular fractal dimension (FD) and age, as well as other vascular parameters in healthy eyes using swept-source optical coherence tomography angiography (SS-OCTA). METHODS: The study cohort consisted of 222 eyes of 116 healthy participants with no ocular or systemic disease. SS-OCTA images were captured and analyzed using the Plex Elite 9000 and software tools available in the advanced retinal imaging (ARI) network hub. The retinal vascular layers were defined by the instrument's automatic retinal layer segmentation. The fractal analysis was performed on the superficial capillary plexus (SCP), deep capillary plexus (DCP), and the whole retina. Grayscale OCTA images were standardized and binarized using ImageJ and fractal box-counting analyses were performed using Fractalyse software. Pearson's correlation was used to analyze the correlation between FD and retinal vascular parameters. RESULTS: The results showed that FD values were significantly higher in the 6 mm ring and the whole 6 × 6 scan region when compared to the 1 mm ETDRS central subfield. The correlation between age and FD was weak with a significant positive correlation between age and FD of the SCP in the 6 mm ring and between age and FD of the DCP in the 1 mm ring. Overall, differences in FD values in these healthy eyes were extremely small regardless of age or macular location. CONCLUSION: FD values in normal eyes show little variation with age and are relatively stable across the macula. This suggests that FD values may not need adjustment for age or location when evaluated in the context of retinal disease.

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.

Structural and functional changes among diabetics with no diabetic retinopathy and mild non-proliferative diabetic retinopathy using swept-source optical coherence tomography angiography and photopic negative response.

PURPOSE: To assess the structural and functional changes among diabetics with no diabetic retinopathy (NDR) and mild non-proliferative diabetic retinopathy (NPDR) using swept-source optical coherence tomography angiography (SSOCTA) and photopic negative response (PhNR) and to find the earliest changes. METHODS: This was a prospective, cross-sectional, case-control study. Participants with minimum 5 years of diabetes mellitus (DM) were recruited and classified as NDR and mild NPDR based on fundus findings. Age-matched normals with nil ocular pathology were considered as controls. SSOCTA scan acquisition (6*6 mm angiography), followed by full field photopic electroretinography (FFERG) and red on blue PhNR (R/B PhNR) were done with complete pupillary dilatation. RESULTS: A total of 88 participants were included with 35 controls, 39 NDR and 14 mild NPDR subjects. Vessel density of the superficial capillary plexus (SCP) and deep capillary plexus (DCP) of mild NPDR were significantly reduced compared to the controls (17.12 ± 2.65 mm-1 vs. 18.75 ± 0.90 mm-1, p = 0.025 and 7.96 ± 3.92 mm-1 vs. 11.83 ± 3.05 mm-1, p = 0.001 respectively). None of the parameters of controls had significant difference compared to NDR group (p > 0.05). The amplitudes of white on white (W/W) a-wave, W/W b-wave, red on blue (R/B) PhNR baseline to trough (BT) and R/B PhNR peak to trough in controls were significantly high compared to NDR and mild NPDR. Amplitude of R/B PhNR BT had the maximum area under the curve of 75.9% with a sensitivity and specificity of 94.3and 77.4%, respectively. CONCLUSION: A significant decrease in functional changes as measured by ERG especially PhNR, is seen even among the NDR group compared to controls unlike SSOCTA parameters that measures very early vascular structural changes. PhNR is a sensitive test to identify early preclinical changes in DR when microvascular structural changes as determined by SSOCTA are normal.

The application of clinical registries in ophthalmic trauma-the International Globe and Adnexal Trauma Epidemiology Study (IGATES).

Ophthalmic trauma is a leading cause of preventable monocular blindness worldwide. The prevalence of ophthalmic trauma varies considerably based on geographic location, socio-economic status, age groups, occupation, and cultural practices such as firework celebrations. Clinical registries are known to be valuable in guiding the diagnosis, management, and prognostication of complex diseases. However, there is currently a lack of a centralized international data repository for ophthalmic trauma. We draw lessons from past and existing clinical registries related to ophthalmology and propose a new suitable international multicenter clinical registry for ophthalmic trauma: the International Globe and Adnexal Trauma Epidemiology Study (IGATES). IGATES is hosted on a secure web-based platform which exhibits user-friendly smart features, an integrated Ocular Trauma Score (OTS) prognosis calculator, efficient data collection points, and schematic graphical software. IGATES currently has 37 participating centers globally. The data collected through IGATES will be primarily used to develop a more robust and improved ophthalmic trauma prognostic classification system, the Ocular Trauma Score-2 (OTS-2), which builds on previous systems such as the Birmingham Eye Trauma Terminology System (BETTS) and Ocular Trauma Score (OTS). Furthermore, IGATES will act as a springboard for further research into the epidemiology, diagnosis, and management of ophthalmic trauma. Ultimately, IGATES serves to advance the field of ophthalmic trauma and improve the care that patients with ophthalmic trauma receive.

Treatment outcomes of combination of anti-vascular endothelial growth factor injection and laser photocoagulation in Type 1 ROP and APROP.

PURPOSE: To study treatment outcomes of combination treatment of intravitreal anti-vascular endothelial growth factor (VEGF) injection and laser photocoagulation in Type 1 Retinopathy of Prematurity (ROP) and Aggressive Posterior ROP (APROP). METHODS: This is a retrospective observational study of 87 eyes of 48 premature babies who presented with Type I ROP or APROP and were treated with combination of laser and anti-VEGF therapy. Retrospective evaluation of case records was done to collect data on gestational age, birth weight, age at intervention, anterior segment and fundus findings, intervention with laser and anti-VEGF and response to treatment. Outcome measure was defined as attached retina at posterior pole at last follow-up. RESULTS: Mean gestational age was 29.1 weeks, and mean birth weight was 1226.9 gms. Sixty-six (75.8%) eyes had Type I ROP and 21 (24.1%) eyes had APROP at presentation. Five eyes (3 patients) were lost to follow-up after treatment. Of 82 eyes, 80.5% (66 eyes) showed regression of ROP following combination treatment and 19.5% (16 eyes) needed surgery. Of these, 15 underwent surgery and 12 had successful outcome. Mean follow-up duration of patients was 52 weeks. Finally, 95.1% (78 eyes) had attached retina at posterior pole and 4.9% (4 eyes) had detached retina. CONCLUSION: We conclude that combination therapy is an effective and safe treatment strategy for Type I ROP and APROP.

Epidemiology and outcomes of open globe injuries: the international globe and adnexal trauma epidemiology study (IGATES).

PURPOSE: To detail the methodology for a novel ocular trauma registry and utilize the registry to determine the demographics, nature of injury, and associations of severe visual loss for open globe injuries (OGI). METHODS: Thirteen hospitals in 7 countries used International Globe and Adnexal Trauma Epidemiology Study (IGATES) platform. Patients presenting between April 2009 and 2020 with OGI (with or without) adnexal involvement or intraocular foreign body (IOFB) were included. RESULTS: Analyses of presenting and final VA, using "severe vision loss" (VA ≤ 6/60) and "no severe loss" (VA > 6/60), were performed. Four hundred fifty-four (64%) patients had VA < 6/60 at presentation and 327 (44.8%) at final follow-up, with a highly significant association between presenting and final VA (p < 0.0001). From the cohort of 746 patients, 37 were missing VA at presentation and 16 at follow-up and complete clinical data was available for 354 patients. The male to female ratio is 6:1, and mean age 36.0 ± 20.0 years old. Relative afferent pupillary defect (RAPD), zone III injury, IOFB, and eyelid injury at presentation were recorded in 50 (6.7%), 55 (7.8%), 97 (13%), and 87 (11.7%) patients, respectively, and were significantly associated with VA < 6/60 at follow-up. Older age, ≥ 61 years, was associated with 3.39 times (95% CI: 1.95-5.89) higher risk than ≤20-year-old patients (p < 0.0001) and males 0.424 times (95% CI: 0.27-0.70) lower risk than female (p = 0.0001) of severe vision loss (SVL). CONCLUSION: In OGIs from 13 hospitals, female gender, older age, zone III injury, eyelid injury, and IOFB were associated with higher risk of visual outcome of SVL.

ANATOMICAL AND VISUAL OUTCOMES IN STAGE 5 RETINOPATHY OF PREMATURITY WITH MICROINCISION VITRECTOMY SURGERY.

PURPOSE: To report anatomical and visual outcomes and potential prognostic factors with microincision vitrectomy surgery in Stage 5 retinopathy of prematurity. METHODS: The medical records of premature babies who underwent microincision vitrectomy surgery for Stage 5 retinopathy of prematurity using 23G, 25G, or 27G instrumentation and had a minimum follow-up of 6 weeks were, retrospectively, analyzed. Primary outcome measures were anatomical success at last follow-up defined as retinal attachment at the posterior pole and visual outcomes. Potential risk factors and complications influencing anatomical outcomes were also analyzed. RESULTS: One hundred seventy eyes of 115 infants underwent lensectomy and vitrectomy with microincision vitrectomy surgery. After a mean follow-up of 30.59 ± 33.24 weeks, anatomical success was achieved in 56 eyes (33.7%) of 166 eyes that had a minimum follow-up of 6 weeks. Occurrence of vitreous hemorrhage was more with 23 gauge (62.27%) as compared to 25 gauge (37.73%) (P = 0.024). With increase in age with each week, the probability of achieving anatomical success was found to be significantly more (odds ratio 1.030; confidence interval = 1.010-1.060; P = 0.008). Presence of anterior segment pathology was associated with poor anatomical outcomes (odds ratio 2.480; confidence interval = 1.190-5.160; P = 0.010). Seventeen children with attached retina had a follow-up of 14 months-5 years, of which ambulatory vision was recorded in five eyes and the ability to identify objects close to face in 12 eyes. CONCLUSION: Although surgery for Stage 5 retinopathy of prematurity is challenging, anatomical success can be seen in one-third of cases with microincision vitrectomy surgery. Visual prognosis may be limited but still beneficial.

Outcome of sutured scleral fixated intraocular lens in Marfan syndrome in pediatric eyes.

PURPOSE: To report the clinical outcomes and complications in eyes with Marfan syndrome with subluxated/dislocated lens undergoing sutured scleral fixated intraocular lens (SSFIOL) implantation. METHODS: A retrospective review was done for a consecutive series of 73 eyes of 43 patients with Marfan syndrome, with age less than 18 years who underwent SSFIOL from July 2000 to June 2017. Postoperative best corrected visual acuity, intraocular pressure and refractive error, intraoperative and postoperative complications and time for the development of these complications were analyzed. RESULTS: Visual acuity improved significantly to 0.43 ± 0.30 (p = 0.01), 0.40 ± 0.3 (p = 0.00) and 0.39 ± 0.3 (p = 0.00) logMAR units at 6 weeks, 1 year and at last follow-up, respectively. The refractive error reduced significantly (p = 0.056, 0.039 and 0.031) at 6 weeks, 1 year and final follow-up following surgery. Intraoperative complications included iatrogenic retinal break (n = 3) and surgical trauma to the iris (n = 1). Postoperative complications included increased intraocular pressure in 3 eyes (4.1%), intraocular lens dislocation/subluxation in 5 eyes (6.8%), retinal detachment in 3 eyes (4.1%), choroidal detachment in 1 eye (1.3%), pupillary capture in 15 eyes (20.5%), vitreous hemorrhage in 1 eye (1.3%), pre-retinal hemorrhage in 1 eye (1.3%) and hyphema in 1 eye (1.3%). CONCLUSION: SSFIOL provides good visual outcomes in eyes with ectopia lentis associated with Marfan syndrome. Complications can be seen in some cases, and the parents need to be counseled regarding the same before surgical intervention.

Elevated serum OxLDL is associated with progression of type 2 Diabetes Mellitus to diabetic retinopathy.

Hyperlipidemia is associated with the progression of diabetic retinopathy (DR). Paraoxonase 1 (PON1), an esterase is known to prevent systemic LDL oxidation. This study assessed if serum oxLDL is associated with the progression of Type 2 DM to DR. This study is part of a three-year hospital based prospective study where 87 subjects were recruited. This included T2DM without DR (n = 22); Non-Proliferative (NPDR) (n = 21) and Proliferative DR (PDR) (n = 22) along with age/sex matched controls (n = 22). Serum oxLDL-Ab was estimated by ELISA. Serum PON esterase activity and plasma Malondialdehyde (MDA) level were estimated by spectrophotometry and the serum Advanced Glycation End products (AGE) level by spectroflourimetry. The systemic levels of oxLDL, AGE and MDA were increased with the progression of T2DM without DR to DR as seen by ANOVA (P < 0.05). Serum oxLDL-Ab levels showed a positive correlation to total cholesterol (P = 0.04) as evaluated in the DR group. Statin intake was found to lower PON esterase activity (P < 0.05). Based on this pilot study, it is proposed that elevated serum oxLDL should be validated in larger cohort studies to ensure it could be potential risk factor for the progression of T2DM to DR.

Comparison between broadband and monochromatic photopic negative response in full-field electroretinogram in controls and subjects with primary open-angle glaucoma.

PURPOSE: A prospective, cross-sectional, case-control study was conducted to investigate the role of broadband and monochromatic photopic negative response (PhNR) of the full-field flash electroretinogram (ERG) in the evaluation of ganglion cell damage in primary open-angle glaucoma (POAG) subjects. METHODS: Subjects with POAG and age-matched normal subjects were recruited from the outpatient department of a tertiary eye care center in South India. A total of 25 patients with POAG and 50 age-matched normal subjects were recruited. ERG was recorded using broadband (3.5 cd.s/m2 white stimulus on 10 cd/m2 white background) and monochromatic (3.5 cd.s/m2 red stimulus on 10 cd/m2 blue background and 1 cd.s/m2 blue stimulus on 10 cd/m2 yellow background) stimuli. RESULTS: The reduction in PhNR amplitude in POAG compared to normal individuals was higher in red-on-blue PhNR [26.37 µV; p < 0.001, confidence interval (CI) 19.34 to 33.4] as compared to broadband stimuli (16.41 µV; p < 0.001, CI 8.68 to 24.13), and blue on yellow (21.96 µV; p < 0.001, CI 10.12 to 33.8). Red-on-blue PhNR amplitudes correlated better with mean deviation (MD; r = - 0.66, p < 0.05), pattern standard deviation (PSD; r = - 0.4, p = 0.04), visual field index (VFI; r = - 0.58, p < 0.05), and retinal nerve fiber layer thickness (r = - 0.67, p < 0.05) in comparison with broadband and monochromatic blue-on-yellow PhNR. Receiver operating characteristic curve revealed largest area under the curve (0.89) in red-on-blue PhNR compared to broadband (0.76) and blue on yellow (0.74). The sensitivity and specificity was also higher in red-on-blue PhNR (72% and 80%, respectively) as compared to the other stimuli (sensitivity and specificity of broadband 0.68 and 0.7, blue on yellow 0.64 and 0.7, respectively). CONCLUSION: Correlation of PhNR with Humphrey visual field parameters and retinal nerve fiber layer thickness showed that red-on-blue PhNR can be a useful additional tool for clinical assessment of retinal ganglion cell dysfunction in glaucoma patients. Red-on-blue PhNR was more sensitive as compared to white-on-white and blue-on-yellow PhNR in identifying ganglion cell dysfunction and correlates well with other structural and functional tests for glaucoma such as MD, PSD, VFI, and RNFL thickness.

Screening for mutation hotspots in Bardet-Biedl syndrome patients from India.

BACKGROUND & OBJECTIVES: Bardet-Biedl syndrome (BBS) is a genetically heterogeneous autosomal recessive disorder characterized by multiple organ defects involving retina, kidney, liver and brain. Disease-causing mutations in BBS genes narrowed down by homozygosity mapping in small consanguineous and non-consanguineous pedigrees were reported in 80 per cent of the study population. This study was aimed to screen these genes (BBS3, BBS10) and specific exons of BBS genes (BBS1, BBS5, MKKS, BBS9, BBS11 and BBS12) for recurrent mutations in a selected sample of BBS patients. METHODS: The recurrent mutations in BBS genes were screened in the BBS affected individuals by PCR based direct sequencing. The pathogenicity of the observed mutations were confirmed by co-segregation analysis, screening of healthy unrelated controls and in silico analysis. RESULTS: In the 64 BBS patients (44 males, 20 females) were studied, mutations were predominant in BBS10 and ARL6 genes; the c.272T>C; p.(I91T) mutation in ARL6 gene was a recurrent mutation. One novel non-sense mutation c.425T>G; p(L142FNx01) was obtained in BBS5 gene (family BSI-31). INTERPRETATION & CONCLUSIONS: BBS10 gene mutations clustered in exon 2 of the gene suggesting the exon as a probable hotspot for mutations in Indian population. A cost- and time-effective strategy for the molecular diagnosis of BBS was designed based on these results.

Homozygosity mapping guided next generation sequencing to identify the causative genetic variation in inherited retinal degenerative diseases.

Inherited retinal degeneration (IRD) are a group of genetically heterogeneous disease of which retinitis pigmentosa (RP) and Leber congenital amaurosis (LCA) are the most common and severe type. In our study we had taken three unrelated South Indian consanguineous IRD families. Homozygosity mapping was done using Affymetrix 250K Nsp1 GeneChip in each of LCA, Cone-Rod dystrophy (CRD) and autosomal recessive RP (arRP) families followed by targeted re-sequencing by next generation sequencing (NGS) on Illumina MiSeq. Known candidate genes ranging from 1-8 in numbers within the homozygous blocks were identified by homozygosity mapping and targeted NGS revealed the causative mutations; RDH12 c.832A>C, ABCA4 c.1462G>T, CDHR1c.1384_1392delCTCCTGGACinsG, in the LCA, CRD and arRP families, respectively. The identified mutations were validated by Sanger sequencing, segregation in the families and their absence in 200 control chromosomes. Homozygosity mapping guided targeted NGS, especially when more numbers of known candidate genes within the homozygous blocks are observed is a comprehensive method for mutation identification. Molecular data from a larger retinal degenerative disease cohort would reveal the spectrum and prevalence of mutations and genes in Indian population. Molecular diagnosis also aids in genetic counseling, offering carrier and prenatal testing to family members.

Serum Paraoxonase activity in relation to lipid profile in Age-related Macular Degeneration patients.

Age-related Macular Degeneration (AMD) is a multifactorial disease causing visual impairment in old age. Oxidative stress is one of the main contributors for the disease progression. Paraoxonase (PON), a HDL-resident antioxidant enzyme which removes oxidized low density lipoprotein (oxLDL), which is not studied much in AMD. This study assesses the PON activities in relation to the lipid status and genetic variants in AMD patients. In this prospective case-control study, a total of 48 AMD patients and 30 unrelated healthy controls were recruited. The serum oxLDL and Plasma Homocysteine (Hcy) levels were estimated by ELISA. Plasma Homocysteine thiolactone (HCTL) was estimated by HPLC. Serum PON activities were estimated by spectrophotometry. PON gene expression was assessed by qPCR and protein expression by western blot, immunofluorescence and FACS analysis. Two known single nucleotide polymorphisms (SNPs) in the coding region of PON1, Q192R and L55M variants were checked in the AMD patients and controls and their association with PON activity and lipid levels were determined. Serum paraoxonase (PONase) and thiolactonase (PON-HCTLase) activities were significantly elevated in AMD patients than in controls apart from elevated serum levels of total cholesterol (TC), triglycerides (TG), oxLDL. While serum LDL levels in AMD patients correlate positively with PON HCTLase activity, the serum high density lipoprotein (HDL) correlates with both PONase and PON-HCTLase activities. However, multiple regression analysis showed that, amongst the parameters, only serum TG was a significant risk factor for AMD, after adjusting for demographic parameters as well as cataract. PON2 was significantly increased at the level of gene expression (p = 0.03) as seen in circulating peripheral blood mononuclear cells (PBMC) of AMD patients possibly mediated by the transcription factor SP1, that showed 2-fold increase. PON1 and 2 protein expressions also showed significant increase in the PBMC of AMD patients. At serum level, PON1 protein was significantly increased in AMD patients. Cholesterol transporters such as CD36, SR-B1 and ABCA1 gene expressions were also found to be higher (1.5, 1.9 and 2.4-fold respectively) in AMD, though not statistically significant. While the wet AMD (CNV) was found to be associated with increase in oxLDL and serum PONase activity, the dry AMD was associated with increased HDL and serum PON-HCTLase activity. The genotype and allele frequencies of Q192R & L55M were not significantly different between AMD patients and controls. However, altered lipid status and PON activities were associated with the genotype in AMD patients. A higher enzyme activity was observed for the RR genotype of Q192R in the cohort, irrespective of case and control. Thus the PON genotype and phenotype seem to play a role in the pathogenesis of AMD.

Molecular profiling of complete congenital stationary night blindness: a pilot study on an Indian cohort.

PURPOSE: Congenital stationary night blindness (CSNB) is a non-progressive retinal disorder that shows genetic and clinical heterogeneity. CSNB is inherited as an autosomal recessive, autosomal dominant, or X-linked recessive trait and shows a good genotype-phenotype correlation. Clinically, CSNB is classified as the Riggs type and the Schubert-Bornschein type. The latter form is further sub-classified into complete and incomplete forms based on specific waveforms on the electroretinogram (ERG). There are no molecular genetic data for CSNB in the Indian population. Therefore, we present for the first time molecular profiling of eight families with complete CSNB (cCSNB). METHODS: The index patients and their other affected family members were comprehensively evaluated for the phenotype, including complete ophthalmic evaluation, ERG, fundus autofluorescence, optical coherence tomography, and color vision test. The known gene defects for cCSNB, LRIT3, TRPM1, GRM6, GPR179, and NYX, were screened by PCR direct sequencing. Bioinformatic analyses were performed using SIFT and PolyPhen for the identified missense mutations. RESULTS: All eight affected index patients and affected family members were identified as having cCSNB based on their ERG waveforms. Mutations in the TRPM1 gene were identified in six index patients. The two remaining index patients each carried a GPR179 and GRM6 mutation. Seven of the patients revealed homozygous mutations, while one patient showed a compound heterozygous mutation. Six of the eight mutations identified are novel. CONCLUSIONS: This is the first report on molecular profiling of candidate genes in CSNB in an Indian cohort. As shown for other cohorts, TRPM1 seems to be a major gene defect in patients with cCSNB in India.

Surgical management of a case of non-resolving bullous retinal detachment due to probable Vogt-Koyanagi-Harada syndrome.

A 45-year-old male with Vogt-Koyanagi-Harada (VKH) syndrome presented with vision loss in his right eye after discontinuing treatment during the COVID-19 pandemic. He was found to have bullous retinal detachment (RD) in the right eye and was started on subcutaneous adalimumab with oral corticosteroid following three doses of pulse corticosteroid. But when RD did not resolve after 4 months of treatment and ultrasound B scan showed bullous RD with retino-retinal adhesion, he was planned for surgical intervention. During surgery, there was retino-retinal adhesions due to long-standing "kissing exudative RD", causing non-settling exudative RD. Following surgery, the vision improved to 2/60, with attached retina. The patient has been under follow-up with us for the last one year now and developed no recurrence of RD till now. This case emphasises the significance of retinoretinal adhesion in long-standing bullous RD that does not respond to conventional aggressive medical therapy.