Search Results (1,930)

Purpose: The aim of this study is to describe a slit-modified 23-gauge infusion trocar designed to enable early postoperative hypotony-free sclerotomy closure by allowing scleral suturing prior to complete trocar removal, and to report initial clinical outcomes in eyes with proliferative diabetic retinopathy with or without vitreous hemorrhage (PDR + H and PDR). Methods: A standard 23-gauge metallic (titanium) trocar was modified by creating a longitudinal slit that permitted passage of a suture needle while the trocar remained partially engaged within the scleral tunnel. At the end of pars plana vitrectomy, a transscleral suture was placed through the slit with the knot prepared prior to trocar removal, followed by simultaneous trocar extraction and suture tightening. Eighteen consecutive patients undergoing vitrectomy for PDR (fourteen with vitreous hemorrhage [PDR + H]; four without) were included. Intraocular pressure (IOP) was recorded preoperatively, immediately after sclerotomy closure (postoperative baseline), and at 8 and 24 h postoperatively. The study was designed as an exploratory pilot feasibility and safety evaluation of a slit-modified infusion trocar in 23-gauge vitrectomy. The primary outcomes were postoperative IOP stability and wound leakage. Secondary outcomes included early hypotony, postoperative hemorrhage, choroidal effusion, and the need for additional suturing. Results: All procedures were completed without intraoperative complications. The mean IOP was 14.83 ± 2.50 mmHg preoperatively, 13.33 ± 1.53 mmHg immediately after closure, 14.17 ± 3.01 mmHg at 8 h, and 15.17 ± 1.79 mmHg at 24 h. No cases of wound leakage or early postoperative hypotony were observed in either subgroup. One eye exhibited a transient IOP increase at 8 h; no choroidal effusion, postoperative hemorrhage, or need for secondary suturing occurred. Endotamponade consisted of balanced salt solution (BSS) in eight eyes, SF6 in seven eyes, silicone oil in two eyes, and air in one eye. Conclusions: The slit-modified infusion trocar enables secure, hypotony-free closure of the infusion sclerotomy by eliminating the open-wound interval during trocar removal. This simple biomedical device modification provides stable early postoperative IOP across different tamponade agents and appears safe and feasible in high-risk eyes with PDR. Full article

Background/Objectives: Inflammation is a critical contributor to the development of diabetic retinopathy (DR). In the early stages of DR, the compromised permeability of the blood–retina barrier facilitates the infiltration of macrophages and the activation of microglia. These specific retinal immune cells can adopt morphologies M1 or M2, linked to pro- or anti-inflammatory responses, respectively. This dual response represents a new therapeutic target against DR progression. This study aimed to investigate the modulation of the response M1/M2 and the molecular mechanism of two algal diterpenoids, rugukadiol A (RK) and ruguloptone A (RL), in the early inflammatory events associated with DR. Methods: LPS-stimulated microglial (Bv.2) and macrophage (RAW264.7) cells and an ex vivo physiological model of DR were used to analyze the effects of RK and RL on M1 and M2 inflammatory markers. Results: Compounds RK and RL, besides decreasing the expression of the M1 pro-inflammatory factors iNOS, Il6 mRNA, and NLRP3 in LPS-stimulated Bv.2 cells, caused enhancements in Arg-1 mRNA and Il10 mRNA expression consistent with the induction of an M2 anti-inflammatory response. RK promoted p38α-MAPK phosphorylation, suggesting a non-classical activation of p38α related to the induction of anti-inflammatory responses. Consistently, treatment of retinal explants of BB rats in the early stages of DR with RL decreased M1 pro-inflammatory mediators and induced M2 anti-inflammatory markers, with a reduction in gliosis and a phenotype switch from activated to resting microglia. Conclusions: This study provides the first evidence of algal diterpenoids attenuating pro-inflammatory mediators and promoting the resolution of inflammation in a diabetic retinopathy context, thus opening the way to further explore this class of marine natural products and analogs for early DR management. Full article

Background/Objectives: Diabetic retinopathy (DR) is a major microvascular complication of type 1 diabetes mellitus (T1DM) and remains an important cause of preventable visual impairment. Region-specific data on the incidence and clinical predictors of DR among patients with T1DM in Saudi Arabia remain limited. This study aimed to determine the incidence of DR and identify associated demographic and systemic risk factors among patients with T1DM at a tertiary care center in Riyadh, Saudi Arabia. Methods: This retrospective cohort study included 449 patients with T1DM aged ≥9 years who were followed at King Abdulaziz Medical City, Riyadh, between 2015 and 2025. Patients were selected using a consecutive non-probability sampling technique. Data were extracted from the BESTCare 2.0A electronic medical record system and supplemented, when required, by phone-based interviews to verify selected clinical and demographic variables. Patients were classified as controls without DR or cases with DR, including non-vision-threatening DR and vision-threatening DR (VTDR), according to the International Clinical Diabetic Retinopathy Severity Scale. Multivariable logistic regression, Cox proportional hazards models, and temporal trend analysis were performed, with statistical significance set at p < 0.05. Results: The overall incidence rate of DR was 92.66 per 1000 person-years, with similar rates among males and females. In multivariable logistic regression, older age at T1DM diagnosis, longer diabetes duration, hypertension, hyperlipidemia, and albuminuria were independently associated with DR. Mean HbA1c and HbA1c variability were not independently associated with DR after adjustment. In Cox regression, older age at T1DM diagnosis was associated with higher hazards of both DR and VTDR, while hypertension was associated with VTDR. Among patients with DR, younger age at T1DM diagnosis was associated with higher odds of proliferative disease in exploratory severity analysis. Conclusions: DR was common among patients with T1DM in this tertiary-care cohort and was mainly associated with disease duration, age at diagnosis, and systemic vascular comorbidities. These findings support the importance of routine ophthalmologic screening and integrated management of systemic risk factors in patients with T1DM. Full article

Background/Objectives: General-purpose and domain-specific multimodal foundation models show considerable promise in medical image analysis. In this study, we evaluated the classification accuracy of diabetic retinopathy vs. normal fundus images using general-purpose conversational models (Gemini 3 Flash, GPT-5.2, and Pixtral-Large), a medical conversational model (MedGemma-1.5), and its image-encoder (MedSigLIP), as well as ophthalmology-specific models (RETFound and EyeCLIP). Methods: We applied zero-/few-shot to general-purpose conversational models, linear probing, and fine-tuning approaches to domain-specific models for evaluation purposes. Results: We found that the zero-shot accuracies for Pixtral-Large (70.7%) and fine-tuned RETFound (77.1%) were comparable but lower than those of GPT-5.2 (77.9%), MedGemma-1.5 (88.2%), and Gemini 3 (88.5%) as well as the fine-tuned EyeCLIP (85.8%) and MedSigLIP (94.8%). The accuracy gains from few-shot prompting were substantial for Pixtral-Large (+7.4%) but were limited for GPT-5.2 (+3.6%), Gemini 3 (−3.4%), and MedGemma-1.5 (−1.1%). Embedding-based linear probing further improved accuracy over fine-tuning for RETFound (+9.7%) and yielded only marginal gains for EyeCLIP (+2.3%) but did not benefit MedSigLIP (−0.8%). Overall, with minimal prompting enhancement, general-purpose conversational models such as Gemini 3 and GPT-5.2 achieved performance comparable to ophthalmology-specific models that were either fine-tuned or enhanced via embedding-based linear probing, but remained inferior to MedSigLIP and its conversational counterpart, MedGemma-1.5. Conclusions: The findings highlight a trade-off between specialization and flexibility, where domain-specific models provide higher accuracy and stability, while general-purpose multimodal models offer greater accessibility, adaptability, and interactive reasoning, serving as complementary tools for retinal disease screening and clinical decision support. Full article

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) and newer dual-incretin therapies have become central to the treatment of diabetes mellitus and obesity, with benefits extending beyond glycemic control. Their expanding use has prompted growing interest in their potential ocular effects. Experimental data support plausible protective mechanisms, including reduction in oxidative stress and neuroprotective effects on retinal and optic nerve tissues. Clinical evidence, however, remains heterogeneous. In diabetic retinopathy, the main concern appears to be transient early worsening associated with rapid glycemic improvement rather than direct retinal toxicity. A potential semaglutide-associated signal for non-arteritic anterior ischemic optic neuropathy has raised concern, although the absolute risk appears low and causality remains unproven. Emerging studies also suggest possible beneficial associations with glaucoma, ocular surface diseases, and certain retinal vascular outcomes, whereas the evidence regarding age-related macular degeneration and cataract remains conflicting or preliminary. Overall, ocular outcomes associated with incretin-based therapies seem to reflect a complex interplay among drug-specific pharmacology, systemic metabolic changes, and individual patient susceptibility rather than a class effect. Baseline ophthalmic assessment and individualized follow-up may be advisable in selected high-risk patients. Further prospective ophthalmology-focused studies are needed to clarify long-term safety and identify the patients most likely to benefit or develop adverse events. Full article

This review is intended to highlight the need for non-invasive and earlier therapies for diabetic retinal disease (DRD), one of the most common complications of diabetes, with a high and increasing socioeconomic burden. Due to the growing evidence regarding the key role of neurodegeneration in the earliest stages of the disease and the underlying pathophysiological mechanisms, the relevance of evaluating the potential efficacy of neuroprotective therapies is emphasized. More specifically, the review addresses the current state of a promising neuroprotective approach based on the inhibition of the enzyme dipeptidyl peptidase-4 (DPP-4) using specific inhibitors administered via eyedrops, which allow direct retinal action on the neurovascular unit. The review discusses the main preclinical findings of a therapeutic strategy based on one DPP-4 inhibitor, sitagliptin, against early DRD in different experimental animal models and in vitro studies. In summary, sitagliptin eyedrops exhibit neuroprotective, anti-inflammatory, and antioxidant properties while reducing glial activation, hyperpermeability of the blood–retinal barrier, and the formation of acellular capillaries, leading to a functional improvement of the diabetic retina. However, as sitagliptin efficacy has only been evaluated at the preclinical level, clinical studies are needed to validate the translational applicability and long-term efficacy of topical administration not only of sitagliptin but also of other DPP-4 inhibitors for treating retinal diseases in which neurodegeneration plays a pathogenic role. Full article

Background/Objectives: Cystatin C-based and combined creatinine–cystatin C estimated glomerular filtration rate (eGFR) equations improve early chronic kidney disease (CKD) detection and prediction of adverse outcomes compared to creatinine alone. However, their role in predicting microvascular complications such as diabetic retinopathy (DR) is less clear. We examined the association between diabetic kidney disease (DKD), defined using creatinine-, cystatin C-, and combined eGFR measures, as well as albuminuria, and the risk of incident DR among Asian adults in Singapore. Methods: We analysed 1135 Chinese and Indian adults with diabetes aged ≥40 years from a population-based cohort study with baseline (2007–2011) and 6-year follow-up (2013–2017) data. DR was graded from retinal photographs, and incident DR was defined as new-onset at follow-up. DKD was defined as eGFR < 60 mL/min/1.73 m² using eGFRcr, eGFRcys, combined eGFRcr-cys, and albuminuria (UACR ≥ 30 mg/g), assessed individually and jointly. Modified Poisson regression models adjusted for age, sex, ethnicity, diabetes duration, HbA1c, and systolic blood pressure were used to estimate relative risks (RRs). Results: Overall, incident DR occurred in 13.0% of participants. Among those with DKD, incidence was 18.2% (eGFRcr), 16.7% (eGFRcys), 23.7% (eGFRcr-cys), and 18.3% (albuminuria). eGFRcr-DKD (RR = 2.18, 95% CI 1.33–3.58), eGFRcys-DKD (2.38 [1.51–3.78]), and eGFRcr-cys-DKD (3.15 [1.94–5.12]) were independently associated with incident DR, whereas albuminuria alone was not. Risk increased with increasing number of markers,2.00 (1.02–3.92) by dual and 4.91 (2.50–9.65) by triple markers. Conclusions: DKD defined using multiple kidney markers, particularly combined creatinine–cystatin C, was strongly associated with incident DR. These findings support the use of multiple kidney function markers to improve risk stratification for developing DR. Full article

Background/Objectives: Using a well-established model of streptozotocin-induced diabetic retinopathy (DR), this study sought to evaluate the neuroprotective effect of intravitreal Forskolin (FSK) on retinal ganglion cell survival and glial activation and explore the association of circulating miR-200b with metabolic and oxidative stress in DR. Methods: A total of 18 male Wistar rats were divided into a control group (n = 6) and a streptozotocin-induced diabetic group (n = 12), which were further divided into diabetic control and FSK-treated groups (n = 6 each). Total antioxidant capacity (TAC), total peroxide (TP), triglycerides (TGs), total cholesterol, and high-density lipoprotein cholesterol (HDL-C) were measured. qRT-PCR analysis for miRNA-200b and immunohistochemistry were performed. Results: Diabetic rats showed oxidative stress and hyperlipidemia associated with increased circulating miR-200b levels. The retina showed reduced neuron numbers (Caspase-3), altered glial and astrocyte staining (IBA1, GFAP), and changes in microglia/macrophage morphology and distribution. Intravitreal FSK improved retinal ganglion cell survival and reduced glial activation, while systemic lipid profile and oxidative stress markers remained largely unchanged. Circulating miR-200b levels showed a positive correlation with oxidative stress markers across groups. Conclusions: Intravitreal FSK was able to limit the disease exacerbation via improved neuronal survival through inhibition of apoptosis. FSK did not produce observable qualitative changes in GFAP expression or IBA1+ cell morphology under the conditions tested. Full article

Background: Diabetic macular edema (DME) is a leading cause of vision loss. Although real-world data on faricimab, a bispecific antibody targeting vascular endothelial growth factor-A and Angiopoietin-2, are expanding, its long-term durability in routine clinical practice has not yet been fully established. We evaluated effectiveness, anatomic response and treatment durability of first-line faricimab in treatment-naïve DME. Methods: We conducted a single-center, retrospective cohort study of treatment-naïve DME eyes initiated on intravitreal faricimab (August 2023–October 2024) in a real-world setting. After a loading phase, eyes were managed with a treat-and-extend or pro re nata regimen. The primary endpoint was retreatment interval at 48 weeks. Secondary endpoints were retreatment interval at weeks 12, 24 and 36; change in visual acuity (VA); central subfield thickness (CST); and optical coherence tomography (OCT) fluid. Results: Fifty-two eyes from 40 consecutive patients were included (baseline VA 65.96 ± 13.55 letters; CST 426.56 ± 106.72 µm). Mean injections were 4.02 ± 1.11 between months 1–6 and 1.90 ± 0.98 between months 7–12. VA improved by +8.46, +7.57, +7.65 and +7.72 letters at 12, 24, 36, and 48 weeks (all p < 0.0001), respectively. Relative CST decreased by −28.05%, −27.01%, −29.46% and −25.22% at the same time points (all p < 0.0001). At week 48, 15.4% of eyes were on a treatment interval of less than 12 weeks, 23.1% were between 12 and 16 weeks, and 46.1% were on 16 or more weeks; 15.4% were managed PRN. Conclusions: First-line faricimab in treatment-naïve DME in a real-world setting yielded clinically meaningful and durable extensions in treatment intervals, alongside sustained functional and anatomical improvements. Full article

Background: Posterior segment eye diseases, including age-related macular degeneration and diabetic retinopathy, are preeminent causes of vision loss worldwide. Effective drug delivery to the retina poses an ongoing therapeutic difficulty due to the presence of the anatomical and physiological barriers. Nanotechnology-based drug delivery systems represent a promising strategy to overcome those limitations. Methods: A narrative literature review was conducted using the PubMed, Scopus, and Google Scholar databases, covering publications published between 2019 and 2026. Publications evaluating nanoparticles for the treatment of the vitreoretinal disorders, including pre-clinical in vitro and in vivo studies, were analyzed. Results: Nanocarriers, including liposomes, polymeric nanoparticles, and lipid-based systems, established improved drug bioavailability, stability, and targeted delivery. The analyzed systems facilitate sustained drug release and potentially reduce the prevalence of invasive intravitreal injections. The nanocarriers’ effectiveness is primarily influenced by their physicochemical properties, such as particle size, surface charge, and encapsulation efficiency. Nonetheless, the production costs and safety aspects, including cytotoxicity, oxidative stress, and inflammatory responses, remain as significant limitations. Conclusions: Nanotechnology-based drug delivery systems serve as an auspicious therapeutic approach for posterior segment eye diseases. However, further standardized preclinical and clinical research is required to assure long-term safety and enable successful clinical transition. Full article

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have revolutionized the management of type 2 diabetes mellitus (T2DM) by providing robust glycemic control alongside significant cardioprotective and renoprotective benefits. This review synthesizes current mechanistic, preclinical, and clinical evidence regarding the impact of GLP-1RAs on retinal microvasculature and summarizes the current clinical evidence of GLP-1RA-induced retinal complications. GLP-1RAs exert pleiotropic effects on the retinal microvasculature, offering protection by amelioration of endothelial function, reduction in oxidative stress, inflammation, microvascular remodeling, and preservation of the blood–retinal barrier (BRB). Despite these mechanistic advantages, emerging clinical data have raised concerns regarding potential retinal adverse events associated with GLP-1RA therapy. Observational studies and pharmacovigilance analyses have suggested possible associations with non-arteritic anterior ischemic optic neuropathy (NAION), diabetic macular edema (DME), vitreous hemorrhage, retinal detachment, macular hole formation, and progression of diabetic retinopathy (DR), particularly in the context of semaglutide use. Most evidence comes from retrospective studies or secondary endpoints, limiting causal inference. Retinal complications associated with GLP-1RAs remain heterogeneous and inconclusive, requiring careful evaluation of potential risks across diverse patient populations. Future research should conduct large, randomized trials with standardized ocular endpoints, detailed imaging, and stratified analyses to clarify GLP-1RA retinal safety. Full article

The gut microbiome regulates host metabolism, barrier integrity, and immune homeostasis through microbe–host signaling and bioactive metabolites. Growing evidence suggests that dysbiosis may also influence ocular immune privilege and blood–retinal barrier stability, supporting the emerging concept of the gut–eye axis. This narrative review aimed to integrate retinal, uveal, and ocular surface disorders within a shared functional framework, with emphasis on recurring mechanistic pathways and their translational relevance rather than on single diseases or isolated taxonomic findings. The review was based on a literature search of PubMed and Scopus and primarily included English-language studies published between 2015 and 2025, with earlier seminal papers included when needed. The search was last updated in March 2026, and 101 sources were included in the final narrative synthesis. Across age-related macular degeneration, diabetic retinopathy, glaucoma, uveitis, dry eye disease, and Sjögren’s syndrome, the most consistent microbiome-related signals were functional rather than taxonomic. Recurrent mechanistic themes included Th17/Treg immune programming, barrier dysfunction with microbial product translocation, and systemic metabolite signaling, particularly involving short-chain fatty acids, bile acid receptor pathways, and tryptophan-derived metabolites. Age-related macular degeneration and diabetic retinopathy showed the strongest multi-layered support, whereas uveitis provided a compelling immune-centered biological model that remains limited by treatment-related confounding in human studies. In glaucoma and ocular surface disease, evidence supports biological plausibility, especially in relation to neuroinflammation, mucosal immune dysregulation, and metabolite-dependent anti-inflammatory pathways, although much of the available human literature remains associative. Overall, current evidence supports dysbiosis as a disease modifier that may influence ocular inflammation, angiogenesis, neurodegeneration, and barrier stability. However, clinical translation remains limited by cohort heterogeneity, methodological variability, and incomplete control of confounding factors. Further progress will depend on longitudinal multi-omics cohorts and controlled intervention trials focused on actionable microbial functions. Full article

While diabetic retinal disease (DRD) has classically been viewed as a microvascular complication, emerging evidence places the photoreceptor at the center of its pathogenesis. Recognizing this central role provides a critical framework for resolving a major clinical paradox in diabetes: why the retina exhibits profound susceptibility to hyperglycemic damage, whereas closely related neural tissues like the brain are mostly spared. In this review, we synthesize the evidence for photoreceptor-driven DRD pathology by evaluating two primary mechanistic paradigms. In the first, hyperglycemia-induced damage to the blood vessels limits perfusion, creating an ischemic environment that selectively devastates tissues dependent on exceptionally high blood flow and energy delivery—specifically, the photoreceptors. In the second paradigm, hyperglycemia induces a direct shift in the metabolic profile of photoreceptors, triggering oxidative stress and dysregulated lipogenesis that subsequently place pathological strain on the local microvasculature. Regardless of whether the initial insult is vascular or neuronal, the photoreceptor remains the critical node of disease progression. Because current and investigational DRD treatments predominantly target downstream vascular consequences, exploring these dual mechanisms highlights an urgent need and a significant opportunity to develop novel therapies that target the photoreceptor to address DRD at its root. Full article

Diabetic retinopathy (DR) is a leading cause of vision impairment and permanent blindness worldwide, requiring accurate and automated systems for multi-grade severity classification. However, standard Convolutional Neural Networks (CNNs) often struggle to capture fine, high-frequency microvascular patterns critical for diagnosis. This study proposes a Robust Intelligent CNN Model (RICNN) that integrates Gabor-based feature extraction with deep learning to improve DR classification. Specifically, Gabor filters are applied during preprocessing to extract orientation- and frequency-sensitive texture features, which are transformed into feature maps and concatenated with CNN feature representations at the fully connected layer (feature-level fusion). The model also incorporates the Synthetic Minority Oversampling Technique (SMOTE) for data balancing and the Adam optimizer for efficient convergence. This integration enhances sensitivity to microvascular structures such as microaneurysms and hemorrhages. The proposed RICNN was evaluated on the Messidor dataset (1200 images) across four severity levels: Mild, Moderate, Severe, and Proliferative DR. The model achieved an accuracy of 89%, a precision of 88.75%, a recall of 89%, and an F1-score of 89%, with AUCs of 97% for Severe DR and 99% for Proliferative DR. Comparative analysis confirms that the proposed texture-aware Gabor enhancement significantly outperforms LBP and Color Histogram approaches, indicating its potential for reliable clinical decision support. Full article

Diabetic retinopathy is one of the most important complications of diabetes. It is a leading cause of visual loss in the world. While adequate control of hyperglycemia, hypertension and hyperlipidemia can decrease the prevalence of diabetic retinopathy, 60% of patients with type 2 diabetes develop this complication whereas it is estimated that most patients with type 1 diabetes will develop diabetic retinopathy. Upregulation of various pro-inflammatory molecules and vascular endothelial growth factor (VEGF) play a central role in the pathogenesis of the disease. Here we review the role of CD40 as an upstream inducer of these abnormalities and the development of diabetic retinopathy. Full article