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Here, we communicate the draft genome sequence of an ocular Mycobacterium tuberculosis strain (SNMICRO 2047-20) that was isolated from the vitreous fluid of a patient diagnosed with endophthalmitis. The genome sequence was 4,391,538 bp long with 3,898 protein-encoding genes and clustered to the East African-Indian lineage.

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). 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. 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. We conclude that combination therapy is an effective and safe treatment strategy for Type I ROP and APROP.

Purpose To compare metastasis-related mortality, local treatment failure, and globe salvage after retinoblastoma in countries with different national income levels. Design International, multicenter, registry-based retrospective case series. Participants Two thousand one hundred ninety patients, 18 ophthalmic oncology centers, and 13 countries on 6 continents. Methods Multicenter registry-based data were pooled from retinoblastoma patients enrolled between January 2001 and December 2013. Adequate data to allow American Joint Committee on Cancer staging, eighth edition, and analysis for the main outcome measures were available for 2085 patients. Each country was classified by national income level, as defined by the 2017 United Nations World Population Prospects, and included high-income countries (HICs), upper middle-income countries (UMICs), and lower middle-income countries (LMICs). Patient survival was estimated with the Kaplan-Meier method. Logistic and Cox proportional hazards regression models were used to determine associations between national income and treatment outcomes. Main Outcome Measures Metastasis-related mortality and local treatment failure (defined as use of secondary enucleation or external beam radiation therapy). Results Most (60%) study patients resided in UMICs and LMICs. The global median age at diagnosis was 17.0 months and higher in UMICs (20.0 months) and LMICs (20.0 months) than HICs (14.0 months; P Conclusions This international, multicenter, registry-based analysis of retinoblastoma management revealed that lower national income levels were associated with significantly higher rates of metastasis-related mortality, local treatment failure, and lower globe salvage.

Purpose To evaluate the ability of the American Joint Committee on Cancer (AJCC) 8th edition to predict local tumor control and globe salvage for children with retinoblastoma (RB). Design International, multicenter, registry-based retrospective case series. Participants A total of 2854 eyes of 2097 patients from 18 ophthalmic oncology centers from 13 countries over 6 continents. Methods International, multicenter, registry-based data were pooled from patients enrolled between January 2001 and December 2013. All RB eyes with adequate records to allow tumor staging by the AJCC 8th edition criteria and follow-up to ascertain treatment outcomes were included. Main Outcome Measures Globe-salvage rates were estimated by AJCC clinical (cTNMH) categories and tumor laterality. Local treatment failure was defined as use of enucleation or external beam radiation therapy (EBRT), with or without plaque brachytherapy or intra-arterial chemotherapy (IAC). Results Unilateral RB occurred in 1340 eyes (47%). Among the 2854 eyes, tumor categories were cT1 to cT4 in 696 eyes (24%), 1334 eyes (47%), 802 eyes (28%), and 22 eyes (1%), respectively. Of these, 1275 eyes (45%) were salvaged, and 1179 eyes (41%) and 400 eyes (14%) underwent primary and secondary enucleation, respectively. The 2- and 5-year Kaplan–Meier cumulative globe-salvage rates without the use of EBRT by cTNMH categories were 97% and 96% for category cT1a tumors, 94% and 88% for cT1b tumors, 68% and 60% for cT2a tumors, 66% and 57% for cT2b tumors, and 32% and 25% for cT3 tumors, respectively. Risk of local treatment failure increased with increasing cT category (P Conclusions Multicenter, international, internet-based data sharing validated the 8th edition AJCC RB staging to predict globe-salvage in a large, heterogeneous, real-world patient population with RB.

Purpose To evaluate the ability of the 8th edition of the American Joint Committee on Cancer (AJCC) Cancer Staging Manual to estimate metastatic and mortality rates for children with retinoblastoma (RB). Design International, multicenter, registry-based retrospective case series. Participants A total of 2190 patients from 18 ophthalmic oncology centers from 13 countries over 6 continents. Methods Patient-specific data fields for RB were designed and selected by subcommittee. All patients with RB with adequate records to allow tumor staging by the AJCC criteria and follow-up for metastatic disease were studied. Main Outcome Measures Metastasis-related 5- and 10-year survival data after initial tumor staging were estimated with the Kaplan–Meier method depending on AJCC clinical (cTNM) and pathological (pTNM) tumor, node, metastasis category and age, tumor laterality, and presence of heritable trait. Results Of 2190 patients, the records of 2085 patients (95.2%) with 2905 eyes were complete. The median age at diagnosis was 17.0 months. A total of 1260 patients (65.4%) had unilateral RB. Among the 2085 patients, tumor categories were cT1a in 55 (2.6%), cT1b in 168 (8.1%), cT2a in 197 (9.4%), cT2b in 812 (38.9%), cT3 in 835 (40.0%), and cT4 in 18 (0.9%). Of these, 1397 eyes in 1353 patients (48.1%) were treated with enucleation. A total of 109 patients (5.2%) developed metastases and died. The median time (n = 92) from diagnosis to metastasis was 9.50 months. The 5-year Kaplan–Meier cumulative survival estimates by clinical tumor categories were 100% for category cT1a, 98% (95% confidence interval [CI], 97–99) for cT1b and cT2a, 96% (95% CI, 95–97) for cT2b, 89% (95% CI, 88–90) for cT3 tumors, and 45% (95% CI, 31–59) for cT4 tumors. Risk of metastasis increased with increasing cT (and pT) category (P Conclusions Multicenter, international, internet-based data sharing facilitated analysis of the 8th edition AJCC RB Staging System for metastasis-related mortality and offered a proof of concept yielding quantitative, predictive estimates per category in a large, real-life, heterogeneous patient population with RB.

Purpose Although there have been many population-based studies of age-related macular degeneration (AMD), only limited information is available in Asia on the epidemiology of geographic atrophy (GA). We aimed to determine the prevalence and patterns of GA through an analysis of multiple studies conducted within the Asian Eye Epidemiology Consortium (AEEC). Design Cross-sectional meta-analyses. Participants A total of 97 213 individuals aged 40 years and older. Methods Data from 22 population-based studies from countries belonging to the AEEC were included. In all studies, AMD was defined on the basis of standardized grading systems. Geographic atrophy was defined as an area of pallor in the fundus with visibility of the underlying choroidal blood vessels and sharply defined borders. Random-effects meta-analysis was performed to estimate overall and age-, gender-, and region-specific pooled prevalence of GA. Main Outcome Measures Prevalence of GA per 1000 persons. Results The mean age was 60.8 ± 10.0 years, and 42 673 (43.9%) were male. Overall, a total of 223 individuals (0.2%) had GA. The pooled overall prevalence of GA was 1.57 per 1000 persons (95% confidence interval [CI], 1.04–2.10), which was 3 times less than that of neovascular AMD of 5.20 per 1000 persons (95% CI, 3.97–6.43). Compared with those aged 50 to 59 years, the prevalence of GA increased from 0.34 per 1000 persons (95% CI, 0.07–0.62) to 2.90 per 1000 persons (95% CI, 1.55–4.25) in those aged ≥70 years. The GA prevalence per 1000 persons was similar between urban (2.22; 95% CI, 1.22–3.23) and rural residents (1.33; 95% CI, 0.70–1.96). Geographic atrophy was more prevalent in South Asia (based on studies from India and Nepal, 3.82 per 1000 persons; 95% CI, 1.72–5.93) compared with East Asia (based on studies from China, Korea, Hong Kong, Taiwan, and Japan, and the Singapore Chinese Eye Study, 0.76 per 1000 persons; 95% CI, 0.31–1.22, P = 0.005). Conclusions Geographic atrophy is uncommon in Asian populations compared with those of European ancestry. Even within Asia, geographic differences in GA prevalence were seen. The findings of this meta-analysis suggest that better dissection of risk factors in the Asian population for GA may provide insights into the biological pathways that drive these late-stage manifestations, thus suggesting better targets for prevention.

PURPOSE: To evaluate presenting features, tumor size, and treatment methods for risk of metastatic death due to advanced intraocular retinoblastoma (RB). DESIGN: International, multicenter, registry-based retrospective case series. PARTICIPANTS: A total of 1841 patients with advanced RB. METHODS: Advanced RB was defined by 8th edition American Joint Committee on Cancer (AJCC) categories cT2 and cT3 and new AJCC-Ophthalmic Oncology Task Force (OOTF) Size Groups (1: < 50% of globe volume, 2: > 50% but < 2/3, 3: > 2/3, and 4: diffuse infiltrating RB). Treatments were primary enucleation, systemic chemotherapy with secondary enucleation, and systemic chemotherapy with eye salvage. MAIN OUTCOME MEASURES: Metastatic death. RESULTS: The 5-year Kaplan-Meier cumulative survival estimates by patient-level AJCC clinical subcategories were 98% for cT2a, 96% for cT2b, 88% for cT3a, 95% for cT3b, 92% for cT3c, 84% for cT3d, and 75% for cT3e RB. Survival estimates by treatment modality were 96% for primary enucleation, 89% for systemic chemotherapy and secondary enucleation, and 90% for systemic chemotherapy with eye salvage. Risk of metastatic mortality increased with increasing cT subcategory (P < 0.001). Cox proportional hazards regression analysis confirmed a higher risk of metastatic mortality in categories cT3c (glaucoma, hazard ratio [HR], 4.9; P = 0.011), cT3d (intraocular hemorrhage, HR, 14.0; P < 0.001), and cT3e (orbital cellulitis, HR, 19.6; P < 0.001) than in category cT2a and with systemic chemotherapy with secondary enucleation (HR, 3.3; P < 0.001) and eye salvage (HR, 4.9; P < 0.001) than with primary enucleation. The 5-year Kaplan-Meier cumulative survival estimates by AJCC-OOTF Size Groups 1 to 4 were 99%, 96%, 94%, and 83%, respectively. Mortality from metastatic RB increased with increasing Size Group (P < 0.001). Cox proportional hazards regression analysis revealed that patients with Size Group 3 (HR, 10.0; P = 0.002) and 4 (HR, 41.1; P < 0.001) had a greater risk of metastatic mortality than Size Group 1. CONCLUSIONS: The AJCC-RB cT2 and cT3 subcategories and size-based AJCC-OOTF Groups 3 (> 2/3 globe volume) and 4 (diffuse infiltrating RB) provided a robust stratification of clinical risk for metastatic death in advanced intraocular RB. Primary enucleation offered the highest survival rates for patients with advanced intraocular RB.

Purpose Ocular manifestations of snake bite are rare, ranging from direct injury to the eye from snake venom or indirect injury due to antivenom. We report a rare case of cobra bite causing panophthalmitis due to indirect injury as a result of snake venom toxin related tissue necrosis and susceptibility to secondary infections. Methods Observational case report. External photographs, slit lamp photos, ultrasonography of the eye and histopathology of the eviscerated eye were used to characterize and describe the clinical findings. Thirty-nine-years-old male farmer presented with history of cobra snake bite on his right index finger and developed right eye sudden onset pain and redness 3 days later. On examination, features were suggestive of panophthalmitis and the eye had to be eviscerated with scleral excision. Conclusion It is important for ophthalmologist to be aware of such grave consequences of snake bite to be prepared for the emergency management of such cases.

To compare metastasis-related mortality, local treatment failure, and globe salvage after retinoblastoma in countries with different national income levels.International, multicenter, registry-based retrospective case series.Two thousand one hundred ninety patients, 18 ophthalmic oncology centers, and 13 countries on 6 continents.Multicenter registry-based data were pooled from retinoblastoma patients enrolled between January 2001 and December 2013. Adequate data to allow American Joint Committee on Cancer staging, eighth edition, and analysis for the main outcome measures were available for 2085 patients. Each country was classified by national income level, as defined by the 2017 United Nations World Population Prospects, and included high-income countries (HICs), upper middle-income countries (UMICs), and lower middle-income countries (LMICs). Patient survival was estimated with the Kaplan-Meier method. Logistic and Cox proportional hazards regression models were used to determine associations between national income and treatment outcomes.Metastasis-related mortality and local treatment failure (defined as use of secondary enucleation or external beam radiation therapy).Most (60%) study patients resided in UMICs and LMICs. The global median age at diagnosis was 17.0 months and higher in UMICs (20.0 months) and LMICs (20.0 months) than HICs (14.0 months; P0.001). Patients in UMICs and LMICs reported higher rates of disease-specific metastasis-related mortality and local treatment failure. As compared with HICs, metastasis-related mortality was 10.3-fold higher for UMICs and 9.3-fold higher for LMICs, and the risk for local treatment failure was 2.2-fold and 1.6-fold higher, respectively (all P0.001).This international, multicenter, registry-based analysis of retinoblastoma management revealed that lower national income levels were associated with significantly higher rates of metastasis-related mortality, local treatment failure, and lower globe salvage.

To evaluate the ability of the American Joint Committee on Cancer (AJCC) 8th edition to predict local tumor control and globe salvage for children with retinoblastoma (RB).International, multicenter, registry-based retrospective case series.A total of 2854 eyes of 2097 patients from 18 ophthalmic oncology centers from 13 countries over 6 continents.International, multicenter, registry-based data were pooled from patients enrolled between January 2001 and December 2013. All RB eyes with adequate records to allow tumor staging by the AJCC 8th edition criteria and follow-up to ascertain treatment outcomes were included.Globe-salvage rates were estimated by AJCC clinical (cTNMH) categories and tumor laterality. Local treatment failure was defined as use of enucleation or external beam radiation therapy (EBRT), with or without plaque brachytherapy or intra-arterial chemotherapy (IAC).Unilateral RB occurred in 1340 eyes (47%). Among the 2854 eyes, tumor categories were cT1 to cT4 in 696 eyes (24%), 1334 eyes (47%), 802 eyes (28%), and 22 eyes (1%), respectively. Of these, 1275 eyes (45%) were salvaged, and 1179 eyes (41%) and 400 eyes (14%) underwent primary and secondary enucleation, respectively. The 2- and 5-year Kaplan-Meier cumulative globe-salvage rates without the use of EBRT by cTNMH categories were 97% and 96% for category cT1a tumors, 94% and 88% for cT1b tumors, 68% and 60% for cT2a tumors, 66% and 57% for cT2b tumors, and 32% and 25% for cT3 tumors, respectively. Risk of local treatment failure increased with increasing cT category (P0.001). Cox proportional hazards regression analysis confirmed a higher risk of local treatment failure in categories cT1b (hazard ratio [HR], 3.5; P = 0.004), cT2a (HR, 15.1; P0.001), cT2b (HR, 16.4; P0.001), and cT3 (HR, 45.0; P0.001) compared with category cT1a. Use of plaque brachytherapy and IAC improved local tumor control in categories cT1a (P = 0.031) and cT1b (P0.001).Multicenter, international, internet-based data sharing validated the 8th edition AJCC RB staging to predict globe-salvage in a large, heterogeneous, real-world patient population with RB.

Purpose: To report two rare cases of chronic myeloid leukemia (CML) on tyrosine kinase inhibitors presenting as bilateral serous retinal detachment and ocular inflammation, simulating Vogt-Koyanagi-Harada (VKH) disease. Methods: Case series and review of literature. Result: Two young patients (one male and one female) with CML on treatment with tyrosine kinase inhibitors (imatinib and dasatanib) under remission presented with bilateral sudden vision loss. One patient had bilateral multiple pockets of serous retinal fluid while the other had panuveitis with exudative retinal detachment. There was neither prodromal symptoms nor systemic signs and symptoms suggestive of VKH in both cases. They responded well to systemic steroid therapy without recurrences with complete visual recovery. Conclusion and importance: CML patients can have features similar to VKH even during stable hematological phase and may be possibly associated with the use of tyrosine kinase inhibitors. Hence it is important not to misdiagnose and treat such patients with long term immunomodulators. Keywords: Chronic myeloid leukemia, Panuveitis, Vogt-Koyanagi-Harada disease, Tyrosine kinase inhibitors, Dasatinib, Imatinib

To evaluate the ability of the 8th edition of the American Joint Committee on Cancer (AJCC) Cancer Staging Manual to estimate metastatic and mortality rates for children with retinoblastoma (RB).International, multicenter, registry-based retrospective case series.A total of 2190 patients from 18 ophthalmic oncology centers from 13 countries over 6 continents.Patient-specific data fields for RB were designed and selected by subcommittee. All patients with RB with adequate records to allow tumor staging by the AJCC criteria and follow-up for metastatic disease were studied.Metastasis-related 5- and 10-year survival data after initial tumor staging were estimated with the Kaplan-Meier method depending on AJCC clinical (cTNM) and pathological (pTNM) tumor, node, metastasis category and age, tumor laterality, and presence of heritable trait.Of 2190 patients, the records of 2085 patients (95.2%) with 2905 eyes were complete. The median age at diagnosis was 17.0 months. A total of 1260 patients (65.4%) had unilateral RB. Among the 2085 patients, tumor categories were cT1a in 55 (2.6%), cT1b in 168 (8.1%), cT2a in 197 (9.4%), cT2b in 812 (38.9%), cT3 in 835 (40.0%), and cT4 in 18 (0.9%). Of these, 1397 eyes in 1353 patients (48.1%) were treated with enucleation. A total of 109 patients (5.2%) developed metastases and died. The median time (n = 92) from diagnosis to metastasis was 9.50 months. The 5-year Kaplan-Meier cumulative survival estimates by clinical tumor categories were 100% for category cT1a, 98% (95% confidence interval [CI], 97-99) for cT1b and cT2a, 96% (95% CI, 95-97) for cT2b, 89% (95% CI, 88-90) for cT3 tumors, and 45% (95% CI, 31-59) for cT4 tumors. Risk of metastasis increased with increasing cT (and pT) category (P0.001). Cox proportional hazards regression analysis confirmed a higher risk of metastasis in category cT3 (hazard rate [HR], 8.09; 95% CI, 2.55-25.70; P0.001) and cT4 (HR, 48.55; 95% CI, 12.86-183.27; P0.001) compared with category cT1. Age, tumor laterality, and presence of heritable traits did not influence the incidence of metastatic disease.Multicenter, international, internet-based data sharing facilitated analysis of the 8th edition AJCC RB Staging System for metastasis-related mortality and offered a proof of concept yielding quantitative, predictive estimates per category in a large, real-life, heterogeneous patient population with RB.

Although there have been many population-based studies of age-related macular degeneration (AMD), only limited information is available in Asia on the epidemiology of geographic atrophy (GA). We aimed to determine the prevalence and patterns of GA through an analysis of multiple studies conducted within the Asian Eye Epidemiology Consortium (AEEC).Cross-sectional meta-analyses.A total of 97 213 individuals aged 40 years and older.Data from 22 population-based studies from countries belonging to the AEEC were included. In all studies, AMD was defined on the basis of standardized grading systems. Geographic atrophy was defined as an area of pallor in the fundus with visibility of the underlying choroidal blood vessels and sharply defined borders. Random-effects meta-analysis was performed to estimate overall and age-, gender-, and region-specific pooled prevalence of GA.Prevalence of GA per 1000 persons.The mean age was 60.8 ± 10.0 years, and 42 673 (43.9%) were male. Overall, a total of 223 individuals (0.2%) had GA. The pooled overall prevalence of GA was 1.57 per 1000 persons (95% confidence interval [CI], 1.04-2.10), which was 3 times less than that of neovascular AMD of 5.20 per 1000 persons (95% CI, 3.97-6.43). Compared with those aged 50 to 59 years, the prevalence of GA increased from 0.34 per 1000 persons (95% CI, 0.07-0.62) to 2.90 per 1000 persons (95% CI, 1.55-4.25) in those aged ≥70 years. The GA prevalence per 1000 persons was similar between urban (2.22; 95% CI, 1.22-3.23) and rural residents (1.33; 95% CI, 0.70-1.96). Geographic atrophy was more prevalent in South Asia (based on studies from India and Nepal, 3.82 per 1000 persons; 95% CI, 1.72-5.93) compared with East Asia (based on studies from China, Korea, Hong Kong, Taiwan, and Japan, and the Singapore Chinese Eye Study, 0.76 per 1000 persons; 95% CI, 0.31-1.22, P = 0.005).Geographic atrophy is uncommon in Asian populations compared with those of European ancestry. Even within Asia, geographic differences in GA prevalence were seen. The findings of this meta-analysis suggest that better dissection of risk factors in the Asian population for GA may provide insights into the biological pathways that drive these late-stage manifestations, thus suggesting better targets for prevention.

The study assessed the four-year incidence of diabetic peripheral neuropathy (DPN) and the risk factors that can predict incident neuropathy in a south Indian population with type 2 diabetes.1175 diabetic individuals were identified with known diabetes at baseline. At baseline, individuals underwent assessment of fasting plasma glucose and HbA1c levels, body mass index, waist-hip ratio, blood pressure, blood cholesterol and lipid levels, and ophthalmic evaluation including visual acuity, specular microscopy of the corneal endothelium, cataract grading and diabetic retinopathy assessment. Subjects were re-examined after four years for the assessment of incident neuropathy; 713 individuals were found eligible at follow-up. The presence of neuropathy was assessed at baseline and at follow-up and was defined as a Vibration Perception Threshold of ≥ 20 Volts.: The four-year incidence of any neuropathy was 28.4%. Factors predictive of incident diabetic neuropathy were greater age at baseline (OR =1.068), higher body mass index (OR =1.034), presence of diabetic retinopathy (OR =4.879) and lower socioeconomic status (OR =4.841), when adjusted for several potential confounding factors.The four-year incidence of diabetic neuropathy in a south Indian population with type 2 diabetes is 28% and can be predicted by ophthalmic and clinical variables. These factors may be utilized in the assessment, monitoring and intervention in individuals with diabetes in an effort to prevent or delay the development of diabetic peripheral neuropathy.

Purpose To explore any relationship between the markers of early retinal neuronal damage and peripheral diabetic neuropathy in subjects with no diabetic retinopathy (DR). Methods A cross-sectional study in which type 2 diabetic subjects (n=743) without DR were studied. Visual functions including visual acuity, contrast sensitivity, colour vision, retinal sensitivity using microperimeter and retinal thicknesses by spectral domain optical coherence tomography were measured. Vibration perception thresholds of greater than or equal to 20 µV, measured by sensitometer using a biothesiometer probe, were defined as having peripheral diabetic neuropathy. Statistical analyses were performed using independent t-test, multivariate logistic regression and Pearson9s correlation. Results Of 743 subjects who had no DR, 24.9% had diabetic neuropathy. Independent comparisons among subjects who had diabetic neuropathy compared with those who did not showed statistically significant retinal nerve fibre layer thinning (p=0.01), reduced contrast sensitivity (p=0.0001), reduced retinal sensitivity (p=0.03), impaired colour vision (p=0.04) and reduced visual acuity (p=0.0001). Multivariate analysis showed significant association between the mean retinal sensitivity (measured using a microperimeter) and diabetic neuropathy (adjusted OR (95% CI): 0.76 (0.60 to 0.95), p=0.01). Conclusions Significant association of neuroretinal dysfunction with the presence of diabetic neuropathy was noted among subjects with no DR.

Retinoblastoma (RB) is a childhood eye tumor, caused by RB1 mutation. Though diagnosing RB is easier, prognosticating RB is limited to examining the patient under anesthesia and imaging technique. The aim of the study is to find exosomal miRNA biomarkers to prognosticate RB. Exosomes were isolated from one control – MIO-M1 and two RB cell lines – WERI-Rb-1 and NCC-RbC-51. Small RNA sequencing was performed on exosomal miRNA isolated from the three cell lines. miRNAs specific to each cell line were shortlisted. A total of 243, 606 and 400 miRNAs were identified in MIO-M1, WERI-Rb-1 and NCC-RbC-51 cell lines respectively. Nine miRNAs were shortlisted based on adjusted p value and literature, MIO-M1 specific (n = 1), WERI-RB-1 specific (n = 2), NCC-RbC-51 specific (n = 2) and miRNAs common to both RB cell lines (n = 4) were chosen. Validation was done using specific Taqman miRNA assays.miRNA validation was carried out on cell lines, cell line derived exosomes, primary RB tissues and exosomes isolated from serum of the RB patients. Validation of the miRNAs in cell lines and exosomes derived from the cell lines, confirmed the sequencing data. However, only 2 miRNAs – hsa-miR-301b-3p and hsa-miR-216b-5p were upregulated in the primary RB tissues. None of the miRNAs had significant expression in the serum exosomes of RB patients. Therefore, serum exosomal miRNA may not be ideal for prognosticating RB.Further research on other body fluids like CSF and vitreous could serve as potential source for biomarkers for prognosticating RB.

Retinoblastoma (RB) is a childhood eye cancer. Currently, chemotherapy, local therapy, and enucleation are the main ways in which these tumors are managed. The present work is the first study that uses constraint-based reconstruction and analysis approaches to identify and explain RB-specific survival strategies, which are RB tumor specific. Importantly, our model-specific secretion profile is also found in RB1-depleted human retinal cells in vitro and suggests that novel biomarkers involved in lipid metabolism may be important. Finally, RB-specific synthetic lethals have been predicted as lipid and nucleoside transport proteins that can aid in novel drug target development.

To report the incidence and progression of posterior vitreous detachment (PVD) and factors influencing the same in a cohort of patients with type 2 diabetes in a South Indian population.A subset of 615 subjects from Sankara Nethralaya Diabetic Retinopathy Epidemiology and Molecular Genetics Study II were included in this study. All of the subjects underwent detailed ophthalmic evaluation including stereo fundus photography. The status of PVD was assessed using B-scan ultrasonography. A p value of0.05 was considered statistically significant.The incidence of either incomplete PVD (IPVD) or complete PVD (CPVD) from no PVD at baseline visit was 80.8%. Of them, 32.63% converted to CPVD from IPVD at baseline. High prevalence of emmetropia was observed in subjects with stable No PVD. Risk factors associated with the conversion of CPVD from no PVD and IPVD at baseline were age (OR: 1.04, p = 0.002), myopia (OR: 2.14, p = 0.009), and increase in axial length (OR: 1.35, p = 0.004). Subjects undergoing cataract surgery were at 2.32 times higher risk of converting to CPVD (p = 0.038).Independent risk factors for the progression of PVD were increase in age, myopia, increased axial length, and cataract surgery.

Purpose: The purpose of this study is to assess color vision abnormalities in a cohort of subjects with type II diabetes and elucidate associated risk factors. Methods: Subjects were recruited from follow-up cohort of Sankara Nethralaya Diabetic Retinopathy Epidemiology and Molecular Genetics Study I. Six hundred and seventy-three eyes of 343 subjects were included from this population-based study. All subjects underwent detailed ophthalmic evaluation, including the Farnsworth-Munsell 100 hue test. Results: The prevalence of impaired color vision (ICV) was 43% (CI: 39.2–46.7). Risk factors for ICV were higher heart rate (odds ratio [OR]: 1.043, [1.023–1.064]) and a higher intraocular pressure (IOP) (OR: 1.086, [1.012–1.165]). Subjects with clinically significant macular edema (CSME) had three times higher chance of having ICV. C1, C2, and C3 are the commonly found Early Treatment Diabetic Retinopathy Study (ETDRS) patterns. The moment of inertia method showed that the angle did not reveal any specific pattern of color vision defect. Although the major and minor radii were high in those with ICV, we did not observe polarity. Confusion index was high in subjects with ICV, indicating a severe color vision defect. Conclusions: The prevalence of ICV was 43% among subjects with type II diabetes. The most commonly observed patterns were increasing severities of the blue–yellow defect on ETDRS patterns, but no specific pattern was observed at the moment of inertia analysis. The presence of CSME, a higher heart rate, and IOP was significant risk factors for ICV. This functional impairment in color vision could significantly contribute to morbidity among subjects with diabetes.

To evaluate the 4-year incidence and progression of and risk factors for diabetic retinopathy (DR) in an Indian population.From a cross-sectional study of 1425 subjects with diabetes, 911 (63.9%) returned for 4-year follow-up. After excluding 21 with ungradable retinal images, data from 890 subjects were analyzed. Participants underwent examinations based on a standard protocol, which included grading of retinal photographs.The incidences of DR, diabetic macular edema (DME), and sight-threatening diabetic retinopathy (STDR) were 9.2%, 2.6%, and 5.0%, respectively. In subjects with DR at baseline, the incidence of DME and STDR had increased (11.5% and 22.7%, respectively). 1-step and 2-step progressions of DR were seen in 30.2% and 12.6% of participants, respectively, and 1-step and 2-step regressions were seen in 12.0% and 1.8%, respectively. Incident DR, DME, and STDR were associated with higher systolic blood pressure (odds ratio, OR, 1.21, 2.11 and 1.72, respectively, for every 10 mmHg increase). Incident DR and DME were associated with increasing duration of diabetes (OR 2.29 and 4.77, respectively, for every 10-year increase) and presence of anemia (OR 1.96 and 10.14, respectively). Incident DR was also associated with higher hemoglobin A1c (OR 1.16 for every 1% increase). Variables associated with 1-step progression were every 10 mg/dL increase in serum total cholesterol (OR 15.65) as a risk factor, and 10 mg/dL increase in serum triglyceride (OR 0.52) as a protective factor.The incidences of STDR and DME were higher in people with pre-existing DR than in those without DR at baseline.

Background: The present study aims to report the influence of dietary-fibre intake on diabetes and diabetic microangiopathies among subjects >40 years in Urban India Design: Population-based cross-sectional study. Participants: A total of 1383 patients were included in the study, 1261 diabetics and 122 controls. Methods: All subjects underwent comprehensive eye examination including assessment of diabetic retinopathy using fundus photography. Dietary-fibre intake was assessed using a validated questionnaire. All questions were validated based on factor analysis (overall communalities value >0.5). The cut-off for low-fibre diet was calculated by the average of study scores (≤ 32 for low-fibre diet). Main Outcome Measures: Prevalence of diabetes in subjects with low-fibre diet versus healthy diet and risk of microangiopathies. Results: Subjects with low-fibre diet intake, had 1.51 times more risk of microalbuminuria than those with a healthy-fibre diet. Similarly, the odds of having diabetic retinopathy and sight-threatening diabetic retinopathy (odds ratio 1.41 [95% CI 1.02–1.94] and odds ratio 2.24 [95% CI 1.01–5.02], respectively) in low-fibre diet subjects were more. Low-fibre diet was consumed predominantly by lower socioeconomic status group (11.9 vs. 6.5, P = 0.002). Conclusions: Subjects with type II diabetes had a lower dietary-fibre intake. The presence of diabetic retinopathy, sight-threatening diabetic retinopathy and microalbuminuria were also associated with lower dietary-fibre intake.

Aim To evaluate retinal sensitivity (RS) in subjects with diabetes in a population-based study and to elucidate associated risk factors for abnormal RS. Methods A subset of 357 subjects from Sankara Nethralaya Diabetic Retinopathy Epidemiology and Molecular Genetics Study-II was included in this study. All subjects underwent detailed ophthalmic evaluation including microperimetry and spectral domain optical coherence tomography. Results The prevalence of abnormal mean retinal sensitivity (MRS) was 89.1%. MRS was significantly reduced in subjects with diabetes but no retinopathy when compared with non-diabetic subjects. MRS was reduced in moderate non-proliferative diabetic retinopathy (DR) and macular oedema (ME) at 8° (p=0.04, p=0.01, respectively) and in ME at 10° (p=0.009) and 12° (p=0.036) compared with no DR. Significant negative correlation was found between MRS and best corrected visual acuity, duration of diabetes, glycosylated haemoglobin and central foveal thickness. Increased retinal thickness remained a significant risk factor (OR, 1.02; p=0.044) for abnormal MRS. Altered inner retinal layers and foveal contour were associated with reduced MRS among subjects with DR and presence of epiretinal membrane, altered foveal contour and altered retinal pigment epithelium were associated with reduced MRS. Conclusions Reduced RS in those subjects with diabetes but no retinopathy suggests the early neuronal damage in type 2 diabetes mellitus.

Purpose We report the 4-year incidence, progression, and risk factors of cataract subtypes in type 2 diabetes. Methods A total of 779 subjects completed baseline and 4-year follow-up. Results The incidences of nuclear opalescence (NO), nuclear color (NC), cortical cataract (CC), and posterior subcapsular cataract (PSC) were 70%, 55.2%, 25.7%, and 7.3%, respectively. One-step progressions of NO, NC, CC, and PSC were 14.3%, 16.1%, 8.8%, and 8.1%, respectively, and two-step or more progressions were 5.0%, 6.0%, 0.8%, and 6.0%, respectively. Incident NO was seen in patients 50 to 59 (odds ratio [OR] = 3.3), NC in those 50 to 59 (OR = 2.7) and 60 to 69 (OR = 3.9), and CC in those 60 to 69 (OR = 3.3) years old. A lower hemoglobin A1c (HbA1c; OR = 0.7), longer diabetes duration (OR = 1.1), and hyperopia (OR = 4.0) were associated with incident PSC. Women (OR = 1.7) and patients with higher total cholesterol (OR = 1.3) at baseline showed one-step NO progression. Patients 60 to 69 (OR = 2.8) and ≥70 (OR = 3.8) years old showed one-step NC progression, while those 60 to 69 years old showed one-step CC progression (OR = 6.3). A lower HbA1c (OR = 0.3) was associated with one-step PSC progression. A higher low-density lipoprotein (OR = 1.6) was associated with two-step or more NO progression. Patients 60 to 69 years old (OR = 6.7) had a greater risk, while those with hyperopia at baseline (OR = 0.2) had lower risk of two-step or more NC progression. Patients 40 to 49 years old constituted the reference group for all. Conclusions The 4-year cumulative incidence of cataract is higher than that of progression. Greater age is a risk factor for incidence and progression of most types of cataract.

To evaluate fixation and scotoma characteristics among subjects with diabetes in a population-based study.Cohort study.A subset of 357 subjects was recruited from follow-up cohort of Sankara Nethralaya Diabetic Retinopathy Epidemiology and Molecular Genetics Study I.All subjects underwent detailed ophthalmic evaluation including microperimetry and spectral domain optical coherence tomography. Fixation parameters such as stability of fixation, fixation location, and presence of scotoma were evaluated. A p value less than 0.05 was considered statistically significant.The mean age of the study sample was 56.86 ± 8.63 years. Relatively unstable fixation was observed in 73 and poor central fixation in 25 subjects. Among subjects with poor central fixation, 72% (18 subjects) had relatively unstable fixation. Poor central and relatively unstable fixation were significantly associated with best corrected visual acuity (BCVA; p = 0.002 and p = 0.017, respectively). Prevalence rate of scotoma was 24.4%, which was highly prevalent in females (p = 0.035) and among subjects with reduced BCVA (p0.001), reduced contrast sensitivity (p0.001), cataract (p0.001), impaired retinal sensitivity (p0.001), and presence of sight-threatening diabetic retinopathy (STDR; p0.001). Presence of scotoma was significantly associated with abnormal foveal contour (p = 0.046) and altered inner retinal layers (p0.001).We report that fixation characteristics are independent of ocular characteristics except for BCVA. Female sex, reduced visual acuity and contrast sensitivity, cataract, and STDR were significantly associated with presence of scotoma.

Purpose: The aim of this study is to investigate the 4-year incidence and progression of visual impairment (VI) and the associated risk factors for incident VI in a South Indian population with type 2 diabetes. Methods: A total of 634 participants with type 2 diabetes were found eligible after 4 years. Visual acuity (VA) was estimated using the modified Early Treatment Diabetic Retinopathy Study protocol. VA in the better eye was considered for the assessment of VI based on the World Health Organization criteria. Mild VI was defined as VA 4.0 (odds ratio [OR]: 2.612 [1.148–5.942], P = 0.022) and lower socioeconomic score (OR: 0.965 [95% confidence interval, (0.933-0.998)], P = 0.040) were associated with the risk of future incident VI. Refractive error (47%) and cataract (30%) were identified as the leading causes of incident VI at follow-up. Conclusions: VI seems to be a significant problem among diabetic participants in the South Indian population. Refractive error and cataract are the leading but treatable causes of incident VI in this population and would benefit from intervention.

Objective: To report the prevalence of myopia and its association with diabetic retinopathy in subjects with type II diabetes mellitus and compare the diabetic retinopathy status in the myopic group vs the emmetropic group. Design: Population-based study. Materials and Methods: The population-based study estimated the prevalence of myopia from 1058 subjects, who were more than 40 years old and had type II diabetes mellitus; the patients were enrolled from a cross-sectional study. Participants answered a detailed questionnaire and underwent biochemical, physical and comprehensive ocular examination which included grading of nuclear sclerosis by lens opacities classification system III (LOCS III), seven field fundus photography and ultrasonography. Diabetic retinopathy and diabetic maculopathy were graded using the Klein's classification and early treatment diabetic retinopathy study (ETDRS) criteria respectively. Results: The prevalence of mild, moderate and high myopia in type 2 diabetes was 15.9, 2.1 and 1.9% respectively. The prevalence of any myopia was found to be 19.9% in our study population. After adjusting the age, gender, duration of diabetes, hemoglobin A1c and other factors, increasing age was associated with mild and moderate myopia [OR 1.11 (95% CI 1.05 - 1.18)]. Compared to emmetropia, complete posterior vitreous detachment (CPVD) was associated with high myopia (50% Vs 12.2%, P < 0.0001). Myopia had no association with diabetic retinopathy. Conclusion: The prevalence of myopia and high myopia was found to be 19.9 and 1.9% respectively among subjects with type II diabetes. Myopia was not associated with diabetic retinopathy, thereby, suggesting the need for a longitudinal study.