Search Results (525)

Background/Objectives: This retrospective cohort study compared hospitalization and follow-up rates in patients with newly diagnosed proliferative diabetic retinopathy (PDR) versus those without prior diabetic retinopathy (DR) screening. Methods: Using TriNetX, a global electronic health record database, 57,964 patients aged ≥ 40 years with type 2 diabetes and newly diagnosed PDR without diabetic macular edema (DME) requiring panretinal photocoagulation or intravitreal injection were included. Patients were stratified based on the presence or absence of prior DR screening in the last 5 years and balanced using propensity score matching (PSM). Primary outcomes included 30-, 60-, and 90-day hospitalization rates and repeat ophthalmic follow-up as estimated using repeat PDR diagnosis codes and repeat retinal imaging codes, including OCT, fundus photography, and fluorescein angiography. Results: Of 57,964 patients, 25,003 had no prior DR screening and 32,961 had prior DR screening. After matching, 19,316 patients were included per cohort. Patients without known DR screening had significantly higher hospitalization rates at 30 days (RR = 1.78, 95% CI 1.67–1.89), 60 days (RR = 1.59, 95% CI 1.51–1.67), and 90 days (RR = 1.51, 95% CI 1.44–1.58), and lower repeat ophthalmic visits by PDR codes at 30 days (RR = 0.458, 95% CI 0.440–0.476), 60 days (RR = 0.450, 95% CI 0.437–0.463) and 90 days (RR = 0.420, 95% CI 0.408–0.432) or by repeat retinal imaging codes at 30 days (RR = 0.450, 95% CI 0.423–0.478), 60 days (RR = 0.394, 95% CI 0.377–0.411), and 90 days (RR = 0.381, 95% CI 0.366–0.396) (all p < 0.0001). Conclusions: Absence of known prior DR screening in PDR patients is associated with higher hospitalization risk and reduced ophthalmic follow-up, suggesting that a lack of screening indicates broader gaps in healthcare engagement and disease control. Tailored strategies are needed to prevent vision loss as well as systemic complications. 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: Branch retinal vein occlusion (BRVO) represents a segmental retinal ischemic disorder characterized by localized oxidative–inflammatory activation. While redox-driven cytokine responses have been described in central retinal vein occlusion, their role in BRVO-specific macular edema and treatment responsiveness remains unclear. This study investigated whether novel redox-related inflammatory mediators in the aqueous humor are associated with disease severity and structural response to anti-vascular endothelial growth factor (VEGF) therapy in BRVO. Methods: Aqueous humor samples were collected from 30 treatment-naïve patients with BRVO and 19 control patients. Levels of VEGF and the novel redox-related inflammatory factors FMS-related tyrosine kinase 3 ligand (Flt-3L), fractalkine, CXCL-16, and endocan-1 were measured by suspension array, and the severity of macular edema was evaluated by measuring central macular thickness and neurosensory retinal thickness (TNeuro) by spectral-domain optical coherence tomography. Therapeutic response was assessed one month after intravitreal ranibizumab injection (IRI). Results: Aqueous levels of VEGF, Flt-3L, and endocan-1 were significantly higher in the BRVO group, and levels of Flt-3L, CXCL-16, and endocan-1—markers associated with oxidative endothelial damage and leukocyte recruitment—correlated significantly with each other and with aqueous flare values. Notably, baseline Flt-3L levels significantly correlated with the reduction in TNeuro, suggesting that this redox-sensitive signaling molecule is a potential biomarker for treatment sensitivity. Conclusions: These findings suggest that novel inflammatory factors, potentially driven by oxidative-nitrosative stress, play a pivotal role in the pathophysiology of BRVO. Baseline Flt-3L may serve as a predictive biomarker for structural responsiveness to anti-VEGF therapy in BRVO, suggesting that oxidative–inflammatory signaling contributes not only to disease severity but also to therapeutic heterogeneity. Full article

Background: Retinal vascular diseases, including neovascular age-related macular degeneration (nAMD), diabetic macular edema (DME), retinal vein occlusion (RVO), and myopic choroidal neovascularization (mCNV), often require repeated intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy. Although ranibizumab is well established, long-term affordability remains challenging. Objective: To compare the functional, anatomical, treatment-burden, and safety outcomes of biosimilar ranibizumab (Ranieyes) and innovator ranibizumab (Lucentis/Accentrix) in routine clinical practice. Methods: This multicenter retrospective comparative study included 4997 eyes from 3577 patients treated across five tertiary eye-care centers in India. The biosimilar group comprised 2543 eyes from 1812 patients (10,893 injections), and the innovator group comprised 2454 eyes from 1765 patients (10,136 injections). Eligible indications were nAMD, DME, BRVO, CRVO, mCNV, and an exploratory miscellaneous preoperative adjunct subgroup. BCVA (logMAR), central subfield thickness (CST; µm), injection burden, and ocular/systemic adverse events were assessed over 24 months. Results: Both groups showed early improvement in BCVA and CST across the major disease categories, followed by long-term stabilization. Between-group differences were generally small, not sustained over follow-up, and of limited clinical magnitude. Serious ocular and systemic adverse events were rare in both groups, and no new safety signal emerged. Conclusions: In this large real-world cohort, the biosimilar ranibizumab Ranieyes showed outcomes broadly comparable to innovator ranibizumab across the major retinal disease subgroups, although these findings should be interpreted as observational comparative evidence rather than formal proof of equivalence. 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

Background/Objectives: Retinal vein occlusion (RVO) commonly causes vision loss from macular edema (ME). OCT biomarkers (IRF, SRF, HRF, and ELM/EZ disruption) inform prognosis and treatment but are rarely quantified routinely due to time burden and interobserver variability. We aimed to validate a deep-learning algorithm for automated detection and quantification of key OCT biomarkers in RVO-ME versus expert assessment. Methods: In this retrospective single-center study, 93 eyes with RVO-ME imaged with spectral-domain OCT were analyzed. The AI quantified IRF/SRF volumes, ELM/EZ interruption, and HRF counts. Two masked expert clinicians provided reference evaluations. Performance and agreement were assessed using ROC AUC, Cohen’s kappa, intraclass correlation coefficient (ICC), Pearson correlation, and Bland–Altman analysis. Image-quality metrics (foveal centration and retinal layer segmentation) were recorded. Results: The AI showed high diagnostic performance (AUC: SRF 0.969; ELM 0.871; EZ 0.958) and substantial-to-almost-perfect agreement (kappa: SRF 0.807; ELM 0.788; EZ 0.914). HRF quantification correlated strongly with experts (r = 0.89, p < 0.001), with very good agreement (ICC = 0.87) and minimal bias. Image-quality accuracy exceeded 98% for foveal centration and layer segmentation. Conclusions: This AI software enables reliable, rapid automated assessment of major OCT biomarkers in RVO-ME, supporting streamlined personalized management; prospective studies should confirm longitudinal monitoring and treatment-guidance value. Full article

Purpose: To determine the optimal treatment sequence for combination therapy using intravitreal faricimab (IVF) and direct photocoagulation (PC) in eyes with non-center-involved diabetic macular edema (DME). Methods: This retrospective study included 35 eyes with focal DME treated with IVF and PC targeting microaneurysms (MAs). Treatment success was defined as resolution of focal edema, indicated by disappearance of the white area (WA) on optical coherence tomography. Eyes were assigned to a PC-IVF group (initial PC followed by IVF if edema persisted after 2 months; n = 20) or an IVF-PC group (initial IVF followed by PC for residual edema; n = 15). Additional PC was performed every 2 months as needed. Results: Cumulative success rates at 2, 4, and 6 months were 35.0%, 70.0%, and 90.0% in the PC-IVF group and 60.0%, 93.3%, and 100% in the IVF-PC group, respectively. Macular volume significantly decreased at all time points in the IVF-PC group (all p < 0.01), whereas a significant reduction was observed only after 6 months in the PC-IVF group (p < 0.01). The number of MAs and the extent of edema were significantly reduced after 2 months in both groups, with greater reductions in the IVF-PC group (p < 0.05). The number of laser shots required for initial PC was significantly lower in the IVF-PC group (p < 0.0001), and the mean number of PC sessions was also reduced (0.6 vs. 1.8). In the PC-IVF group, baseline edema size was significantly smaller in successfully treated eyes (p < 0.001). Conclusions: Initiating treatment with IVF prior to PC may be advantageous in focal DME, particularly in eyes with larger edema, enabling faster anatomical improvement and reducing the need for laser treatment. Direct PC alone may be sufficient for small focal lesions with limited edema, supporting an individualized treatment strategy. Full article

Diabetic retinopathy (DR) is a common cause of vision loss in diabetes, and it often progresses without early symptoms. DR reflects injury of the retinal neurovascular unit (NVU), which includes neurons, Müller glia, astrocytes, endothelial cells, pericytes, and immune cells. Chronic hyperglycemia drives oxidative stress, advanced glycation end products–receptor for advanced glycation end products (AGE–RAGE) signaling, mitochondrial injury, and low-grade inflammation. These changes disrupt endothelial junctions, promote leukostasis, weaken pericyte support, increase basement membrane thickening, and lead to capillary dropout and hypoxia. Hypoxia-related signaling increases anti-vascular endothelial growth factor (VEGF) activity, which raises vascular leakage and supports neovascular disease. Glial stress and microglial activation add cytokines and reactive oxygen species, and neural dysfunction can appear early and can weaken neurovascular coupling. Modern diabetes care changes the short-term risk landscape because potent therapies can lower HbA1c quickly. Large and rapid HbA1c reductions can trigger early worsening of diabetic retinopathy (EWDR), mainly in patients with high baseline HbA1c and moderate-to-severe baseline DR. Semaglutide’s retinopathy complication signal in SUSTAIN-6 fits an EWDR-like pattern that tracks with rapid glycemic improvement in vulnerable eyes. In parallel, surgery adds acute stress, inflammation, glucose swings, hemodynamic shifts, and medication interruptions. These factors can worsen microvascular instability during recovery. Current perioperative guidelines and regulatory recommendations describe glucose targets and medication safety considerations, including preoperative interruption of SGLT2 inhibitors to reduce euglycemic ketoacidosis risk; however, the retina-specific implications of these measures remain indirect. This review summarizes current evidence linking NVU biology, EWDR risk, and perioperative diabetes-related factors. It discusses how these factors may interact in patients with diabetes and how they may influence retinal outcomes. The review is intended to synthesize current evidence and mechanistic interpretations rather than to provide formal clinical practice recommendations. Full article

Objectives: The aim of this study was to analyze the association between cardiovascular risk factors such as glycated hemoglobin (HbA1c), low-density lipoprotein cholesterol (LDL-C), hypertension, overweight, and smoking and longitudinal anatomical and functional changes in diabetic macular edema (DME) during intravitreal therapy. Materials and Methods: This is a retrospective, observational, descriptive study conducted on a sample of 318 patients with DME associated with some degree of diabetic retinopathy (DR). They were treated with aflibercept, ranibizumab, and/or dexamethasone, assessing anatomical and functional outcomes through visual acuity, retinal thickness, and macular volume. Simultaneously, serum HbA1c and LDL-C levels, blood pressure, body mass index (BMI) and tobacco use were measured at baseline, 6, and 12 months to determine their association with treatment response using linear mixed models. Results: Of the variables analyzed in this study, HbA1c and degree of retinopathy were significantly associated with greater retinal thickness over time. Likewise, we found that, compared with aflibercept, dexamethasone intravitreal treatment was associated with greater retinal thickness over time. Concerning visual acuity, we found an inverse relationship with age, tobacco use and degree of retinopathy. Associations between outcomes and the initial intravitreal agent were observed; however, these findings should be interpreted cautiously. Conclusions: This study was consistent with previous research suggesting an association between glycemic control and DME response and progression. It also highlighted the importance of degree of retinopathy and intravitreal treatment in diabetic macular edema progression. Treatment-related findings represent exploratory associations and should not be interpreted as evidence of comparative effectiveness. Full article

Werner syndrome is a rare autosomal recessive premature aging syndrome characterized by its development after puberty and death in patients in their 50s due to cancer or atherosclerotic disease. Early diagnosis can improve the management of disease, quality of life and prolong the lifespan of patients with Werner syndrome. Ophthalmologists should include Werner syndrome in the general work-up in patients with bilateral early-onset cataracts. We present a case of Werner syndrome with initial signs of juvenile cataracts. The patient had a high-pitched voice, a bird-like face and progeroid hair. We performed routine ophthalmological examinations including slit-lamp examinations, fundus examinations, and optical coherence tomography, and genetic analysis. The patient had plateau iris and pachychoroid-like features in addition to bilateral cataracts. The gene analysis revealed compound heterozygosity of Mut4 and Mut25 in WRN and the patient was diagnosed with Werner syndrome. After cataract surgeries, his visual acuities were improved. Additionally, we performed a thorough literature review to better understand the previously reported ocular manifestations in patients with Werner syndrome. Full article

Diabetic retinopathy (DR) is a leading cause of vision loss worldwide and represents a complex neurovascular complication of diabetes mellitus driven by chronic hyperglycemia. Increasing evidence identifies oxidative stress—defined as an imbalance between reactive oxygen species (ROS) production and antioxidant defenses—as a central pathogenic mechanism linking metabolic dysregulation to retinal injury. The retina is particularly vulnerable to oxidative damage due to its high metabolic demand, elevated oxygen consumption, and abundance of polyunsaturated fatty acids. Hyperglycemia activates multiple interconnected biochemical pathways, including the polyol and hexosamine pathways, protein kinase C signaling, advanced glycation end-product formation, and lipid peroxidation, all of which converge on excessive ROS production and mitochondrial dysfunction. Growing attention has focused on oxidative stress biomarkers as tools to characterize DR severity and progression. Elevated systemic markers of lipid, protein, and DNA oxidation, together with impaired antioxidant capacity, correlate with disease stage, while oxidative biomarkers detected in aqueous and vitreous humor reflect localized retinal injury. Importantly, oxidative stress biomarkers are also associated with functional outcomes, including best-corrected visual acuity and diabetic macular edema. Integration of systemic and ocular oxidative biomarkers with clinical staging may improve risk stratification and support personalized therapeutic strategies in DR. Full article

Background: Sutureless intrascleral intraocular lens (IOL) fixation using the Yamane technique is an option for visual rehabilitation in eyes without capsular support. The aim of this study is to report long-term visual outcomes and clinical predictors in consecutive real-world cohorts, a topic addressed by very few previous studies. Methods: This was a single-center, single-surgeon consecutive case series including 87 eyes of 85 patients who underwent Yamane SFIOL for aphakia or lens/posterior chamber IOL ectopia, with at least 12 months of follow-up. BCVA was measured using a Snellen chart and recorded in decimal notation. To identify predictors of postoperative BCVA, univariable screening was first performed, followed by a clinically driven multivariable linear mixed-effect regression. Results: Mean age was 68.2 ± 11.4 years, and 70.6% were male. Median follow-up was 26.5 months. Median BCVA improved from 0.2 ± 0.2 (range 0.001–1.0) preoperatively to 0.9 ± 0.2 (range 0.2–1.0) postoperatively (p < 0.001). Surgical indication and preoperative comorbidity burden were not linked to postoperative BCVA. In the multivariable analysis, older age (B = −0.005, p = 0.027), macular edema (B = −0.242, p = 0.035), and prior silicone oil removal (B = −0.237, p = 0.046) independently predicted lower postoperative BCVA. Conclusions: Yamane SFIOL provides significant long-term visual improvement, with outcomes mainly determined by patient age and retinal status. This study offers new data on functional outcomes and clinically relevant predictors in a consecutive real-world cohort, supporting the reliability and long-term efficacy of sutureless scleral IOL fixation. Full article

Retinal vein occlusion (RVO) is a common vascular disease that leads to vision loss due to macular edema (ME). This study investigated the role of autotaxin (ATX), a lysophospholipase D, in the pathogenesis of RVO. In mice, RVO was induced by intravenous administration of rose bengal followed by laser irradiation of retinal veins. ATX expression in the retina was evaluated using immunohistochemistry. Intravitreal ATX was administered, and retinal changes were assessed using fluorescence angiography and optical coherence tomography (OCT). In human retinal microvascular endothelial cells (HRMECs), intercellular barrier function was evaluated using transepithelial electrical resistance (TEER). In the murine RVO model, the ATX inhibitor HA130 was administered intravitreally, and retinal thickness was measured and compared using OCT. ATX expression was increased in retinal vessels in the RVO model. Intravitreal administration of ATX induced retinal edema and serous retinal detachment (SRD). ATX significantly disrupted the barrier integrity of HRMECs and promoted the expression of vascular endothelial growth factor (VEGF), which was ameliorated by HA130. Intravitreal administration of HA130 significantly reduced retinal thickening caused by retinal edema secondary to RVO and the elevated expression of intercellular adhesion molecule (ICAM)-1 in the retina. These findings suggest that ATX plays a critical role in RVO-induced ME by disrupting endothelial barrier integrity, potentially through the upregulation of VEGF in retinal endothelial cells and subsequent ICAM-1 upregulation in the retina. Full article

Background/Objectives: The PHOTON trial established the efficacy of aflibercept 8 mg using fixed-interval dosing in treatment-naïve patients; however, real-world evidence regarding pro re nata (PRN) regimens in switch cases remains limited. This pilot study evaluated the short-term efficacy and safety of switching to aflibercept 8 mg with PRN dosing in eyes with DME. Methods: This retrospective study included 20 eyes from 12 patients with DME who switched to aflibercept 8 mg and were followed for 6 months. Patients received initial induction doses (1–3 injections based on predetermined anatomical and functional criteria) followed by PRN dosing based on clinical findings. Primary outcomes were changes in best-corrected visual acuity (BCVA) and central retinal thickness (CRT). Treatment intervals and injection frequency were also analyzed. Results: Mean logMAR BCVA was maintained from baseline (0.242 ± 0.252) throughout the follow-up period: 0.164 ± 0.218 at 1 month, 0.138 ± 0.241 at 2 months, 0.145 ± 0.204 at 3 months, 0.143 ± 0.181 at 4 months, 0.149 ± 0.166 at 5 months, and 0.180 ± 0.224 at 6 months. No statistically significant changes in BCVA from baseline were observed at any time point. Mean CRT decreased from baseline (369.6 ± 138.3 μm) at all follow-up time points: 251.5 ± 82.1 μm at 1 month, 269.1 ± 104.5 μm at 2 months, 255.8 ± 67.8 μm at 3 months, 275.2 ± 76.6 μm at 4 months, 301.4 ± 81.2 μm at 5 months, and 302.7 ± 86.8 μm at 6 months. Statistically significant reductions in CRT were observed at 1 through 4 months (1 month: p = 0.000010; 2 months: p = 0.000243; 3 months: p = 0.000035; 4 months: p = 0.000597), whereas the reductions at 5 months (p = 0.0317) and 6 months (p = 0.0424) were not statistically significant. The mean number of injections over 6 months was 1.45 ± 1.05 (median 1; range 1–4), with 70% of eyes achieving treatment intervals ≥ 4 months. Five eyes (25%) required only the switching dose with no additional treatment during follow-up. No intraocular inflammation or retinal vasculitis was observed. Conclusions: Switching to aflibercept 8 mg with PRN dosing provided sustained anatomical improvement and maintained visual acuity in DME, with one quarter of the cases maintaining these outcomes with only a single additional injection. These real-world findings from a pilot study suggest that the PRN approach appears feasible and effective in real-world practice, offering a practical treatment option that may help reduce treatment burden while maintaining disease control. Full article

Background/Objectives: Hyperreflective foci (HRF) are supportive optical coherence tomography (OCT) imaging biomarkers that have been examined for their association with disease progression and severity in various retinal disorders. The accurate identification and segmentation of these tiny structures of lipid extravasation remain complicated because of their small size, class imbalance, similarity in the reflectivity patterns with the surrounding structures and imaging artifacts. While U-Net-based models have promised exceptional results for medical image segmentation, optimal architectural settings and suitable preprocessing methods for HRF detection remain unclear. Methods: This research assessed optimal settings for U-Net-based models for HRF segmentation by evaluating standard U-Net and attention U-Net under different preprocessing regimes. Attention U-Net employed Z-score normalization and contrast-limited adaptive histogram equalization (CLAHE) enhancement with soft dice loss. The standard U-Net was trained on OCT images with CLAHE using focal Tversky loss. A total of 435 fovea-centered OCT B scans with the corresponding, consensus-annotated HRF masks were utilized for this research. Results: The standard U-Net outperformed attention U-Net with a dice score of 0.5207, an AUC of 0.8411, and a recall of 0.6439 on raw OCT images. The attention U-Net with preprocessing (dice: 0.5033, AUC: 0.6987, recall: 0.5391) demonstrated satisfactory performance. The results showed that the U-Net model with CLAHE and focal Tversky loss improved recall by 19.4% relative to the attention U-Net, and this corresponds roughly to a 23% relative decline in false negatives. This indicates increased sensitivity in identifying HRF regions. Conclusions: The best-performing configuration using U-Net-based architectures for segmentation of HRFs combines the standard U-Net model with CLAHE and focal Tversky loss for handling class imbalance. This approach yields relatively higher sensitivity, indicating that the standard U-Net model delivers a simple and robust framework for automated HRF segmentation on the evaluated dataset, promising further validation in broader clinical datasets. Full article