Eye Disease Study Research Articles

Copula link-based additive models for bivariate time-to-event outcomes with general censoring scheme

Bivariate survival outcomes arise frequently in applied studies where the occurrence of two events of interest are associated. Often the exact event times are unknown due to censoring which can manifest in various forms. A general and flexible copula regression model that can handle bivariate survival data subject to various censoring mechanisms, which include a mixture of uncensored, left-, right-, and interval-censored data, is proposed. The proposal permits to specify all model parameters as flexible functions of covariate effects, flexibly model the baseline survival functions by means of monotonic P-splines, characterise the marginals via transformations of the survival functions which yield, e.g., the proportional hazards and odds models as special cases, and model the dependence between events using a wide variety of copulae. The algorithm is based on a computationally efficient and stable penalised maximum likelihood estimation approach with integrated automatic multiple smoothing parameter selection. The proposed model is evaluated in a simulation study and illustrated using data from the Age-Related Eye Disease Study. The modelling framework has been incorporated in the newly-revised R package GJRM, hence allowing any user to fit the desired model(s) and produce easy-to-interpret numerical and visual summaries.

Is There an Optimal Combination of AREDS2 Antioxidants Zeaxanthin, Vitamin E and Vitamin C on Light-Induced Toxicity of Vitamin A Aldehyde to the Retina?

Vitamins C and E and zeaxanthin are components of a supplement tested in a large clinical trial—Age-Related Eye Disease Study 2 (AREDS2)—and it has been demonstrated that they can inhibit the progression of age-related macular degeneration. The aim of this study was to determine the optimal combinations of these antioxidants to prevent the phototoxicity mediated by vitamin A aldehyde (ATR), which can accumulate in photoreceptor outer segments (POS) upon exposure to light. We used cultured retinal pigment epithelial cells ARPE-19 and liposomes containing unsaturated lipids and ATR as a model of POS. Cells and/or liposomes were enriched with lipophilic antioxidants, whereas ascorbate was added just before the exposure to light. Supplementing the cells and/or liposomes with single lipophilic antioxidants had only a minor effect on phototoxicity, but the protection substantially increased in the presence of both ways of supplementation. Combinations of zeaxanthin with α-tocopherol in liposomes and cells provided substantial protection, enhancing cell viability from ~26% in the absence of antioxidants to ~63% in the presence of 4 µM zeaxanthin and 80 µM α-tocopherol, and this protective effect was further increased to ~69% in the presence of 0.5 mM ascorbate. The protective effect of ascorbate disappeared at a concentration of 1 mM, whereas 2 mM of ascorbate exacerbated the phototoxicity. Zeaxanthin or α-tocopherol partly ameliorated the cytotoxic effects. Altogether, our results suggest that the optimal combination includes upper levels of zeaxanthin and α-tocopherol achievable by diet and/or supplementations, whereas ascorbate needs to be at a four-fold smaller concentration than that in the vitreous. The physiological relevance of the results is discussed.

Long-term Outcomes of Adding Lutein/Zeaxanthin and ω-3 Fatty Acids to the AREDS Supplements on Age-Related Macular Degeneration Progression

After the Age-Related Eye Disease Study 2 (AREDS2) study, the beta carotene component was replaced by lutein/zeaxanthin for the development of the revised AREDS supplement. However, it is unknown if the increased risk of lung cancer observed in those assigned beta carotene persists beyond the conclusion of the AREDS2 trial and if there is a benefit of adding lutein/zeaxanthin to the original AREDS supplement that can be observed with long-term follow-up. To assess 10-year risk of developing lung cancer and late age-related macular degeneration (AMD). This was a multicenter epidemiologic follow-up study of the AREDS2 clinical trial, conducted from December 1, 2012, to December 31, 2018. Included in the analysis were participants with bilateral or unilateral intermediate AMD for an additional 5 years after clinical trial. Eyes/participants were censored at the time of late AMD development, death, or loss to follow-up. Data were analyzed from November 2019 to March 2022. During the clinical trial, participants were randomly assigned primarily to lutein/zeaxanthin and/or ω-3 fatty acids or placebo and secondarily to no beta carotene vs beta carotene and low vs high doses of zinc. In the epidemiologic follow-up study, all participants received AREDS2 supplements with lutein/zeaxanthin, vitamins C and E, and zinc plus copper. Outcomes were assessed at 6-month telephone calls. Analyses of AMD progression and lung cancer development were conducted using proportional hazards regression and logistic regression, respectively. Self-reported lung cancer and late AMD validated with medical records. This study included 3882 participants (mean [SD] baseline age, 72.0 [7.7] years; 2240 women [57.7%]) and 6351 eyes. At 10 years, the odds ratio (OR) of having lung cancer was 1.82 (95% CI, 1.06-3.12; P = .02) for those randomly assigned to beta carotene and 1.15 (95% CI, 0.79-1.66; P = .46) for lutein/zeaxanthin. The hazard ratio (HR) for progression to late AMD comparing lutein/zeaxanthin with no lutein/zeaxanthin was 0.91 (95% CI, 0.84-0.99; P = .02) and comparing ω-3 fatty acids with no ω-3 fatty acids was 1.01 (95% CI, 0.93-1.09; P = .91). When the lutein/zeaxanthin main effects analysis was restricted to those randomly assigned to beta carotene, the HR was 0.80 (95% CI, 0.68-0.92; P = .002). A direct analysis of lutein/zeaxanthin vs beta carotene showed the HR for late AMD was 0.85 (95% CI, 0.73-0.98; P = .02). The HR for low vs high zinc was 1.04 (95% CI, 0.94-1.14; P = .49), and the HR for no beta carotene vs beta carotene was 1.04 (95% CI, 0.94-1.15; P = .48). Results of this long-term epidemiologic follow-up study of the AREDS2 cohort suggest that lutein/zeaxanthin was an appropriate replacement for beta carotene in AREDS2 supplements. Beta carotene usage nearly doubled the risk of lung cancer, whereas there was no statistically significant increased risk with lutein/zeaxanthin. When compared with beta carotene, lutein/zeaxanthin had a potential beneficial association with late AMD progression.

Reticular Pseudodrusen: The Third Macular Risk Feature for Progression to Late Age-Related Macular Degeneration: Age-Related Eye Disease Study 2 Report 30

To analyze reticular pseudodrusen (RPD) as an independent risk factor for progression to late age-related macular degeneration (AMD), alongside traditional macular risk factors (soft drusen and pigmentary abnormalities) considered simultaneously. Post hoc analysis of 2 clinical trial cohorts: Age-Related Eye Disease Study (AREDS) and AREDS2. Eyes with no late AMD at baseline in AREDS (6959 eyes, 3780 participants) and AREDS2 (3355 eyes, 2056 participants). Color fundus photographs (CFPs) from annual visits were graded for soft drusen, pigmentary abnormalities, and late AMD. Presence of RPD was from grading of fundus autofluorescence images (AREDS2) and deep learning grading of CFPs (AREDS). Proportional hazards regression analyses were performed, considering AREDS AMD severity scales (modified simplified severity scale [person] and 9-step scale [eye]) and RPD presence simultaneously. Progression to late AMD, geographic atrophy (GA), and neovascular AMD. In AREDS, for late AMD analyses by person, in a model considering the simplified severity scale simultaneously, RPD presence was associated with a higher risk of progression: hazard ratio (HR), 2.15 (95% confidence interval [CI], 1.75-2.64). However, the risk associated with RPD presence differed at different severity scale levels: HR, 3.23 (95% CI, 1.60-6.51), HR, 3.81 (95% CI, 2.38-6.10), HR, 2.28 (95% CI, 1.59-3.27), and HR, 1.64 (95% CI, 1.20-2.24), at levels 0-1, 2, 3, and 4, respectively. Considering the 9-step scale (by eye), RPD presence was associated with higher risk: HR, 2.54 (95% CI, 2.07-3.13). The HRs were 5.11 (95% CI, 3.93-6.66) at levels 1-6 and 1.78 (95% CI, 1.43-2.22) at levels 7 and 8. In AREDS2, by person, RPD presence was not associated with higher risk: HR, 1.18 (95% CI, 0.90-1.56); by eye, it was HR, 1.57 (95% CI, 1.31-1.89). In both cohorts, RPD presence carried a higher risk for GA than neovascular AMD. Reticular pseudodrusen represent an important risk factor for progression to late AMD, particularly GA. However, the added risk varies markedly by severity level, with highly increased risk at lower/moderate levels and less increased risk at higher levels. Reticular pseudodrusen status should be included in updated AMD classification systems, risk calculators, and clinical trials.

Different impact of early and late stages irreversible eye diseases on vision-specific quality of life domains

To determine the differential impact of the irreversible eye diseases on vision-related quality of life (VRQoL) in a multi-ethnic Asian population. 2652 participants from the Singapore Epidemiology of Eye Disease Study, with any of the following early and late-stage eye conditions including age-related macular degeneration (AMD, n = 158), diabetic retinopathy (DR, n = 105; non vision threatening [non-VTDR]; VTDR), glaucoma (n = 57) and myopic macular degeneration (MMD, n = 106), or none of the above (controls, 2226 [83.9%]) were included. Rasch-scaled scores of the Emotional well-being Mobility and Reading subscales of the Impact of Vision Impairment (IVI) questionnaire, collectively referred to as “VRQoL” were assessed. Multivariable linear regression analyses and pairwise comparisons adjusting for age, gender, ethnicity, socio-economic status, BMI, smoking, alcohol use, presence of systemic diseases and presenting VI were performed to assess and compare the impact of the presence and severity of each eye condition on the three IVI domains. Multivariable adjusted pairwise comparisons of VRQoL between early stages of the four eye diseases showed no significant differences (all P > 0.05). For late stage diseases, individuals with VTDR had significantly larger decrements in Emotional well-being compared to glaucoma (β − 0.81; 95% CI − 1.47 to − 0.16) and MMD (β − 1.17; 95% CI − 2.16 to − 0.18); and Reading decrements compared to glaucoma (β − 0.66; 95% CI − 1.22 to − 0.11). When compared to late glaucoma, individuals with late AMD (β − 0.76; 95% CI − 1.50 to − 0.01) had significantly larger IVI Mobility subscale decrements. VTDR and late AMD, appear to have the greatest impact on VRQoL, compared to late glaucoma and MMD, suggesting a differential impact of late-stage eye disease categorization on VRQoL.

MULTIMODAL ASSESSMENTS OF DRUSENOID PIGMENT EPITHELIAL DETACHMENTS IN THE AGE-RELATED EYE DISEASE STUDY 2 ANCILLARY SPECTRAL-DOMAIN OPTICAL COHERENCE TOMOGRAPHY STUDY COHORT.

To identify features correlating with drusenoid pigment epithelial detachment (DPED) progression in the Age-Related Eye Disease Study 2 Ancillary spectral-domain optical coherence tomography study cohort. In this retrospective analysis of a prospective longitudinal study, eyes with intermediate age-related macular degeneration and DPEDs were followed longitudinally with annual multimodal imaging. Thirty-one eyes of 25 participants (mean age 72.6 years) in the Age-Related Eye Disease Study 2 Ancillary spectral-domain OCT substudy (A2A study) had DPED identified in color fundus images. Spectral-domain optical coherence tomography inspection confirmed a subretinal pigment epithelium drusenoid elevation of ≥433 µm diameter in 25 eyes (80.6%). Twenty-four of these eyes were followed longitudinally (median 4.0 years), during which 7 eyes (29.2%) underwent DPED collapse (with 3/7 further progressing to geographic atrophy), 6 (25.0%) developing neovascular age-related macular degeneration, and 11 (45.8%) maintaining DPED persistence without late age-related macular degeneration. On Kaplan-Meier analysis, mean time to DPED collapse was 3.9 years. Both DPED collapse and progression to neovascular age-related macular degeneration were preceded by the presence of hyperreflective foci over the DPED. The natural history of DPED comprises collapse (sometimes followed by the development of atrophy), vascularization followed by exudation, or DPED persistence. Spectral-domain optical coherence tomography can confirm retinal pigment epithelial elevation caused by drusenoid accumulation and facilitate the identification of high-risk features that correlate with progression.

The longitudinal association between cognitive impairment and incident visual impairment in a multiethnic Asian population: a prospective cohort study.

The relationship between baseline cognitive impairment (CI) and incident visual impairment (VI) in Asians is unclear. To determine the associations between baseline CI with incident VI and visual acuity (VA) at 6-year follow-up in multiethnic Asians. Cohort. Population-based. Two thousand three hundred and twenty-four adults aged ≥60years from the Singapore Epidemiology of Eye Diseases Study (response rate 64%). CI was defined using the validated Abbreviated Mental Test (AMT). VA was objectively measured using a LogMAR chart. Any incident VI was defined as having no VI (Snellen's VA better than or equal to 20/40) at baseline but present (VA worse than 20/40) at 6-year follow-up. VI severity was defined according to the International Classification of Diseases, 11th Revision. Associations were assessed using logistic and linear regression models. Of the 2,324 participants, 248 had CI at baseline. Presence of baseline CI was associated with more than twice the odds of any incident VI, incident mild and moderate-severe VI (OR [95% confidence interval]: 2.48 [1.55-3.90], 2.07 [1.17-3.55], and 2.61 [1.36-4.93], respectively) and worse VA (β [95% confidence interval]: 0.026 [0.006-0.046]) at 6-year follow-up. The leading causes of incident VI were cataract and under-corrected refractive error. Older adults with CI had more than double the odds of VI development and poorer VA than their cognitively intact counterparts, and most causes of incident VI were correctable. Strategies such as targeted vision screening and early intervention for early detection and management of vision loss in patients with cognitive decline are warranted.

Machine Learning OCT Predictors of Progression from Intermediate Age-Related Macular Degeneration to Geographic Atrophy and Vision Loss

PurposeTo describe spectral-domain OCT (SD-OCT) features, age, gender, and systemic variables that may be used in machine/deep learning studies to identify high-risk patient subpopulations with high risk of progression to geographic atrophy (GA) and visual acuity (VA) loss in the short term.DesignProspective, longitudinal study.ParticipantsWe analyzed imaging data from patients with intermediate age-related macular degeneration (iAMD) (N = 316) enrolled in the Age-Related Eye Disease Study 2 (AREDS2) Ancillary SD-OCT with adequate SD-OCT imaging for repeated measures.MethodsQualitative and quantitative multimodal variables from the database were derived at each yearly visit over 5 years. Based on statistical analyses developed in the field of cardiology, an algorithm was developed and used to select person-years without GA on color fundus photography or SD-OCT at baseline. The analysis used machine learning approaches to generate classification trees. Eyes were stratified as low, average, above average, and high risk in 1 or 2 years, based on OCT and demographic features by the risk of GA development or decreased VA by 5+ and 10+ letters.Main Outcome MeasuresNew onset of SD-OCT–determined GA and VA loss.ResultsWe identified multiple retinal and subretinal SD-OCT and demographic features from the baseline visit, each of which independently conveyed low to high risk of new-onset GA or VA loss on each of the follow-up visits at 1 or 2 years.ConclusionsWe propose a risk-stratified classification of iAMD based on the combination of OCT-derived retinal features, age, gender, and systemic variables for progression to OCT-determined GA or VA loss. After external validation, the composite early end points may be used as exclusion or inclusion criteria for future clinical studies of iAMD focused on prevention of GA progression or VA loss.

Gene-level association analysis of ordinal traits with functional ordinal logistic regressions.

In this paper, we develop functional ordinal logistic regression (FOLR) models to perform gene-based analysis of ordinal traits. In the proposed FOLR models, genetic variant data are viewed as stochastic functions of physical positions and the genetic effects are treated as a function of physical positions. The FOLR models are built upon functional data analysis which can be revised to analyze the ordinal traits and high dimension genetic data. The proposed methods are capable of dealing with dense genotype data which is usually encountered in analyzing the next-generation sequencing data. The methods are flexible and can analyze three types of genetic data: (1) rare variants only, (2) common variants only, and (3) a combination of rare and common variants. Simulation studies show that the likelihood ratio test statistics of the FOLR models control type I errors well and have good power performance. The proposed methods achieve the goals of analyzing ordinal traits directly, reducing high dimensionality of dense genetic variants, being computationally manageable, facilitating model convergence, properly controlling type I errors, and maintaining high power levels. The FOLR models are applied to analyze Age-Related Eye Disease Study data, in which two genes are found to strongly associate with four ordinal traits.

Vitamin D and Ocular Diseases: A Systematic Review.

The contributory roles of vitamin D in ocular and visual health have long been discussed, with numerous studies pointing to the adverse effects of vitamin D deficiency. In this paper, we provide a systematic review of recent findings on the association between vitamin D and different ocular diseases, including myopia, age-related macular degeneration (AMD), glaucoma, diabetic retinopathy (DR), dry eye syndrome (DES), thyroid eye disease (TED), uveitis, retinoblastoma (RB), cataract, and others, from epidemiological, clinical and basic studies, and briefly discuss vitamin D metabolism in the eye. We searched two research databases for articles examining the association between vitamin D deficiency and different ocular diseases. One hundred and sixty-two studies were found. There is evidence on the association between vitamin D and myopia, AMD, DR, and DES. Overall, 17 out of 27 studies reported an association between vitamin D and AMD, while 48 out of 54 studies reported that vitamin D was associated with DR, and 25 out of 27 studies reported an association between vitamin D and DES. However, the available evidence for the association with other ocular diseases, such as glaucoma, TED, and RB, remains limited.

Adherence to a Mediterranean Diet and Geographic Atrophy Enlargement Rate: Age-Related Eye Disease Study 2 Report 29

To determine whether closer adherence to a Mediterranean diet was associated with altered speed of geographic atrophy (GA) enlargement. Post hoc analysis of a cohort within the Age-Related Eye Disease Study 2. The study included 1155 eyes (850 participants; mean age, 74.9 years) with GA at 2 or more visits. Geographic atrophy area was measured from color fundus photographs at annual visits. An alternative Mediterranean Diet index (aMedi) was calculated for each participant by food frequency questionnaire. Mixed-model regression of square root GA area was performed by aMedi. Change in square root of GA area over time. Over a mean follow-up of 3.1 years, the mean GA enlargement rate was 0.282 mm/year (95% confidence interval, 0.270-0.293). Enlargement was significantly slower in those with higher aMedi at 0.256 mm/year (0.236-0.276), 0.290 (0.268-0.311), and 0.298 (0.280-0.317; P = 0.008) for aMedi tertiles 3, 2, and 1, respectively. Of the 9 aMedi components considered separately, significant differences in enlargement rate were observed for 4 (whole fruit [P = 0.0004], red meat [P = 0.0002], alcohol [P = 0.006], and monounsaturated fatty acid to saturated fatty acid ratio ([MUFA:SFA] [P = 0.040]) but not for fish (P = 0.14). Enlargement was slower in those with higher whole fruit, lower red meat, moderate alcohol, and higher MUFA:SFA intake. In the 768 eyes with noncentral GA, aMedi was not associated with slower progression to central involvement: hazard ratios were 1.11 (0.83-1.48) and 0.95 (0.71-1.26) for tertiles 2 and 3, respectively. A Mediterranean-type diet was associated with slower GA enlargement. Diet patterns like this may therefore lead to clinically meaningful delays in vision loss. Several components seemed to contribute most to this association in a pattern that differed from those most associated with decreased progression to GA. Hence, the Mediterranean diet is associated with protection against both faster progression to GA and faster enlargement of GA but for partially distinct reasons. These findings may help inform evidence-based dietary recommendations. Understanding the mechanisms responsible may provide insights into the underlying biology and lead to the development of nutritional supplements.

The Potential of Current Polygenic Risk Scores to Predict High Myopia and Myopic Macular Degeneration in Multiethnic Singapore Adults

To evaluate the transancestry portability of current myopia polygenic risk scores (PRSs) to predict high myopia (HM) and myopic macular degeneration (MMD) in an Asian population. Population-based study. A total of 5894 adults (2141 Chinese, 1913 Indian, and 1840 Malay) from the Singapore Epidemiology of Eye Diseases study were included in the analysis. The mean ± standard deviation age was 57.05± 9.31 years. A total of 361 adults had a diagnosis of HM (spherical equivalent [SE] < -5.00 diopters [D]) from refraction measurements, 240 individuals had a diagnosis of MMD graded by the International Photographic Classification and Grading System for Myopic Maculopathy criteria from fundus photographs, and 3774 individuals were control participants without myopia (SE > -0.5 D). The PRS, derived from 687 289 HapMap3 single nucleotide polymorphisms (SNPs) from the largest genome-wide association study of myopia in Europeans to date (n= 260 974), was assessed on its ability to predict patients with HM and MMD versus control participants. The primary outcomes were the area under the receiver operating characteristic curve (AUC) to predict HM and MMD. The PRS had an AUC of 0.73 (95% confidence interval [CI], 0.70-0.75) for HM and 0.66 (95% CI, 0.63-0.70) for MMD versus no myopia. The inclusion of the PRS with other predictors (age, sex, educational attainment [EA], and ancestry; age-by-ancestry, sex-by-ancestry, and EA-by-ancestry interactions; and 20 genotypic principal components) increased the AUC to 0.84 (95% CI, 0.82-0.86) for HM and 0.79 (95% CI, 0.76-0.82) for MMD. Individuals with a PRS in the top 5% showed up to a 4.66 (95% CI, 3.34-6.42) times higher risk of HM developing and up to a 3.43 (95% CI, 2.27-5.05) times higher risk of MMD developing compared with the remaining 95% of individuals. The PRS is a good predictor for HM and facilitates the identification of high-risk children to prevent myopia progression to HM. In addition, the PRS also predicts MMD and helps to identify high-risk adults with myopia who require closer monitoring for myopia-related complications.

LONGL-Net: temporal correlation structure guided deep learning model to predict longitudinal age-related macular degeneration severity.

Age-related macular degeneration (AMD) is the principal cause of blindness in developed countries, and its prevalence will increase to 288 million people in 2040. Therefore, automated grading and prediction methods can be highly beneficial for recognizing susceptible subjects to late-AMD and enabling clinicians to start preventive actions for them. Clinically, AMD severity is quantified by Color Fundus Photographs (CFP) of the retina, and many machine-learning-based methods are proposed for grading AMD severity. However, few models were developed to predict the longitudinal progression status, i.e. predicting future late-AMD risk based on the current CFP, which is more clinically interesting. In this paper, we propose a new deep-learning-based classification model (LONGL-Net) that can simultaneously grade the current CFP and predict the longitudinal outcome, i.e. whether the subject will be in late-AMD in the future time-point. We design a new temporal-correlation-structure-guided Generative Adversarial Network model that learns the interrelations of temporal changes in CFPs in consecutive time-points and provides interpretability for the classifier's decisions by forecasting AMD symptoms in the future CFPs. We used about 30,000 CFP images from 4,628 participants in the Age-Related Eye Disease Study. Our classifier showed average 0.905 (95% CI: 0.886–0.922) AUC and 0.762 (95% CI: 0.733–0.792) accuracy on the 3-class classification problem of simultaneously grading current time-point's AMD condition and predicting late AMD progression of subjects in the future time-point. We further validated our model on the UK Biobank dataset, where our model showed average 0.905 accuracy and 0.797 sensitivity in grading 300 CFP images.

Rapid Objective Testing of Visual FunctionMatched to the ETDRS Grid and ItsDiagnostic Power in Age-Related MacularDegeneration.

PurposeTo study the power of an 80-second multifocal pupillographic objective perimetry (mfPOP) test tailored to the ETDRS grid to diagnose age-related macular degeneration (AMD) by Age-Related Eye Disease Study (AREDS) severity grade.DesignEvaluation of a diagnostic technology.MethodsWe compared diagnostic power of acuity, ETDRS grid retinal thickness data, new 80-second M18 mfPOP test, and two wider-field 6-minute mfPOP tests (Macular-P131, Widefield-P129). The M18 stimuli match the size and shape of bifurcated ETDRS grid regions, allowing easy structure–function comparisons. M18, P129, and P131 stimuli test both eyes concurrently. We recruited 34 patients with early-stage AMD with a mean ± standard deviation (SD) age of 72.6 ± 7.06 years. The M18 and P129 plus P131 stimuli had 26 and 51 control participants, respectively with mean ± SD ages of 73.1 ± 8.17 years and 72.1 ± 5.83 years, respectively. Multifocal pupillographic objective perimetry testing used the Food and Drug Administration-cleared Objective FIELD Analyzer (OFA; Konan Medical USA).Main Outcome MeasuresPercentage area under the receiver operator characteristic curve (AUC) and Hedge’s g effect size.ResultsAcuity and OCT ETDRS grid thickness and volume produced reasonable diagnostic power (percentage AUC) for AREDS grade 4 eyes at 83.9 ± 9.98% and 90.2 ± 6.32% (mean ± standard error), respectively, but not for eyes with less severe disease. By contrast, M18 stimuli produced percentage AUCs from 72.8 ± 6.65% (AREDS grade 2) to 92.9 ± 3.93% (AREDS grade 4), and 82.9 ± 3.71% for all eyes. Hedge’s g effect sizes ranged from 0.84 to 2.32 (large to huge). Percentage AUC for P131 stimuli performed similarly and for P129 performed somewhat less well.ConclusionsThe rapid and objective M18 test provided diagnostic power comparable with that of wider-field 6-minute mfPOP tests. Unlike acuity or OCT ETDRS grid data, OFA tests produced reasonable diagnostic power in AREDS grade 1 to 3 eyes.

Six-Year Incidence and Risk Factors for Primary Angle-Closure Disease: The Singapore Epidemiology of Eye Diseases Study

To determine the incidence and risk factors of primary angle-closure disease (PACD) over 6 years in a multi-ethnic Asian population. Population-based, longitudinal study. The Singapore Epidemiology of Eye Diseases study is a population-based cohort study conducted among adults aged 40 years or more. The baseline examination was conducted between 2004 and 2010, and the 6-year follow-up visit was conducted between 2011 and 2017. Of 6762 participants who attended the follow-up examination, 5298 at risk for primary angle-closure glaucoma (PACG) and 5060 at risk for PACD were included for analyses. Standardized examinations including slit-lamp biomicroscopy, indentation gonioscopy, intraocular pressure (IOP) measurement, and static automated perimetry were performed. In this study, PACD includes primary angle-closure suspect (PACS), primary angle-closure (PAC), and PACG. The 6-year PACD incidence was evaluated among an at-risk population excluding adults with baseline glaucoma, PACS, PAC, pseudophakia at baseline or follow-up, or laser peripheral iridotomy or iridectomy at baseline visit. Logistic regression analysis adjusting for age, gender, and ethnicity was performed to evaluate associations between PACD development and demographic or ocular characteristics. Forward selection based on the Quasi-likelihood Information Criterion was used in multivariable analysis to reduce potential multicollinearity. The 6-year age-adjusted PACD incidence was 3.50% (95% confidence interval [CI], 2.94-4.16). In multivariable analysis, increasing age per decade (odds ratio [OR], 1.35; 95% CI, 1.15-1.59), higher IOP (OR, 1.04; 95% CI, 1.00-1.08), and shallower anterior chamber depth (OR, 1.11; 95% CI, 1.08-1.14) at baseline were associated with higher odds of PACD, whereas late posterior subcapsular cataract (PSC) (OR, 0.60; 95% CI, 0.48-0.76) was associated with lower odds of PACD. The 6-year age-adjusted incidences of PACG, PAC, and PACS were 0.29% (95% CI, 0.14-0.55), 0.46% (95% CI, 0.29-0.75), and 2.54% (95% CI, 2.07-3.12), respectively. Our study showed that the 6-year incidence of PACD was 3.50%. Increasing age, higher IOP, and shallower anterior chamber were associated with a higher risk of incident PACD, whereas late PSC was associated with a lower odds of PACD. These findings can aid in future projections and formulation of health care policies for screening of at-risk individuals for timely intervention.

Three-dimensional modelling of the choroidal angioarchitecture in a multi-ethnic Asian population

This study aimed to describe the topographic variation of the macula’s choroidal angioarchitecture using three-dimensional (3D) choroidal vascularity index (CVI) of healthy eyes from an Asian population and to investigate the associations of CVI. 50 participants were recruited via stratified randomisation based on subfoveal choroidal thickness from the Singapore Epidemiology of Eye Diseases Study. Macular volume scans were acquired using spectral-domain optical coherence tomography with enhanced depth imaging. CVI was assessed based on B-scan binarisation and choroid segmentation. The 3D CVI of the whole, superior, central, and inferior macula were 62.92 ± 1.57%, 62.75 ± 1.93%, 63.35 ± 1.72%, and 62.66 ± 1.70%, respectively, pairwise comparisons P all > 0.05). 3D CVI (Whole Macula) and 2D CVI (Subfoveal) were associated only with each other and not with other ocular and systemic factors. 2D CVI (Subfoveal) had a moderate agreement with 3D CVI (Central Macula) [intraclass corelation coefficient (ICC) = 0.719], and had poorer agreement with 3D CVI of the whole macula, superior, and inferior macula (ICC = 0.591, 0.483, and 0.394, respectively). Scanning volume did not influence 3D CVI measurements. In conclusion, 3D CVI demonstrated no significant topographic variation. CVI was not correlated with demographic or ocular structural features. 2D CVI of the fovea is partially representative of 3D CVI of the macula.

Determining the effect of climate and profession on dry eye disease: A prevalence study among young males in north, north-west and central India

BackgroundOcular tear film and the ocular surface together represent a dynamic playground of various protective factors against environmental influencers. Surrounding environment and geoclimatic milieu are the pertinent and continuous influencing factors. Prevalence study of Dry eye disease (DED) in various climatic conditions and professions provides an insight into this peculiar aspect of DED and human geography. MethodsThis was a hospital based, cross-sectional, comparative, analytical observational study. 1840 young soldiers between 25 and 45 years of age were studied. Divided in five climate groups based on Köppen–Geiger climate classification system the subjects were sub-grouped into professions exposed to known aggravating environmental factors. The ocular surface was examined for signs and symptoms of DED and its prevalence and risk ratio for different climates and professions were calculated. ResultsHighest prevalence of DED was found in cold desert climate and among visual display unit (VDU) users. Least prevalence was seen in highland type of climate and among people involved in professional exposed to high temperature. Prevalence of DED based upon the signs and ocular surface disease index (OSDI) was calculated and stratified with risk ratio for climatic conditions and professions. ConclusionDifferent climatic conditions and professions had different prevalence of signs, symptoms of OSD and DED which indicated its influence on prevalence of the disease.

Tribal Odisha Eye Disease Study (TOES). Report # 10. Disability inclusive eye health survey in a tribal district (Rayagada) in Odisha, India.

Purpose:To estimate seeing and other disabilities in a population cohort in a tribal district, Rayagada, in the Indian state of Orissa.Methods:A door-to-door survey was conducted to identify the disabilities. The vision was measured at the residence of the subject, and other disabilities were documented from the history obtained from the subject/household/neighbor. All people with seeing disabilities were reexamined in the community eye center (primary or secondary), and required treatment was given at no cost to the patients. People with other disabilities were transported to the public health facility for appropriate care and disability certification. The results were compared with the 2011 national census data.Results:A total of 147,699 people were enumerated, and 106,339 (72%) were examined over one year period, 2016–17. In this cohort, 47.3% (n = 50,320) were male and 27.5% (n = 29,215) were 40 years or older. We recorded systemic disease in 0.6% (n = 689) people; hypertension was two times higher than diabetes mellitus. Disability was identified in 2.8% (n = 3022). Common disabilities were seeing (46.7%; n = 1411), hearing (36.8%; n = 1112), mobility (10.4%; n = 315), and mental retardation (3.2%; n = 98). Dual sensory disability (seeing and hearing) was seen in 6.4% (n = 251), and it was higher in the older age group. Seeing and hearing disabilities were higher than the 2011 state (P =< 0.001) and national (P =< 0.001) disability census.Conclusion:The first population-based survey in Rayagada, Odisha (India) in 2017 showed a higher proportion of people with seeing and hearing disabilities. It calls for an appropriate service strategy.

OCTA Derived Vessel Skeleton Density Versus Flux and Their Associations With Systemic Determinants of Health.

PurposeTo examine the associations of optical coherence tomography angiography (OCTA)–derived retinal capillary flux with systemic determinants of health.MethodsThis is a cross-sectional study of subjects recruited from the African American Eye Disease Study. A commercially available swept-source (SS)-OCTA device was used to image the central 3 × 3 mm macular region. Retinal capillary perfusion was assessed using vessel skeleton density (VSD) and flux. Flux approximates the number of red blood cells moving through vessel segments and is a novel metric, whereas VSD is a previously validated measure commonly used to quantify capillary density. The associations of OCTA derived measures with systemic determinants of health were evaluated using multivariate generalized linear mixed-effects models.ResultsA total of 154 eyes from 83 participants were enrolled. Mean VSD and flux were 0.148 ± 0.009 and 0.156 ± 0.016, respectively. In a model containing age, systolic blood pressure, diabetes status, hematocrit, and presence of retinopathy as covariates, there was a negative correlation between VSD and age (P < 0.001) and retinopathy (P = 0.02), but not with hematocrit (P = 0.85) or other factors. There was a positive correlation between flux and hematocrit (P = 0.02), as well as a negative correlation for flux with age (P < 0.001), systolic blood pressure (P = 0.04), and diabetes status (P = 0.02). A 1% decrease in hematocrit was associated with the same magnitude change in flux as ∼1.24 years of aging. Signal strength was associated with flux (P < 0.001), but not VSD (P = 0.51).ConclusionsSS-OCTA derived flux provides additional information about retinal perfusion distinct from that obtained with skeleton density-based measures. Flux is appropriate for detecting subclinical changes in perfusion in the absence of clinical retinopathy.

Telescreening satisfaction: disparities between individuals with diabetic retinopathy and community health center staff

BackgroundThe success of telescreening and the management of diabetic retinopathy (DR) in communities depends on stakeholder satisfaction, including both individuals with diabetes and community health center (CHC) staff. In this study, we investigated the satisfaction of both individuals with vision-threatening DR (VTDR) and CHC staff within the Shanghai Eye Disease Study (SEDS) comprehensive system for managing diabetic eye diseases at the primary care level.MethodsThe cross-sectional survey of patients receiving the service included 3,817 respondents with VTDR and focused on their satisfaction with the SEDS system, including the telescreening process, speed of feedback, interpretation of results, increased awareness of related diseases, and eye care services. The survey of the providers included 234 CHC staff respondents and focused on their satisfaction and the main barriers encountered during the implementation of the system. Sociodemographic characteristics and perceived barriers related to satisfaction were identified by conducting univariate and multivariate logistic regression analyses.ResultsThe overall satisfaction of service recipients was 96.0%, and 75.8% of them were willing to undergo future telescreening for DR. The convenience of telescreening, organization of telescreening, and improvement in related disease awareness significantly correlated with satisfaction. Only 48.3% of the providers were satisfied with the SEDS system. The most frequently mentioned barriers to the development of the system were the inadequate levels of staffing (particularly technical staff), insufficient funding, and incomplete information transmission systems.ConclusionsDisparities between high patient satisfaction and low provider satisfaction with the SEDS system were mainly related to the current weak level of ophthalmic expertise in the CHCs and the low awareness of screening for diabetic eye diseases among both patients and providers.