Search Results (163)

The correct classification of retinal lesions in retinal fundus images is important for supporting the analysis of diabetic retinopathy and age-related macular degeneration. State-of-the-art methods for this task are often based on black-box deep learning architectures that, despite their high performance, pose significant interpretability challenges, incur high computational costs, and lack computational interpretability at the feature-decision level. In this paper, a method based on surrogate-optimized features extracted by regular expressions is proposed for the classification of two retinal lesion categories (Drusen and Cotton Wool Spots). The method uses a compact and computationally interpretable row-by-row and column-by-column regular expression feature extractor together with a two-phase surrogate search over its discrete hyperparameters. Across 100 independent stratified executions under the repeated patch-level benchmark, the proposed method achieved a mean MCC of $0.7829\pm 0.0448$, a mean accuracy of $0.9008\pm 0.0217$, and a mean F1 score of $0.8529\pm 0.0294$. The best execution reached an MCC of $0.8433$, an accuracy of $0.9286$, and a macro F1 score of $0.8966$, which was the highest result among the evaluated baselines within that same benchmark. Additional source–image disjoint grouped analyses were carried out as leakage-aware robustness checks under stricter source–image separation and to examine validation overfitting. Together, these analyses support the usefulness of the compact run-based descriptor under the present experimental conditions, while indicating that the two-phase search should be interpreted as a practical hyperparameter selection heuristic rather than as a statistically superior search strategy. Full article

Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss worldwide. Geographic atrophy (GA) is an advanced, currently incurable stage of non-exudative AMD and is characterized by progressive atrophy of the retinal pigment epithelium and outer retina, resulting in substantial visual impairment. Optical coherence tomography (OCT) has revolutionized the diagnosis and monitoring of AMD by enabling in vivo visualization of retinal microstructure and identification of imaging biomarkers associated with progression to late-stage disease. Improved understanding of these lesions may clarify disease pathogenesis and inform the development of new therapeutic strategies and clinical trial endpoints. This review summarizes OCT-based biomarkers reported as predictors of progression to late atrophic forms of AMD, with emphasis on early atrophic changes that precede GA. Full article

Optical coherence tomography plays a critical role in diagnosing retinal diseases, yet automated deep learning classification is hindered by severe class imbalance in which rare pathologies are underrepresented and frequently misclassified, a limitation rarely exposed by the aggregate metrics reported in most prior work. We investigate a targeted intermediate-supervision framework, in which a secondary classifier head is attached to mid-level backbone features and jointly optimized with the primary classifier using inverse-frequency weighted loss. Unlike conventional deep supervision, which is primarily aimed at optimizing stability, the proposed formulation is used here to improve minority-class representation under severe OCT class imbalance. The method is evaluated on ResNet-18, ResNet-50, EfficientNet-B0, and ViT-B/16 using a four-class OCT dataset, with full per-class metrics reported across a systematic ablation of the auxiliary weight λ. EfficientNet-B0 achieved the best performance at λ = 0.3, attaining 97.78% accuracy, an AUROC of 0.995, and a Drusen F1-score of 93.51%, a gain of 2.64 percentage points over the unweighted baseline. Vision Transformers showed greater sensitivity to background padding artifacts than convolutional models. Grad-CAM and Attention Rollout analyses confirm that auxiliary supervision improves the localization of clinically relevant retinal structures, supporting its potential for interpretable, class-balanced automated OCT diagnosis. Full article

Objectives: To assess the association of structural biomarkers derived from optical coherence tomography (OCT) and choriocapillaris (CC) flow information with point-wise retinal sensitivity (PWS) measured by microperimetry (MP) in intermediate age-related macular degeneration (iAMD). Methods: Patients with iAMD received imaging with spectral-domain (SD)-OCT (Spectralis, Heidelberg Engineering) and OCT-angiography (OCT-A) (PLEX Elite 9000, ZEISS). In addition, MP examinations in photopic setting (MP-3, NIDEK) and mesopic background illumination (MAIA2, ICare) were performed. The thickness of the ellipsoid-zone (EZ) and the outer nuclear layer (ONL), as well as the volume of drusen and HRF, were segmented using deep-learning (DL)-based approaches. CC flow deficit percentage (FD%) was extracted from OCT-A slabs using a novel binarization method. Semiautomatic co-registration of MP examinations, OCT-A slabs, and OCT volumes was performed. Three exploratory models were calculated using multivariable mixed-effects models: (1) structure–function (SF) using structural OCT biomarkers, (2) flow–function (FF) utilizing OCT-A derived flow information, and (3) structure–flow–function (SFF) incorporating both OCT and OCT-A data. Model performance was evaluated using AIC and BIC criterion. Results: 19 eyes of 19 patients were evaluated, totalling 3297 MP-stimuli, 1873 B-scans, and 19 OCT-A slabs. Mean (SD) age was 76 (7) years, and sensitivity was 26.0 (3.36) dB in the MP-3 and 22.42 (3.64) dB in the MAIA2. Mesopic MAIA2 examinations showed significantly lower PWS values (−3.56 to −3.63 dB; p < 0.001). Drusen and HRF volume decreased PWS (−0.6 [95% CI: −1.04; −0.16] dB/nL; p = 0.007 and −9.56 [95% CI: −12.86; −6.26] dB/nL; p < 0.001), while ONL was positively associated with PWS (0.06 [0.05; 0.07] at an eccentricity of 5.2°; p < 0.001) in the SF model. CC FD% was not significantly associated with PWS in the FF and the SFF model (p > 0.05 in both cases). In the SFF model drusen volume (−1.69 [95% CI: −2.09; −1.29] dB/nL; p < 0.001), EZ (0.04 [95% CI: 0.02; 0.06] dB/µm; p < 0.001), and ONL thickness (0.03 [95% CI: 0.02; 0.04] dB/µm; p < 0.001) were significant predictors for PWS. The SF model exhibited the lowest AIC and BIC indicating best model performance. Conclusions: Structural parameters derived from SD-OCT such as HRF, drusen volume, and outer retinal layer thickness may be more closely associated with PWS, with CC FD% as an OCT-A-derived metric contributing limited additional explanatory benefit in cross-sectional analyses. Full article

Age-related macular degeneration (AMD) remains the leading cause of irreversible central vision loss in the elderly. Increasing attention has been directed toward lipid metabolism as a potential contributor to disease onset and progression. The overlap between AMD and atherosclerosis—particularly regarding lipid accumulation, endothelial dysfunction, and chronic inflammation—has prompted interest in lipid-lowering therapies. This narrative review synthesizes the clinical evidence published between 2020 and 2025 on the potential role of statins and fenofibrate in AMD risk modification and disease progression. A structured literature search was conducted in PubMed, Scopus, and Web of Science using combined MeSH and free-text terms related to lipid-lowering agents and AMD. Human studies evaluating clinical incidence or progression outcomes were considered alongside contextual evidence from prior evidence syntheses. Overall, findings remain heterogeneous. Most studies did not demonstrate a consistent association between statin therapy and AMD incidence or progression in unselected populations. However, selected reports suggested a potential delay in dry AMD onset or slower disease progression among patients receiving prolonged or higher-intensity statin treatment. Evidence regarding fenofibrate was more limited and heterogeneous, with only a tentative protective signal observed in adherent users, particularly for non-exudative AMD. The current literature does not support lipid-lowering therapy as a universal preventive strategy for AMD. Nonetheless, subgroup-specific benefits cannot be excluded, especially in early disease stages or metabolically high-risk populations. Further well-designed prospective and randomized studies are needed to clarify therapeutic relevance and identify the patients who are most likely to benefit. Full article

Background/Objectives: Pachydrusen are a drusen subtype associated with the pachychoroid disease spectrum; however, their long-term natural history and pathophysiological significance remain unclear. We investigated 5-year morphological and topographic changes in pachydrusen using diagnostic criteria incorporating late-phase indocyanine green angiography (ICGA) hyperfluorescence. Methods: This retrospective observational study included fellow eyes with pachydrusen from patients with unilateral neovascular age-related macular degeneration. Pachydrusen were defined as sub-retinal pigment epithelium (RPE) deposits ≥ 125 µm in size with corresponding hyperfluorescence on late-phase ICGA. Lesion number, size, and spatial distribution (ETDRS grid and quadrant-based classification) were evaluated at baseline and 5 years. The incidence of macular neovascularization (MNV) and its colocalization with pachydrusen were assessed. Results: Among 57 fellow eyes with pachydrusen, incident MNV developed in 8 eyes (14.0%) during follow-up; the mean time to onset was 25.6 ± 16.3 months. No clear colocalization between pachydrusen and incident MNV was observed. Nineteen eyes completed the 5-year follow-up period. Pachydrusen were predominantly located outside the 6000 µm ETDRS grid at baseline (63.4%) and 5 years (66.3%), significantly exceeding the expected proportion based on the area ratio (p < 0.001). The lesions were most frequently observed in the superotemporal quadrant (52.6%). Over 5 years, 19.8% of the lesions increased in size, 67.2% remained stable, and 12.9% regressed; none of the regressed lesions were accompanied by RPE atrophy. Conclusions: Pachydrusen, defined as late-phase ICGA hyperfluorescence, was predominantly distributed outside the ETDRS grid with a superotemporal predilection and could increase or decrease over a 5-year follow-up period. No colocalization with MNV was observed, and no accompanying RPE atrophy after pachydrusen regression was identified, suggesting that late-phase ICGA–hyperfluorescent pachydrusen may represent a pathophysiology distinct from that of soft drusen. Full article

Background and Objectives: Optic disc drusen (ODD) are deposits in the optic nerve head that can look like true swelling, and in some patients, slowly damage the optic nerve and cause visual field loss. We aimed to identify which eyes are most likely to worsen over time using common clinic tests. Methods: We studied 131 adults with OCT-confirmed ODD who also had OCT-angiography (a scan that measures small blood vessels around the optic nerve) and repeated visual field tests over at least 18 months. We measured (1) the size of the drusen (maximum drusen height), (2) blood vessel density around and inside the optic nerve, and (3) change in visual field performance over time. “Fast progression” was defined as visual field worsening of ≥0.5 dB per year. Results: Eyes with superficial ODD had larger drusen than buried ODD (382.6 ± 110.9 vs. 247.2 ± 92.8 µm; p < 0.001) and more frequent visual field defects (78.6% vs. 58.7%; p = 0.02). When blood vessel density around the optic nerve was low, fast progression was much more common (52.3%) than in the middle (16.3%) or highest groups (13.6%; p < 0.001). In the adjusted model, fast progression was more likely with superficial ODD (OR 6.3) and larger drusen (OR 2.0 per 100 µm), and less likely when the vessel density was higher (OR 0.8 per 1% increase). Adding the vessel measurements improved the prediction accuracy (AUC 0.8 → 0.9; p = 0.011). Conclusions: Combining drusen size and blood vessel measurements helps identify ODD patients at higher risk of faster visual field loss and may guide closer follow-up. Full article

Background/Objective: To evaluate the association between optical coherence tomography angiography (OCTA)-derived choriocapillaris flow (CCflow), retinal vascular fractal dimension (FD), and drusen burden in eyes with dry age-related macular degeneration (AMD). Methods: This retrospective study included 113 eyes from 73 patients with dry AMD. Eyes were classified into large and small drusen groups based on median drusen area. OCTA-derived CCflow and FD indices of the superficial and deep capillary plexuses were analyzed. Patient-level clustered analyses were performed using linear mixed-effects and generalized estimating equation models to account for inter-eye correlation. Results: Eyes with large drusen showed significantly lower CCflow compared with those with small drusen (p < 0.001), whereas FDsup did not differ between groups, and FDdeep demonstrated only a near-significant trend toward higher values. CCflow was moderately and negatively correlated with drusen area (ρ = −0.452, p < 0.001), whereas FDdeep showed no significant correlation in unadjusted analyses (ρ = 0.137, p = 0.148). In patient-level age-adjusted multivariable models accounting for inter-eye dependency, CCflow remained independently associated with drusen burden, while FDdeep demonstrated an independent association only after adjustment for age. Conclusions: Reduced CCflow is independently associated with increased drusen burden in dry AMD. FD metrics provide complementary descriptive information regarding microvascular remodeling but do not function as independent biomarkers. CCflow may serve as a robust quantitative indicator of early choroidal compromise in dry AMD. Full article

Alagille syndrome (ALGS) is a rare autosomal dominant multisystem disorder characterized by bile duct paucity, congenital heart defects, characteristic facial features, skeletal anomalies, and distinctive ocular findings. Although anterior segment anomalies such as posterior embryotoxon are well recognized, posterior segment involvement has recently gained attention. We present fundus findings in a 2-year-old boy with genetically confirmed Alagille syndrome. Under general anesthesia, fundus examination revealed pink optic discs with blurred margins and drusen-like deposits, absence of the foveal reflex, and mottled hypopigmented and hyperpigmented areas that were consistent with retinal pigment epithelium (RPE) degeneration. Peripheral pigment clumping and RPE atrophy were also observed, while retinal vessels appeared normal. These features are characteristic of pigmentary retinopathy associated with ALGS and highlight the expanding spectrum of posterior segment changes in this condition. Recognition of such findings is essential, as they may contribute to visual impairment and support the systemic diagnosis. Full article

Geleophysic dysplasia (GD) is a rare genetic skeletal disorder belonging to the acromelic group, characterized by short stature, distinctive facial features, thickened skin, and progressive cardiac involvement. We report a case of a 3-year-old boy with GD caused by a heterozygous c.5198G>A variant in the FBN1 gene, presenting with ocular abnormalities. The patient demonstrated coarse facial features, short hands and feet, and a history of mitral valve stenosis requiring mechanical valve replacement. He was referred to the ophthalmology department for evaluation of left eye strabismus and elevated intraocular pressure. Fundus examination revealed a pink optic disc with blurred margins, slightly elevated above the retinal plane, absent foveal reflex, and tortuous vessels, consistent with optic disc drusen on ocular ultrasonography. Photopic negative response (PhNR) testing showed markedly reduced amplitudes in both eyes, indicating retinal ganglion cell dysfunction. Pattern VEP revealed normal P100 latencies in both eyes, with a 30% reduction in amplitude in the left eye, likely related to poorer fixation. This case highlights optic disc drusen and retinal ganglion cell dysfunction as potential ocular manifestations of geleophysic dysplasia, emphasizing the need for comprehensive ophthalmologic evaluation in affected patients. Full article

Dry age-related macular degeneration (AMD) is the leading cause of central vision loss among the elderly, yet no curative treatment exists. While exudative AMD can be managed with anti-vascular endothelial growth factor (VEGF) therapy, dry AMD—accounting for more than 85% of cases—progresses insidiously from drusen accumulation to geographic atrophy (GA). Although the recent U.S. Food and Drug Administration (FDA) approvals of pegcetacoplan and avacincaptad pegol represent major milestones, their therapeutic effects remain modest. This review provides an integrated overview of the molecular and cellular mechanisms underlying dry AMD, highlighting key pathogenic pathways involving oxidative stress, lipid dysregulation, complement activation, mitochondrial impairment, and RPE-specific bisretinoid lipofuscin accumulation. We further summarize mechanistic mouse models that replicate these pathological processes and discuss how each model contributes to understanding the disease. Finally, we review current and emerging therapeutic strategies—including complement inhibitors, visual cycle modulators, and mitochondrial-protective approaches—and outline future directions for translational research. Collectively, this review synthesizes mechanistic insights, disease models, and therapeutic innovation to support the development of targeted and stage-specific interventions for dry AMD. Full article

Background/Objectives: Pigment migration is a key biomarker of progression in age-related macular degeneration (AMD). This study assessed the diagnostic performance of ring aperture Retro mode (RAR) imaging for detecting pigment migration and compared its performance with established multimodal imaging techniques. Methods: This retrospective study included 80 eyes from 61 consecutive patients with AMD who underwent multimodal imaging with color fundus images (CFIs), fundus autofluorescence (FAF), RAR imaging (Mirante, NIDEK), and en face optical coherence tomography (OCT) with B-scans (Cirrus HD-OCT 5000, Zeiss). Two independent retina specialists graded the AMD stage and the presence of pigment migration across modalities. Sensitivity and positive predictive value (PPV) of RAR were calculated using en face OCT as the reference standard. Results: RAR demonstrated high diagnostic performance, with a sensitivity of 94.7% and a PPV of 93.4% relative to en face OCT. RAR frequently identified pigment migration that was not visible on CFI or FAF, particularly in early AMD and in eyes with media opacity. Distinct morphologic patterns—including hyperreflective foci, thickened retinal pigment epithelium, refractile drusen, and cuticular drusen—were consistently identifiable on RAR. In four eyes with geographic atrophy, RAR detected perifoveal pigment redistribution at least six months before foveal involvement was confirmed by OCT and FAF. Conclusions: RAR imaging is a rapid, sensitive, and clinically practical technique for detecting pigment migration in AMD. By complementing en face OCT and enhancing visualization in cases where standard imaging is limited, RAR may strengthen early disease surveillance, support prognostic assessment, and improve multimodal diagnostic workflows in routine practice. Full article

Background/Objectives: Optic disc drusen (ODD) are an under-recognized cause of optic neuropathy, and the impact of structure–function damage on quality of life (QoL) is poorly defined. We compared systemic risk factors, ocular structure–function, and QoL in adults with ODD versus matched controls and identified determinants of impaired vision-related QoL. Methods: In a tertiary clinic, 60 adults with ultrasonography- or OCT-confirmed ODD were age- and sex-matched 1:1 to 60 controls without ODD. Retrospective clinical and imaging data (BCVA, RNFL thickness, standard automated perimetry) were combined with cross-sectional NEI VFQ-25 and EQ-5D-5L scores. Results: ODD patients more often had hypertension (51.7% vs. 31.7%, p = 0.026) and migraine (38.3% vs. 21.7%, p = 0.046). They showed worse BCVA (0.2 vs. 0.1 logMAR, p < 0.001), thinner RNFL (95.3 vs. 103.8 µm, p < 0.001), more depressed mean deviation (−4.7 vs. −1.3 dB, p < 0.001), and more frequent reproducible visual field defects (68.3% vs. 11.7%, p < 0.001). Vision-specific QoL was reduced (VFQ-25 composite 77.3 ± 11.4 vs. 89.7 ± 8.6, p < 0.001) and generic health status lower (EQ-5D utility 0.8 ± 0.1 vs. 0.9 ± 0.1, p < 0.001). In ODD, worse BCVA, more negative mean deviation and lower EQ-5D were independently associated with poorer VFQ-25 (model R² = 0.57), while older age, thinner RNFL and migraine predicted visual field defects. Conclusions: ODD are associated with substantial visual field loss and clinically meaningful decrements in vision-related and generic QoL. Full article

Background and Objectives: The aim of this study is to employ quantitative proteomics to elucidate the molecular mechanism and signaling pathways modulated by plasma rich in growth factors (PRGF) in a murine model of geographic atrophy (GA)-like retinal degeneration. Materials and Methods: C57BL/6J mice were used as a model GA-like retinal degeneration by a single systemic NaIO₃ administration. Animals were divided into three groups: Control (PBS), Disease (NaIO₃ + PBS), and PRGF-treated (NaIO₃ + PRGF). After 7 days, retinas and retinal pigment epithelium were collected for proteomic analysis. Proteins were extracted, digested using the FASP method, and analyzed by Data-Independent Acquisition (DIA-PASEF) mass spectrometry; data were processed with DIA-NN and statistically analyzed with Perseus. Functional pathway analysis was performed using Ingenuity Pathway Analysis. Results: A total of 6511 proteins were identified. The Disease model showed the expected deregulation of pathways related to oxidative stress, inflammation, and fibrosis. Comparison between the PRGF and Control groups showed that PRGF significantly reduced oxidative and cellular stress proteins/pathways. In the same way, when PRGF and Disease groups were compared, PRGF treatment showed a significant reduction in pathways associated with inflammation, oxidative stress, and cellular stress. PRGF also activated several homeostatic pathways not only related to neuroprotective pathways but also with the lipid deposition (drusen) reduction. All these results suggest that PRGF treatment exerts a protective effect against NaIO₃-induced retinal damage. Conclusions: These findings suggest that PRGF effectively mitigates the degenerative effects of NaIO₃ by activating specific protective and compensatory signaling pathways in the retina. PRGF is indicated as a promising new therapeutic option for ameliorating age-related macular degeneration progression. Full article

Background/Objectives: Oxidative stress plays a significant role in the development and progression of age-related macular degeneration (AMD). Retinal pigment epithelium (RPE) cells are specialized multifunctional cells indispensable for the maintenance of vision. The dysfunction and death of RPE cells in the macula characterize the onset and development of AMD. Of the various toxic agents that impact the health of the RPE, particular focus has been given to various forms of lipoproteins and their cytotoxic derivatives normally present in the retina. Oxidized low-density lipoprotein (OxLDL), derived from LDL in a pro-oxidative environment, is found adjacent to RPE cells as part of drusen, extracellular deposits that are a hallmark feature of AMD. OxLDL is a potent inflammatory agent and it has been implicated in cardiovascular and neurodegenerative conditions. The cellular molecular mechanisms triggered by OxLDL are only partially understood. The focus of this study was to characterize changes in the proteome of RPE cells after exposure to OxLDL, with a focus on the characterization and quantification of ubiquitinated proteins. Methods: Identification and quantification were performed with a high-resolution LC-MS/MS-based proteomics workflow after immune-enrichment for ubiquitinated peptides. Results: In total, out of the more than 1000 RPE ubiquitinated peptides quantified, OxLDL treatment caused a significant increase in ubiquitinated peptides compared to LDL and untreated cells. Principal component analysis (PCA) of the differentially ubiquitinated proteins (265) reduced the data complexity in two main groups of variables (proteins). Conclusions: Gene ontology enrichment analysis of the grouped proteins with the highest loading contribution to principal component 1 (PC1) and principal component 2 (PC2) revealed significant ubiquitination changes upon OxLDL treatment in proteins of the ubiquitin–proteasome system (UPS) responsible for proteasome-mediated catabolic processes and in protein members of the cellular translation machinery. Full article