Search Results (556)

Diabetic retinopathy (DR) has been classically considered a microvascular disease with all diagnostic and therapeutic resources focusing on its vascular components. However, during the past years, the obtained evidence highlighted the critical pathogenic role of early neuronal impairment redefining DR as a neurovascular complication. Retinal neurodegeneration is triggered by chronic hyperglycemia, which activates harmful biochemical pathways that lead to oxidative stress, metabolic overload, glutamate excitotoxicity, inflammation, and neurotrophic factor deficiency. These drivers of neurodegeneration can precede detectable vascular abnormalities. Simultaneously, endothelial injury, pericyte loss, and breakdown of the blood–retinal barrier compromise neurovascular unit integrity and establish a damaging cyclic loop in which neuronal and vascular dysfunctions reinforce each other. The interindividual variability of these processes highlights the need to properly redefine patient phenotyping by using advanced imaging and functional biomarkers. This would allow early detection of neurodegeneration and patient subtype classification. Nonetheless, translation of therapies based on neuroprotection has been limited by classical focus on vascular impairment. To meet this need, several strategies are emerging, with the most promising being those delivered through innovative ocular routes such as topical formulations, sustained-release implants, or nanocarriers. Future advances will depend on proper guidance of these therapies by integrating personalized medicine with multimodal biomarkers. Full article

Background/Objectives: Vitamin B₁₂ deficiency is increasingly recognized as a contributor in both vascular and neurodegenerative aging-related disorders. Its deficiency disrupts one-carbon metabolism, leading to impaired homocysteine (Hcy) cycling. Elevated Hcy is a well-established risk factor for vascular dysfunction. Previously, we established that elevated Hcy contributes to aging retinal diseases and plays a central role in blood retinal barrier (BRB) dysfunction. Building on this foundation, the present study examines how B-vitamin deficiency disrupts one-carbon metabolism and whether restoring these vitamins can serve as a preventive or therapeutic strategy. Since B-vitamins (B₆, B₉, and B₁₂) are crucial cofactors in the metabolism of Hcy, we investigated how dietary changes in these vitamins affect serum Hcy levels and retinal vascular integrity in mice. Methods: C57BL/6- Wild-type (WT) and cbs^+/− mice (Cystathionine Beta-Synthase heterozygotes, common mouse model for elevated Hcy) were fed specially formulated diets, which contained different levels of B-vitamins (normal, deficient (B-Vit (−)) or enriched (B-Vit (+)). Initially, two groups of mice were placed on either a normal or a deficient diet. After 12–16 weeks, the success of the diet regimes was confirmed by observing serum B₁₂ deficiency in the B-Vit (−) group, along with elevated Hcy levels. Subsequently, a subgroup of the B-Vit (−) mice was switched to an enriched diet. The BRB integrity was evaluated in living mice using fluorescein angiography (FA), optical coherence tomography (OCT), and in the perfused mice retinas with Western blot analysis of leaked retinal albumin and tight junction proteins (occludin and ZO-1) levels. Results: The B-vitamin deficiency caused significant drop in serum vitamin B₁₂ and an increase in plasma Hcy, leading to vascular leakage, altered retinal thickness, choroidal neovascular changes, increased retinal albumin leak, and decreased tight junction protein expression, indicating BRB disruption, which was restored with B-vitamin supplementation. Conclusions: a long-term deficiency of vitamins B₆, B₉, and B₁₂ can lead to disruptions in the BRB. However, supplementation with these B-vitamins has the potential to reverse these effects and help maintain the integrity of BRB. This under-score the significance of one-carbon metabolism for retinal health and suggests that ensuring adequate levels of B-vitamins may aid in preventing aging retinal diseases with BRB disruption such as diabetic retinopathy and age-related macular degeneration. Full article

Background: Laser Speckle Flowgraphy (LSFG) is a non-invasive imaging technology that quantitatively evaluates retinal and choroidal blood flow by analyzing speckle patterns generated by laser light scattering. This systematic review summarizes the application of LSFG in two major degenerative retinal diseases: age-related macular degeneration (AMD) and diabetic retinopathy (DR). Methods: A comprehensive literature search (2010–2025) was conducted in PubMed, Cochrane Library and EMBASE according to PRISMA guidelines. Twenty-three studies including a total of 974 eyes (191 AMD, 783 DR) were analyzed. Results: In AMD, LSFG detected baseline reductions in choroidal and retinal perfusion in non-exudative disease, often extending beyond atrophic regions. Anti-VEGF injections produced acute reductions in MBR, particularly with brolucizumab, with partial recovery over time; drug-specific differences suggest a potential impact on geographic atrophy progression. In DR, LSFG revealed early microvascular dysfunction even in asymptomatic eyes. Retinal and choroidal MBR and blowout score correlated with HbA1c, DR severity, and inflammatory mediators. Intravitreal anti-VEGF therapy consistently reduced retinal and choroidal MBR and RFV, while conventional panretinal photocoagulation decreased choroidal flow and vascular caliber more robustly than patterned laser, reflecting oxygenation-driven VEGF modulation. Low baseline MBR predicted higher central macular thickness and reduced therapeutic response in diabetic macular edema. Conclusions: LSFG provides reproducible, rapid, and non-invasive quantitative insights into ocular hemodynamics across degenerative retinal diseases. Its integration into multimodal imaging may facilitate early diagnosis, support personalized management, and assist in the prognostic assessment of retinal and choroidal vascular disorders. Full article

As the central hub of retinal metabolism, mitochondria are vital for sustaining the integrity of the inner blood-retinal barrier (iBRB), which is fundamental to retinal homeostasis. Mitochondrial dysfunction accelerates severe iBRB disruption, a process which is increasingly implicated in a cascade of mitochondrial pathologies including mitochondrial DNA destabilization, oxidative stress, calcium homeostasis disruption, mitochondrial autophagy deficiency, and dysregulated dynamic regulation. This review establishes the iBRB as a crossroads for metabolic, redox, and inflammatory signaling. By analyzing evidence from diabetic retinopathy and retinal vein occlusion models, we clarify how mitochondrial decline translates local energy deficiency into chronic barrier dysfunction. We posit that restoring mitochondrial function is indispensable for vascular resilience and regeneration, a conclusion drawn from integrating molecular, cellular, and translational findings. To advance mitochondrial discoveries into clinical practice, subsequent studies must prioritize achieving spatiotemporally controlled, cell-type-specific interventions with robust in vivo efficacy, thereby successfully translating mitochondrial science into clinical vascular medicine. Full article

Diabetic retinopathy (DR) and diabetic macular edema (DME) remain major causes of vision loss among working-age adults. Artificial intelligence (AI), particularly deep learning, has gained attention in ophthalmic imaging, offering opportunities to improve both diagnostic accuracy and efficiency. This review examined applications of AI in DR and DME published between 2010 and 2025. A narrative search of PubMed and Google Scholar identified English-language, peer-reviewed studies, with additional screening of reference lists. Eligible articles evaluated AI algorithms for detection, classification, prognosis, or treatment monitoring, with study selection guided by PRISMA 2020. Of 300 records screened, 60 met the inclusion criteria. Most reported strong diagnostic performance, with sensitivities up to 96% and specificities up to 98% for detecting referable DR on fundus photographs. Algorithms trained on optical coherence tomography (OCT) data showed high accuracy for identifying DME, with area under the receiver operating characteristic curve (AUC) values frequently exceeding 0.90. Several models also predicted anti-vascular endothelial growth factor (anti-VEGF) treatment response and recurrence of fluid with encouraging results. Autonomous AI tools have gained regulatory approval and have been implemented in clinical practice, though performance can vary depending on image quality, device differences, and patient populations. Overall, AI demonstrates strong potential to improve screening, diagnostic consistency, and personalized care, but broader validation and system-level integration remain necessary. Full article

Systemic lupus erythematosus (SLE) is a chronic multisystem autoimmune disorder in which ocular involvement represents a clinically significant yet frequently underrecognized contributor to morbidity. Ocular manifestations in SLE may arise from disease activity itself, but also as adverse effects of long-term pharmacological therapy. With the advent of targeted immunomodulatory agents, the therapeutic landscape of SLE has expanded beyond conventional drugs such as hydroxychloroquine and corticosteroids toward biologics and small molecules designed to interfere with specific immunological pathways. These advances have improved systemic disease control and survival; however, their ophthalmological safety profiles remain only partially defined. This review synthesizes current evidence on ocular adverse events associated with both traditional and emerging SLE therapies. Established agents, particularly hydroxychloroquine and corticosteroids, are consistently linked to complications including retinopathy, posterior subcapsular cataracts, steroid-induced glaucoma, and central serous chorioretinopathy. In contrast, recently approved or investigational therapies—such as belimumab, anifrolumab, voclosporin, dual BAFF/APRIL inhibitors, rituximab, JAK inhibitors, CD40/CD40L blockade, CD38 inhibition, and mesenchymal stromal cell-based strategies—have limited but evolving safety data, with potential ocular adverse events spanning inflammatory, vascular, neuro-ophthalmic, and structural domains. Although ocular complications appear infrequent in clinical trials, underdetection in real-world practice and insufficient long-term monitoring may underestimate their true incidence. These findings highlight the need for systematic ophthalmological surveillance in patients receiving immunomodulatory therapies for SLE. Early recognition and timely management of ocular toxicity are crucial to safeguarding visual function and optimizing long-term therapeutic outcomes in this vulnerable patient population. Full article

Background: Nutritional imbalances significantly affect ocular physiology, contributing to dry eye disease, cataracts, age-related macular degeneration (AMD), and optic neuropathies. This review summarizes recent evidence on how micronutrient deficiencies and obesity influence eye health. Methods: A narrative search was performed in PubMed, Scopus, and ScienceDirect (last 10 years). Human studies evaluating associations between micronutrients, dietary patterns, obesity, and ocular diseases were included. Out of 843 records, 50 studies met the eligibility criteria. Results: Deficiencies in vitamins A, D, E, C, and B-complex were consistently linked to ocular surface inflammation, retinal oxidative stress, cataracts, AMD, and nutritional optic neuropathies. Altered levels of zinc, copper, selenium, and magnesium were associated with impaired photoreceptor function, glaucoma risk, and retinal degeneration. Obesity emerged as an independent risk factor for AMD, diabetic retinopathy, and glaucoma through mechanisms involving oxidative stress and vascular dysfunction. Evidence from AREDS/AREDS2 supports targeted antioxidant supplementation in intermediate AMD. Conclusions: Adequate nutritional status and metabolic balance play a critical role in preserving ocular health. Early detection and correction of deficiencies may prevent or slow the progression of several eye diseases. Further high-quality trials are needed to define optimal nutritional recommendations. Full article

Background/Objectives: Evaluate outcomes and treatment patterns with 2 mg intravitreal aflibercept injection among patients who completed the phase 3 PANORAMA trial and enrolled in the VOYAGE (ClinicalTrials.gov identifier, NCT04708145; 12 January 2021) long-term extension study. Methods: During VOYAGE, patients were evaluated every 16 weeks and treated with 2 mg intravitreal aflibercept injection as needed depending on ophthalmoscopic examination findings. Those with no history of panretinal photocoagulation (PRP) received aflibercept if their clinician-determined diabetic retinopathy severity scale (DRSS) level was ≥47, corresponding to moderately severe non-proliferative diabetic retinopathy (NPDR). Patients with a history of PRP received aflibercept if active neovascularization was present. New or worsening diabetic retinopathy (DR) severity prompted more frequent treatment. Results: 320 patients (1 eye per patient) from 87 sites completed the PANORAMA trial. Of these, 41 patients (13% of PANORAMA completers) from 14 sites (16%) enrolled in VOYAGE after a mean interim period of 33.7 months, and 35 patients (85%) completed study visits through 1 year. At year 1 in VOYAGE, the mean number of anti-vascular endothelial growth factor (VEGF) injections increased from 1.1 per year during the interim period to 3.4 per year and was associated with stabilization or improvement in DRSS level in 81% (26/32) of patients. Mean best-corrected visual acuity (BCVA) remained relatively stable, and mean central subfield thickness (CST) improved by 24.4 µm to 269.5 μm through year 1 of VOYAGE. There were no unexpected safety events. Conclusions: Following a mean of 3 years of routine clinical care with associated declines in DRSS level, CST, and BCVA, stabilization of DRSS level and BCVA with reductions in CST was achieved through year 1 of the VOYAGE extension study, with a concurrent increase in aflibercept dosing frequency. Full article

Objectives: The aim of this study was to determine which color imaging facilitated easier detection of the persistent avascular retina (PAR) in ultra-widefield (UWF) fundus imaging in children undergoing retinopathy of prematurity (ROP). Methods: A total of 20 eyes of 10 children aged between 6 and 9 who underwent diagnostic and therapeutic procedures for ROP were included. Fundus images were obtained using Optos confocal scanning laser ophthalmoscopy (cSLO; Optos PLC, Daytona, Dunfermline, UK). The images were divided and recorded into three groups as original imaging (composite), red reflectance imaging, and green reflectance imaging. These images were prepared as a slideshow for 10 ophthalmology specialists and they were surveyed to determine in which color imaging the peripheral avascular area was more easily detected. The results were evaluated. Results: The rate of detecting the PAR in green reflectance imaging by the participants included in the study was found to be statistically higher compared to other colors of imaging (composite 0.63 ± 0.09 (0.5–0.8), red 0.12 ± 0.05 (0.05–0.2), and green 0.94 ± 0.06 (0.85–1), p < 0.0001). All respondents reported that the boundaries of the peripheral avascular area were more clearly defined in the UWF (Optos PLC, Daytona, Dunfermline, UK) green reflectance imaging. Conclusions: Each color imaging used in UWF fundus imaging helps to visualize different layers of the retina. Our study showed that retinal vascular endings appear more distinct due to the lower penetration of the green laser into the choroidal vessels. Based on these findings, we believe that UWF fundus green reflectance imaging is more useful for detecting and monitoring PAR. Full article

Retinal ischemia is a key factor in the progression of vision-threatening ocular diseases, including central retinal artery/vein occlusion, exudative age-related macular degeneration (eAMD), and proliferative diabetic retinopathy. This study investigates the effects of paeoniflorin along with its related neuroprotective molecular pathways in the treatment of retinal ischemia. Free radical or ischemic-like damage was induced by incubating retinal pigment epithelium (RPE) cells for 24 h with 1 mM hydrogen peroxide (H₂O₂) or by subjecting retinal neuronal cells to 8 h of oxygen–glucose deprivation (OGD). Both treatments caused significant cell loss. Treatment with paeoniflorin significantly increased cell viability at 0.5 mM in both cell types. In a Wistar rat model of retinal ischemia and reperfusion (I/R) elicited by sustained high intraocular pressure (HIOP), pre-treatment with 0.5 mM paeoniflorin mitigated the ischemia-induced decline in ERG b-wave amplitude, reduction in whole and inner retinal thickness, loss of fluorogold-labeled retinal ganglion cells, and formation of apoptotic cells. Meanwhile, paeoniflorin effectively downregulated pro-neovascular mediators β-catenin, hypoxia-inducible factor 1-alpha (HIF-1α), vascular endothelial growth factor (VEGF), and the pro-inflammatory/angiogenic biomarker angiopoietin-2 (Ang-2), producing effects similar to the Wnt/β-catenin inhibitor (dickkopf-related protein 1), anti-angiogenic pigment epithelium-derived factor (PEDF), and anti-VEGF Avastin (bevacizumab). These findings suggest that paeoniflorin may protect against retinal ischemia through its anti-inflammatory, anti-neovascular/angiogenic, antioxidative, and neuroprotective properties. Full article

Background: Cutaneous manifestations are frequent in diabetes mellitus and may reflect systemic vascular injury. Among them, diabetic dermopathy, necrobiosis lipoidica, scleredema diabeticorum, bullosis diabeticorum, and eruptive xanthomas are clinically significant. Aim: To synthesize current evidence on the associative and potential predictive role of diabetic dermopathies as non-invasive indicators of cardiovascular and renal complications. Methods: A narrative review of studies published between 2010 and 2023 in PubMed, Scopus, and Web of Science was conducted, focusing on links between specific dermopathies and systemic outcomes. Results: Diabetic dermopathy shows consistent associations with microvascular complications such as retinopathy and nephropathy. Necrobiosis lipoidica and scleredema correlate with macrovascular disease and metabolic syndrome, whereas eruptive xanthomas indicate severe dyslipidemia and heightened cardiovascular risk. Evidence is predominantly cross-sectional, with limited sample sizes and heterogeneous diagnostic criteria. Conclusions: Diabetic dermopathies represent emerging clinical indicators of systemic vascular and metabolic burden. Their potential prognostic value supports the integration of dermatological assessment into comprehensive diabetes care. However, due to methodological limitations, these findings should be interpreted as associative rather than causal, and prospective studies are warranted to confirm their predictive significance. Full article

Retinal laser therapy has been a mainstay for treating proliferative diabetic retinopathy, retinal vascular disease, and retinal breaks since 1961. However, conventional millisecond photocoagulation can cause permanent scarring and procedure discomfort, motivating the development of damage-sparing approaches that preserve the neurosensory retina. Clinically, panretinal photocoagulation remains effective for proliferative disease but trades off peripheral visual field and night vision. This review synthesizes development, mechanisms, and clinical evidence for laser modalities, including short-pulse selective retinal therapy (SRT), subthreshold diode micropulse (SDM), and pattern-scanning photocoagulation. We conducted a targeted narrative search of PubMed/MEDLINE, Embase, Web of Science, and trial registries (1960–September 2025), supplemented by reference list screening. We prioritized randomized/prospective studies, large cohorts, systematic reviews, mechanistic modeling, and relevant preclinical work. Pulse duration is the primary determinant of laser–tissue interaction. In the microsecond regime, SRT yields retinal pigment epithelium (RPE)-selective photodisruption via microcavitation and uses real-time optoacoustic or OCT feedback. SDM 100–300 µs delivers nondamaging thermal stress with low duty cycles and titration-based dosing. Pattern-scanning platforms improve throughput and tolerance yet remain destructive photocoagulation. Feedback-controlled SRT shows anatomic/functional benefit in chronic central serous chorioretinopathy and feasibility in diabetic macular edema. SDM can match threshold macular laser for selected DME and may reduce anti-VEGF injection burden. Sub-nanosecond “rejuvenation” lasers show no overall benefit in intermediate AMD and may be harmful in specific phenotypes. Advances in delivery, dosimetry, and closed-loop feedback aim to minimize collateral damage while retaining therapeutic effect. Key gaps include head-to-head trials (SRT vs. PDT/SDM), standardized feedback thresholds across pigmentation and devices, and long-term macular safety to guide broader clinical adoption. Full article

Diabetic retinopathy (DR) is a serious complication of diabetes, leading to vision loss worldwide. The prevalence of DR has increased in recent decades. To understand the pathophysiology of DR, various experimental models have been developed and used. In this review article, we first outline what is currently known of the general pathology of DR, including the mechanisms involved in hyperglycemia, vascular dysfunction, retinal ischemia, retinal inflammation, and retinal degeneration. We next summarize various pathologies detected in experimental models in vivo, such as in chemically and genetically induced murine, rat, and monkey models, surgical methods in larger animals like cats, and a novel murine DR model using occlusion of the carotid artery under early diabetic conditions. A general overview of the in vitro models, including cell monocultures, co-cultures, and 3D models, is also provided. This current summary enables further research to obtain a more thorough understanding of DR pathogenesis and develop appropriate treatment measures. Full article

Objective: The aim of this study was to assess the efficacy of laser photocoagulation (LPC) combined with anti-vascular endothelial growth factor (VEGF), in comparison with routine LPC monotherapy, in the treatment of retinopathy of prematurity (ROP). Methods: This retrospective study included data from 142 eyes treated according to the standard criteria of the Early Treatment for Retinopathy of Prematurity (ETROP). Group A patients had received LPC alone, and Group B had received anti-VEGF therapy followed by routine LPC. Group B was further categorized into two subgroups: Groups B1 and B2 had received bevacizumab and ranibizumab, respectively. Data collected included ROP stage, gestational week, postmenstrual week, birth weight, number of laser spots and sessions. Results: Group B required significantly fewer laser spots than was the case with Group A (Group A: 583.0 ± 350.72, Group B: 274.9 ± 124.77, p < 0.0001). The number of LPC sessions differed significantly between the groups (Group A: 1.8 ± 1.28, Group B: 1.2 ± 0.45, p = 0.0003). Conclusions: Combining anti-VEGF therapy with routine LPC reduced the number of laser spots required. This approach offers an effective treatment strategy for managing severe ROP, potentially reducing long-term complications associated with extensive laser use. Full article

Diabetic retinopathy (DR) is a leading cause of vision loss globally and represents one of the most common microvascular complications of diabetes. In addition to metabolic disturbances associated with hyperglycemia, oxidative stress has emerged as a critical contributor to the onset and progression of DR. Oxidative stress, defined as an imbalance between the production of reactive oxygen species (ROS) and antioxidant defense mechanisms, leads to cellular injury, inflammation, and increased vascular permeability. In the diabetic retina, excessive ROS production promotes endothelial cell apoptosis, breakdown of the blood-retinal barrier (BRB), and induction of angiogenic factors such as vascular endothelial growth factor (VEGF). This review provides a comprehensive overview of the pathophysiology of DR, focusing on the molecular mechanisms of oxidative stress. Relevant studies were identified through a structured search of PubMed, Web of Science, and Scopus (2000–2025) using terms such as ‘diabetic retinopathy’, ‘oxidative stress’, and ‘antioxidants’. We explore current knowledge on oxidative stress-related biomarkers and therapeutic strategies targeting oxidative damage, including antioxidant compounds and mitochondrial protective agents. Recent findings from both experimental and clinical studies are summarized, highlighting the translational potential of oxidative stress modulation in DR management. Finally, future research directions are discussed, including biomarker standardization, personalized medicine approaches, and long-term clinical validation of antioxidant-based therapies. A deeper understanding of oxidative stress may offer valuable insights into novel diagnostic and therapeutic strategies for DR. Full article