We explored differences in the DNA methylation statuses of PSMA6, PSMB5, HIF1A, and KEAP1 gene promoter regions in patients with type 1 diabetes and different diabetic retinopathy (DR) stages. Study subjects included individuals with no DR (NDR, n = 41), those with non-proliferative DR (NPDR, n = 27), and individuals with proliferative DR or those who underwent laser photocoagulation (PDR/LPC, n = 46). DNA methylation was determined by Zymo OneStep qMethyl technique. The methylation of PSMA6 (NDR 5.9 (3.9-8.7) %, NPDR 4.5 (3.8-5.7) %, PDR/LPC 6.6 (4.7-10.7) %, p = 0.003) and PSMB5 (NDR 2.2 (1.9-3.7) %, NPDR 2.2 (1.9-3.0) %, PDR/LPC 3.2 (2.5-7.1) %, p < 0.01) differed across the groups. Consistent correlations were observed between the methylation levels of HIF1A and PSMA6 in all study groups. DNA methylation levels of PSMA6, PSMB5, and HIF1A genes were positively correlated with the duration of diabetes, HbA1c, and albuminuria in certain study groups. Univariate regression models revealed a significant association between the methylation level z-scores of PSMA6, PSMB5, and HIF1A and severe DR (PSMA6: OR = 1.96 (1.15; 3.33), p = 0.013; PSMB5: OR = 1.90 (1.14; 3.16), p = 0.013; HIF1A: OR = 3.19 (1.26; 8.06), p = 0.014). PSMB5 remained significantly associated with DR in multivariate analysis. Our findings suggest significant associations between the severity of DR and the DNA methylation levels of the genes PSMA6, PSMB5, and HIF1A, but not KEAP1 gene.

BACKGROUND: Diabetic eye disease is a common micro-vascular complication of diabetes and a leading cause of decreased vision and blindness in people of working age worldwide.Although previous studies have shown that chemokines system may be a player in pathogenesis of diabetic eye disease, it is unclear which chemokines play the most important role.To date, there is no meta-analysis which has investigated the role of chemokines in diabetic eye disease.We hope this study will contribute to a better understanding of both the signaling pathways of the chemokines in the pathophysiological process, and more reliable therapeutic targets for diabetic eye disease.
METHODS: Embase, PubMed, Web of Science and Cochrane Library systematically searched for relevant studies from inception to Sep 1, 2023. A random-effect model was used and standardized mean differences (SMDs) and 95% confidence intervals (CIs) were calculated to summarize the associated measure between chemokines concentrations and diabetic eye disease. Network meta-analysis to rank chemokines-effect values according to ranked probabilities.
RESULTS: A total of 33 different chemokines involving 11,465 subjects (6559 cases and 4906 controls) were included in the meta-analysis. Results of the meta-analysis showed that concentrations of CC and CXC chemokines in the diabetic eye disease patients were significantly higher than those in the controls. Moreover, network meta-analysis showed that the effect of CCL8, CCL2, CXCL8 and CXCL10 were ranked highest in terms of probabilities. Concentrations of CCL8, CCL2, CXCL8 and CXCL10 may be associated with diabetic eye disease, especially in diabetic retinopathy and diabetic macular edema.
CONCLUSIONS: Our study suggests that CCL2 and CXCL8 may play key roles in pathogenesis of diabetic eye disease. Future research should explore putative mechanisms underlying these links, with the commitment to develop novel prophylactic and therapeutic for diabetic eye disease.

Diabetic eye disease (DED) is a leading cause of blindness in the world. Early detection and treatment of DED have been shown to be both sight-saving and cost-effective. As such, annual testing for DED is recommended for adults with diabetes and is a Healthcare Effectiveness Data and Information Set (HEDIS) measure. However, adherence to this guideline has historically been low, and access to this sight-saving intervention has particularly been limited for specific populations, such as Black or African American patients. In 2018, the US Food and Drug Agency (FDA) De Novo cleared autonomous artificial intelligence (AI) for diagnosing DED in a primary care setting. In 2020, Johns Hopkins Medicine (JHM), an integrated healthcare system with over 30 primary care sites, began deploying autonomous AI for DED testing in some of its primary care clinics. In this retrospective study, we aimed to determine whether autonomous AI implementation was associated with increased adherence to annual DED testing, and whether this was different for specific populations. JHM primary care sites were categorized as \"non-AI\" sites (sites with no autonomous AI deployment over the study period and where patients are referred to eyecare for DED testing) or \"AI-switched\" sites (sites that did not have autonomous AI testing in 2019 but did by 2021). We conducted a difference-in-difference analysis using a logistic regression model to compare change in adherence rates from 2019 to 2021 between non-AI and AI-switched sites. Our study included all adult patients with diabetes managed within our health system (17,674 patients for the 2019 cohort and 17,590 patients for the 2021 cohort) and has three major findings. First, after controlling for a wide range of potential confounders, our regression analysis demonstrated that the odds ratio of adherence at AI-switched sites was 36% higher than that of non-AI sites, suggesting that there was a higher increase in DED testing between 2019 and 2021 at AI-switched sites than at non-AI sites. Second, our data suggested autonomous AI improved access for historically disadvantaged populations. The adherence rate for Black/African Americans increased by 11.9% within AI-switched sites whereas it decreased by 1.2% within non-AI sites over the same time frame. Third, the data suggest that autonomous AI improved health equity by closing care gaps. For example, in 2019, a large adherence rate gap existed between Asian Americans and Black/African Americans (61.1% vs. 45.5%). This 15.6% gap shrank to 3.5% by 2021. In summary, our real-world deployment results in a large integrated healthcare system suggest that autonomous AI improves adherence to a HEDIS measure, patient access, and health equity for patients with diabetes - particularly in historically disadvantaged patient groups. While our findings are encouraging, they will need to be replicated and validated in a prospective manner across more diverse settings.

BACKGROUND:  Intravitreal injection of anti-vascular endothelial growth factor (VEGF) agents is accepted as the gold standard treatment for center-involving diabetic macular edema (CI-DME). Adjunctive administration of topical dorzolamide may enhance the therapeutic effects of anti-VEGF agents. In this study, we compared the efficacy of topical dorzolamide plus intravitreal injection of bevacizumab (IVB) versus IVB alone in patients with bilateral DME.
METHODS: This prospective, randomized contralateral eye study was carried out in a tertiary referral ophthalmology center, Al-Zahra Eye Hospital, Zahedan, Iran, between April 2021 and April 2022. This study included 50 eyes of 25 patients with bilateral DME. All eyes received three consecutive monthly injections of IVB. For each patient, one eye was randomized to instill dorzolamide eye drops three times a day as an intervention, and the other received artificial tear drops as a placebo. Best-corrected visual acuity (BCVA), central macular thickness (CMT), and intraocular pressure (IOP) were evaluated before starting treatment and then monthly for the first three months.
RESULTS: Among 25 included patients, the average age was 56.64 ± 7.97 years, and 48% were female. BCVA did not improve significantly in any groups (P > 0.05). No significant difference was observed in terms of BCVA between the intervention and control groups (P > 0.05). The present study showed a decrease in CMT in both study groups (P < 0.05). At month 3, the decrease in mean CMT from baseline was significantly higher in eyes receiving topical dorzolamide compared to the control group (-88.92 ± 82.90 vs. -37.64 ± 86.16 µM, respectively; P = 0.037). IOP decreased significantly only in eyes receiving dorzolamide (P < 0.001).
CONCLUSIONS: The results of the present study indicate that adjunctive administration of topical dorzolamide has a beneficial effect on CMT reduction from baseline, but it did not have an additive effect on BCVA improvement compared to IVB monotherapy.

BACKGROUND: With a rising prevalence of age-related eye diseases, prevention and early diagnosis of these conditions are key goals of public eye health. Disease-related knowledge in the general public supports these goals but there is little data available. Thus, we have assessed knowledge of cataract, glaucoma, age-related macular degeneration (AMD) and diabetic eye disease in the German adult general population in a cross-sectional study and identified target groups for health education interventions.
METHODS: Knowledge assessment content was identified based on a literature review, expert input, and a list of items was generated after a qualitative selection process. The resulting 16-item instrument (4 items per condition) was administered to 1,008 participants from a survey panel, demographically representative of the adult German population. Test properties were evaluated based on a Rasch model and multiple correspondence analysis (MCA). Binary-logistic regression analysis was performed to investigate associations with age, sex, education level, employment status, marital status, income, reported health status, visual difficulties, and recent general practitioner (GP) and ophthalmologist consultations.
RESULTS: Replies were correct for a median of 9 out of 16 (range 2 - 16) items, which differed between conditions (p < 0.0001). Most responses were correct for cataract items (median: 3 / 4) and least were correct for AMD items (median: 2 / 4). 27%, 9%, 1% and 19% of respondents replied correctly to all cataract, glaucoma, AMD and diabetic eye disease-related items, respectively. Rasch analysis suggested an adequate targeting of items and in MCA, no evidence of multidimensionality was present. Older age, being retired, decreased general health and recent GP or ophthalmology consultations were significantly associated with more knowledge about common eye conditions (p ≤ 0.005). GP or ophthalmology consultations remained significant in a multivariable model (p ≤ 0.011).
CONCLUSIONS: Knowledge gaps regarding eye health are considerable in the German general population and should therefore be addressed in educational interventions targeting the public. Special attention when designing such campaigns needs to be paid to infrequent users of the healthcare system. Knowledge of AMD seems to be poorer compared to other eye conditions.

Background Diabetes mellitus (DM) is a chronic metabolic disorder characterized by hyperglycemia. Globally, 382 million people have diabetes mellitus, and 90% of these patients suffer from type 2 diabetes. Saudi Arabia has the second-highest prevalence of diabetes among all Middle Eastern countries. Diabetic retinopathy (DR) is a significant complication of diabetes; early detection and proper intervention are important for its management and prognosis. Aim This study aims to assess the awareness of diabetic patients of diabetic retinopathy symptoms and complications in the western region of Saudi Arabia. Methods This is a cross-sectional study in which a convenience sampling technique was implemented for collecting data from all patients who fulfilled the inclusion criteria within the timeframe between February 2022 and October 2022 among diabetic patients at the National Guard Health Affairs in the western region. We included both type 1 and type 2 diabetic participants who are older than 18 years of age and have at least one visit to any outpatient ophthalmology clinic. Results This study involved 259 participants. The mean age of the participants is 46.69 (standard deviation {SD}: 15.59). Type 2 was more prevalent among the applicants (58.3%). A total of 242 (93%) participants were aware that diabetes could affect their eyes. Surprisingly, 130 (50.2%) do not know about diabetic retinopathy therapy options. The most significant obstacle to being examined early for ophthalmological diseases among diabetic patients was the deficient knowledge of diabetic retinopathy. Also, a significant statistical relationship was found between the year of diagnosis and the level of awareness regarding eye complications. Conclusion Despite the high level of awareness of diabetic retinopathy among diabetic patients shown in our study, it did not correspond to a high level of self-awareness on the importance of preventive measures such as annual diabetic retinopathy screening.

OBJECTIVE: (1) To assess the feasibility of conducting tablet-based vision tests in hospital clinic waiting areas; (2) To test the hypothesis that increasing severity of diabetic macular oedema (DME) is associated with the performance of tablet-based surrogates of everyday tasks and self-reported visual function.
METHODS: Sixty-one people with mild (n = 28), moderate (n = 24) or severe (n = 9) DME performed two tablet-based tests of \'real-world\' visual function (visual search and face recognition) while waiting for appointments in a hospital outpatient clinic. Participants also completed a tablet-based version of a seven-item, visual-functioning (VF-7) patient-reported outcome measure. Test performance was compared to previously published 99% normative limits for normally sighted individuals.
RESULTS: Thirty-four participants (56%; 95% confidence interval [CI] 43%-68%) exceeded normative limits for visual search, while eight (13%; 95% CI 65%-24%) exceeded normative limits for face discrimination. Search duration was significantly longer for people with severe DME than those with mild and moderate DME (p = 0.01). Face discrimination performance was not significantly associated with DME severity. VF-7 scores were statistically similar across DME severity groups. Median time to complete all elements (eligibility screening, both tablet-based tasks and the VF-7) was 22 (quartiles 19, 25) min. Further, 98% and 87% of participants, respectively, reported the search task and face discrimination task to be enjoyable, while 25% and 97%, respectively, reported finding the two tasks to be difficult.
CONCLUSIONS: Portable tablet-based tests are quick, acceptable to patients and feasible to be performed in a clinic waiting area with minimal supervision. They have the potential to be piloted in patients\' homes for self-monitoring.

To evaluate the association of social determinants of health (SDoH) with eye care utilization among people with diabetes mellitus using the 2013-2017 National Health Interview Survey (NHIS).
Retrospective cross-sectional study.
Participants ≥ 18 years of age with self-reported diabetes.
The SDoH in the following domains were used: (1) economic stability; (2) neighborhood, physical environment, and social cohesion; (3) community and social context; (4) food environment; (5) education; and (6) health care system. An aggregate SDoH score was calculated and divided into quartiles, with Q4 representing those with the highest adverse SDoH burden. Survey-weighted multivariable logistic regression models evaluated the association of SDoH quartile with eye care utilization in the preceding 12 months. A linear trend test was conducted. Domain-specific mean SDoH scores were calculated, and the performance of domain-specific models was compared using area under the curve (AUC).
Eye care utilization in the preceding 12 months.
Of 20 807 adults with diabetes, 43% had not used eye care. Greater adverse SDoH burden was associated with decrements in odds of eye care utilization (P < 0.001 for trend). Participants in the highest quartile of adverse SDoH burden (Q4) had a 58% lower odds (odds ratio [OR], 0.42; 95% confidence interval [CI], 0.37-0.47) of eye care utilization than those in Q1. The domain-specific model using economic stability had the highest performing AUC (0.63; 95% CI, 0.62-0.64).
Among a national sample of people with diabetes, adverse SDoH were associated with decreased eye care utilization. Evaluating and intervening upon the effects of adverse SDoH may be a means by which to improve eye care utilization and prevent vision loss.
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Autonomous Artificial Intelligence (AI) has the potential to reduce disparities, improve quality of care, and reduce cost by improving access to specialty diagnoses at the point-of-care. Diabetes and related complications represent a significant source of health disparities. Vision loss is a complication of diabetes, and there is extensive evidence supporting annual eye exams for prevention. Prior to the use of autonomous AI, store-and-forward imaging approaches using remote reading centers (asynchronous telemedicine) attempted to increase diabetes related eye exams with limited success. In 2018, after rigorous clinical validation, the first fully autonomous AI system [LumineticsCore™ (formerly IDx-DR), Digital Diagnostics Inc., Coralville, IA, United States] received U.S. Food and Drug Administration (FDA) De Novo authorization. The system diagnoses diabetic retinopathy (including macular edema) without specialist physician overread at the point-of-care. In addition to regulatory clearance, reimbursement, and quality measure updates, successful adoption requires local optimization of the clinical workflow. The general challenges of frontline care clinical workflow have been well documented in the literature. Because healthcare AI is so new, there remains a gap in the literature about challenges and opportunities to embed diagnostic AI into the clinical workflow. The goal of this review is to identify common workflow themes leading to successful adoption, measured as attainment number of exams per month using the autonomous AI system against targets set for each health center. We characterized the workflow in four different US health centers over a 12-month period. Health centers were geographically dispersed across the Midwest, Southwest, Northeast, and West Coast and varied distinctly in terms of size, staffing, resources, financing and demographics of patient populations. After 1 year, the aggregated number of diabetes-related exams per month increased from 89 after the first month of initial deployment to 174 across all sites. Across the diverse practice types, three primary determinants underscored sustainable adoption: (1) Inclusion of Executive and Clinical Champions; (2) Underlining Health Center Resources; and (3) Clinical workflows that contemplate patient identification (pre-visit), LumineticsCore Exam Capture and Provider Consult (patient visit), and Timely Referral Triage (post-visit). In addition to regulatory clearance, reimbursement and quality measures, our review shows that addressing the core determinants for workflow optimization is an essential part of large-scale adoption of innovation. These best practices can be generalizable to other autonomous AI systems in front-line care settings, thereby increasing patient access, improving quality of care, and addressing health disparities.

UNASSIGNED: The utility of screening for early diagnosis of glaucoma remains a widely debated topic in the care of ophthalmic patients. There are currently no population-based guidelines regarding screening for glaucoma. The purpose of this study is to determine the utility of optical coherence tomography (OCT) for early glaucoma screening in a population of diabetic patients. The results of this study may inform future screening practices.
UNASSIGNED: The current study is a post hoc analysis of OCT data collected from diabetic patients screened for eye disease over 6 months. Glaucoma suspects (GS) were identified based on abnormal retinal nerve fiber layer (RNFL) thickness on OCT. Fundus photographs of GS were graded by two independent raters for vertical cup-to-disc ratio (CDR) and other signs of glaucomatous changes.
UNASSIGNED: Of the 807 subjects screened, 50 patients (6.2%) were identified as GS. The mean RNFL thickness for GS was significantly lower than the mean RNFL in the total screening population (p < .001). Median CDR for GS was 0.44. Twenty-eight eyes of 17 GS were marked as having optic disc notching or rim thinning by at least one grader. Cohen\'s kappa statistic for inter-rater reliability was 0.85. Racial differences showed that mean CDR was significantly higher in non-whites (p < .001). Older age was associated with thinner RNFL (r = -0.29, p = .004).
UNASSIGNED: Results of this study suggest that in a sample of diabetic patients, a small but clinically significant minority may be flagged as GS based on OCT. Nearly one-third of GS eyes were found to have glaucomatous changes on fundus photography by at least one grader. These results suggest screening with OCT may be useful in detecting early glaucomatous changes in high-risk populations, particularly older, non-white patients with diabetes.