Association of age at diagnosis of diabetes with subsequent risk of age-related ocular diseases and vision acuity.

BACKGROUND: The importance of age on the development of ocular conditions has been reported by numerous studies. Diabetes may have different associations with different stages of ocular conditions, and the duration of diabetes may affect the development of diabetic eye disease. While there is a dose-response relationship between the age at diagnosis of diabetes and the risk of cardiovascular disease and mortality, whether the age at diagnosis of diabetes is associated with incident ocular conditions remains to be explored. It is unclear which types of diabetes are more predictive of ocular conditions. AIM: To examine associations between the age of diabetes diagnosis and the incidence of cataract, glaucoma, age-related macular degeneration (AMD), and vision acuity. METHODS: Our analysis was using the UK Biobank. The cohort included 8709 diabetic participants and 17418 controls for ocular condition analysis, and 6689 diabetic participants and 13378 controls for vision analysis. Ocular diseases were identified using inpatient records until January 2021. Vision acuity was assessed using a chart. RESULTS: During a median follow-up of 11.0 years, 3874, 665, and 616 new cases of cataract, glaucoma, and AMD, respectively, were identified. A stronger association between diabetes and incident ocular conditions was observed where diabetes was diagnosed at a younger age. Individuals with type 2 diabetes (T2D) diagnosed at < 45 years [HR (95%CI): 2.71 (1.49-4.93)], 45-49 years [2.57 (1.17-5.65)], 50-54 years [1.85 (1.13-3.04)], or 50-59 years of age [1.53 (1.00-2.34)] had a higher risk of AMD independent of glycated haemoglobin. T2D diagnosed < 45 years [HR (95%CI): 2.18 (1.71-2.79)], 45-49 years [1.54 (1.19-2.01)], 50-54 years [1.60 (1.31-1.96)], or 55-59 years of age [1.21 (1.02-1.43)] was associated with an increased cataract risk. T2D diagnosed < 45 years of age only was associated with an increased risk of glaucoma [HR (95%CI): 1.76 (1.00-3.12)]. HRs (95%CIs) for AMD, cataract, and glaucoma associated with type 1 diabetes (T1D) were 4.12 (1.99-8.53), 2.95 (2.17-4.02), and 2.40 (1.09-5.31), respectively. In multivariable-adjusted analysis, individuals with T2D diagnosed < 45 years of age [ß 95%CI: 0.025 (0.009,0.040)] had a larger increase in LogMAR. The ß (95%CI) for LogMAR associated with T1D was 0.044 (0.014, 0.073). CONCLUSION: The younger age at the diagnosis of diabetes is associated with a larger relative risk of incident ocular diseases and greater vision loss.

Using choroidal thickness to detect myopic macular degeneration.

AIM: To explore the usage of choroidal thickness measured by swept-source optical coherence tomography (SS-OCT) to detect myopic macular degeneration (MMD) in high myopic participants. METHODS: Participants with bilateral high myopia (≤-6 diopters) were recruited from a subset of the Guangzhou Zhongshan Ophthalmic Center-Brien Holden Vision Institute High Myopia Cohort Study. SS-OCT was performed to determine the choroidal thickness, and myopic maculopathy was graded by the International Meta-Analysis for Pathologic Myopia (META-PM) Classification. Presence of MMD was defined as META-PM category 2 or above. RESULTS: A total of 568 right eyes were included for analysis. Eyes with MMD (n=106, 18.7%) were found to have older age, longer axial lengths (AL), higher myopic spherical equivalents (SE), and reduced choroidal thickness in each Early Treatment Diabetic Retinopathy Study (ETDRS) grid sector (P<0.001). The area under the receiver operating characteristic (ROC) curves (AUC) for subfoveal choroidal thickness (0.907) was greater than that of the model, including age, AL, and SE at 0.6249, 0.8208, and 0.8205, respectively. The choroidal thickness of the inner and outer nasal sectors was the most accurate indicator of MMD (AUC of 0.928 and 0.923, respectively). An outer nasal sector choroidal thickness of less than 74 µm demonstrated the highest odds of predicting MMD (OR=33.8). CONCLUSION: Choroidal thickness detects the presence of MMD with high agreement, particularly of the inner and outer nasal sectors of the posterior pole, which appears to be a biometric parameter more precise than age, AL, or SE.

Quantitative analysis of dynamic iris changes in primary angle-closure disease with long axial lengths: the Handan Eye Study.

OBJECTIVE: To investigate dynamic iris changes in patients with primary angle-closure disease (PACD) with long axial length (AL) compared to those with short and medium AL. METHODS: This observational cross-sectional study enrolled participants aged 35 years or older from the Handan Eye Study follow-up examination who were diagnosed with PACD and underwent Visante anterior segment optical coherence tomography (ASOCT) imaging under light and dark conditions. The right eye of each participant was included in the analysis. AL was categorized as short (<22.0 mm), medium (≥22.0 to ≤23.5 mm), or long (>23.5 mm). Anterior segment parameters, including iris dynamic changes, were compared among the three groups with different ALs. RESULTS: Data from 448 patients with PACD were analyzed. We found that 10.9% of included eyes had a long AL with a flatter cornea; larger central anterior chamber depth, angle opening distance, anterior chamber width, anterior chamber area, and volume; and smaller lens thickness and lens vault (LV) (P < 0.05) than those with short AL. No significant difference existed between the three groups in iris thickness, iris cross-sectional area (IA), iris curvature, or pupil diameter (PD) change between light and dark (P > 0.05). The significant associated factors for IA changes were area recess area (ARA) in the dark, LV in the dark, and PD change from light to dark (P < 0.05). CONCLUSIONS: Dynamic and static iris parameters were consistent across patients with PACD with short, medium, or long AL and may contribute to the pathogenesis of angle closure in atypical PACD.

Electroacupuncture alleviates ciliary muscle cell apoptosis in lens-induced myopic guinea pigs through inhibiting the mitochondrial signaling pathway.

AIM: To investigate the effect of electroacupuncture (EA) on the mitochondria-dependent apoptotic signaling pathway in the ciliary muscle of guinea pigs with negative lens-induced myopia (LIM). METHODS: Guinea pigs were randomly divided into normal control (NC) group, LIM group, LIM+SHAM acupoint (LIM+SHAM) group, and LIM+EA group. Animals in the NC group received no intervention, while those in other three groups were covered with -6.0 diopter (D) lenses on right eyes. Meanwhile, animals in the LIM+EA group received EA at Hegu (LI4) combined with Taiyang (EX-HN5) acupoints, while those in the LIM+SHAM group were treated at sham points. After treatments for 1, 2, and 4wk, morphological changes in ciliary muscles were observed with hematoxylin and eosin (H&E) staining and nick end labeling (TUNEL), and the expression of the mitochondrial apoptotic signaling pathway-related molecules in ciliary muscles was measured by real-time quantitative polymerase chain reaction (qPCR) and Western blot. Additionally, the adenosine triphosphate (ATP) contents were also determined in ciliary muscles. RESULTS: Axial length increased significantly in the LIM and LIM+SHAM groups and decreased in the LIM+EA group. The ciliary muscle fibers were broken and destroyed in both LIM and LIM+SHAM groups, whereas those in the LIM+EA group improved significantly. TUNEL assay showed the number of apoptotic cells increased in the LIM and LIM+SHAM groups, whereas reduced in the LIM+EA group. ATP contents showed a significant decrease in the LIM and LIM+SHAM groups, whereas increased after EA treatment. Compared with the NC group, the dynamin-related protein 1 (DRP1), Caspase3, and apoptotic protease activator 1 (APAF1) levels were significantly increased in the LIM group and decreased in the LIM+EA group. CONCLUSION: The results provide evidence of EA inhibiting the development of myopia by regulating the mitochondrial apoptotic signaling pathway.

Axial length shortening in myopic children with Stickler syndrome after repeated low-level red-light therapy.

AIM: To report the myopia-controlling effect of repeated low-level red-light (RLRL) therapy in patients with Stickler syndrome (STL), an inherited collagenic disease typically presenting with early onset myopia. METHODS: Three STL children, aged 3, 7, and 11y, received RLRL therapy throughout the follow-up period of 17, 3, and 6mo, respectively after exclusion of fundus anomalies. Data on best-corrected visual acuity (BCVA), intraocular pressure, cycloplegic subjective refraction, ocular biometrics, scanning laser ophthalmoscope, optical coherence tomography, genetic testing, systemic disease history, and family history were recorded. RESULTS: At the initiation of the RLRL therapy, the spherical equivalent (SE) of 6 eyes from 3 patients ranged from -3.75 to -20.38 D, axial length (AL) were from 23.88 to 30.68 mm, and BCVA were from 0.4 to 1.0 (decimal notation). Myopia progression of all six eyes slowed down after RLRL therapy. AL in five out of the six eyes shortened -0.07 to -0.63 mm. No side effects were observed. CONCLUSION: Three cases of STL whose progression of myopic shift and AL elongation are successfully reduced and even reversed after RLRL therapy.

Anterior segment measurements and determinants of angle width with short, medium, and long axial lengths in a rural Chinese population.

Purpose: To report the anterior segment measurements and investigate the determinants of angle width with short, medium, and long axial length (AL) in a rural Chinese population. Design: Observational, population-based, cross-sectional study. Methods: Subjects aged ≥35 years who underwent complete ocular examinations during the follow-up of the Handan Eye Study were included. Ocular data of the right eye were analyzed. Anterior segment parameters were obtained and stratified by age and sex. AL was categorized into short (<22.0 mm), medium (22.0-23.5 mm), and long (>23.5 mm) subgroups. Linear regression analyses were performed to identify the parameters associated with angle width (angle opening distance at 500 µm from the scleral spur (SS) [AOD500]). Results: The final analysis included 4435 subjects (58.0 [49.0, 64.0] years old, 44.1% males). Smaller AOD500 was significantly associated with female sex (P = 0.032), larger iris thickness at 750 µm from the SS (IT750) (P < 0.001), larger lens vault (LV) (P < 0.001), and smaller anterior chamber volume (ACV) (P < 0.001) in the short AL subgroup; larger sphere equivalent (SE), IT750, iris curvature (IC), and LV and smaller ACV (all P < 0.001) in the medium AL subgroup; and larger SE, IT750, IA, IC, and LV and smaller ACV (all P < 0.001) in the long AL subgroup. Conclusions: Our study provides the anterior segment parameters of a large rural Chinese population. IT750, ACV, and LV were found to be the most important factors associated with angle width.

Anterior Segment Characteristics and Risk Factors for Primary Angle Closure Disease With Long Axial Lengths: The Handan Eye Study.

Purpose: To investigate the anterior segment characteristics of primary angle closure disease (PACD) with long axial length (AL) compared with that of those with short and medium AL and explore the risk factors associated with AC with different AL levels. Methods: This observational cross-sectional study enrolled subjects aged 35 years or older who completed the follow-up examinations of the Handan Eye Study and dichotomized them into normal and PACD groups. Ocular data of the right eye were analyzed. AL was categorized into short (<22.0 mm), medium (22.0-24.0 mm), or long (>24.0 mm) subgroups. Demographic and anterior segment parameters of PACD subjects were compared between the three AL subgroups. Logistic regression analysis was performed to identify the risk factors for PACD in the three subgroups. Results: Data from 715 PACD and 1446 normal subjects were analyzed. Only 6.6% of the PACD eyes had long AL, with lower spherical equivalent, larger anterior chamber depth (P < 0.001), and smaller lens thickness (P < 0.001) than those with short and medium AL. No significant differences were found for angle opening distance and iris parameters on comparing the values of eyes with long AL with that of those with short and medium AL. Significant risk factors for the development of PACD with long AL were peripheral iris thickness, anterior chamber width, and lens vault. Conclusions: PACD with long AL was uncommon. A thicker peripheral iris, larger lens vault, and smaller ACW contributed to angle closure in these patients.

Who needs myopia control?

Myopia has become a major visual disorder among school-aged children in East Asia due to its rising prevalence over the past few decades and will continue to be a leading health issue with an annual incidence as high as 20%-30%. Although various interventions have been proposed for myopia control, consensus in treatment strategies has yet to be fully developed. Atropine and orthokeratology stand out for their effectiveness in myopia progression control, but children with rapid progression of myopia require treatment with higher concentrations of atropine that are associated with increased rates of side effects, or with orthokeratology that carries risk of significant complication. Therefore, improved risk assessment for myopia onset and progression in children is critical in clinical decision-making. Besides traditional prediction models based on genetic effects and environmental exposures within populations, individualized prediction using machine learning and data based on age-specific refraction is promising. Although emerging treatments for myopia are promising and some have been incorporated into clinical practice, identifying populations who require and benefit from intervention remains the most important initial step for clinical practice.

IMI Prevention of Myopia and Its Progression.

The prevalence of myopia has markedly increased in East and Southeast Asia, and pathologic consequences of myopia, including myopic maculopathy and high myopia-associated optic neuropathy, are now some of the most common causes of irreversible blindness. Hence, strategies are warranted to reduce the prevalence of myopia and the progression to high myopia because this is the main modifiable risk factor for pathologic myopia. On the basis of published population-based and interventional studies, an important strategy to reduce the development of myopia is encouraging schoolchildren to spend more time outdoors. As compared with other measures, spending more time outdoors is the safest strategy and aligns with other existing health initiatives, such as obesity prevention, by promoting a healthier lifestyle for children and adolescents. Useful clinical measures to reduce or slow the progression of myopia include the daily application of low-dose atropine eye drops, in concentrations ranging between 0.01% and 0.05%, despite the side effects of a slightly reduced amplitude of accommodation, slight mydriasis, and risk of an allergic reaction; multifocal spectacle design; contact lenses that have power profiles that produce peripheral myopic defocus; and orthokeratology using corneal gas-permeable contact lenses that are designed to flatten the central cornea, leading to midperipheral steeping and peripheral myopic defocus, during overnight wear to eliminate daytime myopia. The risk-to-benefit ratio needs to be weighed up for the individual on the basis of their age, health, and lifestyle. The measures listed above are not mutually exclusive and are beginning to be examined in combination.

Willingness to pay for cataract surgery in baiyin district, northwestern China.

PURPOSE: To investigate willingness to pay for cataract surgery, and its associations, in Northwestern China. METHODS: Four hundred thirty-eight persons aged 50 years and above, diagnosed with cataract indicated for surgery, identified in an outreach screening program were included. Subjects were offered a willingness-to-pay interview for the maximal amount that the subjects would be willing to pay for a cataract surgery. Age, gender, literacy, education level, occupation, and annual household income were recorded. RESULTS: Among 328 (74.9%) subjects who completed the interview, 197 (60.1%) participants were willing to pay something for the cataract surgery (mean, 902.9 ± 856.7 renminbi[RMB], [US$ 145 ± 137]; median, 500RMB, US$ 78). Individuals with presenting visual acuity (PVA) in the worse eye ≤6/60 (OR: 2.1, 95% CI: 1.3-3.2) and a high annual household incomes (OR: 2.0, 95% CI: 0.9-4.6) were likely to be willing to pay for the surgery, as revealed in the regression models. Willingness to pay any amount for cataract surgery was more likely among literate persons (OR: 1.5, 95% CI: 1.0-2.4) and persons with non-agricultural occupation (OR: 1.8, 95% CI: 1.0-3.2). CONCLUSIONS: The amount that subjects were willing to pay is significantly less than the current cost of cataract surgery (5000 RMB, US$320) in the area. Providing low-cost cataract surgery to patients in a financially sustainable manner is important to increase uptake of cataract surgery among rural residents in Northwest China.

Detection of primary angleclosure suspect with different mechanisms of angle closure using multivariate prediction models.

PURPOSE: We had found that a multivariate prediction model used for the detection of primary angle-closure suspects (PACS) by combining multiple static and dynamic anterior segment optical coherence tomography (ASOCT) parameters had an area under the receiver operating characteristic curve (AUC) of 0.844. We undertook this study to evaluate this method in screening of PACS with different dominant mechanisms of angle closure (AC). METHODS: The right eyes of subjects aged ≥40 years who participated in the 5-year follow-up of the Handan Eye Study and had undergone gonioscopy and ASOCT examinations under light and dark conditions were included. All ASOCT images were analysed by the Zhongshan Angle Assessment Program. The dominant AC mechanism in each eye was determined to be pupillary block (PB), plateau iris configuration (PIC) or thick peripheral iris roll (TPIR). Backward logistic regression (LR) was used for inclusion of variables in the prediction models. LR, Naïve Bayes' classification (NBC) and neural network (NN) were evaluated and compared using the AUC. RESULTS: Data from 796 subjects (413 PACS and 383 normal eyes) were analysed. The AUCs of LR, NBC and NN in the PB group were 0.920, 0.918 and 0.917. The AUCs of LR, NBC and NN in the PIC group were 0.715, 0.708 and 0.707. The AUCs of LR, NBC and NN in TPIR group were 0.867, 0.833 and 0.886. CONCLUSIONS: Prediction models showed the best performance for detection of PACS with PB mechanism for AC and have potential for screening of PACS.

Establishment and Comparison of Algorithms for Detection of Primary Angle Closure Suspect Based on Static and Dynamic Anterior Segment Parameters.

Purpose: To establish and evaluate algorithms for detection of primary angle closure suspects (PACS), the risk factor for primary angle closure disease by combining multiple static and dynamic anterior segment optical coherence tomography (ASOCT) parameters. Methods: Observational, cross-sectional study. The right eyes of subjects aged ≥40 years who participated in the 5-year follow-up of the Handan Eye Study, and underwent gonioscopy and ASOCT examinations under light and dark conditions were included. All ASOCT images were analyzed by Zhongshan Angle Assessment Program. Backward logistic regression (BLR) was used for inclusion of variables in the prediction models. BLR, naïve Bayes' classification (NBC), and neural network (NN) were evaluated and compared using the area under the receiver operating characteristic curve (AUC). Results: Data from 744 subjects (405 eyes with PACS and 339 normal eyes) were analyzed. Angle recess area at 750 µm, anterior chamber volume, lens vault in light and iris cross-sectional area change/pupil diameter change were included in the prediction models. The AUCs of BLR, NBC, and NN were 0.827 (95% confidence interval [CI], 0.798-0.856), 0.826 (95% CI, 0.797-0.854), and 0.844 (95% CI, 0.817-0.871), respectively. No significant statistical differences were found between the three algorithms (P = 0.622). Conclusions: The three algorithms did not meet the requirements for population-based screening of PACS. One possible reason could be the different angle closure mechanisms in enrolled eyes. Translational Relevance: This study provides a promise for basis for future research directed toward the development of an image-based, noncontact method to screen for angle closure.

Diagnostic Accuracy of Rapid Assessment of Avoidable Blindness: A Population-based Assessment.

OBJECTIVES: To evaluate the diagnostic accuracy of rapid assessment of avoidable blindness (RAAB). DESIGN: Population-based diagnostic accuracy study. METHODS: A total of 2145 (95.3%, 2145/2250) subjects aged 50 years and older who participated in the RAAB survey were included. All the recruited participants underwent ophthalmic examination according to the RAAB protocol and then were reexamined with instruments in a mobile eye clinic set up in a village center on the same day. Examination in the mobile clinic included standardized visual acuity (VA) tests using logMAR charts, refraction, slit-lamp biomicroscopy, and dilated fundal examination with a binocular indirect ophthalmoscope. Blindness and economic blindness were defined as VA in the better-seeing eye <3/60 and <6/60, respectively. Visual impairment (VI) was defined as VA <6/18 in the better eye. The primary cause of blindness and VI was defined according to the cause of VI in the participant's better eye. MAIN OUTCOME MEASURES: The sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and area under the curve (AUC) of receiver operating characteristics of RAAB for detection of blindness and the principal causes of VI. RESULTS: A total of 1816 subjects (84.7%), including 686 men (37.8%) and 1130 women (62.2%), underwent ophthalmic examination in the mobile eye clinic. The mean (±standard deviation) age was 64.4 ± 9.6 years. The sensitivities, specificities, AUC, PLR, and NLR of RAAB were 90.3%, 99.3%, 0.948, 124.0, and 0.10, respectively, for detection of blindness (presenting visual acuity, PVA <3/60); 89.5%, 98.7%, 0.940, 69.2, and 0.11, respectively, for detection of economic blindness (PVA <6/60); and 90.3%, 97.7%, 0.940, 38.7, and 0.10, respectively, for detection of VI (PVA <6/18). The sensitivities, specificities, AUC, PLR, and NLR were 90.5%, 98.1%, 0.943, 48.1, and 0.10; and 60.4%, 98.7%, 0.796, 46.4, and 0.40 for detection of VI (PVA <6/18) owing to cataract and refractive error, respectively. CONCLUSION: The diagnostic performances of RAAB were high for detecting the prevalence of blindness, VI, and VI owing to cataract.

Artificial Intelligence Screening for Diabetic Retinopathy: the Real-World Emerging Application.

PURPOSE OF REVIEW: This paper systematically reviews the recent progress in diabetic retinopathy screening. It provides an integrated overview of the current state of knowledge of emerging techniques using artificial intelligence integration in national screening programs around the world. Existing methodological approaches and research insights are evaluated. An understanding of existing gaps and future directions is created. RECENT FINDINGS: Over the past decades, artificial intelligence has emerged into the scientific consciousness with breakthroughs that are sparking increasing interest among computer science and medical communities. Specifically, machine learning and deep learning (a subtype of machine learning) applications of artificial intelligence are spreading into areas that previously were thought to be only the purview of humans, and a number of applications in ophthalmology field have been explored. Multiple studies all around the world have demonstrated that such systems can behave on par with clinical experts with robust diagnostic performance in diabetic retinopathy diagnosis. However, only few tools have been evaluated in clinical prospective studies. Given the rapid and impressive progress of artificial intelligence technologies, the implementation of deep learning systems into routinely practiced diabetic retinopathy screening could represent a cost-effective alternative to help reduce the incidence of preventable blindness around the world.

Influence of severity and types of astigmatism on visual acuity in school-aged children in southern China.

AIM: To investigate the influence of astigmatism on visual acuity in school-aged children, and to define a cutoff for clinically significant astigmatism. METHODS: This is a population-based, cross-sectional study. Among 5053 enumerated children aged 5-15y in Guangzhou, 3729 (73.8%) children aged 7-15 with successful cycloplegic auto-refraction (1% cyclopentolate) and a reliable visual acuity measurement were included. Ocular measurement included external eye, anterior segment, media and fundus and cycloplegic auto-refraction. Primary outcome measures included the relationship between severity and subtypes of astigmatism and the prevalence of visual impairment. Three criteria for visual impairment were adopted: best-corrected visual acuity (BCVA) ≤0.7, uncorrected visual acuity (UCVA) ≤0.5 or <0.7 in the right eye. RESULTS: Increases of cylinder power was significantly associated with worse visual acuity (UCVA: ß=0.051, P<0.01; BCVA: ß=0.025, P<0.001). A substantial increase in UCVI and BCVI was seen with astigmatism of 1.00 diopter (D) or more. Astigmatism ≥1.00 D had a greater BCVI prevalence than cylinder power less than 1.00 D (OR=4.20, 95%CI: 3.08-5.74), and this was also true for hyperopic, emmetropic and myopic refraction categories. Oblique astigmatism was associated with a higher risk of BCVI relative to with the rule astigmatism in myopic refractive category (OR=12.87, 95%CI: 2.20-75.38). CONCLUSION: Both magnitude and subtypes of astigmatism influence the prevalence of visual impairment in school children. Cylinder ≥1.00 D may be useful as a cutoff for clinically significant astigmatism.

Development and Validation of a Deep Learning System for Diabetic Retinopathy and Related Eye Diseases Using Retinal Images From Multiethnic Populations With Diabetes.

Importance: A deep learning system (DLS) is a machine learning technology with potential for screening diabetic retinopathy and related eye diseases. Objective: To evaluate the performance of a DLS in detecting referable diabetic retinopathy, vision-threatening diabetic retinopathy, possible glaucoma, and age-related macular degeneration (AMD) in community and clinic-based multiethnic populations with diabetes. Design, Setting, and Participants: Diagnostic performance of a DLS for diabetic retinopathy and related eye diseases was evaluated using 494 661 retinal images. A DLS was trained for detecting diabetic retinopathy (using 76 370 images), possible glaucoma (125 189 images), and AMD (72 610 images), and performance of DLS was evaluated for detecting diabetic retinopathy (using 112 648 images), possible glaucoma (71 896 images), and AMD (35 948 images). Training of the DLS was completed in May 2016, and validation of the DLS was completed in May 2017 for detection of referable diabetic retinopathy (moderate nonproliferative diabetic retinopathy or worse) and vision-threatening diabetic retinopathy (severe nonproliferative diabetic retinopathy or worse) using a primary validation data set in the Singapore National Diabetic Retinopathy Screening Program and 10 multiethnic cohorts with diabetes. Exposures: Use of a deep learning system. Main Outcomes and Measures: Area under the receiver operating characteristic curve (AUC) and sensitivity and specificity of the DLS with professional graders (retinal specialists, general ophthalmologists, trained graders, or optometrists) as the reference standard. Results: In the primary validation dataset (n = 14 880 patients; 71 896 images; mean [SD] age, 60.2 [2.2] years; 54.6% men), the prevalence of referable diabetic retinopathy was 3.0%; vision-threatening diabetic retinopathy, 0.6%; possible glaucoma, 0.1%; and AMD, 2.5%. The AUC of the DLS for referable diabetic retinopathy was 0.936 (95% CI, 0.925-0.943), sensitivity was 90.5% (95% CI, 87.3%-93.0%), and specificity was 91.6% (95% CI, 91.0%-92.2%). For vision-threatening diabetic retinopathy, AUC was 0.958 (95% CI, 0.956-0.961), sensitivity was 100% (95% CI, 94.1%-100.0%), and specificity was 91.1% (95% CI, 90.7%-91.4%). For possible glaucoma, AUC was 0.942 (95% CI, 0.929-0.954), sensitivity was 96.4% (95% CI, 81.7%-99.9%), and specificity was 87.2% (95% CI, 86.8%-87.5%). For AMD, AUC was 0.931 (95% CI, 0.928-0.935), sensitivity was 93.2% (95% CI, 91.1%-99.8%), and specificity was 88.7% (95% CI, 88.3%-89.0%). For referable diabetic retinopathy in the 10 additional datasets, AUC range was 0.889 to 0.983 (n = 40 752 images). Conclusions and Relevance: In this evaluation of retinal images from multiethnic cohorts of patients with diabetes, the DLS had high sensitivity and specificity for identifying diabetic retinopathy and related eye diseases. Further research is necessary to evaluate the applicability of the DLS in health care settings and the utility of the DLS to improve vision outcomes.

Dynamic Iris Changes as a Risk Factor in Primary Angle Closure Disease.

PURPOSE: We studied the association between dynamic iris changes and the spectrum of primary angle closure disease (PACD), using the anterior segment optical coherence tomography (ASOCT). METHODS: Eligible primary angle closure (PAC), primary angle closure glaucoma (PACG), age, and sex comparable primary angle closure suspects (PACS) and normal subjects from the 5-year follow-up of the Handan Eye Study underwent ASOCT testing in dark and light conditions. The right eye of each subject was analyzed and biometric parameters including iris cross-sectional area (IA), lens vault (LV), pupil diameter (PD), and centroid-to-centroid distance (CCD) were calculated using the Zhongshan Angle Assessment Program. RESULTS: Totals of 31 PACS, 31 PAC/PACG, and 31 normal eyes were eligible for analysis. Loss of IA per mm PD increase in the dark compared to light was 0.18 mm in PACS, 0.13 mm in PAC/PACG, and 0.24 mm in normal (P = 0.015 between groups) groups. Diagnoses of normal (P = 0.001) and a smaller PD in light (P = 0.003) were statistically significant determinants of a larger IA loss per mm PD increase in the dark compared to light. Logistic regression analysis showed that LV (P = 0.002) and IA loss per mm PD increase (P = 0.017) were risk factors for an occludable angle. CONCLUSIONS: Significant differences in iris behavior in the dark compared to light in PACS, PACD, and normal eyes add to the evidence that dynamic iris change has a role in the pathogenesis of PAC in a rural Chinese population.

Quantitative analysis of iris changes following mydriasis in subjects with different mechanisms of angle closure.

PURPOSE: We estimate and compare change in iris cross-sectional area (IA) after physiologic and pharmacologic mydriasis in subjects with different dominant mechanisms for primary angle closure. METHODS: Anterior segment optical coherence tomography (AS-OCT) measurements in light, dark, and following pharmacologic dilation were obtained on primary angle closure suspects (PACS), primary angle closure (PAC), and primary angle closure glaucoma (PACG) examined during the 5-year follow-up of the Handan Eye Study. Subjects were categorized into three subgroups according to their dominant angle closure (AC) mechanisms as determined by AS-OCT: pupillary block (PB), plateau iris configuration (PIC), and thick peripheral iris roll (TPIR). The IA and other biometric parameters measured using the Zhongshan Angle Assessment Program in the right eyes of all subjects were analyzed. RESULTS: A total of 364 right eyes of subjects with PACS (333), and PAC/PACG (31) was included in the analysis. Significant differences in the change of IAs (P = 0.030), IA loss per mm pupil diameter (PD) increase (P = 0.001) in light versus pharmacologic dilation, and IA loss per mm PD increase (P = 0.011) from dark versus pharmacologic dilation were observed among the three groups. The smallest decrease occurred in the PB group. CONCLUSIONS: There are significant differences in IA and IA loss per mm of pupil change following physiologic or pharmacologic mydriasis in Chinese subjects with dissimilar dominant mechanisms for AC. Dynamic iris change may have a more important role in angle closure where PB is the dominant mechanism.

Determinants of posterior corneal biometric measurements in a multi-ethnic Asian population.

PURPOSE: To describe the corneal and anterior segment determinants of posterior corneal arc length (PCAL) and posterior corneal curvature (PCC). METHODS: Cross-sectional, population-based study of 1069 subjects (1069 eyes) aged 40-80 years, from three major Asian ethnic groups. All underwent anterior segment optical coherence tomography imaging and analysis with Zhongshan Angle Assessment Program. Our main outcome measures were determinants of PCAL and PCC using adjusted, multivariate linear regression analysis, adjusted for confounders to obtain the estimated marginal means (EMM) with standard error (SE). RESULTS: The overall mean (± SD) of PCC was: 6.51±0.39 mm; and PCAL was: 12.52±0.59 mm. Malays had a relatively longer PCAL (EMM = 12.74 mm, SE = 0.04 mm) than Chinese (EMM = 12.48 mm, SE = 0.03 mm, P<0.001), and Indians (EMM = 12.42 mm, SE = 0.03 mm, P<0.001). Anterior segment parameters had weak-moderate correlations with PCAL, which included: anterior chamber depth (ACD) (r = 0.55, P<0.001), PCC (r = 0.27, P<0.001), anterior corneal curvature (ACC) (r = 0.14, P<0.001) and central corneal thickness (CCT) (r = -0.07, P = 0.023). In multivariate analysis, anterior segment parameters explained only 37.6% of the variance of PCAL, with ACD being the most important determinant (partial R2  = 0.300; P<0.001). The determinants of PCC included ACC, PCAL and CCT (explaining 72.1% variation of PCC), with ACC being the most important determinant (partial R2  = 0.683; P<0.001). CONCLUSION: There was moderate correlation of PCAL with ACD, but anterior segment parameters accounted for only a small proportion of the variation in PCAL. The significant differences in PCAL and PCC amongst different Asian ethnic groups suggests that there is a need to consider this factor when planning for anterior segment surgeries such as endothelial keratoplasty.

Quantitative analysis of iris changes after physiologic and pharmacologic mydriasis in a rural Chinese population.

PURPOSE: To estimate and compare the change in iris cross-sectional area (IA) and iris volume (IV) following physiologic and pharmacologic pupil dilation in primary angle closure suspects (PACS) and normal subjects. METHODS: Anterior segment-optical coherence tomography (AS-OCT) measurements in light, dark, and following pharmacologic dilation were obtained on 186 PACS and 224 normal subjects examined during the 5-year follow-up of the Handan Eye Study. Iris cross-sectional area, IV, and other biometric parameters calculated using the Zhongshan angle assessment program in the right eyes of all subjects were analyzed. RESULTS: The mean IA and IV decreased in dark compared with light and after pharmacologic dilation in both PACS and normal eyes. This change was statistically significant in normal eyes: light versus pharmacologic dilation for IA (P = 0.038) and for IV, both light versus dark (P = 0.031) and light versus pharmacologic dilation (P = 0.012). A longer axial length (P = 0.028) and a greater change in pupil diameter (PD) (P < 0.001) were associated with a larger decrease of IA for the light to dark comparison. A diagnosis of normal eyes (P = 0.011), larger PD in dark (P = 0.001), and a larger change in PD (P = 0.001) were associated with a larger decrease of IV from light to dark. CONCLUSIONS: The differences in iris behavior between PACS and normal rural Chinese subjects following physiologic or pharmacologic pupillary dilation may help provide insights into the pathogenesis of angle closure.