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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 report the prevalence and risk factors of cataract and its subtypes in older age group. Methods: A total of 6617 subjects were recruited from both rural and urban areas. A detailed history including data on demographic, socioeconomic and ocular history was obtained. Lens opacity was graded according to the Lens Opacity Classification System III (LOCS III). Results: Cataract was present in 1094 of the rural and 649 subjects in the urban population. Monotype subtype cataracts were found in 32% and 25% in rural and urban population and 12.68% and 18.6% were mixed cataracts in the rural and urban groups. In baseline characteristics history of diabetes, alcohol intake and presence of age-related macular degeneration were the risk factors in urban group. On multivariate analysis, the only significant risk factors for any cataract in subjects ≥60 years were increasing age in both rural [odds ratio (OR), 1.07] and urban (OR, 1.08) population, and HbA1c (OR, 1.14) in rural population. Overweight (OR, 0.6) was found to be a protective factor, and lower social economic status (OR, 1.52) a risk factor for cataract in urban population. A significant urban–rural difference was found in the prevalence of cataract and its subtypes (P ≤ 0.05). Conclusion: We found the risk factors for any cataract in older age group to be increasing age and HbA1c in rural group. Age and lower social economic status were found to be the risk factors in urban arm. A statistically significant difference was found on comparison of the prevalence of cataract and its subtypes between the rural and urban population.

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

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.

A 44-year-old male patient presented with features suggestive of transient central retinal artery occlusion (CRAO) followed by permanent CRAO and lateral posterior ciliary artery occlusion. He had diagnostic features of polycythemia vera (PV). When presented for the first time, the patient had features of ocular ischemia such as ocular pain, conjunctival congestion, and retinal opacification but with normal arm-to-retina time and normal arteriovenous transit time. During the second presentation, he had ocular pain, congested conjunctiva, retinal opacification, cherry red spot with box-carrying of retinal vessels, and choroidal infarct (Amalric's sign). He had lost light perception in that eye. Patients with polycythemia are prone to multifocal vascular occlusions and this can be the presenting feature in PV. A timely diagnosis and prompt management can prevent these repeated thromboembolic occlusive episodes.

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.

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.

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.