Worsening Of Diabetic Retinopathy Research Articles

Exploring the Association of VEGF-A and ANGPTL2 with the Prognosis of Non-proliferative and Proliferative Diabetic Retinopathy.

Introduction Diabetic retinopathy (DR) is a microvascular ailment that can arise from the long-term effects of diabetes mellitus. It can potentially cause retinal damage that could endanger vision and cause blindness. The worsening of DR is mainly linked to poor glycemic control, uncontrolled hypertension, and dyslipidemia. There is a need for alternative and clinically significant novel molecules involved in the pathogenesis of DR because the diagnostic and prognostic markers have reached a limit. Materials and method This study included sex and age-matched diabetic patients with proliferative stage (N = 70), non-proliferative stage (N = 80), and control (N = 80, without the sign of DR). These patients were recruited from outpatients in the Department of Ophthalmology, Sri Ramachandra Institute of Higher Education and Research, Chennai, India. A random blood sample was collected from each study participant, and the serum was separated after centrifugation and stored at -80 °C for batch analysis. The biomarkers vascular endothelial growth factor (VEGF-A) and angiopoietin-like protein-2 (ANGPTL2) were measured using a sandwich enzyme-linked immunosorbent assay (ELISA) technique, and the laboratory parameters such as fasting blood sugar (FBS), lipid profile, blood urea nitrogen (BUN), creatine, and glycated hemoglobin (HbA1C) were also assessed. Results We observed statistically significant differences in theduration of diabetes, FBS, total cholesterol (TC), triglyceride level (TGL), BUN, and creatine (p<0.05), and the mean age of study participants was 52.95±8.20 years in the control group, 53.85±10.20 years in the proliferative diabetic retinopathy (PDR) group, and 55.02±7.65 in the non-proliferative diabetic retinopathy (NPDR) group. Furthermore, ANGPTL2 levels were statistically significant according to the severity of the disease (p<0.001*), and they were also linked (p<0.05) with established markers such as VEGF-A. Conclusion Thus, our research implies that the up-regulated markers might be linked to the disease's advancement and could serve as a prognostic indicator or therapeutic target for DR.

Novel Agents in the Management of Diabetes and Risk of Worsening Diabetic Retinopathy.

Novel therapies for diabetes have potent effects on glycemic control, obesity and cardiovascular risk reduction but some, including the popular drug semaglutide, have also been implicated in worsening of diabetic retinopathy (DR). Given the ubiquity of these new agents, understanding the risks to vision is important. Here we review the data for several newly available agents in terms of systemic efficacy and retinal safety. Literature review. Novel antihyperglycemic treatments include incretin mimetics and enhancers, sodium-glucose cotransporter inhibitors, long-acting insulins, and insulin delivery systems. All improve glycemic control and some have been shown to reduce major cardiovascular outcomes. In a pivotal trial, semaglutide was associated with ∼75% increased risk of DR worsening. The novel long-acting insulin icodec, formulated for once-weekly dosing, showed increased risk of DR worsening over a once-daily insulin. No other recent antihyperglycemic agent was associated with DR worsening, though following the semaglutide trials, nearly all studies excluded patients with pre-existing DR. Cases of DR worsening were rare in all instances. Dedicated safety studies for semaglutide in DR are currently underway. For most patients being considered for treatment with a novel anti-hyperglycemic agent, benefits on systemic metabolic and cardiovascular health are very likely to outweigh potential retinal harms. Although the true risks of the new agents on DR are unclear since their safety data come from secondary endpoints, the most vulnerable patients are those with pre-existing high-risk DR, poor baseline glycemic control and using insulin.

The Effect of Glucagon-Like Peptide-1 Receptor Agonists on Diabetic Retinopathy at a Tertiary Care Center

The potential association between diabetic retinopathy (DR) worsening and glucagon-like peptide-1 receptor agonists (GLP-1RA) has affected therapeutic management of diabetic patients but remains controversial. This study compared rates of DR development or progression in patients on GLP-1RA to those on SGLT-2 inhibitors (SGLT-2I). Retrospective cohort study. Nine hundred eighty-one patients with diabetes mellitus taking GLP-1RA or SGLT-2I, the latter serving as controls, between 2012 and2023. Patients were one-to-one greedy matched by propensity scores on race/ethnicity, age, smoking status, baseline body mass index and hemoglobin A1c %, type of diabetes mellitus, baseline DR status and history of DR procedures, duration of drug use, whether they had taken both drug types, and change in hemoglobin A1c % after 1year on the drug. The primary outcome was clinical DR development or progression (termed "worsening") detected by International Classification of Diseases (ICD), 10th edition codes, confirmed by manual review, on GLP-1RA compared with SGLT-2I after propensity score matching. Secondary outcomes included DR worsening indicated by need for procedures due to complications, and time-to-first DR worsening event. The study included 692 GLP-1RA users and 289 SGLT-2I users. The mean follow-up periods for GLP-1RA versus SGLT-2I use were 1.54 (standard deviation [SD] 1.82) years and 1.38 (SD 1.56) years, respectively. The rates of clinical worsening were 2.3% and 2.8%, respectively. After propensity score matching, an association was not identified between GLP1-RA and DR worsening neither clinically by ICD-10 codes (odds ratio [OR]=0.33, 95% confidence interval [CI]: 0.11-1.03) nor by indication for procedures (OR=0.50, 95% CI 0.13-2.00). Time-to-first DR worsening did not differ between the groups in Kaplan-Meier analysis. The most common type of clinical worsening event for both drug types was vitreous hemorrhage (43.7% and 50% of worsening events in GLP-1RA and SGLT-2I users, respectively). The most common DR procedure indicated was anti-VEGF injections (34% and 35% of GLP-1RA and SGLT-2I events, respectively). Diabetic retinopathy worsening, either clinically or by procedures, was not associated with GLP-1RA compared with SGLT-2I, both before and after propensity score matching on all analyses, including time-to-first worsening event. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Current Trends in Diagnosis and Treatment Approach of Diabetic Retinopathy during Pregnancy: A Narrative Review.

Diabetes mellitus during pregnancy and gestational diabetes are major concerns worldwide. These conditions may lead to the development of severe diabetic retinopathy during pregnancy or worsen pre-existing cases. Gestational diabetes also increases the risk of diabetes for both the mother and the fetus in the future. Understanding the prevalence, evaluating risk factors contributing to pathogenesis, and identifying treatment challenges related to diabetic retinopathy in expectant mothers are all of utmost importance. Pregnancy-related physiological changes, including those in metabolism, blood flow, immunity, and hormones, can contribute to the development or worsening of diabetic retinopathy. If left untreated, this condition may eventually result in irreversible vision loss. Treatment options such as laser therapy, intravitreal anti-vascular endothelial growth factor drugs, and intravitreal steroids pose challenges in managing these patients without endangering the developing baby and mother. This narrative review describes the management of diabetic retinopathy during pregnancy, highlights its risk factors, pathophysiology, and diagnostic methods, and offers recommendations based on findings from previous literature.

Fenofibrate and diabetic retinopathy.

Diabetic retinopathy (DR), a sight-threatening ocular complication of diabetes mellitus, is one of the main causes of blindness in the working-age population. Dyslipidemia is a potential risk factor for the development or worsening of DR, with conflicting evidence in epidemiological studies. Fenofibrate, an antihyperlipidemic agent, has lipid-modifying and pleiotropic (non-lipid) effects that may lessen the incidence of microvascular events. Relevant studies were identified through a PubMed/MEDLINE search spanning the last 20 years, using the broad term "diabetic retinopathy" and specific terms "fenofibrate" and "dyslipidemia". References cited in these studies were further examined to compile this mini-review. These pivotal investigations underwent meticulous scrutiny and synthesis, focusing on methodological approaches and clinical outcomes. Furthermore, we provided the main findings of the seminal studies in a table to enhance comprehension and comparison. Growing evidence indicates that fenofibrate treatment slows DR advancement owing to its possible protective effects on the blood-retinal barrier. The protective attributes of fenofibrate against DR progression and development can be broadly classified into two categories: lipid-modifying effects and non-lipid-related (pleiotropic) effects. The lipid-modifying effect is mediated through peroxisome proliferator-activated receptor-α activation, while the pleiotropic effects involve the reduction in serum levels of C-reactive protein, fibrinogen, and pro-inflammatory markers, and improvement in flow-mediated dilatation. In patients with DR, the lipid-modifying effects of fenofibrate primarily involve a reduction in lipoprotein-associated phospholipase A2 levels and the upregulation of apolipoprotein A1 levels. These changes contribute to the anti-inflammatory and anti-angiogenic effects of fenofibrate. Fenofibrate elicits a diverse array of pleiotropic effects, including anti-apoptotic, antioxidant, anti-inflammatory, and anti-angiogenic properties, along with the indirect consequences of these effects. Two randomized controlled trials-the Fenofibrate Intervention and Event Lowering in Diabetes and Action to Control Cardiovascular Risk in Diabetes studies-noted that fenofibrate treatment protected against DR progression, independent of serum lipid levels. Fenofibrate, an oral antihyperlipidemic agent that is effective in decreasing DR progression, may reduce the number of patients who develop vision-threatening complications and require invasive treatment. Despite its proven protection against DR progression, fenofibrate treatment has not yet gained wide clinical acceptance in DR management. Ongoing and future clinical trials may clarify the role of fenofibrate treatment in DR management.

Bariatric surgery in individuals with type 2 diabetes is not associated with short or long-term risk of diabetic retinopathy progression: results from a nationwide cohort study.

Bariatric surgery is used to induce weight loss and glycemic stability in type 2 diabetes (T2D). It has been a concern that this may lead to early worsening of diabetic retinopathy (DR) due to a rapid decline in HbA1c. In this study, we evaluated the risk of short and long-term DR development and need for ocular intervention in an entire nation of individuals with T2D undergoing bariatric surgery. The study comprised a national, register-based cohort of individuals with T2D screened for DR. Cases were matched by age, sex and DR level at the date of surgery (index date) with non-bariatric controls. We extracted information on DR levels, in- and outpatient treatments, pharmaceutical prescriptions and laboratory values. We evaluated worsening of DR (incident and progressive DR) at follow-up (6 and 36months). Amongst 238,967 individuals with T2D, who attended diabetic eye screening, we identified 553 that underwent bariatric surgery (0.2%) and 2677 non-bariatric controls. Median age was 49years, and 63% were female. Cases had more comorbidities, lower HbA1c as well as more frequent use of glucose-lowering and antihypertensive medication than controls at index date. In a fully adjusted logistic regression model, the risk of DR worsening for cases was not significantly different compared to controls, neither short-term (OR 0.41 [CI 95% 0.13; 1.33], p = 0.14) nor long-term (OR 0.64 [CI 95% 0.33; 1.24], p = 0.18). In this nationwide study, bariatric surgery did not associate with increased risk of short- or long-term DR worsening.

25-LB: Oral APX3330 Reduces the DRSS Worsening after 24-weeks of Daily Treatment—Efficacy and Safety Results of the ZETA-1 Phase 2 Trial in Diabetic Retinopathy

APX3330 is an oral, novel, small-molecule inhibitor of Ref-1, in diabetic retinopathy (DR) patients. ZETA-1 was a multi-center, placebo-controlled, double-masked Phase 2 trial. Subjects were randomized 1:1 to receive APX3330 (total 600 mg/day) or placebo BID for 24 weeks. Eligible subjects had non-proliferative DR (NPDR) or mild proliferative DR, corresponding to DR severity scale (DRSS) scores of 47, 53, or 61 as confirmed by the Duke reading center. The primary efficacy endpoint was the % of subjects with ≥ 2-step DRSS improvement in the study eye at week 24 compared to baseline. Several key pre-specified endpoints were evaluated. Results: ZETA-1 trial enrolled 103 DR subjects with 90% having NPDR with a baseline DRSS of 47 or 53. The primary endpoint was not met with 8% of study eyes showing ≥ 2-step DRSS improvement in each treatment group. Consistent with its mechanism of action of bringing VEGF and inflammation to physiologic levels, APX3330 demonstrated a statistically significant reduction in binocular ≥ 3-step worsening after 24 weeks, with 16% of placebo subjects worsening compared to 0% of APX3330 subjects (p=0.04). 19% of placebo subjects lost ≥5 BCVA letters compared to 5% of APX3330 subjects (p=0.07). AEs that occurred in ≥5% of subjects were pruritis, rash, and worsening of DR or DME in the placebo group. No subjects withdrew due to rash or pruritis. Disclosure V. H. Gonzalez: Consultant; Alimera, Bausch + Lomb, Research Support; Adverum Biotechnologies, AbbVie Inc., Apellis, Genentech, Inc., IQVIA Inc., Iveric Bio, Regeneron. P. K. Kaiser: Consultant; Ocuphire, AbbVie Inc., Bausch + Lomb, Bayer Inc., Regeneron, Ocular Therapeutix, Novartis, REGENXBIO Inc. D. S. Boyer: Advisory Panel; 3Boehringer Ingelheim Canada Ltd. /Ltée, AbbVie Inc., Adverum Biotechnologies, Alexion Pharmaceuticals, Inc., Alkahest, Allergan, Amgen Inc., Apellis, Bausch + Lomb, Chengdu Pharmaceuticals, F. Hoffmann-La Roche Limited, Genentech, Inc., Iveric Bio, Gyroscope, Janssen Pharmaceuticals, Inc., Kodiak Pharmaceuticals, NGM Biopharmaceuticals, Oxurion, Novartis, ocuphire, Roche Pharmaceuticals, REGENXBIO Inc., Other Relationship; 4D Pharma PLC. M. G. Brigell: Consultant; Ocuphire Pharma, ONL Therapeutics. D. Su: None. R. Patel: Employee; Ocuphire Pharma. B. Withers: Employee; Ocuphire. M. Kelley: None. L. Haddad: None. M. Sooch: Board Member; Ocuphire Pharma, Employee; Ocuphire Pharma, Stock/Shareholder; Ocuphire Pharma. J. S. Pepose: Consultant; Acufocus, Bausch + Lomb, Brim Biotechnology, Johnson &amp; Johnson Medical Devices Companies, Kala Pharmaceuticals, Mimetogen, Ocuphire Pharma, OKYO Pharma, Stuart Therapeutics, Thea Pharma.

Association of OCT and OCT angiography measures with the development and worsening of diabetic retinopathy in type 2 diabetes.

To assess if optical coherence tomography (OCT) and OCT angiography (OCTA) measures are associated with the development and worsening of diabetic retinopathy (DR) over four years. 280 participants with type 2 diabetes underwent ultra-wide field fundus photography, OCT and OCTA. OCT-derived macular thickness measures, retinal nerve fibre layer and ganglion cell-inner plexiform layer thickness and OCTA-derived foveal avascular zone area, perimeter, circularity, vessel density (VD) and macular perfusion (MP) were examined in relation to the development and worsening of DR over four years. After four years, 206 eyes of 219 participants were eligible for analysis. 27 of the 161 eyes (16.7%) with no DR at baseline developed new DR, which was associated with a higher baseline HbA1c and longer diabetes duration. Of the 45 eyes with non-proliferative DR (NPDR) at baseline, 17 (37.7%) showed DR progression. Baseline VD (12.90 vs. 14.90 mm/mm2, p = 0.032) and MP (31.79% vs.36.96%, p = 0.043) were significantly lower in progressors compared to non-progressors. Progression of DR was inversely related to VD ((hazard ratio [HR] = 0.825) and to MP (HR = 0.936). The area under the receiver operating characteristic curves for VD was AUC = 0.643, with 77.4% sensitivity and 41.8% specificity for a cut-off of 15.85 mm/mm2 and for MP it was AUC = 0.635, with 77.4% sensitivity and 25.5% specificity for a cut-off of 40.8%. OCTA metrics have utility in predicting progression rather than the development of DR in individuals with type 2 diabetes.

Update on the Management of Diabetic Retinopathy: Anti-VEGF Agents for the Prevention of Complications and Progression of Nonproliferative and Proliferative Retinopathy.

Diabetic retinopathy (DR) is a microvascular disease caused by poorly controlled blood glucose, and it is a leading cause of vision loss in people with diabetes. In this review we discuss the current management of DR with particular focus on the use of intraocular anti-vascular endothelial growth factor (anti-VEGF) agents. Intraocular anti-VEGF agents were first studied in the 1990s, and now several of these agents are either FDA approved or used off-label as first-line treatments for DR. Recent evidence shows that anti-VEGF agents can halt the progression of markers of DR severity, reduce the risk of DR worsening, and reduce the onset of new macular edema. These significant benefits have been demonstrated in patients with proliferative DR and the milder nonproliferative DR (NPDR). A wealth of evidence from recent trials and meta-analyses has detailed the intraoperative and postoperative benefits of adjunctive anti-VEGF therapy prior to pars plana vitrectomy (PPV) for proliferative DR with vitreous hemorrhage. In this review, we also discuss literature comparing various anti-VEGF injection regimens including monthly, quarterly, as-needed, and treat and extend protocols. Combination protocols with panretinal photocoagulation (PRP) or PPV are also discussed. Current evidence suggests that anti-VEGF therapies are effective therapy for NPDR and PDR and may also provide significant benefits when used adjunctively with other DR treatment modalities such as PRP or PPV.

Glucagon-like peptide 1-receptor agonists and A1c: Good for the heart but less so for the eyes?

Background and aimsGlucagon-like peptide1-receptor agonists (GLP1-RA) decrease major adverse cardiovascular events (MACE) in people with type 2 diabetes mellitus and cardiovascular disease (CVD). Caution is recommended for semaglutide and dulaglutide with risk of exacerbating diabetic retinopathy (DR). Analyses were performed to determine if worsening of DR was dependent on drug class or fall in A1c.Research Design and Methods: Meta-analyses and meta-regressions (MR) were performed on the 7 major cardiovascular outcome trial (CVOTs) (n = 56004 patients) of GLP1-RA. A second analysis of 11 studies (n = 11894 subjects) with semaglutide documenting DR followed. ResultsSix of the CVOTs evaluated DR. For the GLP1-RA class, there was no increase in the relative rate (rr) for retinopathy (rr = 1.09,95%CI; 0.925,1.289, p = 0.30), with only an increase with parenteral semaglutide (rr = 1.73; 1.10:2.71, p = 0.02).MR showed that decreases in A1c correlated with decreases in MACE (log rr = 0.364∗(Δ A1c), p = 0.014), but increases in DR (log rr= (−0.67∗(ΔA1c), p = 0.076). The change in DR was predominantly found for subcutaneous semaglutide given for >1 year (rr = 1.559,1.068,2.276, p = 0.022) and with decreases in A1c > 1.0% (rr = 1.59; 1.092,2.316, p = 0.016).For the class of GLP1-RA, the rate difference (rd) for worsening retinopathy was = 0.001 (and number needed to harm [NNH] = 1000) compared with rd for MACE = -0.013 (number needed to treat [NNT] = 77). The computation for semaglutide was NNH = 77 and NNT = 43. ConclusionsThis meta-analysis may assist in decisions balancing the relative risk (of existing retinopathy) versus benefits (to existing CVD). There should be close collaboration with ophthalmology to grade the baseline degree of retinopathy when initiating and following patients.

Elevated Retinol Binding Protein 3 Concentrations Are Associated With Decreased Vitreous Inflammatory Cytokines, VEGF, and Progression of Diabetic Retinopathy.

To correlate inflammatory cytokines and vascular endothelial growth factor (VEGF) in vitreous and plasma with vitreous retinol binding protein 3 (RBP3), diabetic retinopathy (DR) severity, and DR worsening in a population with type 1 and type 2 diabetes. RBP3, VEGF, and inflammatory cytokines were measured in plasma and vitreous samples (n = 205) from subjects of the Joslin Medalist Study and Beetham Eye Institute. Higher vitreous RBP3 concentrations were associated with less severe DR (P < 0.0001) and a reduced risk of developing proliferative DR (PDR) (P < 0.0001). Higher RBP3 correlated with increased photoreceptor segment thickness and lower vitreous interleukin-12 (IL-12), tumor necrosis factor-α (TNF-α), and TNF-β (P < 0.05). PDR was associated with lower vitreous interferon-γ and IL-10 and higher VEGF, IL-6, and IL-15 (P < 0.05), but was not associated with their plasma concentrations. Higher vitreous RBP3 concentrations are associated with less severe DR and slower rates of progression to PDR, supporting its potential as a biomarker and therapeutic agent for preventing DR worsening, possibly by lowering retinal VEGF and inflammatory cytokines.

Assessment of Serum Levels of the WNT Pathway Antagonist (Dickkopf-1) in a Sample of Type 2 Diabetic Patients with Retinopathy using Two Groups of Antidiabetics

Objectives: Dickkopf-1 (DKK-1) is WNT/b-catenin pathway antagonist which plays a detrimental role in the development of diabetic retinopathy (DR). This research aimed to assess serum DKK-1 levels in diabetic patients who have and have not developed DR and, compare them with the control subjects finding out whether we can use it as an indicator for DR early diagnosis and to find out which one of the widely used two groups of antidiabetic treatments had the greater effect on this biomarker and hence on the progression of DR. Methods: The study participants were divided into two subgroups: First, 70 patients (36 male, 34 female) with type 2 diabetes mellitus, among them 35 patients diagnosed with DR and 35 with no evidence of DR, and secondly, non-diabetic controls (11 male, 9 female) were selected from the patients attending Ibn AL-Haitham hospital for ophthalmology and a specialized center for endocrinology and diabetes. Venous blood samples of all participants were drawn after an overnight fast, and serum samples were stored at -20ºC until DKK-1 assay. Results: Serum DKK-1 showed significantly lower levels in diabetic patients with (6.1 ± 2 ng/mL) or without DR (14 ± 6.2 ng/mL) when compared to those of controls (34 ± 12.25 ng/mL) (p 0.05). Furthermore, serum DKK-1 levels were lower in the late stage of DR compared to the early stage 5.6 ± 1.7 and 7 ± 1.9 ng/mL, respectively. Furthermore, DPP-4 inhibitors cause a better increment in DKK-1 levels when compared to SU in the NDR group. Conclusions: Reduced serum levels of DKK-1 are related to the existence and worsening of DR and have the prospect to serve as an indicator for this condition.

Abstract #1181499: Glucagon-like peptide 1-receptor agonists and A1c: Good for the heart but less so for the eyes?

Glucagon-like peptide 1- receptor agonists (GLP1-RA) are preferred treatments for people with DM type 2 and risk for cardiovascular disease. The FDA has recommended caution in the use of semaglutide and dulaglutide because of the risk of exacerbating diabetic retinopathy (DR). Others have suggested that the worsening of DR, is independent of the class of drug, but related to the rate of fall of A1C. We have performed meta-analyses of the major trials of GLP1-RA regarding alterations in major adverse cardiovascular events (MACE) and DR and the association of these differences with changes in A1C.

Assessment of Diabetic Choroidopathy Using Ultra-Widefield Optical Coherence Tomography.

PurposeThe purpose of this study was to investigate a confocal scanning laser ophthalmoscopy (cSLO) ultra-widefield (UWF) swept-source optical coherence tomography (S-SOCT) in assessment of diabetic choroidopathy and to evaluate the agreement of measurements with a spectral-domain OCT (SD-OCT) instrument.MethodsWe conducted a cross-sectional study of patients with diabetes evaluating the choroidal vascularity index (CVI) in the nasal, temporal, and central macula segments of a UWF SS-OCT scan centered to the fovea. UWF pseudocolored fundus images were used for diabetic retinopathy (DR) severity staging. The CVI values were compared between different degrees of severity of DR and different posterior-pole sectors with linear mixed models. Central macula CVI measurements were repeated on SD-OCT scans; the interobserver intraclass coefficient (ICC) was calculated between SS-OCT and SD-OCT.ResultsA total of 151 eyes of 85 patients were included. The CVI values decreased from nonproliferative DR to proliferative DR, with high-risk proliferative DR having significantly lower CVI values than moderate to severe nonproliferative DR (P = 0.03). The central macula region was the most evidently affected; the nasal sector was the least affected. The agreement between SS-OCT and SD-OCT was moderate (ICC = 0.50).ConclusionsDiabetic choroidopathy progresses with worsening of DR toward proliferative disease; choroidal depletion is more prominent in the macula. Caution is recommended in comparing CVI values between different devices.Translational RelevanceChoroidal vascularity informs about the severity of DR and its complications, such as macular edema. The agreement between readers and between instruments may be suboptimal in certain cases.

Association of midlife cognition impairment with diabetic retinopathy in type 2 diabetes mellitus in an Indian population

Abstract Purpose: Cognitive impairment is associated with worsening of diabetic retinopathy (DR). While cognitive impairment has been observed in the elderly with DR, no report on cognition is available in middle‐aged patients with DR. We explored the association between midlife cognitive impairment and DR in an Indian population cohort.Methods: We undertook an institutional analytical cross‐sectional study with middle‐aged type 2 diabetes mellitus patients; there were 36 cases with DR and 36 patients without DR (NODR). Cognition was assessed by mini‐mental state examination (MMSE) questionnaires and compared between both groups.Results: The median age was 55 years in the DR group and 53.5 years in the NODR group. The MMSE score in DR (23.5 ± 3.3, 95% CI 22.3–24.6) was lower (p = 0.015) than in NODR (25.3 ± 3.3, 95% CI 24.2–26.5). The MMSE score in DR was lower in all the domains except for that of language. MMSE score in females (23.1 ± 3.4) was lower (p = 0.001) than in males (25.8 ± 3.0). Education‐adjusted MMSE score was normal among 31 (86.1%) in NODR and 21 (58.3%) in DR (p = 0.009). Dementia was present in 36.1% of cases with DR and 13.9% of cases with NODR. Those with DR had a 4.8 times chance of having education‐adjusted cognitive impairment compared to NODR (p = 0.046, odds ratio 4.8, 95% CI 1.0–22.7). Compared to NODR cases, the chances of having education‐adjusted cognitive impairment increased in mild non‐proliferative DR (p &lt; 0.001, odds ratio 1.8, 95% CI 0.3–11.1), moderate non‐proliferative DR (p = 0.002, odds ratio 4.3, 95% CI 1.1–16.8), and advanced DR (p &lt; 0.001, odds ratio 9.30, 95% CI 1.92–45.10).Conclusions: DR was positively associated with cognitive impairment in middle age in this sample of the Indian population. Copyright © 2022 John Wiley &amp; Sons.

Outcomes of Diabetic Retinopathy Post-Bariatric Surgery in Patients with Type 2 Diabetes Mellitus.

Bariatric surgery is an emerging therapeutic approach for obese type 2 diabetes mellitus (T2DM) patients, with proven benefits for achieving target glucose control and even remission of diabetes. However, the effect of bariatric surgery upon diabetic retinopathy is still a subject of debate as some studies show a positive effect while others raise concerns about potential early worsening effects. We performed a systematic review, on PubMed, Science Direct, and Web of Science databases regarding the onset and progression of diabetic retinopathy in obese T2DM patients who underwent weight-loss surgical procedures. A total of 6375 T2DM patients were analyzed. Most cases remained stable after bariatric surgery (89.6%). New onset of diabetic retinopathy (DR) was documented in 290 out of 5972 patients (4.8%). In cases with DR at baseline, progression was documented in 50 out of 403 (12.4%) and regression in 90 (22.3%). Preoperative careful preparation of hemoglobin A1c (HbA1c), blood pressure, and lipidemia should be provided to minimize the expectation of DR worsening. Ophthalmologic follow-up should be continued regularly in the postoperative period even in the case of diabetic remission. Further randomized trials are needed to better understand the organ-specific risk factors for progression and provide personalized counseling for T2DM patients planned for bariatric surgery.

Characteristics Associated with Early Worsening of Retinopathy in Patients with Type 2 Diabetes Diagnosed with Retinopathy at Their First Visit: A Retrospective Observational Study.

Materials and Methods Our study design was a retrospective observational study. Subjects with type 2 diabetes diagnosed with either simple or preproliferative diabetic retinopathy by ophthalmologists at their first visit and followed up for 6–18 months thereafter were included and divided into worsening and nonworsening groups. Thereafter, baseline characteristics and changes in HbA1c and therapy over a year were investigated. Results Among the 88 subjects with simple diabetic retinopathy, 16% improved to no retinopathy, 65% retained their simple diabetic retinopathy, 18% worsened to preproliferative diabetic retinopathy, and 1% worsened to proliferative diabetic retinopathy. Among the 47 subjects with preproliferative diabetic retinopathy, 9% improved to simple diabetic retinopathy, 72% retained their preproliferative diabetic retinopathy, and 19% worsened to proliferative diabetic retinopathy. Patients with simple diabetic retinopathy had an odds ratio of 1.44 for worsening retinopathy with a 1% increase in baseline HbA1c. Meanwhile, the odds ratios for worsening retinopathy with a 1% decrease in HbA1c from baseline at 3, 6, and 12 months were 1.34, 1.31, and 1.38, respectively. Among patients with simple diabetic retinopathy, significantly more new interventions were introduced in the worsening group than in the nonworsening group. Conclusions Increased baseline HbA1c, a substantial decrease in HbA1c, and intensified therapy were identified as risk factors for early worsening of diabetic retinopathy in patients with simple diabetic retinopathy at the first visit. Patients should therefore be intimately followed for retinopathy after their first visit.

Risk factors associated with progression of diabetic retinopathy in eyes treated with panretinal photocoagulation

Uncontrolled diabetes has been associated with progression of diabetic retinopathy (DR) in several studies. Therefore, we aimed to investigate systemic and ophthalmic factors related to worsening of DR even after completion of panretinal photocoagulation (PRP). We retrospectively reviewed DR patients who had completed PRP in at least one eye with a 3-year follow-up. A total of 243 eyes of 243 subjects (mean age 52.6 ± 11.6 years) were enrolled. Among them, 52 patients (21.4%) showed progression of DR after PRP (progression group), and the other 191 (78.6%) patients had stable DR (non-progression group). The progression group had higher proportion of proliferative DR (P = 0.019); lower baseline visual acuity (P < 0.001); and higher platelet count (P = 0.048), hemoglobin (P = 0.044), and hematocrit, (P = 0.042) than the non-progression group. In the multivariate logistic regression analysis for progression of DR, baseline visual acuity (HR: 0.053, P < 0.001) and platelet count (HR: 1.215, P = 0.031) were identified as risk factors for progression. Consequently, we propose that patients with low visual acuity or high platelet count are more likely to have progressive DR despite PRP and require careful observation. Also, the evaluation of hemorheological factors including platelet counts before PRP can be considered useful in predicting the prognosis of DR.

Progression of diabetic retinopathy after cataract extraction with intraocular lens implantation

Aim of the study is to observe the progression of diabetic retinopathy in patients after cataract extraction and placement of intraocular lens implantation. Diabetes affects both the anterior as well as the posterior segment of the eyes. In this study we observed the progression of the diabetic retinopathy following uncomplicated cataract surgery with intraocular lens implantation over a one year period and found that the maximum progression was seen at the end of 1 year in patients of age group 56-65 with no gender predilection. Cataract surgery in diabetic patients can be performed with an acceptable risk of complications and worsening of diabetic retinopathy seems to be correlated not with the cataract surgery but with the natural course of diabetic vascular disease. Keywords: Cataract, Diabetic retinopathy, Intraocular lens implantation, Maculopathy, Progression.

575-P: Improvement in HbA1c after Flash Monitoring Is Not Associated with Risk of Retinopathy Progression in Type 1 Diabetes

Background: Rapid improvement in HbA1c has been associated with significant short-term worsening of diabetic retinopathy. Flash monitoring (FM) is associated with significant improvement in HbA1c, particularly in those with high HbA1c at baseline. Methods: We identified all adults with type 1 diabetes, using NHS reimbursed FM, attending our center. This assessment was limited to those with high microvascular risk defined as duration of diabetes &amp;gt; 3 years and pre-FM HbA1c &amp;gt;9%. From this cohort 40 individuals were selected with the largest post-FM fall in HbA1c (responders) and compared with a further 35 with the smallest change in HbA1c (non-responders). Information on retinopathy status and laser photocoagulation was derived from electronic patient records. Results: Baseline HbA1c was significantly higher in the responder category (10.5 vs. 9.8%, P = 0.002). Median change in HbA1c, following FM, was -2.5% in responders and +0.2% in non-responders. At baseline, 32% had retinopathy classed as more severe than background (25% had proliferative retinopathy). Median duration from FM commencement to next ophthalmological assessment was 36 weeks (IQR 16 - 50). The percentage with worsening retinopathy did not significantly differ between responders (18%) and non-responders (11%) (P = 0.458). The percentage requiring laser photocoagulation after FM commencement did not differ between responders (17.5%) and non-responders (14.3%) (P = 0.704). Logistic regression analysis identified previous laser (OR 19.9, P = 0.001) but not baseline HbA1c (P = 0.139), age (P = 0.115) or HbA1c response after FM (P = 0.473) as predictive of requiring laser photocoagulation after FM commencement. Discussion: These data suggest that rapid improvement in HbA1c following FM, in a high-risk population, is not independently predictive of subsequent requirement for laser photocoagulation. Disclosure K. Linton: None. F.W. Gibb: None.