Six-Year Incidence and Risk Factors of Primary Glaucoma in the Singapore Indian Eye Study.

PURPOSE: To determine the 6-year incidence of primary glaucoma and its risk factors in an Indian population in Singapore. DESIGN: Cohort population-based study. PARTICIPANTS: Indian adults between 40 and 80 years of age living in Singapore. A total of 3400 participants underwent the baseline examination between 2007 and 2009. Of them, 2200 (response rate, 75.5% of those eligible) participated in the 6-year follow-up visit between 2013 and 2015. METHODS: Standardized examination and investigations were performed, including indentation gonioscopy, intraocular pressure (IOP) measurement, optic disc examination, and static automated perimetry. Glaucoma was defined according to the International Society Geographical and Epidemiological Ophthalmology criteria. MAIN OUTCOME MEASURES: Incidences of primary open-angle glaucoma (POAG) and primary angle-closure glaucoma (PACG). RESULTS: The age-standardized incidences of primary glaucoma, POAG, and PACG were 1.68% (95% confidence interval [CI], 1.21%-2.32%), 1.37% (95% CI, 0.94%-1.96%), and 0.32% (95% CI, 0.15%-0.66%), respectively. For eyes with ocular hypertension (n = 45) at baseline, the incidence of POAG was 4.83% (95% CI, 1.24%-17.21%) and for eyes with primary angle closure (n = 14) or suspected primary angle closure (n = 101), the incidence of PACG developing was 1.82% (95% CI, 0.37%-9.68%). Baseline factors associated significantly with risk of primary glaucoma developing included older age (per decade; odds ratio [OR], 1.84; 95% CI, 1.44-2.36; P < 0.001), larger vertical cup-to-disc ratio (per 0.1 unit; OR, 2.78; 95% CI, 2.12-3.64; P < 0.001), and higher IOP (per millimeter of mercury; OR, 1.25; 95% CI, 1.13-1.38; P < 0.001). However, 71 of 85 eyes (84.5%) diagnosed with incident glaucoma had IOP of less than 21 mmHg at the time of examination. CONCLUSIONS: Our study showed that the overall age-standardized incidence of primary glaucoma was 1.68% in an Indian population in Singapore. In our population, the incidence of POAG was only half and the incidence of PACG was similar to the incidence reported by the Chennai Eye Disease Study.

Association of Cataract Surgery With Risk of Diabetic Retinopathy Among Asian Participants in the Singapore Epidemiology of Eye Diseases Study.

Importance: Cataracts and diabetic retinopathy (DR) are the leading causes of acquired blindness worldwide. Although extraction is the standard treatment option for cataracts, it is also reported to increase the risk of developing DR among individuals with diabetes. Nevertheless, the association between cataract surgery and risk of DR is still not well understood, and there have been no prior population-based reports in this area. Objective: To assess the risk of developing DR after cataract surgery among individuals with type 2 diabetes. Design, Setting, and Participants: A population-based prospective cohort study was conducted among participants recruited from the Singapore Epidemiology of Eye Diseases Study. The baseline visit was conducted between June 1, 2004, and March 31, 2009, and the 6-year follow-up visit was conducted between June 1, 2011, and July 31, 2016. Statistical analysis was performed from October 1 to 31, 2019. Exposures: Cataract surgery performed before a follow-up visit, determined based on slitlamp evaluation of lens status at baseline and follow-up visits. Main Outcomes and Measures: Eyes with incidence of DR were defined as those with the presence of any DR (level ≥15 based on the modified Airlie House classification system, graded from retinal photographs) at 6-year follow-up with no DR at baseline. The association between cataract surgery and incidence of DR was evaluated using a multivariable Poisson regression model with a generalized estimating equation to account for correlation between both eyes. Results: A total of 1734 eyes from 972 participants with diabetes (392 Malay individuals and 580 Indian individuals; 495 men; mean [SD] age, 58.7 [9.1] years) were included in the analysis. A total of 163 study eyes had already undergone cataract surgery at baseline, and a total of 187 eyes (originally phakic at baseline) underwent cataract surgery any time during the follow-up period. Of these 350 eyes, 77 (22.0%) developed DR. Among the 1384 eyes that never underwent cataract surgery, 195 (14.1%) developed DR. After adjustments for age, sex, race/ethnicity, baseline hemoglobin A1c level, duration of diabetes, random blood glucose level, antidiabetic medication use, hypertension, body mass index, and smoking status, multivariable regression analysis showed that any prior cataract surgery was associated with incidence of DR (relative risk, 1.70; 95% CI, 1.26-2.30; P = .001). Subgroup analyses by race/ethnicity showed similar associations in both Malay individuals (relative risk, 1.73; 95% CI, 1.13-2.69; P = .02) and Indian individuals (relative risk, 1.93; 95% CI, 1.33-2.80; P < .001). Conclusions and Relevance: The findings of this population-based cohort study suggest that prior cataract surgery was associated with a higher risk of developing DR among individuals with diabetes. Further validation is warranted to confirm this association.

Genome-wide association meta-analysis of corneal curvature identifies novel loci and shared genetic influences across axial length and refractive error.

Corneal curvature, a highly heritable trait, is a key clinical endophenotype for myopia - a major cause of visual impairment and blindness in the world. Here we present a trans-ethnic meta-analysis of corneal curvature GWAS in 44,042 individuals of Caucasian and Asian with replication in 88,218 UK Biobank data. We identified 47 loci (of which 26 are novel), with population-specific signals as well as shared signals across ethnicities. Some identified variants showed precise scaling in corneal curvature and eye elongation (i.e. axial length) to maintain eyes in emmetropia (i.e. HDAC11/FBLN2 rs2630445, RBP3 rs11204213); others exhibited association with myopia with little pleiotropic effects on eye elongation. Implicated genes are involved in extracellular matrix organization, developmental process for body and eye, connective tissue cartilage and glycosylation protein activities. Our study provides insights into population-specific novel genes for corneal curvature, and their pleiotropic effect in regulating eye size or conferring susceptibility to myopia.

Glaucoma screening: where are we and where do we need to go?

PURPOSE OF REVIEW: Current recommendations for glaucoma screening are decidedly neutral. No studies have yet documented improved long-term outcomes for individuals who undergo glaucoma screening versus those who do not. Given the long duration that would be required to detect a benefit, future studies that may answer this question definitively are unlikely. Nevertheless, advances in artificial intelligence and telemedicine will lead to more effective screening at lower cost. With these new technologies, additional research is needed to determine the costs and benefits of screening for glaucoma. RECENT FINDINGS: Using optic disc photographs and/or optical coherence tomography, deep learning systems appear capable of diagnosing glaucoma more accurately than human graders. Eliminating the need for expert graders along with better technologies for remote imaging of the ocular fundus will allow for less expensive screening, which could enable screening of individuals with otherwise limited healthcare access. In India and China, where most glaucoma remains undiagnosed, glaucoma screening was recently found to be cost-effective. SUMMARY: Recent advances in artificial intelligence and telemedicine have the potential to increase the accuracy, reduce the costs, and extend the reach of screening. Further research into implementing these technologies in glaucoma screening is required.

The associations of objectively measured sleep duration and sleep disturbances with diabetic retinopathy.

AIMS: To assess the associations between objectively measured sleep duration, sleep disturbances and diabetic retinopathy (DR). METHODS: This cross-sectional study recruited 92 patients with diabetes from retinal clinics. Objective measurements of sleep duration, apnea-hypopnea index (AHI) and minimum oxygen saturations (SaO2) were obtained through polysomnography. The Epworth Sleepiness Scale and Insomnia Severity Index were administered. Retinal photographs were taken and graded according to the modified Airlie House Classification System. Regression analysis used to determine associations with outcomes including moderate DR, vision-threatening DR (VTDR) and diabetic macular edema (DME). RESULTS: Mean age of participants was 57.6 ± 8.3 years. 29 (32%) of them had moderate DR, and 17 (18.5%) had VTDR. Higher AHI (Odds Ratio [OR] 1.04; 95% confidence interval [CI] 1.00, 1.07) and short sleep duration (OR 3.22; 95%CI 1.18, 8.79) were associated with moderate DR. VTDR was associated with moderate obstructive sleep apnea (OSA) (OR 4.73; 95%CI 1.46, 15.31), higher AHI (OR 1.06; 95%CI 1.02, 1.10) and lower minimum SaO2 (OR 0.89; 95%CI 0.83, 0.96). High risk for insomnia was associated with DME (OR 4.01; 95%CI 1.09, 14.73). CONCLUSIONS: Short sleep duration was associated with moderate DR while OSA-related parameters and a high risk for insomnia were associated with moderate DR, VTDR and DME.

Transscleral cyclophotocoagulation and its histological effects on the conjunctiva.

Micropulse transscleral cyclophotocoagulation (MP-TCP) is increasingly being used as an initial procedure prior to conjunctival filtration surgeries. However, it is uncertain whether MP-TCP may cause inflammation and scarring of the bulbar conjunctiva. Thus, we aimed to study the histological effects of MP-TCP (compared to controls and continuous wave [CW]-TCP) on the conjunctiva. Our study included 10 Dutch Belted Rabbits that underwent TCP in their right eyes (n = 5, MP-TCP; n = 5, CW-TCP), while their left eyes served as controls. The rabbits were euthanised at 4 weeks, and their dissected globes underwent histopathological and immunohistochemical examination. We observed greater conjunctival inflammation in MP-TCP or CW-TCP-treated eyes compared to controls, but not between each other. The majority of the lymphocytic infiltrates were CD4 T-cells. Increased conjunctival fibrosis was evident in MP-TCP or CW-TCP-treated eyes, to similar extents, compared to controls. However, the increased staining for myofibroblasts was not statistically significant in TCP-treated eyes. We concluded that MP-TCP causes significantly greater overall conjunctival inflammation and scarring compared to controls, similar to CW-TCP. As these are risk-factors for fibrosis and failure of the conjunctival bleb, further studies are required to explore the effect, if any, of post-TCP conjunctival changes on future bleb morphology and survival.

Case of isolated Rhizobium radiobacter contact lens-related infectious keratitis: A plant microbe now emerging as a human pathogen.

PURPOSE: To report a case of contact lens-related infectious keratitis caused by the Gram-negative plant pathogen Rhizobium radiobacter. OBSERVATIONS: A 26-year old lady with history of contact lens use presented with three weeks history of right eye redness and pain, with the left eye also being involved in the past week. Slit lamp examination of the right eye demonstrated multiple faint subepithelial and stromal infiltrates with no overlying epithelial defect, and no anterior chamber activity. Anterior segment optical coherence tomography demonstrated multiple hyper-reflective foci scattered at various depths of the corneal stroma. Corneal scrapings grew Rhizobium radiobacter, and culture-directed antibiotic therapy with topical gentamicin and levofloxacin resulted in slow clinical improvement of the R. radiobacter keratitis without visual sequelae. CONCLUSIONS AND IMPORTANCE: We have described the clinical features, microbial susceptibilities, and response to treatment in a case of R. radiobacter infectious keratitis.R. radiobacter has recently emerged as a source for several ocular and systemic infections and was identified in a series of polymicrobial keratitis cases. Our case report of monomicrobial R. radiobacter keratitis adds to the sparse literature on this uncommon but potentially sight-threatening infection.

Is Myopia Associated with the Incidence and Progression of Diabetic Retinopathy?

PURPOSE: We sought to determine the association of refractive error and its associated determinants (axial length [AL], anterior chamber depth, and corneal curvature) with the incidence and progression of diabetic retinopathy (DR). DESIGN: Population-based cohort study. METHODS: A total of 1562 eyes of 840 individuals with diabetes and gradable retinal photographs (mean age [SD], 57.0 [8.3] years, 48.2% female) from the Singapore Malay and Indian Eye Studies at baseline (2004-2009) and follow-up (2011-2015) examinations were included in the analyses. Refractive error was calculated as sphere plus half negative cylinder, while AL, anterior chamber depth, and corneal curvature were assessed using optical biometry. Incident DR was defined as having no baseline DR and any DR at follow-up; incident vision-threatening DR as no baseline vision-threatening DR but present at follow-up; and DR progression as an increase in severity at follow-up from at least minimal baseline DR. Eye-specific data and generalized estimating equation models were used to account for between-eye correlation to determine the relationships between the exposures and outcomes, adjusted for traditional DR risk factors. RESULTS: At follow-up, 164 of 1273 (12.9%) eyes had incident DR, 17 of 1542 (1.1%) eyes had incident vision-threatening DR, and 75 of 269 (27.9%) eyes with baseline DR experienced progression. A longer AL (per millimeter increase) (risk ratio 0.58 [95% confidence interval 0.38-0.88) was associated with a lower risk of incident DR. No other associations were found. CONCLUSION: Our findings show that a longer AL is protective of incident DR.

Glaucoma in myopia: diagnostic dilemmas.

Myopic eyes have an increased risk of glaucoma. However, glaucomatous changes in a myopic eye are often difficult to detect. Classic structural and functional investigations to diagnose glaucoma may be confounded by myopia. Here, we identify some of the common pitfalls in interpreting these structural parameters, and the possible solutions that could be taken to overcome them. For instance, in myopic eyes, we discuss the limitations and potential sources of error when using neuroretinal rim parameters, and retinal nerve fibre layer and ganglion cell-inner plexiform layer thickness measurements. In addition, we also review new developments and potential adjuncts in structural imaging such as the assessment of the retinal nerve fibre layer texture, and the examination of the microcirculation of the optic nerve head using optical coherence tomography angiography. For the functional assessment of glaucoma, we discuss perimetric strategies that may aid in detecting characteristic visual field defects in myopic glaucoma. Ultimately, the evaluation of glaucoma in myopia requires a multimodal approach, to allow correlation between structural and functional assessments. This review provides overview on how to navigate this diagnostic dilemma.

Changes in the Anterior Lamina Cribrosa Morphology with Glaucoma Severity.

This study was designed to evaluate if primary open angle glaucoma (POAG) and its severity are associated with the shape of the lamina cribrosa (LC) as measured by a global shape index (LC-GSI), or other indices of LC curvature or depth. Optical coherence tomography (OCT) scans of the optic nerve head (OHN) were obtained from subjects with POAG (n = 99) and non-glaucomatous controls (n = 76). ONH structures were delineated, the anterior LC morphology reconstructed in 3D, and the LC-GSI calculated (more negative values denote greater posterior concavity). Anterior LC depth and 2D-curvature were also measured. Severity of glaucoma was defined by the extent of visual field loss, based on the Hodapp-Parrish-Anderson grading. Linear regression analyses compared LC characteristics between controls, mild-moderate, and advanced POAG groups. After adjusting for age, gender, ethnicity, intraocular pressure, axial length and corneal curvature, the LC-GSI was most negative in the advanced POAG group (mean [standard error] = -0.34 [0.05]), followed by the mild-moderate POAG group (-0.31 [0.02]) and then controls (-0.23 [0.02], PTrend = 0.01). There was also a significant trend of increasing LC depth and greater LC horizontal curvature with increasing severity of glaucoma (PTrend = 0.04 and 0.02, respectively). Therefore, with more severe glaucoma, the LC-GSI was increasingly more negative, and the anterior LC depth and curvature greater. These observations collectively correspond to greater cupping of the ONH at the level of the LC. As the LC-GSI describes the 3D anterior LC morphology, its potential usage may be complementary to existing ONH parameters measured on OCT.

The Effect of Gender on Visual Field Sensitivity: The Singapore Chinese Eye Study.

PURPOSE: Visual field (VF) sensitivity is known to be age-dependent, but there is a paucity of evidence on whether it is gender-dependent. We therefore investigated the effect of gender on VF sensitivity. METHODS: An observational study involving 491 adults from the population-based Singapore Chinese Eye Study (SCES). Study participants underwent a comprehensive and standardised ocular examination and VF assessment on the Humphrey Field Analyzer II (Carl Zeiss Meditec, Inc., Dublin, CA, USA). The effect of gender on the mean deviation (MD) and pattern standard deviation (PSD) was analysed with linear regression models. RESULTS: The mean age was 52.9 ± 5.9 years, and 229 (46.6%) participants were women. A total of 800 reliable VFs from 655 healthy eyes without visual impairment, glaucoma and significant cataract were included. The mean (± standard deviation) MD was -0.45 ± 1.01 dB in men, and -0.84 ± 1.20 dB in women. The MD [95% confidence interval] was 0.28 [-0.44 to -0.12] dB lower in females compared to males (P = 0.001) after adjusting for reliability indices, degree of lens opacity, and other potential confounders. The PSD was not significantly different between the genders. CONCLUSIONS: In the SCES, the population-average of the central VF sensitivity was significantly lower in women compared to men by a small amount (0.28 dB). This effect was observed in healthy eyes, and was not explained by multiple potential confounders. Hence, this likely represents a physiological gender-based difference that is unaccounted for in standard automated perimetry. Further studies in other populations would be needed to corroborate our findings.

Association of Diabetes With Central Corneal Thickness Among a Multiethnic Asian Population.

Importance: Thicker or thinner central corneas may lead to either overestimation or underestimation of intraocular pressure, which is the most important causal and treatable risk factor for glaucoma. However, the findings on the associations between diabetes, random glucose, and glycated hemoglobin A1c (HbA1c) with central corneal thickness (CCT) are conflicting. Objective: To evaluate the associations between diabetes, random glucose, and HbA1c with CCT in a multiethnic Asian population. Design, Setting, and Participants: Cross-sectional analysis of the Singapore Epidemiology of Eye Diseases (SEED) Study conducted from 2004 to 2011. A total of 10 033 Chinese, Malay, and Indian individuals 40 years or older residing in Singapore were recruited. Participants with incomplete information on diabetes status (448 participants), prior refractive or cataract surgery (1940 eyes), and corneal edema or dystrophy (29 eyes) were excluded. A meta-analysis was conducted to estimate the overall association of diabetes with CCT. Exposures: Standardized clinical examinations and interviewer-administered questionnaire to collect information about demographic, systemic, and ocular factors. Main Outcomes and Measures: Measurement of CCT using ultrasound pachymetry. Results: A total of 8846 adults (mean [SD] age, 57.9 [9.9] years; 4447 women [50.3%]) (17 201 eyes) were included in the final analyses. The CCT profile was similar among participants with and without diabetes (mean [SD] CCT, 545.3 [33.7] µm vs 544.8 [33.9] µm; P = .39). Following adjustments of age, sex, ethnicity, corneal curvature, axial length, and body mass index, CCT was a mean (SD) of 4.9 (0.8) µm (95% CI, 3.3-6.5 µm) thicker in patients with diabetes than those without diabetes. Multivariable analyses also showed that thicker CCT was associated with higher random glucose (per 10 mg/dL [to convert to mmol/L, multiply by 0.0555], ß = 0.3; 95% CI, 0.2-0.4) and higher HbA1c (per percentage, ß = 1.5; 95% CI, 1.0-2.1) (all P < .001). These associations were significant in the subgroup with diabetes but not in the subgroup without diabetes. A meta-analysis including 12 previous population- and clinical-based studies showed that CCT was 12.8 µm (95% CI, 8.2-17.5 µm) thicker in eyes of patients with diabetes. Conclusions and Relevance: These findings suggest that diabetes and hyperglycemia were associated with thicker CCT. This study provides useful information on the interpretation of intraocular pressure in patients with diabetes.

Normative pattern and determinants of outer retinal thickness in an Asian population: the Singapore Epidemiology of Eye Diseases Study.

BACKGROUND/AIMS: To evaluate the distribution and determinants of outer retinal thickness in eyes without retinal diseases, using spectral-domain optical coherence tomography (SD-OCT). METHODS: Participants were recruited from the Singapore Epidemiology of Eye Diseases Study, a population-based study among Chinese, Malays and Indians in Singapore. A total of 5333 participants underwent SD-OCT imaging in which a 6×6 mm2 measurement area centred at the fovea. Outer retinal thickness was defined as the distance from the outer plexiform layer to the retinal pigment epithelium layer boundary. RESULTS: 7444 eyes from 4454 participants were included in final analysis. Of them, mean age was 58.4 years (SD 8.3), and 2294 (51.5%) were women. Women (121.0±8.1 µm) had thinner average outer retinal thickness than men (125.6±8.2 µm) (p<0.001). Malays (121.4±8.7 µm) had thinner average outer retinal thickness than Indians (124.3±8.6 µm) and Chinese (123.7±7.9 µm) (both p<0.001). In multivariable models, thinner average outer retinal thickness was associated with older age (per decade, ß=-1.02, p<0.001), hypertension (ß=-0.59, p=0.029), diabetes (ß=-0.73, p=0.013), chronic kidney disease (ß=-1.25, p=0.017), longer axial length (per mm, ß=-0.76, p<0.001), flatter corneal curvature (per mm, ß=-2.00, p<0.001) and higher signal strength (ß=-1.46, p<0.001). CONCLUSION: In this large sample of Asian population, we provided normative SD-OCT data on outer retinal thickness in eyes without retinal diseases. Women had thinner outer retina than men. For the first time, these findings provide fundamental knowledge on normative profile of outer retinal thickness in Asians.

Retinal Nerve Fiber Layer Thickness in a Multiethnic Normal Asian Population: The Singapore Epidemiology of Eye Diseases Study.

PURPOSE: To describe variations in retinal nerve fiber layer (RNFL) thickness based on spectral-domain (SD) OCT in a multiethnic Asian population. DESIGN: Population-based, cross-sectional study. PARTICIPANTS: Ethnic Chinese, Malay, and Indian adults older than 48 years without glaucoma who were recruited from the Singapore Epidemiology of Eye Diseases Study. METHODS: All participants underwent standardized systemic and ocular examinations. Retinal nerve fiber layer thickness was measured using SD OCT. Participants with poor-quality scans were excluded. Linear regression models were used to investigate the associations of ocular and systemic factors with average RNFL thickness. Generalized estimating equation models were used to account for correlation between both eyes. MAIN OUTCOME MEASURE: Average RNFL thickness. RESULTS: Four thousand four hundred seventy-five participants (8178 eyes) consisting of 1371 Chinese, 1303 Malay, and 1801 Indian adults contributed to this analysis. Average RNFL thickness measured was 95.7±9.6 µm in Chinese participants, 94.9±10.6 µm in Malay participants, and 87.3±10.6 µm in Indian participants (P < 0.001). Multivariate analysis adjusted for age, gender, and ethnicity revealed a reduction in RNFL thickness with increased intraocular pressure and axial length (P < 0.001 for both), as well as a diagnosis of diabetes (P = 0.04); greater RNFL thickness was associated with increased disc area (P < 0.001), signal strength (P < 0.001), and low-density lipoprotein cholesterol (P = 0.02). When these significant variables were taken into account, the average RNFL thickness of Indian participants was significantly thinner compared with Chinese participants (7.45 µm thinner on average [95% confidence interval, 6.75-8.15 µm; P < 0.001]), whereas there was no significant difference in average RNFL thickness between Malay and Chinese participants (P = 0.15). CONCLUSIONS: Average and regional RNFL thicknesses were significantly thinner in Indian eyes compared with Chinese and Malay eyes. Results of the study highlight the need to acquire more refined normative data for the comparison of individual patients with others of similar ethnic background while accounting for ocular factors that could influence RNFL thickness. This in turn may improve the sensitivity and specificity of glaucoma detection.

Myopic optic disc changes and its role in glaucoma.

PURPOSE OF REVIEW: Optic nerve head (ONH) changes such as tilt and torsion are associated with the progression of myopia, and may in turn predispose toward glaucoma. At the same time, these ONH deformations also make the structural assessment for glaucoma difficult. Here, we review the mechanisms and changes to the myopic optic disc, and the advances in structural imaging to better evaluate the ONH in myopia. RECENT FINDINGS: The distance, depth, and angle between the optic disc and the deepest point of the elongated eyeball may be related to the degree and direction of optic disc tilt and torsion. It is hypothesized that as the eyeball grows axially, the disc is pulled toward its most protruded point. These ONH deformations in myopia are thought to induce strain on the lamina cribrosa and the axons passing through it. Recent studies have shown unique characteristics of the lamina cribrosa in myopia that may account for susceptibility toward glaucoma. New developments in imaging the ONH in myopia, including the use of optical coherence tomography-angiography may also further our understanding of the relationship between myopia and glaucoma. SUMMARY: Optic disc changes in myopia are secondary to the configuration of the posterior globe. These ONH deformations may predispose toward glaucoma, although the causative relationship between myopia and glaucoma remains to be further clarified.

Time trends, disease patterns and gender imbalance in the top 100 most cited articles in ophthalmology.

We analysed the 100 top cited articles in ophthalmology to identify and characterise the most influential articles of the past four decades. Two independent investigators searched the Scopus database to determine the 100 most frequently cited articles in ophthalmology (T100-Eye) and general non-ophthalmology journals (T100-Gen) published from 1975 to December 2017. The T100-Eye list consisted of 83 original articles and 17 reviews, and the number of citations ranged from 582 to 2833. Seventy-eight of these articles were published in three journals alone (impact factor (IF): 5.05-8.2), led by the Archives of Ophthalmology The T100-Gen list consisted of 84 original articles and 16 reviews and the number of citations ranged from 358 to 3272. Forty-five of these articles were published in four journals alone (IF: 9.66-72.41). In both lists, majority of the first authors were from the USA (T100-Eye, n=80; T100-Gen, n=66), and were men (n=76 in T100-Eye; n=72 in T100-Gen). With regard to the article type, in the T100-Eye, among the 83 original research articles, most were randomised controlled trials (n=26) or clinical observational studies related to description of a new condition or new management (n=26). In the T100-Gen, of the 84 original research articles, many were clinical observational studies (n=27) or basic science research (n=26). In both lists, the most frequently examined diseases were age-related macular degeneration, diabetic retinopathy and glaucoma. Our analysis reveals landmark articles, trends and medical advancements in ophthalmology over the past four decades. It also highlights gender disparity and influence of the USA in seminal ophthalmic research.

Racial differences and determinants of macular thickness profiles in multiethnic Asian population: the Singapore Epidemiology of Eye Diseases Study.

AIM: To evaluate racial differences, and ocular and systemic determinants of macular thickness (MT), measured by spectral-domain optical coherence tomography (SD-OCT) in a normal multiethnic Asian population. METHOD: MT was measured from a 6×6 mm2 central macular area using the Cirrus high-definition OCT (HD-OCT) (Carl Zeiss Meditec, Dublin, CA). The associations between ocular and systemic factors with MT were evaluated using linear regression analyses with generalised estimating equation models to account for intereye correlation. RESULTS: 7447 healthy eyes (2577 Chinese, 2072 Malays and 2798 Indians) of 4510 subjects were included. Multivariable analysis showed that older age (per decade, ß=-4.39), female gender (ß=-5.74), diabetes (ß=-1.10), chronic kidney disease (CKD) (ß=-3.21), longer axial length (per mm, ß=-2.34), flatter corneal curvature (per mm, ß=-1.79) and presence of cataract (ß=-0.94) were associated with thinner overall average MT (OMT) (all p≤0.026); higher total cholesterol (ß=0.44; p=0.010) was associated with thicker OMT. All these factors were also associated with thinner central subfield MT (CSMT) (all p≤0.001), except for cataract, total cholesterol and CKD. Meanwhile, longer axial length (ß=2.51; p<0.001) was associated with thicker CSMT. OMT (mean±SD) was thickest in Chinese (279.9±12.5 µm), followed by Malays (276.5±13.7 µm) and Indians (272.4±13.1 µm), with p≤0.003 for all interethnic comparisons. Similar trend was observed for CSMT. CONCLUSION: There are interethnic differences in MT profile among Asians, particularly between Chinese and Indians. Ocular and systemic factors affect MT measurements as well. This Asian-specific information may be incorporated into existing clinical interpretation of macular OCT scans to aid in improving the diagnostic and monitoring accuracy of macular diseases among Asians.

Falls and Recurrent Falls among Adults in A Multi-ethnic Asian Population: The Singapore Epidemiology of Eye Diseases Study.

We evaluated the rate and risk factors associated with falls and recurrent falls in a multi-ethnic Asian population. 10,009 participants aged ≥40 years (mean[SD] age = 58.9[10.4] years) underwent clinical examinations and completed interviewer-administered questionnaires. Participants who self-reported at least one fall or ≥2 falls in past 12 months were defined as fallers and recurrent fallers, respectively. Age-standardized rates for falls and recurrent falls were 13.8% (95%CI, 13.1-14.6%) and 4.6% (95%CI, 4.2-5.1%), respectively. Multivariable analyses showed older age (OR = 1.20; 95%CI, 1.11-1.30), female gender (OR = 1.79; 95%CI, 1.54-2.07), diabetes (OR = 1.22; 95%CI, 1.07-1.40), cardiovascular disease (CVD, OR = 1.37; 95%CI, 1.14-1.65), ≥3 systemic comorbidities (OR = 1.35; 95%CI, 1.09-1.67), lower European Quality of Life-5 Dimensions (EQ-5D) score (OR = 1.36; 95%CI, 1.29-1.44), alcohol consumption (OR = 1.41, 95%CI, 1.11-1.78) and presenting visual impairment (VI, OR = 1.23; 95%CI, 1.02-1.47) were associated with falls. For recurrent falls, female gender (OR = 2.27; 95%CI, 1.75-2.94), diabetes (OR = 1.28; 95%CI, 1.03-1.61), CVD (OR = 2.00; 95%CI, 1.53-2.62), ≥3 systemic comorbidities (OR = 1.69; 95%CI, 1.19-2.39), lower EQ-5D score (OR = 1.47; 95%CI, 1.35-1.59), living in 1-2 room public flat (OR = 1.57; 95%CI, 1.05-2.33), monthly income <2000 Singapore Dollar (OR = 1.62; 95%CI, 1.13-2.31), alcohol consumption (OR = 1.81, 95%CI, 1.23-2.66) and presenting VI (OR = 1.34; 95%CI, 1.01-1.79) were significant risk factors. These findings will be useful for the formulation of fall prevention programs.

Associations between sleep duration, sleep quality and diabetic retinopathy.

BACKGROUND: Abnormal durations of sleep have been associated with risk of diabetes. However, it is not clear if sleep duration is associated with diabetic retinopathy (DR). METHODS: In a cross-sectional study, we included 1,231 (Malay, n = 395; Indian, n = 836) adults (mean age 64.4 ± 9.0 years, 50.4% female) with diabetes from the second visit of two independent population-based cohort studies (2011-15) in Singapore. Self-reported habitual sleep duration was categorized as short (<6 h), normal (6≤ h <8), and long (≥8 h). Questionnaires were administered to detect risk of obstructive sleep apnea (OSA), excessive daytime sleepiness, and insomnia, all of which may indicate poor quality of sleep. The associations between sleep-related characteristics with moderate DR and vision-threatening DR (VTDR) were analysed using logistic regression models adjusted for potential confounders. RESULTS: Prevalence of moderate DR and VTDR in the study population were 10.5% and 6.3% respectively. The mean duration of sleep was 6.4 ± 1.5 h. Compared to normal sleep duration, both short and long sleep durations were associated with moderate DR with multivariable odds ratio (95% confidence interval) of 1.73 (1.03-2.89) and 2.17 (1.28-3.66) respectively. Long sleep duration (2.37 [1.16-4.89]), high risk of OSA (2.24 [1.09-4.75]), and excessive daytime sleepiness (3.27 [1.02-10.30]) were separately associated with VTDR. CONCLUSION: Sleep duration had a U-shaped association with moderate DR; long sleep duration, excessive daytime sleepiness and high risk of OSA were positively associated with VTDR.