Background/Objectives: We aimed to evaluate the diagnostic accuracy of the MONA.health artificial intelligence (AI) software (Version 1.0.0; MONA.health, Leuven, Belgium) and compare its advantages in screening for diabetic retinopathy (DR) and diabetic macular edema (DME) with standard fundus photography. Methods: This cross-sectional, real-life instrument validation study was conducted at the Vuk Vrhovac University Clinic in Zagreb during routine DR screening and included 296 patients (592 eyes) with diabetes. Following standard fundus photography using a 45° Zeiss VISUCAM NM/FA camera (Carl Zeiss Meditec AG, Jena, Germany), each patient also underwent imaging with an automated portable retinal camera (NFC-600, Crystalvue Ophthalmic Instruments, Taoyuan City, Taiwan). Two retina specialists independently graded images from the standard camera, while images from the NFC-600 were analyzed using the MONA.health AI software. Results: Among the 592 eyes, human grading identified 81 with any DR, including 17 with mild NPDR, 64 with referable DR (moderate/severe NPDR or PDR), and 13 with DME. The MONA.health AI software identified 65 eyes with referable DR and 19 with DME. For MONA DR screening compared to the standard fundus camera, the area under the curve, sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, negative likelihood ratio, kappa agreement, diagnostic odds ratio, and diagnostic effectiveness were 99.74%, 100%, 99.81%, 99.33%, 100%, 528.00, 0.00, 0.99, infinity, and 99.85%, respectively. For MONA DME screening, these metrics were 97.97%, 100%, 98.95%, 85.93%, 100%, 95.67, 0.00, 0.81, infinity, and 99.02%, respectively. The MONA AI screening process required 1 day of training and approximately 5 min for image capture and analysis, compared to 7 days of training and 13 min for image acquisition and grading with the standard method. Conclusions: These findings demonstrate that the MONA.health AI software matches the accuracy of standard fundus photography for screening and early detection of referable DR and DME, while offering a faster, simpler, and more user-friendly workflow that significantly reduces the time to obtain screening results.

Introduction and objectivesSub-Tenon anesthesia techniques are commonly employed in ophthalmology. However, there is speculation that these techniques may have hemodynamic effects on the eye, potentially affecting patients with impaired ocular perfusion. This study aims to evaluate the impact of sub-Tenon anesthesia during cataract surgery on retinal vessel density (VD) and perfusion density (PD) in eyes affected by diabetic maculopathy (DM) or retinal vein occlusion (RVO), using optical coherence tomography angiography (OCTA).MethodsThe study included 20 patients receiving sub-Tenon anesthesia with unpreserved mepivacaine 2% for unilateral cataract surgery: 10 with DM and 10 with RVO, analyzing a total of 40 eyes (20 treated and 20 untreated). Blood pressure, intraocular pressure (IOP), and retinal microvascular changes measured via OCTA (VD, PD) were documented before and shortly after sub-Tenon anesthesia. The contralateral eye, which did not receive anesthesia, served as a control.ResultsA negative association between sub-Tenon anesthesia to VD and PD was observed, with a VD-change of −1.5 ± 2.8 mm/mm2 (p = 0.02) in the treated eye compared to 0.7 ± 3.4 mm/mm2 in the untreated eye (p = 0.36) and a PD-change of −3.7 ± 7.0% (p = 0.029) in the treated eye compared to 1.6 ± 8.2% in the untreated eye (p = 0.38), suggesting a potential hemodynamic effect of sub-Tenon anesthesia. However, the quality of OCTA images strongly influenced these findings. After excluding lower-quality images (signal strength index <6), no statistically significant difference was observed between the intervention and control eyes, indicating a false positive correlation due to image artifacts. In the overall population, no significant changes in blood pressure and intraocular pressure were observed before and after the injection.ConclusionThis study did not prove retinal microvascular changes associated with sub-Tenon anesthesia. The observed VD and PD reductions were likely caused by OCTA image artifacts rather than true hemodynamic changes.

Abstract A 57-year-old male presented with complaints of persistent visual blurring in his right eye, unrelieved by recently dispensed customized progressive addition lenses. Comprehensive ophthalmic evaluation revealed a best-corrected visual acuity (BCVA) of 6/12 in the right eye that did not improve with pinhole testing. The anterior segment and intraocular pressure were within normal limits. However, fundoscopic examination demonstrated classical signs of retinal arteriosclerosis, including arteriolar narrowing, copper wiring, and Grade II and III arteriovenous crossing changes, with no evidence of diabetic retinopathy or maculopathy. These findings raised a strong suspicion of underlying systemic vascular compromise. The patient’s medical history included poorly controlled hypertension, long-standing type 2 diabetes mellitus, hypothyroidism, and persistent gastrointestinal discomfort—factors indicative of a high-risk cardiovascular profile. Based on the ocular findings and systemic risk factors, an urgent cardiology referral was made. A treadmill stress test revealed significant inducible ischemia, and subsequent coronary angiography confirmed diffuse triple-vessel disease with a critical 90% distal stenosis of the left anterior descending (LAD) artery—the classic “Widowmaker” lesion associated with sudden cardiac death. The patient underwent successful percutaneous coronary intervention with stent placement in the distal LAD and balloon angioplasty to the left posterior descending artery. At two-month follow-up, BCVA had normalized to 6/6 in both eyes, and systemic parameters, including blood pressure and cardiac function, had stabilized. This case underscores the pivotal role of retinal and fundoscopic examination as a noninvasive window to systemic vascular disease and highlights the importance of interdisciplinary collaboration between ophthalmology and cardiology in detecting life-threatening cardiovascular conditions at an early stage.

BackgroundLabelled data scarcity and class imbalance are common deep learning system (DLS) development challenges. We investigated if synthetic retinal images from a conditional cascaded diffusion model (CCDM) improves prognostic DLS (pDLS) performance for 2-year incident referable diabetic retinopathy or maculopathy (rDR/rM) prediction.MethodsMacula images from 72,559 eyes (September 2013 to December 2019) from the UK South-East London Diabetic Eye Screening Programme (SEL-DESP) formed the development dataset, whilst 9,071 eyes were used for internal testing. Images from 2,842 eyes from Birmingham DESP were used for external testing. Prognostic DLS were augmented with ×1, ×2, and ×4 additional synthetic positive cases (pDLS-G) and compared to unaugmented (pDLS-N) and ×1 positive-case resampled pDLS (pDLS-R) using the Area-Under-the Receiver Operating Characteristic curve (AUROC).ResultsHere we show that CCDM generate realistic synthetic retinal images that are comparable to real images and demonstrate the utility of synthetic retinal images in augmenting the development of a pDLS. The internal and external test AUROC for the pDLS are 0.827 (95% CI: 0.794–0.861) and 0.756 (0.680–0.831), respectively. Augmentation with ×2 additional synthetic positive cases (pDLS-G ×2) significantly improves the internal test AUROC to 0.845 (95% CI: 0.812–0.877, p = 0.044) but does not improve the external test AUROC 0.717 (0.633–0.828, p = 0.243). Resampling positive real cases alone does not improve pDLS-R performance.ConclusionsAugmenting pDLS with synthetic retinal images significantly improves pDLS performance on internal testing but not external testing suggesting further research is required to enhance the generalisability of synthetic retinal image augmentation.

To assess the outcomes of treatment cessation due to disease stability in eyes with diabetic macular edema (DME). A single-center, retrospective, consecutive case series. Patients with DME who had received their first anti-VEGF treatment between 2012 and 2021, a Snellen best-corrected visual acuity (VA) ≥0.1, and a follow-up of ≥24 months. Baseline characteristics, best-corrected VA, OCT biomarkers over time, and injection details were collected from patients' medical records. Treatment interruption was defined as a treatment-free interval of ≥25 weeks after the last injection for any reason. An active decision for treatment interruption due to a stable retinal situation was defined as treatment cessation. Data are presented as mean ± standard deviation. Percentage of patients experiencing treatment cessation, time to treatment cessation and to reuptake, and change in best-corrected VA and central retinal thickness. Beyond 109 eyes treated over ≥24 months, 81 eyes (62 patients) met the inclusion criteria. During a follow-up of 5.5 ± 2.3 (median 5) years, patients received 22.6 ± 14.9 (median 20) intravitreal injections, 7.7 ± 3.0 (8.0) of these in the first year. Fifty-seven eyes (70.4%) experienced ≥1 planned treatment cessation of ≥25 weeks, while 4 eyes experienced an unplanned treatment interruption. Treatment cessation was documented in 53 eyes (65.4%) 65.2 ± 52.4 (median 42) weeks after treatment initiation for 106.2 ± 110.4 (median 54) weeks. The reason for treatment cessation was patient-driven in 1 eye (1.9%; the patient wished to stop treatment against medical advice), physician-driven in 38 eyes (71.7%; stable VA, despite persisting residual retinal fluid in OCT), and OCT-driven in 14 eyes (26.4%; no retinal fluid in OCT). Baseline parameters were comparable between eyes experiencing treatment cessation and those which did not. Treatment cessation was achieved in 70% of eyes with DME after intensive treatment during the first year. This calls for a discussion about a possible systematic assessment of disease stability by omitting a single injection in eyes with stable residual retinal fluid. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

PurposeThis study aims to analyze corneal densitometry (CD) values in individuals diagnosed with Type 2 Diabetes Mellitus (DM) using the Pentacam Scheimpflug imaging system and to compare the obtained data with those from a control group consisting of healthy individuals.MethodsThe study included 74 eyes of 37 patients diagnosed with Type 2 Diabetes Mellitus (DM) and 54 eyes of 27 healthy volunteers matched for age and gender. All participants underwent measurements of flat keratometry (K1), steep keratometry (K2), maximum keratometry (Kmax), central corneal thickness (CCT), thinnest corneal thickness (TCT), average anterior and posterior elevation at the corneal apex (AAE and APE), corneal volume (CV) and CD. All measurements were performed using the Pentacam HR device (Oculus, Germany), which operates based on the Scheimpflug imaging principle. CD was evaluated in detail according to radial zones (0–2 mm, 2–6 mm, 6–10 mm, 10–12 mm) and corneal depths (anterior, central, posterior, and total). Only newly diagnosed Type 2 DM patients were included in the study, while those with diabetic retinopathy or maculopathy were excluded. HbA1c levels of all patients were recorded. Statistical analysis of the data was conducted using SPSS software version 22.0, and a p-value of < 0.05 was considered statistically significant.ResultsThe mean age of the Type 2 Diabetes Mellitus (DM) group was 50.51 ± 8.93 years, while the mean age of the healthy control group was 50.89 ± 5.71 years. There were no statistically significant differences between the two groups in terms of age and gender distribution (p = 0.42 and p = 0.20, respectively). Similarly, no significant differences were observed between the groups in terms of K1, K2, Kmax, CCT, TCT, AAE,APE and CV (p = 0.51; p = 0.50; p = 0.48; p = 0.95; p = 0.99; p = 0.50; p = 0.29; p = 0,58 respectively).In contrast, CD values were significantly higher in the Type 2 DM group compared to the healthy control group across all zones (0–2 mm, 2–6 mm, 6–10 mm, 10–12 mm) and at all corneal depths (anterior, central, posterior, total) (p < 0.01). A low-level positive correlation was found between HbA1c levels and AAE (r = 0.281; p = 0.015). In addition, a very weak negative correlation was observed between HbA1c levels and CD values in the anterior 2–6 mm zone (r = –0.240; p = 0.035).ConclusionIn this study, CD values were found to be significantly higher in patients with Type 2 DM compared to healthy individuals. This finding suggests that chronic hyperglycemia may lead to both morphological and functional changes in the corneal tissue.

Background: This prospective pilot study included four participants with chronic visual impairment and assessed functional and electrophysiological recovery following visual evoked potential (VEP)-guided auditory biofeedback across diverse etiologies. Low vision affects more than two billion people worldwide and imposes a sustained personal and socioeconomic burden. Conventional rehabilitation emphasizes optical aids and environmental modification without directly stimulating the visual pathway. Emerging evidence indicates that auditory biofeedback based on real-time cortical activity can leverage adult neuroplasticity. Methods: Four men (mean age 58 ± 12 years) with chronic visual impairment attributable to occipital stroke, stage IV macular hole, end-stage open-angle glaucoma, or diabetic maculopathy completed ten 10-min monocular sessions with the Retimax Vision Trainer over three weeks (15 Hz pattern reversal, 90% contrast). Primary end points were best corrected visual acuity (BCVA, ETDRS letters) and P100 amplitude/latency. Fixation stability was recorded with MAIA microperimetry when feasible. A focused PubMed review (2010–2025) mapped current evidence and research gaps. Results: Median BCVA improved by seven letters (IQR 0–15); three of eight eyes gained ≥ 10 letters and none lost vision. Mean P100 amplitude increased from 1.0 ± 1.2 µV to 3.0 ± 1.1 µV, while latency shortened by 3.9 ms. Electrophysiological improvement paralleled behavioural gain irrespective of lesion site. No adverse events occurred. Conclusions: A concise course of VEP-guided auditory biofeedback produced concordant functional and neurophysiological gains across retinal, optic nerve, and cortical pathologies. These pilot data support integration of closed-loop biofeedback into routine low vision care and justify larger sham-controlled trials.

Background: Intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) agents has become increasingly important in managing vitreoretinal diseases such as age-related macular degeneration, central or branch retinal vein occlusion, and diabetic maculopathy, which are rising globally. This study aimed to assess the effect of intravitreal Bevacizumab injection on intraocular pressure (IOP) and mean ocular perfusion pressure (MOPP). Methods: This prospective observational study was conducted in the Department of Ophthalmology, BSMMU, Dhaka from March 2018 to August 2020. Within the period, total 85 cases of different vitreoretinal diseases those meet the inclusion criteria were included in study after receiving informed consent from the patient. Results: Mean IOP was 13.39±3.92 mmHg before injection, 16.65±4.48 mmHg at 30 minutes, 13.40±3.50 mmHg at 1 day, and 13.12±3.27 mmHg at 7 days. Mean MOPP was 50.94±6.87 mmHg before injection, 48.12±7.15 mmHg at 30 minutes, 50.47±6.64 mmHg at 1 day, and 50.66±4.98 mmHg at 7 days. A significant change was observed in IOP and MOPP within 30 minutes post-injection (p &lt; 0.05), but not at 1 or 7 days (p &gt; 0.05). Conclusion: After analyzing the results of present study it can be concluded that IOP is significantly increased within 30 minutes after injection and recover to their pre-injection value within 1 day after injection, this observation continued on 7th day follow up also. And MOPP is significantly decreased within 30 minutes after injection and recover to their pre-injection value within 1 days after injection and this observation continued on 7th day follow up also.

To elucidate the correlation between immunoglobulin G (IgG) N-glycosylation patterns (IGPs) and diabetes complications, including diabetic nephropathy (DN), diabetic retinopathy (DR) and diabetic maculopathy (DM). We performed a two-sample Mendelian randomization (MR) study. We obtained genome-wide association studies (GWAS) summary statistics related to 77 IGPs and diabetic complications from the MRC Human Genetics Unit and the FinnGen consortium. In our two-sample MR, genetic variants associated with IGPs were used to estimate correlations. The inverse-variance weighted (IVW) method was used as the primary analysis. Various complementary methods, including MR-Egger, weighted median (WM), and weighted mode were implemented to detect the causal relationship. Sensitivity analyses including MR-PRESSO, MR-Egger, Cochran's Q and leave-one-out methods were used to validate the robustness of the results. After MR-PRESSO outlier correction and a stringent False Discovery Rate (FDR) correction, a significant causal association was identified: higher levels of IGP48 were robustly associated with an increased risk of diabetic maculopathy (DM) (OR: 1.21, 95% CI: 1.09-1.35, P = 0.001, FDR = 0.004). Additionally, several other nominal associations (P < 0.05) were observed that did not withstand FDR correction but suggest areas for future investigation. These included protective associations with DM for IGP18 (OR: 0.86, P = 0.033) and IGP35 (OR: 0.90, P = 0.015), and risk associations for IGP23 (OR: 1.19, P = 0.028) and IGP28 (OR: 1.17, P = 0.038). For diabetic retinopathy (DR), a nominal protective association was found for IGP35 (OR: 0.94, P = 0.026) and a risk association for IGP48 (OR: 1.07, P = 0.042). Sensitivity analyses detected no significant horizontal pleiotropy, and the results were stable. Our study provides robust genetic evidence identifying IGP48 as a causal risk factor for DM. Other nominal associations with DM and DR require further validation. IGP48 emerges as a promising biomarker and therapeutic target for DM, warranting further research into its underlying mechanisms and clinical utility. Not applicable.

Vitamin D deficiency has been linked to DR progression, its specific role in diabetic maculopathy remains underexplored. This study aimed to evaluate the relationship between serum vitamin D levels and diabetic maculopathy. In this cross-sectional study, 68 patients with diabetic macular edema (DME) underwent comprehensive ophthalmic examinations, including OCTA to assess superficial and deep vascular density and foveal avascular zone (FAZ), alongside measurement of serum vitamin D levels. Patients with renal impairment, granulomatous diseases, or vitamin D supplementation were excluded. Of the 68 patients (54.4% female, 45.6% male; mean age 58 ± 7 years), vitamin D levels showed significant positive correlations with superficial vascular density in foveal (r = 0.711, P < 0.001), parafoveal (r = 0.852, P < 0.001), and perifoveal zones (r = 0.832, P < 0.001), and with deep vascular density in foveal (r = 0.868, P < 0.001), parafoveal (r = 0.790, P < 0.001), and perifoveal zones (r = 0.645, P < 0.001). Negative correlations were observed with FAZ in superficial (r = − 0.806, P < 0.001) and deep layers (r = − 0.801, P < 0.001). Multivariate linear regression, controlling for age, gender, and diabetes duration, confirmed vitamin D as a significant predictor of superficial and deep vascular density and FAZ parameters. Diabetic macular ischemia is closely linked to vitamin D deficiency, as shown by reduced vascular density and enlarged FAZ. These findings suggest that vitamin D may help prevent retinal microvascular damage in diabetic retinopathy.

BackgroundWhile lysosomal cathepsins are crucial in cellular homeostasis and may contribute to diabetic chronic complications, their precise causal relationships remain insufficiently characterized.MethodsThis study employed comprehensive multidimensional Mendelian randomization (MR) analyses to investigate potential causal associations between nine cathepsins (B, E, F, G, H, L2, O, S, and Z) and six diabetic chronic complications encompassing both microvascular (nephropathy, retinopathy, proliferative retinopathy, maculopathy, neuropathy) and macrovascular manifestations (peripheral angiopathy). The analytical framework incorporated generalized summary-data-based MR (GSMR), univariable MR, multivariable MR, summary-data-based MR (SMR), and cis-expression quantitative trait locus (cis-eQTL) MR approaches, utilizing data derived from publicly available genome-wide association studies (GWAS). To further characterize the biological relevance of identified cathepsins, we conducted multi-omics investigations including gene set enrichment analysis, CIBERSORT, single-cell RNA sequencing analysis to explore the expression level, immune infiltration and biological function of identified cathepsins. Furthermore, we performed mediation analyses to assess whether immune cells potentially mediate the causal pathways linking identified cathepsins to diabetic complications.ResultsBoth GSMR and univariable MR showed that Cathepsin H levels were causally associated with increased risks of overall diabetic retinopathy (DR), proliferative diabetic retinopathy (PDR), and diabetic maculopathy, validated by SMR and cis-eQTL MR analyses. Multivariable MR analysis further confirmed the independent causal role of Cathepsin H in PDR {inverse variance weighted (IVW): p = 0.003, OR = 1.054, 95% CI = 1.017–1.093} and diabetic maculopathy (IVW: p = 0.022, OR = 1.068, 95% CI = 1.009–1.130). Sensitivity analyses indicated no significant heterogeneity or pleiotropy for any of these cause associations. Bioinformatic analyses revealed upregulated Cathepsin H expression in DR patients, enriched in immune-inflammatory pathways. Single-cell RNA sequencing further highlighted its specific overexpression in NK cells of DR. No mediation by immunophenotypes was observed.ConclusionsOur integrative approach establishes Cathepsin H as a causal driver for DR and its subtypes, highlighting its potential as a therapeutic target and biomarker.

The LENS trial demonstrated that fenofibrate slowed the progression of diabetic retinopathy compared to placebo in participants with early diabetic eye disease. We assessed its cost-effectiveness for reducing the progression of diabetic retinopathy versus standard care from a UK National Health Service perspective. Resource use and outcome data were collected over follow-up for participants enrolled in LENS. Mean costs were compared at 2 years and per 6-month follow-up (median 4.0 years). Within the trial, cost-effectiveness was assessed in terms of the incremental cost per case of referable disease averted. A microsimulation model, with inputs derived primarily from LENS trial data, was used to assess the incremental cost per quality-adjusted life year (QALY). Fenofibrate resulted in a mean (95% confidence interval) reduction in health service costs of -£254 (-1062 to 624) at 2 years and -£101 (-243 to 42) per 6-month follow-up. This was accompanied by a 4.4% (1.3% to 8.0%) absolute reduction in any referable diabetic retinopathy or treatment thereof at 2 years, and a 27% (9%-42%) relative reduction over follow-up. Modelled over 10 years, fenofibrate use cost an additional £6 per patient for an expected QALY gain of 0.02, costing £406 per QALY versus standard care under base case assumptions. The probability of cost-effectiveness varied from 70% to 79% at a threshold of £20,000 per QALY, depending on the price discount applied to anti-VEGF drugs. Fenofibrate is likely to offer a cost-effective treatment for slowing the progression of diabetic retinopathy in people with early to moderate diabetic retinopathy or maculopathy.

ABSTRACTEpidemiological evidence regarding the association between vitamins and diabetic complications remains inconsistent. This study aims to explore the potential causal relationships between diabetic complications and circulating vitamins in diabetics. We selected vitamin A (VitA) genetic variants (n = 5,006), vitamin B6 (VitB6) genetic variants (n = 64,974), vitamin C (VitC) genetic variants (n = 52,018) and vitamin D (VitD) genetic variants (n = 441,291) as exposures of interest from large‐scale Genome‐Wide Association Studies (GWAS) databases. Then we performed two‐sample Mendelian randomization (MR) analyses to evaluate the causal association of plasma vitamin levels with diabetic complications, which included maculopathy, ketoacidosis, hypoglycemia, neuropathy, nephropathy and retinopathy. Multiple methods were performed and used including the inverse‐variance weighted (IVW), the weighted median, MR‐Egger and MR‐PRESSO regression. Heterogeneity and sensitivity analyses were conducted. The results of the IVW method revealed that the level of VitB6 were associated with diabetic hypoglycemia with (OR: 8.54; 95% CI: 1.77 to 41.2; p: 0.01). No association was detected between other vitamins (VitA, VitC or VitD) and diabetic complications (maculopathy, ketoacidosis, hypoglycemia, neuropathy, nephropathy or retinopathy). After MR‐PRESSO analysis, there was no causal relationship detected between VitD and diabetic hypoglycemia (OR: 0.867, CI: 0.64 to 1.18, p: 0.37), diabetic ketosis (OR: 0.763515, CI: 0.58 to 1.00, p: 0.055), diabetic maculopathy (OR: 0.72, CI: 0.48 to 1.07, p: 0.105). This analysis provided genetic evidence that the level of VitB6 may be the risk factor for diabetic hypoglycemia. VitA, VitC, or VitD were not associated with various diabetic complications. Monitoring for excess VitB6 and suitable supplements might be important, and other vitamins may have limited effects in complications prevention, and further investigations were needed to unveil the mechanisms.

Objectives Delta-like ligand-4 (DLL4) is responsible for normal physiological and pathological retinal vasculature. In this study, we aim to compare DDL4 serum levels in both healthy and diabetic patients. We also aim to correlate the severity of retinopathy and maculopathy with the level of serum DDL4. Patients and methods We analyzed prospectively the DDL4 serum level in 19 diabetic patients without clinical evidence of retinopathy (group 1), 19 diabetic retinopathy (DR) patients (group 2), and 19 control participants (group 3). Patients with DR (group 2) underwent other laboratory tests such as serum glycated hemoglobin, creatinine, and urine microalbuminuria. Also, Macular optical coherence tomography and fundus fluorescein angiography within 1 week of laboratory tests were done. Results The serum level of DLL4 was the lowest among patients with DR (group 2) (281.04±237.16 ng/l), followed by group 1 (220.81±94.18 ng/l). The highest serum levels of DLL4 were reported among patients in group 3 (457.52±351.00 ng/l) (P=0.015). In group 2, the serum level of DLL4 showed statistically insignificantly higher values among nonproliferative retinopathy subgroup (243.63+/–121.8 ng/l) than the proliferative retinopathy subgroup (227.2 +/–59.5 ng/l). Negative insignificant correlation with central ischemia by fundus fluorescein angiography. Positive insignificant correlation with central foveal thickness by optical coherence tomography. Receiver operating characteristic curve analysis indicated that DLL4 was a potential biomarker for identifying both groups 1 and 2. Conclusion The level of serum DLL4 is found to be high in normal healthy eyes but decreases with progression of DR. Low serum DLL4 can point to more retinal ischemia with more proliferative changes including ischemic maculopathy.

Introduction and Objective: Between March and September 2020, routine healthcare in the UK, including diabetic retinopathy (DR) screening, was paused due to the COVID-19 pandemic. This created a natural experiment to explore the impact of extended screening intervals. Methods: Data from Diabetic Eye Screening Wales (DESW) and primary care were linked using the Secure Anonymised Information Linkage databank (SAIL). Individuals screened within 12 months pre-lockdown and rescreened between March 2020 and August 2022 were included. Results: Of 12,424 individuals with no DR pre-lockdown, 84.3% remained free of retinopathy post-lockdown, 15.8% progressed to background retinopathy, and 0.3% to referable retinopathy. Background Retinopathy (Pre-Lockdown): Of 11,694 individuals with background DR pre-lockdown, 30.8% regressed to no retinopathy, 64.9% remained with background DR, and 4.4% progressed to referable diabetic retinopathy (RDR). Of 731 individuals with RDR pre-lockdown, 3.3% had no DR post-lockdown, 36.0% regressed to background DR, and 60.7% remained at referable level. Of 24,866 individuals with no maculopathy pre-lockdown, 94% remained maculopathy-free, while 6.0% developed diabetic maculopathy. Diabetic Of 257 individuals with diabetic maculopathy pre-lockdown, 50.6% regressed to no maculopathy, while 49.4% remained unchanged. Conclusion: The risk of progression from no DR to RDR or maculopathy was low (0.3% and 6.0%, respectively). Only 10% of those referred with suggested maculopathy required treatment. This study provides further evidence that screening biennially is considered safe for those without DR Disclosure R.L. Thomas: None. W. Cheung: None. J. Rafferty: None. L. Pratt: None. J. Cherry: None. R. Reynolds: None. G. Williams: None. S.C. Bain: Research Support; Novo Nordisk A/S, Lilly Diabetes. Speaker's Bureau; Menarini, AstraZeneca. Research Support; Boehringer-Ingelheim, Abbott Diagnostics, Amgen Inc. D.R. Owens: None. Funding Health and Care Research Wales (HRG-20-1776(P))

The detection of Optic Disc (OD) stands as the essential process in color retinal image analysis because it represents the main component of the human retina. The detection of Optic Disc along with its center enables healthcare providers to evaluate the severity of conditions like Diabetic Maculopathy (DM) and glaucoma. This document presents a fresh technique to discover optic disc regions while also determining their central areas. The first process enhances the input image through combination of Gaussian, Median, and Weiner filters to create the enhanced image. After image enhancement the morphological closing operation removes BVs as its next step. Adaptive Histogram Equalization is then applied before extracting Region of Interest using four co-ordinate points that are determined with the help of a drawn grid. The combination of Extended Maxima Transform and Morphological operation produces the OD region as well as its center point. The proposed method delivers evaluation results on MESSIDOR which achieve an accuracy rate of 96.21%. The proposed innovative approach detects OD without using Fovea or Macula while needing grid setup during the first run to obtain Region of Interest (RoI).

Introduction: Diabetic retinopathy (DR) is the leading complication of diabetes with a prevalence of 30% and if not diagnosed timely can cause important vision loss up to blindness. Systematic screening allows diagnosis of retinopathy in its early forms. Taking care of these patients by ophthalmologists is important to perform a tight control in order to prevent or delay sight threatening diabetic retinopathy. Optical Coherence Tomography (OCT) imaging provides significant biomarkers for the follow up of the initial stages of retinopathy. The purpose of this study is to assess their effectiveness in clinical practice especially in clinical pathway performed in Primary Care Setting Methods: A sample of 58 consecutives patients (106 eyes) with mild diabetic retinopathy, coming from digital screening with automatic fundus cameras, were enrolled in this observational study. High definition SD-OCT was performed with a tomographic scan of 6X 6 mm centered to the fovea. We assessed quantitative biomarkers such Central Subfield Thickness (CST) and mean cube volume (MV) and qualitative biomarkers as the presence of intraretinal or subfoveal fluid, of microaneurysms, iperreflective foci and the integrity of Ellipsoid Zone Results: The mean CST was 276,25 ± 54,76 µm ( normal range 257-295), also MV was in the normal range. The prevalence rate (95% confidence interval) of borderline CST was 16,34% ( 9,34- 23,34%). The prevalence rate (95% confidence interval) of pathological CST was 5,76% ( 1,76 – 9,76%). Hyper reflective foci were the most frequent qualitative biomarkers. Conclusion: SD- OCT represents the technique of choice for the detection and the follow up of diabetic maculopathy. Even in mild forms, CST and MV are crucial for monitoring macular thickness and detecting early signs of macular edema. Both quantitative and qualitative OCT biomarkers can guide more accurate follow up strategies, enhancing patient care.

PurposeDiabetic maculopathy (including diabetic macular edema [DME]) is the leading cause of vision loss in people with diabetes. We aimed to identify the genetic determinants of diabetic maculopathy.MethodsWe conducted a genome-wide association study (GWAS) in two cohorts with a meta-analysis. The Australian cohort comprised 551 cases of DME and 599 controls recruited from the states of South Australia and Tasmania. The Scottish cohort comprised 1951 cases of diabetic maculopathy and 6541 controls from the Genetics of Diabetes Audit and Research in Tayside Scotland study (GoDARTS). Genotyping, imputation, and association analysis using logistic regression were conducted in each cohort, before combining summary statistics in a meta-analysis using the GWAMA package.ResultsA locus on chromosome 7 reached genome-wide significance in GoDARTS but showed the opposite direction of effect in the Australian cohort. The meta-analysis identified two suggestive associations (P < 5 × 10−6) for diabetic maculopathy risk with similar effect direction; one at chromosome 1 close to the RNU5E-1 gene and one at chromosome 13 upstream of the ERICH6B gene. The two loci were evaluated in silico for potential functional links to diabetic maculopathy. Both are located in regulatory regions and have annotations indicating regulatory functions. They are also expression quantitative trait locus (eQTLs) for genes plausibly involved in diabetic maculopathy pathogenesis, with links to folate metabolism and the regulation of VEGF.ConclusionsThe study suggests several promising SNPs and genes related to diabetic maculopathy risk. Despite being the largest genetic study of diabetic maculopathy to date, larger, homogeneous cohorts will be required to identify robust genetic risk loci for the disease.

PurposeTo report a case of pernicious anemia in a patient presenting with white-centered hemorrhages.MethodCase report.ResultsA 64-year-old man with uncontrolled hypertension, insulin-dependent type 2 diabetes, dyslipidemia, and diabetic retinopathy presented with significant bilateral visual acuity reduction. Ophthalmological examination revealed severe diabetic maculopathy, multiple peripapillary Roth spots and hemorrhages. Laboratory tests identified macrocytic anemia with severe vitamin B12 deficiency and an endoscopic biopsy of the gastric fundus led to the diagnosis of pernicious anemia. The patient received blood transfusion, vitamin B12 supplementation and underwent intravitreal anti-VEGF (aflibercept) injections and retinal panphotocoagulation. Over two months, the patient exhibited marked improvement in visual acuity and partial resolution of retinal abnormalities.ConclusionRoth spots are a nonspecific sign that can be found in various pathologies, sometimes severe, such as pernicious anemia. In those cases, adequate vitamin B12 supplementation can resolve the signs and symptoms. Therefore, it is vital to carry out a comprehensive systemic etiological work-up to quickly treat the underlying cause, keeping in mind that multiple pathologies may coexist.

This article assesses changes in angiographic parameters of the retinal capillary plexuses after surgical treatment of DM using various methods of internal limiting membrane (ILM) peeling. Vitreoretinal surgery, including vitrectomy with membrane peeling, was performed in comparable groups of patients with proliferative diabetic retinopathy and DM. The surgical methods differed in the approach to retinal ILM peeling: in group 1 the ILM was completely removed; group 2 underwent dosed fovea-sparing peeling (DFSP) of the ILM; in group 3 the ILM was left intact. Postoperative outcomes were compared between groups using optical coherence tomography angiography (OCT-A). Intergroup comparisons across all time points and parameters did not reveal statistically significant differences. The analysis showed no significant changes in angiographic parameters in groups 1 and 3. In group 2 significant changes were observed in the parameters of deep capillary plexus: increased vessel density, vessel skeleton density and vessel perimeter index, as well as reduced foveal avascular zone (FAZ) area. Correlation analysis revealed that high FAZ area values in the deep capillary plexus were predictors of the development of retinal atrophy in the long-term. The obtained results demonstrate the dynamics of changes following DFSP of the ILM in both the neuronal structures of the retina and its capillary plexuses, with these changes tending toward normalization of retinal structure.