JOURNAL/nrgr/04.03/01300535-202602000-00048/figure1/v/2025-05-05T160104Z/r/image-tiff Diabetic retinopathy is a prominent cause of blindness in adults, with early retinal ganglion cell loss contributing to visual dysfunction or blindness. In the brain, defects in γ-aminobutyric acid synaptic transmission are associated with pathophysiological and neurodegenerative disorders, whereas glucagon-like peptide-1 has demonstrated neuroprotective effects. However, it is not yet clear whether diabetes causes alterations in inhibitory input to retinal ganglion cells and whether and how glucagon-like peptide-1 protects against neurodegeneration in the diabetic retina through regulating inhibitory synaptic transmission to retinal ganglion cells. In the present study, we used the patch-clamp technique to record γ-aminobutyric acid subtype A receptor-mediated miniature inhibitory postsynaptic currents in retinal ganglion cells from streptozotocin-induced diabetes model rats. We found that early diabetes (4 weeks of hyperglycemia) decreased the frequency of GABAergic miniature inhibitory postsynaptic currents in retinal ganglion cells without altering their amplitude, suggesting a reduction in the spontaneous release of γ-aminobutyric acid to retinal ganglion cells. Topical administration of glucagon-like peptide-1 eyedrops over a period of 2 weeks effectively countered the hyperglycemia-induced downregulation of GABAergic mIPSC frequency, subsequently enhancing the survival of retinal ganglion cells. Concurrently, the protective effects of glucagon-like peptide-1 on retinal ganglion cells in diabetic rats were eliminated by topical administration of exendin-9-39, a specific glucagon-like peptide-1 receptor antagonist, or SR95531, a specific antagonist of the γ-aminobutyric acid subtype A receptor. Furthermore, extracellular perfusion of glucagon-like peptide-1 was found to elevate the frequencies of GABAergic miniature inhibitory postsynaptic currents in both ON- and OFF-type retinal ganglion cells. This elevation was shown to be mediated by activation of the phosphatidylinositol-phospholipase C/inositol 1,4,5-trisphosphate receptor/Ca 2+ /protein kinase C signaling pathway downstream of glucagon-like peptide-1 receptor activation. Moreover, multielectrode array recordings revealed that glucagon-like peptide-1 functionally augmented the photoresponses of ON-type retinal ganglion cells. Optomotor response tests demonstrated that diabetic rats exhibited reductions in visual acuity and contrast sensitivity that were significantly ameliorated by topical administration of glucagon-like peptide-1. These results suggest that glucagon-like peptide-1 facilitates the release of γ-aminobutyric acid onto retinal ganglion cells through the activation of glucagon-like peptide-1 receptor, leading to the de-excitation of retinal ganglion cell circuits and the inhibition of excitotoxic processes associated with diabetic retinopathy. Collectively, our findings indicate that the γ-aminobutyric acid system has potential as a therapeutic target for mitigating early-stage diabetic retinopathy. Furthermore, the topical administration of glucagon-like peptide-1 eyedrops represents a non-invasive and effective treatment approach for managing early-stage diabetic retinopathy.

This systematic review with meta-analysis explores the global demographic and etiological variations of retinal vasculitis (RV), focusing on differences in frequency, age, sex, and etiology across diverse geographic populations. RV is an inflammatory condition that can lead to visual impairment, making understanding its variations essential for targeted screening and management. Systematic searches were conducted in multiple databases up to February, 2023, following PRISMA guidelines. We included studies with at least 10 RV cases, such that a frequency measurement can be estimated, without restrictions on publication date or language. RV was categorized as Idiopathic RV in the absence of additional ocular or systemic disease, Syndromic RV for ocular involvement without systemic disease, and Secondary RV in those asssociated with systemic disease. The risk of bias was evaluated using standardized tools. A total of 95 studies, including 23,180 patients, were analyzed. The overall RV frequency among uveitis cohorts was 17 %, with European populations showing the highest frequency at 25 %. Idiopathic RV accounted for 1 % of uveitis cohorts and 38 % of RV cohorts, with significant differences across continents. Behçet disease had the highest RV frequency at 56 %. The median age of diagnosis was 33.5 years, and RV was more frequent in males (57 %). Our findings underscore the considerable geographic and demographic variability in RV, particularly in Idiopathic RV, tuberculosis-related RV, and Behçet disease, highlighting the need for tailored, region-specific, and gender-specific approaches to RV diagnosis and treatment.

Gene therapy is an innovative medical approach that offers new treatment options for congenital and acquired diseases by transferring, correcting, inactivating or regulating genes to supplement, replace or modify a gene function. The approval of voretigene neparvovec (Luxturna), a gene therapy for RPE65-associated retinopathy, has marked a milestone for the field of retinal gene therapy, but has also helped to accelerate the development of gene therapies for genetic diseases affecting other organs. Voretigene neparvovec is a vector based on adeno-associated virus (AAV) that delivers a functional copy of RPE65 to supplement the missing function of this gene. The AAV-based gene delivery has proven to be versatile and safe for the transfer of genetic material to retinal cells. However, challenges remain in treating additional inherited as well as acquired retinopathies with this technology. Despite the high level of activity in this field, no other AAV gene therapy for retinal diseases has been approved since voretigene neparvovec. Ongoing research focuses on overcoming the current restraints through innovative strategies like AAV capsid engineering, dual-AAV vector systems, or CRISPR/Cas-mediated genome editing. Additionally, AAV gene therapy is being explored for the treatment of complex acquired diseases like age-related macular degeneration (AMD) and diabetic retinopathy (DR) by targeting molecules involved in the pathobiology of the degenerative processes. This review outlines the current state of retinal gene therapy, highlighting ongoing challenges and future directions.

The global increase in the prevalence of type 2 diabetes has led to the development and implementation of new classes of antidiabetic medications, introducing advanced therapeutic options for the management of the disease. These new medications, though primarily designed to regulate blood glucose levels, also have applications in weight management, potentially transforming the current approaches to diabetes treatment. Newer medications, however, have ophthalmic side effects with controversies in trials and real-life data. We comprehensively assessed the ocular benefits and adverse effects of traditional and newer-generation anti-diabetic drugs. Our primary focus is on how these newer medications affect the stage of diabetic retinopathy. Additionally, we explore the associations between these medications and other ocular conditions, including age-related macular degeneration, glaucoma, orbital conditions, and diseases impacting the ocular surface. Furthermore, we provide contextual background by discussing the ocular effects of traditional anti-diabetic drugs.

Diabetic microvascular complications pose significant health challenges for individuals. The influence of modifiable lifestyle factors, such as coffee intake, on these complications has not been conclusively determined, highlighting the need for a causality assessment.

Utilizing Mendelian randomization (MR), this study explored the causal links between coffee intake, plasma caffeine levels, and diabetic microvascular complications using data from FinnGen. Single nucleotide polymorphisms associated with coffee intake and plasma caffeine levels were identified through genome-wide association study meta-analyses. The univariable MR analysis indicated a slightly increased risk for diabetic retinopathy (OR 1.006; 95 % CI: 1.002-1.010; P = 0.003) and a suggestively elevated risk for nephropathy (OR 1.011; 95 % CI: 1.001-1.022; P = 0.036) associated with genetically predicted higher coffee intake, while no significant effect on neuropathy was observed. Multivariable MR analysis, adjusted for smoking, revealed a significant protective effect of coffee intake on diabetic retinopathy (OR 0.895; 95 % CI: 0.856-0.936; P = 9.468 × 10-7) and a suggestive reduction in risk for diabetic nephropathy (OR 0.828; 95 % CI: 0.712-0.963; P = 0.014). Higher plasma caffeine levels were also suggestively protective against these complications.

Our findings suggest that genetically predicted higher coffee intake and plasma caffeine levels are protective for diabetic retinopathy and nephropathy. Further research is necessary to substantiate these findings and to investigate their potential impact on diabetes management strategies.

Advanced modeling biotechnologies are required to understand retinal diseases and develop effective treatments based on the patient's genetic background, lifestyle, and environment. In this work, recent advances in different types of study models that are used in the retinal disease area of research will be explored. The retinal models to be covered are: in vivo systems (human and animal), in vitro organisms (cell lines, primary cells, patient-derived stem cells, microfluidics, organoids, and spheroids), ex vivo models (explant cultures and retinal tissue preparations), and in silico models (computational and mathematical). Moreover, the unique comprehension of models of retinal disease, advantages, and disadvantages will be scrutinized. Finally, innovations/improvements derived from models towards gene and pharmacological therapy that display promise for treating retinal illnesses are elucidated.

Retinal microangiopathies, such as neovascularization and preretinal and vitreous hemorrhages, are the primary pathological features of diabetic retinopathy (DR). These conditions can worsen visual impairment and may result in blindness. Furthermore, multiple metabolic pathways are associated with microangiopathy in DR. However, the specific underlying pathological mechanisms remain unclear. Several studies have demonstrated the important role of G protein-coupled receptor 124 (Gpr124) in cerebral vascular endothelial cells, but its effect on the retinal endothelium has not been elucidated. In this study, we found that Gpr124 is expressed in both pathological retinal fibrous vascular membranes of DR patients and retinal blood vessels of mice, with elevated protein expression specifically observed in the retinas of DR model mice. Furthermore, Gpr124 expression was elevated after high-glucose treatment of human retinal microvascular endothelial cells (HRMECs). Inhibition of Gpr124 expression affected the high glucose-induced proliferation, migration, and tube-forming ability of HRMECs. We concluded that Gpr124 expression was upregulated in DR and promoted HRMECs angiogenesis in a high-glucose environment. This finding may help to elucidate the pathogenesis of DR and provide a critical research basis for identifying effective treatments.

Diabetic retinopathy (DR) is a serious complication of diabetes caused by long-term hyperglycemia that leads to microvascular and neuronal damage in the retina. The molecular mechanisms of DR involve oxidative stress, inflammatory responses, neurodegenerative changes, and vascular dysfunction triggered by hyperglycemia. Oxidative stress activates multiple metabolic pathways, such as the polyol, hexosamine, and protein kinase C (PKC) pathways, resulting in the production of, which in turn promote the formation of advanced glycation end products (AGEs). These pathways exacerbate vascular endothelial damage and the release of inflammatory factors, activating inflammatory signaling pathways such as the NF-κB pathway, leading to retinal cell damage and apoptosis. Additionally, DR involves neurodegenerative changes, including the activation of glial cells, neuronal dysfunction, and cell death. Research on the multiomics molecular markers of DR has revealed complex mechanisms at the genetic, epigenetic, and transcriptional levels. Genome-wide association studies (GWASs) have identified multiple genetic loci associated with DR that are involved in metabolic and inflammatory pathways. Noncoding RNAs, such as miRNAs, circRNAs, and lncRNAs, participate in the development of DR by regulating gene expression. Proteomic, metabolomic and lipidomic analyses have revealed specific proteins, metabolites and lipid changes associated with DR, providing potential biomarkers for the early diagnosis and treatment of this disease. This review provides a comprehensive perspective for understanding the molecular network of DR and facilitates the exploration of innovative therapeutic approaches.

Diabetic retinopathy (DR) is a leading cause of vision loss, with early detection challenging due to asymptomatic progression and limited predictive tools. To address this, we aimed to develop and validate a risk nomogram for DR prediction in type 2 diabetes patients.

In this retrospective cohort study of 70,073 patients with type 2 diabetes admitted from 2013 to 2019, 2,585 patients were included after exclusions. Patients were randomly assigned to derivation (2/3) and validation (1/3) sets. The prediction model was derived using Cox proportional hazards regression. A nomogram was developed and evaluated for discriminatory capacity and calibration accuracy.

Among 2585 participants (mean age 59 years), 220 (8.5 %) developed retinopathy over a median follow-up of 34 months. We identified key predictors: glycated haemoglobin A1c, serum urea, and diabetes duration. Predictive models for 1-, 3-, and 5-year retinopathy-free survival were constructed and presented as a nomogram, demonstrating good discriminatory power (AUC: 0.941, 0.886, 0.594 in derivation; 0.747, 0.736, 0.670 in validation). Calibration plots further corroborated the improved fit for 3- and 5-year models.

The proposed model shows promise for guiding early interventions and improving outcomes. Further external validation is needed to confirm its applicability across diverse populations.

Glycemic control is important for preventing diabetic retinopathy (DR), but rapid improvements could deteriorate the disease. In some, but not all studies, semaglutide is speculated to worsen DR, but the mechanism is unknown. Central retinal thickness (CRT) is an early marker of DR. Therefore, the objective was to investigate whether increased Time in Range (TIR (3.9-10.0 mmol/L)), was associated with reduced CRT in persons treated with semaglutide.

Forty participants with type 2 diabetes were included in this post-hoc analysis of a 32-week randomised, placebo-controlled, partly open-label trial investigating the separate and combined effects of semaglutide and empagliflozin on target organ damage in 120 participants with type 2 diabetes. Individuals were randomised into four groups: i) semaglutide, ii) empagliflozin, iii) the combination or iv) placebo, n = 30 for each group). In the present study, 10 participants from each of the 4 arms participated. TIR was assessed using Continuous Glucose Measurement for 7-8 days and CRT was assessed using ocular coherence tomography.

In the 10 individuals treated with semaglutide, CRT increased ~1 % (3.76 μm, 95%CI [-0.32; 7.85], p = 0.065) compared to placebo. This was attenuated with adjustment for TIR (p = 0.21). Independently of the four interventions, increased TIR remained associated with increased CRT (0.07 μm, 95%CI[0.03; 0.12]μm, p = 0.002).

Semaglutide treatment did not impact CRT beyond what could be explained by changes in glycaemia. Across all interventions, increased TIR was associated with increases in CRT, thus supporting the link between rapid improved glycemia and DR.

Diabetic retinopathy (DR) is a retinal disease caused by diabetes. If there is no intervention, it may even lead to blindness. Therefore, the detection of diabetic retinopathy is of great significance for preventing blindness in patients. Most of the existing DR detection methods use supervised methods, which usually require a large number of accurate pixel-level annotations. To solve this problem, we propose a self-supervised Equivariant Refinement Classification Network (ERCN) for DR classification. First, we use an unsupervised contrast pre-training network to learn a more generalized representation. Secondly, the class activation map (CAM) is refined by self-supervision learning. It first uses a spatial masking method to suppress low-confidence predictions, and then uses the feature similarity between pixels to encourage fine-grained activation to achieve more accurate positioning of the lesion. We propose a hybrid equivariant regularization loss to alleviate the degradation caused by the local minimum in the CAM refinement process. To further improve the classification accuracy, we propose an attention-based multi-instance learning (MIL), which weights each element of the feature map as an instance, which is more effective than the traditional patch-based instance extraction method. We evaluate our method on the EyePACS and DAVIS datasets and achieved 87.4% test accuracy in the EyePACS dataset and 88.7% test accuracy in the DAVIS dataset. It shows that the proposed method achieves better performance in DR detection compared with other state-of-the-art methods in self-supervised DR detection.

Diabetic retinopathy (DR) is a leading cause of vision impairment in working-age adults, and is driven by complex neurovascular dysfunction. This study aimed to elucidate whether nitric oxide (NO) can modulate the TXNIP/NLRP3 inflammasome pathway and mitigate retinal neurovascular unit (NVU) damage during early DR. In an in vitro co-culture system, silencing TXNIP or NLRP3 in retinal microglia (RMG) significantly upregulated glial cell-derived neurotrophic factor (GDNF) and downregulated inducible nitric oxide synthase (iNOS) expression in retinal ganglion cells (RGC). Moreover, it resulted in decreased iNOS and vascular endothelial growth factor A (VEGFA) levels and enhanced the expression of tight junction proteins (Occludin and ZO-1) in retinal microvascular endothelial cells (RMEC), while also reducing NO release and inhibiting RMEC tube formation. Treatment with S-nitroso-N-acetyl penicillamine (SNAP), an NO donor, significantly downregulated TXNIP/NLRP3 inflammasome signaling in RMG, decreased RGC apoptosis, and inhibited tube formation in RMEC. It also upregulated GDNF, suppressed iNOS in RGC, decreased VEGFA, and improved tight junction proteins in RMEC. Treatment with 1400W, an iNOS inhibitor, resulted in decreased NO concentration and increased IL-1β levels in the co-culture supernatant, without significantly affecting iNOS expression in RGC or RMEC. In an early DR rat model, Electroretinogram (ERG), Optical Coherence Tomography (OCT), Fluorescein Angiography (FFA), Evans blue assays, Immunofluorescence staining, and TUNEL staining confirmed that sodium nitroprusside (SNP), NO donor administration mitigated retinal neural and vascular dysfunction, and preserved retinal NVU integrity. Concurrently, SNP treatment reduced IL-1β expression and increased GDNF and Occludin levels in the early DR retina. Genetic Association Database (GAD) enrichment analysis and protein-protein interaction (PPI) network validation indicated that NO functions as a downstream mediator of the TXNIP/NLRP3 inflammasome pathway and exhibits a strong association with DR. These findings suggest that NO mediates negative feedback in the TXNIP/NLRP3 inflammasome pathway to exert protective effects against retinal NVU dysfunction in early DR, thereby offering potential therapeutic strategies for early intervention in DR.

to investigate the association between vascular endothelial growth factor (VEGF)-2578C/A polymorphism and susceptibility to type 2 diabetic retinopathy (T2DR) by meta-analysis.

According to the search strategy, Four databases were retrieved to identify the literature on the relationship between VEGF polymorphism and the risk of T2DR from inception to July 2024. Stata 15.0 was used for data processing.

Ten articles were involved in this review, covering 1390 cases and 1306 controls. The pooled results exhibited that the risk of T2DR was associated with VEGF-2578C/A polymorphism under the allele model (A/C: OR= 1.33, 95%CI: 1.04-1.72, p = 0.025) and dominant models (AA+CA/CC: OR= 1.38, 95%CI: 1.00-1.91, p = 0.047). However, in recessive, homozygous, and heterozygous models, no significant difference was observed (all p > 0.05).

The VEGF-2578C/A polymorphism is associated with susceptibility to T2DR. In particular, allele A and genotype AA+CA at the VEGF-2578C/A locus were significantly associated with an increased risk of T2DR.

Diabetic retinopathy (DR), the prevalence of which continues to rise, is one of the most common causes of vision loss worldwide. Experimental and clinical research in recent years has contributed to a better understanding of the pathogenesis of DR, which is complex and results from many interrelated processes leading to abnormal permeability and occlusion of the retinal vasculature, with ischemia and subsequent neovascularization. According to the absence or presence of neovascularization, DR is divided into two main forms: nonproliferative and proliferative DR. From nonproliferative to proliferative disease, diabetic macular edema (DME) can develop anywhere along the spectrum. As the majority of diabetics have no ophthalmologic symptoms, screening plays an important role in preventing the development of retinal disease. Specific treatment options beyond metabolic risk factor control, including intravitreal administration of anti-vascular endothelial growth factor (VEGF) agents or corticosteroids, laser photocoagulation, and vitreous surgery, are effective approaches for ocular diabetic complications.

Ophthalmology, like all medical specialities, is continuously evolving to adapt to emerging challenges and advancements. The evidence-based medical practices that previously guided policies and regulations may no longer be sufficient or sustainable in the context of an ageing population, increasing healthcare demands, and the urgent need for sustainability. As the global burden on healthcare systems grows, sustainability must be considered from multiple perspectives, including financial and environmental aspects, without compromising patient outcomes. While financial sustainability is essential to ensure cost-effective resource allocation, accessibility, and affordability for both healthcare providers and patients, environmental sustainability is becoming an increasing priority. Efforts to minimise the carbon footprint associated with medical procedures, transportation, and the production and disposal of ophthalmic equipment and materials are necessary. This paper highlights key examples of areas within ophthalmology where sustainability can be enhanced by practicing high-value care. We describe targeted opportunities that demonstrate how sustainable practices can be successfully integrated into ophthalmology without compromising patient care or operational feasibility.

To examine changes in retinal and choroidal vasculature in diabetes mellitus across the range of diabetic retinopathy (DR) severities using optical coherence tomography angiography (OCTA) and compare the patterns of vascular changes.

We conducted a cross-sectional study enrolling 296 patients (498 eyes) with diabetes mellitus. Swept-Source OCT Angiography variables in both retina and choroid, including perfusion density (PD), vessel density (VD), large vessel density (LVD) in both superficial and deep layer of retina and CC flow voids (FD) density of the choroid were quantified. Correlations between OCTA parameters and DR severity, visual acuity and studied factors were performed.

Totally 498 eyes including 176 had no DR, 160 had mild NPDR, 98 had moderate NPDR, 11 had severe NPDR, 41 had PDR with PRP, and 12 had PDR without PRP. Choriocapillaris (CC) flow voids density increased with increasing DR severity (17.06% vs 17.41% vs 17.60% vs 17.62% vs 18.05% vs 18.41%, p-trend = 0.0004), FAZ area increased with DR severity in both superficial and deep layer (superficial layer p trend=0.0027; deep layer p trend=0.0022). Visual acuity correlated negatively with CC flow voids (Pearson's ρ = 0.09, p = 0.04) and superficial FAZ area (Pearson's ρ = 0.22, p < 0.001), while inversely correlated with SCP PD (Pearson's ρ = -0.15, p < 0.001) and VD (Pearson's ρ = -0.15, p < 0.001), as well as DCP PD (Pearson's ρ = -0.21, p < 0.001) and VD (Pearson's ρ = -0.19, p < 0.001).

Choriocapillaris ischemia increased, FAZ area enlarged, and total retina perfusion density decreased with increasing DR severity. The deep layer and large vessels may change in early stage before DR progresses to PDR. More ischemia and vessel tortuosity are correlated with worse visual acuity and higher HbA1c level. OCTA can be utilized to detect both large and small vascular changes in both the retina and choroid in DR patients.

Delayed diagnosis of diabetic retinopathy (DR) remains a significant challenge, often leading to preventable blindness and visual impairment. Given that physicians are frequently the first point of contact for people with diabetes, there is a critical need for integrated screening programs within diabetes clinics to enhance DR management and reduce the risk of severe vision loss.

We will conduct a prospective cohort study comparing (i) the intervention cohort, screened at diabetes clinics and referred to eye clinics per the proposed pathway, and (ii) the standard-of-care (SOC) eye clinic cohort. The study will be conducted in Hyderabad, India, at LV Prasad Eye Institute and four IDEA (Institute of Diabetes, Endocrinology, and Adiposity) Clinics. The primary objective is to evaluate the effectiveness of a systematic diabetic retinopathy screening program in achieving earlier detection and reducing visual impairment among People With Diabetes (PWD) attending IDEA clinics compared to routine care at eye care settings. The screening program will be operationalized using AI-enabled tools and supported by trained non-medical technicians. We will perform visual acuity tests and non-mydriatic fundus photography using AI-assisted cameras. DR-positive patients will be referred for treatment and follow-up. We aim to achieve high accuracy (>90%) in appropriate referral of DR and high screening coverage (>80%) of eligible PWD. Success metrics include screening uptake, AI diagnostic accuracy, referral rates, cost-effectiveness, patient satisfaction, follow-up adherence, and long-term outcomes.

This study aims to enhance diabetic retinopathy screening and management through an AI-enabled approach at diabetes clinics, improving early detection and care pathways. The findings will contribute to evidence-based strategies for optimizing DR screening and management, with results disseminated through peer-reviewed publications to inform policy and practice.

Trial registration number: CTRI/2024/03/064518 [Registered on: 20/03/2024] (https://ctri.nic.in/).

Retinal neovascularization is the main pathologic feature of ischemic retinopathy, which eventually leads to vision loss and even blindness. Current treatments like laser photocoagulation and intravitreal injection of anti-vascular endothelial growth factor A drugs are invasive, expensive, and incompetent. Therefore, it is urgent to explore optimized therapies, particularly eye drops, to improve treatment effects. Our recent study reported that abnormal up-regulation of stimulator of interferon genes (STING) is closely associated with retinal vascular diseases, and it is highly enriched in retinal endothelial cells with retinopathy. Thus, we evaluated whether endothelial STING affects retinal neovascularization. In addition, we constructed iRGD- and TAT-decorated nanoparticles (NPs) loaded with C-176 (I/T-C-NP), capable of penetrating the cornea and targeting retinal endothelial cells. The I/T-C-NP eye drops were applied to the eyes of oxygen-induced retinopathy mice, resulting in attenuated activation of the STING pathway. Consequently, retinal neovascularization and vascular tortuosity were effectively reduced, astrocyte activation was prohibited, and pericyte coverage was improved. These observations suggest that I/T-C-NP eye drops can be a potential solution for the treatment of retinal neovascularization.

To evaluate the visual and anatomical outcomes of switching diabetic macular oedema (DMO) patients with suboptimal response to aflibercept 2mg to faricimab over a 12-month period.

This retrospective single centre study enrolled 62 eyes from 50 patients with diabetic macular oedema (DMO) who demonstrated a sub-optimal response to aflibercept 2mg. Sub-optimal response was defined by a central subfield thickness (CST) exceeding 325µm or greater than 20% increase from the best CST despite receiving aflibercept 2mg at intervals of 8 weeks or less. Patients had received at least six 4-weekly doses of aflibercept 2mg. Faricimab was administered as four intravitreal loading injections at 4-weekly intervals, followed by a treat-and-extend approach. Outcome measures, including best-recorded visual acuity (BRVA), CST, and treatment intervals, were assessed at baseline, post-loading (6.5 ± 1.9 weeks) and at the latest clinic review (57.1 ± 19.7 weeks). Statistical analysis included paired t-tests (normal distribution) and Wilcoxon signed-rank tests (non-normal distribution), with p < 0.05 considered statistically significant.

Mean age was 63.9 (±11.4) years, 56% participants were male. At baseline, the mean BRVA was 67.6 (±11.8) letters, and CST measured 406.4 (±105.9) µm. The initial mean treatment interval was 6.5 (±1.8) weeks. BRVA increased to 70.4 (±12.7) letters (p=0.008), while CST reduced to 372.8 (±132.0) µm (p=0.002). The mean injection interval extended to 7.4 (±2.6) weeks (p=0.03). At the latest follow-up BRVA was maintained at 68.7 (±14.6) letters (p=0.572), and CST reduced further to 343.1 (±117.5) µm (p=0.020). At the final follow-up 53.2% were on ≥8-weekly intervals. The mean injection interval increased to 9.2 (±3.2) weeks (p < 0.001), and a mean of 7.92 (±2.53) faricimab injections was administered.

DMO patients with sub-optimal response to aflibercept 2mg experienced improved anatomical outcomes and extended treatment intervals while maintaining vision on faricimab, with no new safety concerns.

Diabetic retinopathy (DR) is a significant long-term consequence of diabetes mellitus and is the primary cause of blindness in people of working age. Although acupuncture (AC) and medication are effective, the optimal treatment regimen for DR remains to be further defined. Consequently, we conducted a network meta-analysis to compare the efficacy of AC and the related treatments with that of medicines for DR.

We searched 8 academic electronic databases for randomized controlled trials published before December 1, 2023. The main outcome was the overall effective rate, and the secondary outcomes were the best corrected visual acuity and the central fovea of macula thickness. Two independent researchers identified eligible studies and collected data using pre-made forms. We conducted a network meta-analysis within a Bayesian framework to compare different interventions. The assessment of risk of bias and quality of literature was conducted using the risk of bias assessment tool recommended by the Cochrane Risk of Bias Tool 2 and the Jadad scale. Intervention ranking probabilities for all treatments were performed using the surface under the cumulative ranking curve.

Twenty-eight studies published between 2012 and 2023 were included, involving 2801 patients. Interventions included AC, traditional Chinese medicine (TCM), electroacupuncture (EA), acupoint injections, and calcium dobesilate. In terms of the overall effective rate, EA + AC + TCM was the best treatment (P < .05) and for the best corrected visual acuity, AI + TCM was the best treatment (P < .05). In terms of the central fovea of macula thickness, AC + TCM was the best treatment (P < .05). An integration of AC and the related treatments is more effective than a single therapy.

EA combined with AC combined with TCM may be the most effective treatment for DR. AC and the related treatments have significant efficacy in treating DR, improving vision, and reducing macular edema with relatively few adverse effects. The use of integrative therapies combining AC and its related therapies can be promoted.

To evaluate the efficacy and safety of Qiming Granule as an early treatment for patients with nerve injury associated with non-proliferative diabetic retinopathy (NPDR).

This was a multicenter, randomized, non-inferiority, active-controlled clinical trial. Patients with NPDR complicated with nerve injury, regardless of whether they presented with fundus abnormalities, were randomly assigned in a 1:1 ratio via a randomized number table to orally receive either 4.5 g of Qiming Granule or 0.5 g of calcium dobesilate (CaD), both 3 times daily for 24 weeks. The primary endpoints were changes in retinal nerve fiber layer (RNFL) thickness and foveal avascular zone (FAZ) area from baseline to week 24. The secondary endpoints included changes in RNFL thickness and FAZ area from baseline to week 12, and visual function questionnaire (NEI-VFQ-25) and health survey questionnaire (SF-36 scale), CM syndrome element scale score and the rates of abnormal full-field electroretinogram (ERG), abnormal dilated fundus, and abnormal visual acuity at treatment of weeks 12 and 24. Adverse drug reactions (ADRs) were detected.

A total of 82 patients were enrolled in the study. Changes in RNFL thickness from baseline to week 24 in the Qiming Granule and CaD groups were -1.53 ± 9.88 µm and -4.61 ± 9.23 µm, respectively (a difference of 3.08 µm [97.5% CI: -2.11 to 8.25]). Changes in FAZ area from baseline to week 24 were -0.08 ± 0.39 mm2 and 0.01 ± 0.05 mm2, respectively (a difference of -0.09 mm2 [97.5% CI: -0.26 to 0.08]). Non-inferiority was achieved for both primary endpoints. There were no significant differences between the two groups in secondary endpoints, including changes in RNFL thickness and FAZ area from baseline to week 12, rates of abnormal ERG, dilated fundus, and visual acuity results at weeks 12 and 24, as well as NEI-VFQ-25, SF-36 scale, and CM syndrome element scale scores at week 24. ADRs were detected in 4 (9.76%) and 1 (2.44%) patients in the Qiming Granule and CaD groups, respectively. No serious ADRs occurred.

Qiming Granule demonstrates non-inferiority in terms of efficacy and safety as an early treatment for nerve injury associated with NPDR. (Registration No. ISRCTN39825773).

IntroductionDiabetic retinopathy (DR) is a blindness-causing disease which belongs to the group of neurodegenerative diseases. Neurodegeneration of the retina is a process, in which retinal neurons suffer irreversible damage. This study aimed to assess the involvement of neurotrophins (brain-derived neurotrophic factor [BDNF] and nerve growth factor [NGF]) in the pathogenesis of DR.MethodsThe study was performed using male Lewis rats with type 1 diabetes mellitus induced by streptozotocin, and the control group included rats without drug administration. In vivo examinations performed over four weeks included eye fundus imaging, measurement of intraocular pressure, and glycemia. After sacrifice, serum and eyeballs were harvested. Post-mortem analyses included a histopathological analysis of the retina and the measurement of BDNF and NGF levels in the serum and eyeball homogenate.ResultsIn the experimental group, early-stage DR was confirmed, and changes in the retina were observed: diabetic rats had relatively thicker outer nuclear layers and relatively thinner inner plexiform layers. A lower level of BDNF was observed in the serum of rats with DR, while the level of NGF in the eyeball homogenate positively correlated with vascular changes.ConclusionsThe observed changes in the levels of neurotrophins in early-stage DR may indicate their involvement in the disease pathogenesis.

Retinopathy is a sight-threatening posterior eye disease involving microvascular complications. Diabetic retinopathy (DR) is the most prevalent form of this. Topical biologics (anti-VEGFs) have better therapeutic outcomes compared to steroids because of minimum adverse effects. However, only invasive methods have been approved, which are associated with serious issues related to patient compliance. Non-invasive administrations of anti-VEGFs have challenges, including stability and penetrability. Investigations on the use of cell-penetrating peptides as carriers for the delivery of biologics have shown encouraging results. Loading the polar biologics into the core of liposomes to capitalize on the lipidic nature and small size for retinal access has also received research attention. However, issues related to the controlled release of these topical biologics for continued retinal access need further attention. Despite the challenges of achieving controlled release in topical application of ocular biologics, there is scope to develop their gels or solid scaffolds. Targeting by capitalizing on membrane transporters of endogenous substances and nutrients has succeeded in brain and other tissue-specific delivery. Thus, there is scope to improve penetrability using a membrane transportation system, as the eye has diverse kinds of membrane transporters that uptake nutrients and endogenous substances.

The adoption of standardized imaging protocols in retinal imaging is critical to overcoming challenges posed by fragmented data formats across devices and manufacturers. The lack of standardization hinders clinical interoperability, collaborative research, and the development of artificial intelligence (AI) models that depend on large, high-quality datasets. The Digital Imaging and Communication in Medicine (DICOM) standard offers a robust solution for ensuring interoperability in medical imaging. Although DICOM is widely utilized in radiology and cardiology, its adoption in ophthalmology remains limited. Retinal imaging modalities such as optical coherence tomography (OCT), fundus photography, and OCT angiography (OCTA) have revolutionized retinal disease management but are constrained by proprietary and non-standardized formats. This review underscores the necessity for harmonized imaging standards in ophthalmology, detailing DICOM standards for retinal imaging including ophthalmic photography (OP), OCT, and OCTA, and their requisite metadata information. Additionally, the potential of DICOM standardization for advancing AI applications in ophthalmology is explored. A notable example is the Artificial Intelligence Ready and Equitable Atlas for Diabetes Insights (AI-READI) dataset, the first publicly available standards-compliant DICOM retinal imaging dataset. This dataset encompasses diverse retinal imaging modalities, including color fundus photography, infrared, autofluorescence, OCT, and OCTA. By leveraging multimodal retinal imaging, AI-READI provides a transformative resource for studying diabetes and its complications, setting a blueprint for future datasets aimed at harmonizing imaging formats and enabling AI-driven breakthroughs in ophthalmology. Our manuscript also addresses challenges in retinal imaging for diabetic patients, retinal imaging-based AI applications for studying diabetes, and potential advancements in retinal imaging standardization.

This study validated the artificial intelligence (AI)-based algorithm LuxIA for screening more-than-mild diabetic retinopathy (mtmDR) from a single 45° colour fundus image of patients with diabetes mellitus (DM, type 1 or type 2) in Spain. Secondary objectives included validating LuxIA according to the International Clinical Diabetic Retinopathy (ICDR) classification and comparing its performance between different devices.

In this multicentre, cross-sectional study, retinal colour fundus images of adults (≥18 years) with DM were collected from five hospitals in Spain (December 2021-December 2022). 45° colour fundus photographs were captured using non-mydriatic Topcon and ZEISS cameras. The Discovery platform (RetinAI) was used to collect images. LuxIA output was an ordinal score (1-5), indicating a classification as mtmDR based on an ICDR severity score.

945 patients with DM were included; the mean (SD) age was 64.6 (13.5) years. The LuxIA algorithm detected mtmDR with a sensitivity and specificity of 97.1% and 94.8%, respectively. The area under the receiver-operating characteristic curve was 0.96, indicating a high test accuracy. The 95% CI data for overall accuracy (94.8% to 95.6%), sensitivity (96.8% to 98.2%) and specificity (94.3% to 95.1%) indicated robust estimations by LuxIA, which maintained a concordance of classification (N=829, kappa=0.837, p=0.001) when used to classify Topcon images. LuxIA validation on ZEISS-obtained images demonstrated high accuracy (90.6%), specificity (92.3%) and lower sensitivity (83.3%) as compared with Topcon-obtained images.

AI algorithms such as LuxIA are increasing testing feasibility for healthcare professionals in DR screening. This study validates the real-world utility of LuxIA for mtmDR screening.

The association between caffeine and diabetic retinopathy (DR) risk remains controversial. This study aims to examine the association between urinary caffeine and caffeine metabolites and self-reported DR risk in US individuals with diabetes. This cross-sectional study enrolled 535 participants with diabetes from the National Health and Nutrition Examination Survey (NHANES) 2009-2014. The high-performance liquid chromatography-electrospray ionization-tandem quadrupole mass spectrometry (HPLC-ESI-MS/MS) and internal standards labeled with stable isotopes were used to measure urinary caffeine and fourteen of its metabolites. Urinary caffeine and its metabolites levels were calibrated with urine creatinine for analysis. Caffeine and its metabolites were analyzed as continuous variables and categorical variables (≤ 50% or > 50%). Weighted logistic regression models were used to calculate odds ratios (OR) and 95% confidence intervals (CI). Subgroup analysis by sex was conducted. After adjusting for age, sex, race, BMI, smoking, alcohol drinking, duration of diabetes, glycated hemoglobin, hypertension, and total energy intake, ln-transformed 1-methyluric acid (1-MU) (OR = 1.27, 95% CI, 1.05 to 1.56, P = 0.016) and 5-acetylamino-6-amino-3-methyluracil (AAMU) (OR = 1.16, 95% CI, 1.01 to 1.34, P = 0.043) were associated with an increased DR risk. In median analysis, compared to lower levels (≤ 50%), higher levels (> 50%) of 1,7-dimethyluric acid (1,7-DMU) (OR = 1.92, 95% CI, 1.20 to 3.09, P = 0.008), caffeine (OR = 2.00, 95% CI, 1.27 to 3.16, P = 0.004), and AAMU (OR = 1.48, 95% CI, 1.04 to 2.10, P = 0.029) were associated with an increased DR risk. Sex-based analysis showed that ln-transformed 1-MU (OR = 1.48, 95% CI, 1.10 to 1.98, P = 0.012), 1,3,7-TMU (OR = 1.24, 95% CI, 1.04 to 1.49, P = 0.018) and caffeine (OR = 1.29, 95% CI, 1.03 to 1.60, P = 0.028) were associated with an increased DR risk in males. Compared to lower levels (≤ 50%), higher levels (> 50%) of 1,7-DMU (OR = 2.75, 95% CI, 1.33 to 5.70, P = 0.008), 1,3,7-TMU (OR = 2.26, 95% CI, 1.02 to 5.01, P = 0.044), caffeine (OR = 3.23, 95% CI, 1.53 to 6.82, P = 0.003), and AAMU (OR = 2.93, 95% CI, 1.16 to 7.40, P = 0.024) were associated with an increased DR risk in males. This study indicated that high urinary levels of 1-MU, 1,7-DMU, 1,3,7-TMU, caffeine and AAMU were associated with an increased risk of DR in US males with DM. Prospective studies are needed to verify these findings.

DR represents a major cause of global vision loss; however, the genetic basis of functional homotopy,a critical neurobiological metric reflecting interhemispheric functional synchronization, remains largely unexplored. Emerging evidence suggests that DR patients exhibiting aberrant VMHC may potentially associate with distinct transcriptional profiles. These findings could provide novel mechanistic insights into the neuropathological substrates underlying DR-related visual and cognitive dysfunction.

Resting-state fMRI data from 46 DR patients and 43 HCs were analyzed to compute VMHC for assessing interhemispheric functional connectivity. Spatial transcriptomic-neuroimaging associations were examined using AHBA, revealing genes significantly correlated with VMHC alterations. Subsequent analyses included functional enrichment assessment and PPI network construction.

DR patients demonstrated significantly lower VMHC in bilateral LING, PoCG, and PreCG versus controls, indicating impaired interhemispheric connectivity in visual-sensorimotor networks. VMHC variations spatially correlated with 4,000 genes (2,000 positive/negative each), enriched in transcriptional regulation, mitochondrial function, synaptic activity (BP/CC/MF), and lipid metabolism/N-glycan biosynthesis (KEGG). PPI network identified hub genes (ACTB/MRPL9/MRPS6,positive; H4C6/NDUFAB1/H3C12,negative) regulating mitochondrial dynamics, cytoskeleton, and epigenetics.

This study represents the first integration of fMRI and transcriptomics to elucidate the genetic determinants underlying VMHC disruption in DR. The findings demonstrate that impaired interhemispheric connectivity in DR involves complex interactions among genes regulating neurovascular, metabolic, and neurodegenerative pathways. These results significantly advance the understanding of neurological manifestations in DR and identify potential therapeutic targets for clinical intervention.

We investigate the clinical characteristics and complications of retinal vasculitis (RV), categorizing cases into Secondary RV (associated with systemic disease), Syndromic RV (linked to ocular syndromes without systemic disease), Idiopathic RV (without systemic disease or ocular syndrome diagnoses), and Multiple Etiology RV (cohorts of retinal vasculitis with more than one subcategories of the above). A systematic search was conducted on June 14, 2023, across PubMed, Embase, Cochrane (Ovid), VHL, and ProQuest databases, following PRISMA guidelines (PROSPERO registration: CRD42023489232). Out of 5533 screened articles, 97 studies involving 7619 patients with RV met the eligibility criteria. Bilateral involvement (64 %) and reduced vision (52 %) were common across all RV categories, with Idiopathic RV showing the highest rates of bilateral involvement (80 %) and vision loss (79 %). Syndromic RV was characterized by retinal ischemia (76 %) and vitreous hemorrhage (46 %), while Secondary RV exhibited higher incidences of cystoid macular edema (32 %) and neovascular glaucoma (24 %). Geographic variations were evident in Multiple Etiology RV, with inflammation in more than 1 intraocular structure more prevalent in Asia (64 %) than in Europe (29 %). These findings highlight the heterogeneity in RV presentation and complications, illustrating the need for standardized diagnostic criteria and improved clinical reporting to enable better classification, treatment strategies, and patient outcomes.

Diabetic retinopathy (DR) is a common microvascular complication of diabetes mellitus (DM). A number of studies have investigated if patients with diabetic retinopathy present altered arterial stiffness compared to diabetic individuals without retinopathy.

To compare arterial stiffness parameters in participants with diabetic retinopathy (DR) compared to participants with diabetes without retinopathy.

Medline and Scopus were searched for published articles comparing indices of arterial stiffness in participants with DR and in diabetic participants without retinopathy. Standardized Mean Difference (SMD) with 95% confidence interval (CI) was calculated for the comparisons. The study protocol was registered with PROSPERO with registration ID: CRD42023482577.

The meta-analysis analyzed 3 arterial stiffness parameters brachial ankle PWV, carotid-femoral PWV and augmentation index (AI). 8 studies were included in the analysis of brachial ankle PWV, 4 in the analysis of carotid-femoral PWV and 4 in the analysis of the augmentation index. Brachial ankle PWV, carotid-femoral PWV and augmentation index were found to be increased in participants with DR compared to diabetic participants without DR (SMD = 0.59, 95 %CI = 0.40-0.79, P < 0.00001, I2 = 89 %, SMD = 0.86, 95 %CI = 0.55-1.18P < 0.00001, I2 = 91 % and SMD = 0.23, 95 %CI = 0.13-0.32, P < 0.00001, I2 = 0 %, respectively).

Diabetic participants with DR exhibit increased arterial stiffness compared to diabetic participants without DR.

Diabetic retinopathy (DR), the leading cause of vision loss among diabetic adults worldwide, underscores the importance of early detection and timely treatment using fundus images to prevent vision loss. However, existing deep learning methods struggle to capture the correlation and contextual information of subtle lesion features with the current scale of dataset. To this end, we propose a novel Multi-scale Spatial-aware Transformer Network (MSTNet) for DR classification. MSTNet encodes information from image patches at varying scales as input features, constructing a dual-pathway backbone network comprised of two Transformer encoders of different sizes to extract both local details and global context from images. To fully leverage structural prior knowledge, we introduce a Spatial-aware Module (SAM) to capture spatial local information within the images. Furthermore, considering the differences between medical and natural images, specifically that regions of interest in medical images often lack distinct subjectivity and continuity, we employ a Multiple Instance Learning (MIL) strategy to aggregate features from diverse regions, thereby enhancing correlation to subtle lesion areas. Ultimately, a cross-fusion classifier integrates dual-pathway features to produce the final classification result. We evaluate MSTNet on four public DR datasets, including APTOS2019, RFMiD2020, Messidor, and IDRiD. Extensive experiments demonstrate that MSTNet exhibits superior diagnostic and grading accuracy, achieving improvements of up to 2.0% in terms of ACC and 1.2% in terms of F1 score, highlighting its effectiveness in accurately assessing fundus images.

ObjectiveThis study aimed to examine the association between controlling nutritional status (CONUT) score and diabetic retinopathy (DR) risk, as well as investigate the impact of CONUT score on mortality risk among DR patients.MethodsThis retrospective study included 5,256 patients with diabetes from National Health and Nutrition Examination Surveys. These participants were classified into two groups: the DR group (n = 641) and the non-DR group (n = 4,615). We used weighted univariate and multivariate logistic regression models to assess the correlation of CONUT score and DR risk. Weighted univariate and multivariate Cox models were adopted to explore the association of CONUT score with all-cause mortality and cardiovascular disease (CVD)-related mortality in patients with DR.Results305 patients diagnosed with DR had died by the end of the follow-up period, among whom 111 individuals died due to CVD. After adjusting all potential confounding factors, there was an association between CONUT score and DR development in patients with diabetes [odd ratio (OR) = 1.18, 95% confidence interval (CI): 1.05-1.33]. Additionally, CONUT score was found to be associated with all-cause mortality of patients with DR [hazard ratio (HR) = 1.11, 95%CI: 1.01-1.22, P= 0.041]. However, there was no significant difference in the CONUT score and CVD-related mortality of patients with DR.ConclusionsCONUT score may be a valuable tool for assessing the risk of developing DR, and predicting prognosis in patients with DR. However, as this was a cross-sectional study, we cannot infer the causality of CONUT score and DR risk.

Diabetic macular oedema [DMO] is a prevalent and sight-threatening condition among diabetic patients, which can cause irreversible blindness. Since angiogenesis and inflammation are two key elements in the etiopathogenesis of DMO, intravitreal injections of vascular endothelial growth factor inhibitors [anti-VEGF] and sustained released intravitreal corticosteroid implants are currently considered as treatments of choice. The introduction, 10 years ago, of the 0.19 mg fluocinolone acetonide [FAc] implant for treating eyes with vision impairment associated with recurrent and persistent DMO represented an important advance. Since then, two randomized-control trials and many real-world studies have shown its good efficacy/safety profile and the replicability of its treatment regimen. The FAc implant is, in general terms well tolerated, although it is associated with intraocular pressure-[IOP] and cataract-related adverse events [AEs]. Most IOP-related AEs are effectively controlled with ocular-hypotensive therapies. The objective of this paper is to review the role of FAc implant in the treatment of DMO over the 10 years since its launch, as well as its impact on clinical practice outcomes.

In human eye, structural proteins, known as crystallins, play a crucial role in maintaining the eye's refractive index. These crystallins constitute majority of the total soluble proteins found in the eye lens. Among them, α-crystallins (α-CR) is one of the major components. Under hyperglycaemic conditions, crystallins become susceptible to glycation that ultimately leads to advanced glycation endproducts (AGEs) formation. Glipizide is a well-known oral medication used in controlling levels of blood sugar, this drug stimulates the insulin release from pancreas. However, this drug has not been thoroughly investigated for its impact on α-CR glycation. In this study, we explored glipizide's protective role against glucose-induced α-CR glycation. Remarkably, glipizide effectively inhibited the formation of early glycation products, ultimately reducing AGEs formation. Additionally, glipizide provides protection against modifications of free lysine residues and lowered the carbonyl content. To gain deeper insights into mechanism of inhibition, we turn to binding studies and bioinformatics. Glipizide formed stable complex with α-CR with values of Gibbs energy ranging from -5.848 to -6.695 kcal/mol. Molecular docking revealed the binding energy as -6.5 kcal/mol and lysine residues emerged as a prominent among the key interacting residues. Notably, glipizide appears to mask lysine residues, thereby contributing to the inhibition of α-CR glycation. Furthermore, analysis of molecular simulation data reinforces the stability of this complex. Consequently, the stable α-CR-glipizide complex may prevent glucose from binding to α-CR. Overall, glipizide holds promise as a preventive measure against glycation of eye lens proteins, potentially benefiting in diabetic retinopathy.

Existing deep learning (DL) algorithms lack the capability to accurately identify patients in immediate need of treatment for proliferative diabetic retinopathy (PDR). We aimed to develop a DL segmentation model to detect active PDR in six-field retinal images by the annotation of new retinal vessels and preretinal hemorrhages.

We identified six-field retinal images classified at level 4 of the International Clinical Diabetic Retinopathy Disease Severity Scale collected at the Island of Funen from 2009 to 2019 as part of the Danish screening program for diabetic retinopathy (DR). A certified grader (grader 1) manually dichotomized the images into active or inactive PDR, and the images were then reassessed by two independent certified graders. In cases of disagreement, the final classification decision was made in collaboration between grader 1 and one of the secondary graders. Overall, 637 images were classified as active PDR. We then applied our pre-established DL segmentation model to annotate nine lesion types before training the algorithm. The segmentations of new vessels and preretinal hemorrhages were corrected for any inaccuracies before training the DL algorithm. After the classification and pre-segmentation phases the images were divided into training (70%), validation (10%), and testing (20%) datasets. We added 301 images with inactive PDR to the testing dataset.

We included 637 images of active PDR and 301 images of inactive PDR from 199 individuals. The training dataset had 1381 new vessel and preretinal hemorrhage lesions, while the validation dataset had 123 lesions and the testing dataset 374 lesions. The DL system demonstrated a sensitivity of 90% and a specificity of 70% for annotation-assisted classification of active PDR. The negative predictive value was 94%, while the positive predictive value was 57%.

Our DL segmentation model achieved excellent sensitivity and acceptable specificity in distinguishing active from inactive PDR.

Proliferative diabetic retinopathy (PDR) may lead to vision loss and blindness. The cost-effectiveness of various anti-vascular endothelial growth factor (anti-VEGF) drugs and panretinal photocoagulation (PRP) was assessed to supplement the NICE guideline for treating PDR.

A Markov model including eight levels of visual acuity (ranged between >85 and ≤25 letters) was developed to compare the cost-effectiveness of ranibizumab, aflibercept and bevacizumab with PRP (alone or in combination). Clinical inputs in the model were based on literature, while a published network meta-analysis (NMA) informed visual outcomes. Costs were estimated from a UK NHS perspective.

Assuming initial treatment effects from the NMA continued to be applied for the remainder of lifetime, the probabilistic analysis resulted in bevacizumab plus PRP producing the highest net monetary benefit (NMB [95% CI]) of £221,374 [£203,941-£238,388] at £20,000 per quality-adjusted life-year. However, assuming initial treatment effects stabilised over time resulted in PRP alone producing the highest NMB of £223,416 [£209,318-£236,866]. Results were associated with large uncertainty due to wide confidence intervals around vision-based treatment effects of anti-VEGFs versus PRP, particularly for bevacizumab as data were drawn from trials with small sample size and high risk of bias. Using confidential prices for aflibercept and ranibizumab did not change the overall findings.

PRP is likely to be more cost-effective than anti-VEGFs for PDR. However, the results should be interpreted with caution given the scarcity of long-term visual outcomes with anti-VEGFs in this population. Further research on long-term visual outcomes may resolve these uncertainties.

To evaluate the acceptability, applicability, and cost-utility of AI-powered portable fundus cameras for diabetic retinopathy (DR) screening in Hong Kong, providing a viable alternative screening solution for resource-limited areas.

This pragmatic trial conducted in an optometric clinic and two optical shops. A self-testing system was used, integrating a portable fundus camera and AI software that automatically identified DR. Three months following the screening, selected participants were invited to complete an open-ended questionnaire.

A total of 316 subjects participated, with age of 60.80 ± 8.30 years. The success rate of the self-testing system without active assistance was 89 %. Among 61 subjects who completed follow-up interview, a majority agreed that the system and report were easy to follow and understand (85.3 % and 75.4 %). The satisfaction rate was 64 %, and the willingness to use again was 80 %. The AI screening showed a cost saving of 6312.92 USD per QALY, while the adjusted AI model saved 18639. AI screening and adjusted model outperformed traditional screening (Net Monetary Benefit 367,863.31 and 354,904.76 vs 339,919.83 USD).

The AI-powered portable fundus camera demonstrated high acceptability and applicability in real-world settings, suggesting that AI screening could be a viable alternative in resource-limited settings.

Scleritis, a severe inflammatory condition of the sclera, causes significant ocular pain and potential tissue damage. Often linked with systemic diseases, scleritis can be either infectious or noninfectious. Despite its clinical importance, the global incidence and detailed epidemiology of scleritis are poorly understood due to its heterogeneity and rarity. This systematic review and meta-analysis aim to elucidate the worldwide incidence and epidemiological trends of scleritis, examining variations across geographic regions, etiologies, and time periods.

Systematic Review and Meta-analysis.

Understanding scleritis epidemiology is crucial for enhancing diagnostic accuracy and treatment, especially concerning systemic illnesses commonly associated with this condition. Identifying epidemiological trends can inform healthcare policies and resource allocation, improving patient outcomes.

We systematically reviewed literature across databases, including Embase, PubMed, Virtual Health Library, The Cochrane Library, and medRxiv. Population-based, cohort, case-control, cross-sectional, and claims database studies reporting the frequency, prevalence, or incidence of scleritis diagnosed through clinical or imaging techniques, were included. The screening was based on titles and abstracts, followed by a full-text review. We assessed the risk of bias using standardized tools and systematically extracted data for qualitative and quantitative synthesis. This review is registered with PROSPERO (CRD42022330948).

This review included 74 studies with 169,871 scleritis patients. The incidence was 2.67 per 100,000 in ophthalmological centers and 1.38 per 100,000 in broader population-based studies, both showing a decreasing trend over time. The patient population was predominantly female (67.24%), with an average age of 48.3 years. Epidemiological patterns were significantly influenced by etiology, geographic region, and publication period, with idiopathic cases being the most common. Scleritis was notably associated with systemic diseases such as rheumatoid arthritis, granulomatosis with polyangiitis, Sjögren's syndrome, sarcoidosis, and infectious agents like Mycobacterium tuberculosis and herpes virus.

This is the most extensive study on scleritis to date, providing comparative insights across geographic regions, age groups, and genders. Our meta-analysis highlights significant regional differences in scleritis incidence, reflecting variations in medical practice, access to care, and potential genetic and environmental factors. These findings underscore the need for further research to explore these patterns and their global health implications.

BackgroundDiabetic retinopathy (DR) is one of the serious complications of diabetes mellitus. Laser therapy is the traditional treatment for DR, and the role of vitreous injection of ranibizumab in DR requires evaluation. This meta-analysis aimed to compare the efficacy of ranibizumab combined with laser versus laser monotherapy in treating diabetic retinopathy.Method: We searched PubMed, Scopus, Web of Science, Embase, China Biology Medicine Disc (CBM), China National Knowledge Infrastructure (CNKI), and Wanfang databases, from their inception to October 2024. Randomized controlled trials (RCTs) that compared the effectiveness of ranibizumab combined with laser versus laser monotherapy in the treatment of diabetic retinopathy were searched. We used the Cochrane Collaboration tool to evaluate the risk of bias.ResultsOur analysis included 18 studies. The improvement time for retinal edema in the ranibizumab combined with the laser group was significantly shorter than that in the laser monotherapy group (P < 0.05). The time to absorb fundus hemorrhage in the ranibizumab combined with the laser group was significantly shorter than that in the laser monotherapy group (P < 0.05). The absorption time of fundus exudation in the ranibizumab combined with the laser group was significantly lower than that of the laser monotherapy group (P < 0.05). The rate of improvement in vision in the ranibizumab combined with the laser group was significantly higher than that of the laser monotherapy group (P < 0.05). There were no significant differences in the incidence of adverse reactions (P > 0.05) and retinal thickness in the macula (P > 0.05) between ranibizumab combined with the laser group and the laser monotherapy group.ConclusionThe combination of ranibizumab and laser for diabetic retinopathy is more effective than laser monotherapy.

This study investigated the physicochemical properties of cellulose microfibrils (CMFs) derived from Gelidium amansii (GA) and their potential functionality in preventing retinal pathologies. GA was subjected to microwave-assisted extraction, microfibrillation, centrifugation, and autoclave sterilization, yielding G, GM, GC, and GS, respectively. Each processing steps induced distinct microstructural modifications affecting the final functional properties of the CMFs. To explore their protective effects against anti-endoplasmic reticulum (ER) stress and anti-inflammatory effects, ARPE-19 cells were pretreated with these processed CMFs before exposure to either thapsigargin or lipopolysaccharide. Among the variants, GS most effectively alleviated ocular ER stress by suppressing unfolded protein responses, reducing vascular endothelial growth factor gene and protein expressions, and lowering intracellular calcium levels. Moreover, GS significantly mitigated ocular inflammatory responses by inhibiting the translocation of nuclear factor-kappa B (NF-κB) into the nucleus; consequently preserving tight-junction integrity and downregulating inflammatory cytokine gene expressions. These findings highlight the potential of GS as a protective agent against retinal stress and inflammation.