Search Results (336)

Background/Objectives: This monocentric case–control study prospectively recruited patients with foveal hypoplasia (FH) and compared them with retrospectively selected age- and sex-matched healthy controls. It is the first study to employ AngioTool software to quantitatively assess retinal microvascular alterations in FH using Optical Coherence Tomography Angiography (OCT-A). Methods: In total, 19 patients with FH and 19 age- and sex-matched healthy controls were included at Münster University Hospital, Germany, and underwent OCT-A imaging of the macula. The 3 × 3 mm² angiograms of the superficial (SCP) and deep capillary plexus (DCP) were examined using AngioTool software. Quantified parameters included flow density (FD), number of junctions, total and average vessel length, number of endpoints, and lacunarity. Results: A total of 62 eyes from 38 participants were included in the analysis. Compared with controls, eyes with FH demonstrated significantly lower FD, fewer junctions, shorter total vessel length, and a greater number of endpoints in both SCP and DCP. These differences showed small-to-large effect sizes, depending on the parameter and plexus. Average vessel length remained significantly decreased in the SCP but not the DCP. The difference in SCP lacunarity did not remain significant after adjustment for multiple comparisons. In the exploratory subgroup analysis, there were no significant differences between mild and severe FH in either the SCP or the DCP after correction for multiple testing. Conclusions: FH is associated with alterations of retinal microvasculature involving both the SCP and DCP. These findings are consistent with altered retinal vascular development in FH. OCT-A may provide useful quantitative information for the characterization of FH, although the clinical and prognostic relevance of these vascular parameters remains to be established. Full article

Background/Objectives: Evaluating noninvasive, accessible ocular and blood-based biomarkers could aid in early risk stratification and disease detection during the preclinical phase of Alzheimer’s disease. This study investigates associations between plasma biomarkers of neurodegeneration and retinal structural and microvasculature parameters in cognitively normal adults with familial or genetic risk factors for Alzheimer’s disease. Methods: Forty-one participants underwent plasma sampling for glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), amyloid-beta42 (β42), amyloid-β42/40 ratio, and phosphorylated-tau217 (p-tau217), and also underwent optical coherence tomography (OCT) and OCT angiography (OCTA) imaging. Apolipoprotein E genotyping and family history of Alzheimer’s disease were recorded. Generalized estimating equations adjusting for age, sex, race, treated hypertension, Alzheimer’s disease family history, and APOE ε4 carrier status assessed associations between plasma biomarker concentrations and OCT and OCTA measurements. Results: Higher plasma GFAP and NfL concentrations were significantly associated with reduced superficial capillary plexus perfusion density and vessel density on macular OCTA. In additional analyses restricted to participants with plasma biomarker and retinal imaging assessments obtained within 9 months, associations with GFAP remained significant, whereas NfL associations no longer remained significant after correction for multiple comparisons. Conclusions: Retinal OCTA and OCT metrics may reflect general neurovascular aging in cognitively normal individuals with familial or genetic risk factors for Alzheimer’s disease. Full article

Background: Diabetic retinopathy (DR) is a leading cause of vision loss, with oxidative stress and inflammation serving as critical drivers of its onset and progression. Curcumin, a natural polyphenol, is known for its potent anti-inflammatory and antioxidant properties. Glial fibrillary acidic protein (GFAP) is commonly used as an indicator of retinal macroglial reactivity, whereas the NLRP3 inflammasome is an important mediator of inflammatory signaling in DR. We evaluated retinal vascular abnormalities and retinal GFAP immunoreactivity and examined whether these findings were accompanied by changes in retinal NLRP3 and IL-1β protein abundance and in the levels of cleaved caspase-1 and cleaved GSDMD. Methods: Diabetes was induced in 7-week-old rats via a single intraperitoneal injection of streptozotocin. Following the confirmation of hyperglycemia, curcumin was administered orally. To evaluate the effects, we performed trypsin digestion, haematoxylin and eosin (H&E) staining, fluorescein isothiocyanate (FITC)–dextran permeability assays, immunofluorescence staining, and Western blotting on the harvested retinas. Results: The DM group showed increased acellular capillary formation, vascular leakage, retinal GFAP immunoreactivity, NLRP3 and IL-1β protein abundance, and levels of cleaved caspase-1 and cleaved GSDMD. Compared with the untreated DM group, the DM + curcumin group showed lower values for all of these outcomes. Conclusions: In diabetic rats, oral administration of a curcumin-containing formulation was associated with fewer retinal vascular abnormalities and lower GFAP immunoreactivity, accompanied by parallel differences in inflammasome-related proteins. These findings support the potential of this formulation as an adjunctive therapeutic approach for early diabetic retinopathy. Full article

Backgroundand Objectives: Retinal microcirculation may serve as a surrogate marker of systemic vascular status and can be non-invasively assessed using optical coherence tomography angiography (OCTA). Emerging evidence suggests that retinal and choroidal microvascular alterations may occur following coronavirus disease 2019 (COVID-19) and multisystem inflammatory syndrome in children (MIS-C), potentially reflecting systemic vascular and inflammatory processes. This review summarizes the current evidence regarding retinal and choroidal microvascular changes detected by OCTA in pediatric patients with COVID-19 and MIS-C. Materials and Methods: A structured literature search of the National Center for Biotechnology Information (NCBI) PubMed database was conducted from inception until April 2026. Original English-language studies evaluating retinal and choroidal microcirculation using OCTA in pediatric patients with COVID-19 or MIS-C were identified and reviewed. Results: Available studies suggest variable retinal and choroidal microvascular alterations following COVID-19 and MIS-C, including changes in vessel density, perfusion, and foveal avascular zone parameters. Several investigations reported reduced vessel density, particularly within the deep capillary plexus, whereas others demonstrated increased peripapillary vascular parameters or no significant differences during the observation period. Differences in patient characteristics, disease severity, timing of imaging, OCTA protocols, and study design likely contribute to the heterogeneity of the reported findings. Conclusions: OCTA represents a promising research tool for investigating retinal and choroidal microvascular alterations associated with pediatric COVID-19 and MIS-C. However, the available evidence remains limited by small observational studies, methodological heterogeneity and inconsistent findings. Larger prospective longitudinal studies using standardized imaging protocols are needed to determine the clinical significance and reproducibility of OCTA-derived parameters and to establish whether they may have potential as biomarkers of ocular or systemic vascular involvement. Full article

The aim of this narrative review was to provide a disease-oriented diagnostic framework for selecting and integrating multimodal imaging techniques according to the suspected optic disc disorder. A non-systematic PubMed search was performed to identify relevant literature on optic disc diseases and related imaging appearances. Searches included a combination of terms related to disease features and imaging modalities. The recent introduction of non-invasive imaging devices, such as optical coherence tomography (OCT) and OCT angiography (OCTA), has allowed a remarkable step forward in the knowledge of the optic disc. OCT has revolutionized the diagnosis and monitoring of glaucomatous eyes, providing useful quantitative biomarkers. Fundus examination and color fundus photography are the first step for evaluation of optic disc edema, which requires further exams, including fundus autofluorescence, to exclude the presence of optic disc drusen, ocular ultrasound and in certain cases, fluorescein angiography. Although still limited, OCTA could give a support in the evaluation of vascular diseases that involve the optic disc, such as anterior ischemic optic neuropathy, retinal vein occlusion and proliferative diabetic retinopathy. Analyzing the radial peripapillary capillary plexus, OCTA can also highlight early vascular changes in degenerative diseases (i.e., glaucoma, Alzheimer’s disease or multiple sclerosis). Multimodal imaging is a cornerstone in the neuro-ophthalmology field, offering unparalleled insight into optic nerve head architecture and vascular integrity in both normal and diseased states. Full article

The global prevalence of myopia is increasing, and the combination of myopia and glaucoma is widely expected to become an important clinical and public health issue. Myopic eyes undergo axial elongation and posterior pole remodeling, leading to optic disc tilt, peripapillary deformation, choroidal thinning, and altered spatial relationships between the optic nerve head and its vascular supply. Glaucomatous optic neuropathy is associated with retinal ganglion cell damage, lamina cribrosa deformation, and ocular blood flow impairment. Recent advances in optical coherence tomography angiography and laser speckle flowgraphy have enabled noninvasive assessment of retinal, peripapillary, choroidal, and optic nerve head circulation. These modalities have revealed reduced radial peripapillary capillary density, choroidal microvasculature dropout, and reduced optic nerve head tissue blood-flow signal in glaucomatous eyes. In eyes with myopia and glaucoma, myopia-related structural deformation and glaucoma-associated perfusion abnormalities may coexist and show sectoral correspondence with neural damage, particularly in regions related to the central visual field. This review summarizes the anatomical background of ocular blood flow, myopia-induced structural and vascular changes, glaucoma-associated blood flow impairment, and their interaction in eyes with myopia and glaucoma. Potential therapeutic approaches targeting ocular blood flow are also discussed, although evidence beyond intraocular pressure reduction remains limited. Full article

Disruptions in folate (vitamin B9) and vitamin B12 metabolism, including nutritional deficiency, folate receptor alpha (FRα) autoantibodies, and MTHFR/DHFR polymorphisms, impair one-carbon metabolism and produce measurable retinal structural, microvascular, and functional changes, offering a non-invasive window into systemic and cerebral metabolic dysfunction, particularly cerebral folate deficiency (CFD). This review synthesizes peer-reviewed evidence on retinal alterations linked to folate/B12 deficiency, hyperhomocysteinemia, FRα autoantibody syndromes, and MTHFR/DHFR variants, alongside artificial intelligence (AI) and machine learning (ML) approaches applied to retinal imaging for metabolic, anemic, and nutritional optic neuropathy detection. Three convergent phenotypes emerge: structural changes (retinal nerve fiber layer and ganglion cell complex thinning, optic disc pallor, chorioretinal atrophy), microvascular abnormalities (reduced vessel density, foveal avascular zone enlargement, capillary dropout), and functional deficits (centrocecal scotoma, dyschromatopsia, reduced contrast sensitivity); they arise from homocysteine-mediated endothelial toxicity, mitochondrial impairment, and eNOS uncoupling. Existing AI/ML models for anemia and optic neuropathy establish technical feasibility but do not target folate-specific phenotypes. We propose a dedicated multimodal ML framework integrating structural, perfusion, functional, and biochemical/genetic data as a research agenda for automated, non-invasive CFD detection. Given the established folate–autism spectrum disorder (ASD) risk association reported in FRAA-positive cohorts, such a framework, once validated, could support prenatal and neonatal screening in FRAA-positive or genetically high-risk pregnancies, enabling earlier leucovorin treatment and reducing neurodevelopmental risk. Full article

Background: To compare retinal microvascular parameters assessed by optical coherence tomography angiography (OCTA) among patients with axial spondyloarthritis (axSpA) receiving different biologic and targeted synthetic therapies and to evaluate the association between smoking status and OCTA-derived retinal microvascular parameters. Methods: This cross-sectional study included 159 eyes of 82 patients with radiographic or non-radiographic axSpA receiving tumor necrosis factor inhibitors (TNFi), interleukin-17 inhibitors (IL-17i), or Janus kinase inhibitors (JAKi) for at least one year. At the time of examination, all patients had BASDAI scores below the established threshold for active disease (BASDAI < 4). Comprehensive ophthalmic evaluation and swept-source OCTA imaging were performed. Superficial capillary plexus vessel density and foveal avascular zone (FAZ) areas in both the superficial (SCP) and deep capillary plexus (DCP) were assessed. Statistical analyses were adjusted for age, sex, smoking status, history of uveitis, treatment duration, and ocular variables. Results: Significant differences were observed among treatment groups in the deep foveal avascular zone (DCP-FAZ) area (p = 0.0060). Post hoc analyses demonstrated larger DCP-FAZ values in patients receiving TNFi than in those receiving IL-17i (p = 0.0010), and larger values in the IL-17i group than in the JAKi group (p = 0.0151). No significant differences were observed in superficial FAZ area or superficial capillary plexus vessel density between treatment groups. Patients receiving JAKi were older and had a shorter treatment duration than those in the other groups. Smoking status was associated with a significantly smaller deep FAZ area (p = 0.0019), whereas no significant association was observed for superficial FAZ measurements. A weak positive correlation was found between intraocular pressure and deep FAZ area (r = 0.18, p = 0.0237), and treatment duration was weakly positively correlated with deep FAZ area (rho = 0.16, p = 0.0454). Conclusions: Retinal microvascular parameters differed among patients with axSpA receiving different classes of biologic and targeted synthetic therapies. Differences were observed primarily in the deep FAZ area, while smoking status was also associated with deep retinal microvascular parameters. Because of the cross-sectional design, these findings should be interpreted as associations rather than evidence of treatment effects. OCTA may provide a useful non-invasive method for assessing retinal microvascular characteristics in patients with axSpA. Further longitudinal studies are warranted to clarify the relationship between systemic therapies, smoking status, and retinal microvascular changes. Full article

Diabetic retinopathy (DR) is one of the main causes of vision impairment globally, and it is increasingly recognized as a neurovascular disease characterized by both microvascular and neural dysfunction. Traditional assessment approaches primarily focus on structural retinal alterations and visual acuity, which may fail to identify early functional impairments. Contrast sensitivity (CS), which measures the capacity to distinguish subtle luminance differences, is increasingly recognized as an early manifestation of retinal dysfunction in diabetes mellitus. This narrative review seeks to describe current knowledge on the role of CS in DR, including its pathophysiological foundation, clinical importance, and link to structural retinal alterations. A systematic literature search of PubMed, Scopus, and Google Scholar (2000–2026) was performed to identify studies on CS in diabetes mellitus and diabetic retinopathy. Multiple investigations found that diabetic patients, including those with no clinically evident DR and normal visual acuity, had lower contrast sensitivity. CS impairment was associated with retinal neurodegeneration, ganglion cell dysfunction, microvascular alterations, and diabetic macular edema severity. OCT and OCT-A findings showed important structure–function correlations between reduced CS and retinal thinning, capillary dropout, and impaired perfusion. CS testing may provide additional functional information beyond standard visual acuity assessment and may improve early disease detection and monitoring. In conclusion, contrast sensitivity represents a promising functional biomarker for early diabetic retinal dysfunction and may complement structural imaging and visual acuity testing in DR evaluation. Although methodological variability currently limits widespread clinical implementation, advances in digital technologies and multimodal assessment strategies may facilitate its future integration into routine ophthalmologic practice. Full article

Automated and accurate segmentation of retinal vessels in fundus images provides pivotal evidence for ophthalmologists to effectively and non-invasively diagnose prevalent ocular and systemic diseases. However, existing methods often struggle to maintain the topological continuity of fine-diameter capillaries, leading to severe vascular discontinuity and fragmented segmentation results in challenging scenarios such as complex, irregular microvascular branches, pathological lesions, and high-noise conditions. To address these limitations, we developed a novel symmetric dual-branch network with frequency-aware decomposition and prototype refinement (FDPR-DBNet). Specifically, the network initially utilizes the discrete wavelet transform (DWT) to decompose input retinal images into high-frequency and low-frequency components, which are then processed by a structurally symmetric dual-branch encoder. In the high-frequency branch, the parallel atrous convolution activation (PACA) module is designed to explore fine-grained contour and edge patterns related to vessel terminals and microvessels. Concurrently, within the low-frequency branch, the spatial-frequency characteristic activation (SFCA) unit is constructed by introducing the selective state-space model ($S6$) and Fourier transform to extract salient structural backbones. Moreover, the spatial attention residual fusion (SARF) module and cross-frequency fusion (CFF) block are designed to establish a symmetric guidance mechanism, effectively reinforcing bidirectional feature interaction and alignment across different frequency spectra to eliminate vascular fragmentation. Furthermore, by embedding global and local window self-attention into the Transformer, we formulated the cross-scale enhancement (CSE) module, comprising global semantic enhancement (GSE) and local detail enhancement (LDE), to model multi-scale contextual semantic correlations and enhance the adaptive recognition of vessel structures. Ultimately, we embedded the multi-wise prototype characteristic refinement (MPCR) component into the decoder to correct cross-scale semantic features through a dynamic calibration mechanism, while introducing a new connectivity loss to strictly enforce topological continuity. Experimental results on four publicly available retinal image datasets (DRIVE, CHASE_DB1, STARE, and IOSTAR) demonstrate that the proposed model achieves competitive performance and effectively preserves vascular integrity even in the presence of fundus lesions and noise. Full article

Background: Amyotrophic lateral sclerosis (ALS) is increasingly recognized as a multisystem disorder involving neurovascular dysfunction. The retina allows in vivo assessment of neurovascular changes. This study evaluated retinal structural and microvascular alterations in ALS using optical coherence tomography (OCT) and optical coherence tomography angiography (OCT-A). Methods: This cross-sectional study included 46 participants with ALS and 19 healthy controls. Retinal thickness and vascular density in the superficial and deep retinal capillary plexuses and the choriocapillaris were quantified using OCT and OCT-A. Group comparisons and logistic regression analyses were performed to assess associations with ALS. Subgroup analyses were conducted according to clinical phenotype. Results: In total, 124 eyes were analyzed. ALS was associated with increased average retinal thickness (p = 0.023) and reduced vascular density in the superficial retinal capillary plexus (p = 0.005), deep retinal capillary plexus (p < 0.001), and choriocapillaris (p = 0.004). In logistic regression analyses, retinal thickness was positively associated with ALS status (OR = 1.42, p = 0.023), whereas higher vascular density in the superficial plexus, deep plexus, and choriocapillaris was associated with lower odds of ALS. No significant differences were observed between bulbar- and spinal-onset ALS phenotypes. Conclusions: ALS is associated with structural and microvascular retinal alterations detectable by OCT and OCT-A. These findings support the presence of systemic neurovascular dysfunction and highlight retinal imaging as a promising, non-invasive approach for investigating disease mechanisms and developing potential biomarkers. Full article

Dry age-related macular degeneration (AMD) can progress to wet AMD when leaking capillaries grow under the macula. Although rare, this transition holds significant risk as it causes more rapid and severe vision loss. Oxidative stress is damaging to cellular components and plays a pivotal role in chronic diseases. We aim to determine whether oxidative stress in retinal pigment epithelial (RPE) cells elicits a proangiogenic microenvironment. We exposed human primary RPE cells to hydrogen peroxide (H₂O₂), and we analyzed their metabolic activity, and the production of reactive oxygen species (ROS) and angiogenic factors. In addition, we evaluated the potential of RPE cell-conditioned medium (CM) to induce HUVEC cell tube formation. RPE cells exposed to H₂O₂ displayed a dose-dependent decrease in their metabolic activity, and increased ROS levels. The analysis of the CM of exposed RPE cells revealed differential expression of a panel of proangiogenic factors. Notably, the expression of the major angiogenic factors (VEGF, FGF) was increased. Exposure of HUVEC cells to the CM of H₂O₂-exposed RPE cells promoted tube formation suggestive of microvessel formation. Our findings bring new insights into the role of oxidative stress in altering RPE cell behavior that might have consequences in the progression of AMD towards the exudative form. Full article

Background: Chronic kidney disease (CKD) is associated with systemic microvascular dysfunction, yet the relationship between retinal changes and mineral metabolism disturbances across CKD treatment modalities remains incompletely characterized. Methods: We performed a baseline cross-sectional analysis of 77 participants (29 hemodialysis [HD] patients, and 48 kidney transplant recipients [KTR]) who underwent 7 × 7 mm structural optical coherence tomography (OCT) and 6 × 6 mm OCT angiography (OCTA) imaging. Structural parameters included central macular thickness (CMT), ganglion cell layer plus inner plexiform layer (GCL+), ganglion cell complex (GCL++), and subfoveal choroidal thickness (SCT). Microvascular parameters included superficial and deep capillary plexus vessel density (SVPD, DVPD), choriocapillaris density (CCD), and foveal avascular zone (FAZ) area. Serum mineral metabolism markers were correlated with retinal findings. Eyes were analyzed separately as the primary approach, while generalized estimating equation (GEE) models adjusted for age, sex, body mass index, diabetes, and hypertension (HTN) were used for confirmation. Results: FAZ area, SVPD, DVPD, CCD, GCL+, GCL++, and CMT did not differ significantly between cohorts in either per-eye analyses or adjusted GEE models. SCT was lower in HD patients than in KTR in the right eye (p = 0.019) and remained significantly higher in KTR in the adjusted GEE models (p = 0.016), a difference that persisted after excluding participants with diabetes and after adjustment for HTN grade. HTN grade was associated with FAZ area in HD and SCT in KTR. Serum magnesium was inversely associated with FAZ area in HD (B = −95.27, p = 0.034) and positively associated with GCL+ in KTR (B = 10.55, p = 0.048). Conclusions: Retinal microvascular and inner-retinal structural parameters were largely comparable between HD patients and KTR, with SCT the only parameter showing a consistent between-cohort difference (higher in KTR). Serum magnesium and HTN grade were the metabolic and clinical variables most consistently associated with retinal measures. Full article

Background/Objectives: To evaluate interocular retinal and choroidal microvascular alterations associated with compensatory head tilt in unilateral congenital superior oblique palsy (SOP) and to investigate their relationship with head tilt degree using optical coherence tomography angiography (OCTA). Methods: This retrospective cross-sectional study included 34 patients with congenital SOP and head tilt–dominant abnormal head posture. A paired-eye design compared the tilt-side eye with the opposite-side eye. Superficial and deep capillary plexus (SCP, DCP) vessel density, foveal avascular zone (FAZ) parameters, choroidal vascularity index (CVI), and subfoveal choroidal thickness (SFCT) were assessed. Interocular differences were defined as Δ = opposite-side eye − tilt-side eye. Correlation and multivariable regression analyses were performed to assess associations with head tilt degree. The interocular difference in CVI (ΔCVI) and its association with head tilt degree were defined as the primary outcomes, whereas retinal OCTA parameters, FAZ metrics, and SFCT were considered exploratory secondary outcomes. Results: CVI showed the most prominent interocular difference, being higher in the opposite-side eye than in the tilt-side eye (0.71 ± 0.04 vs. 0.68 ± 0.04; p < 0.001), whereas SFCT did not differ significantly (p = 0.395). SCP foveal vessel density and DCP inferior vessel density showed nominal differences in the unadjusted analyses but did not remain statistically significant after Benjamini–Hochberg false discovery rate correction. ΔCVI correlated positively with head tilt degree (ρ = +0.533, p = 0.001) and remained independently associated in multivariable analysis (p = 0.001). Conclusions: Compensatory head tilt in congenital SOP is associated with measurable interocular microvascular asymmetry, predominantly at the choroidal level. CVI demonstrated the strongest association with head tilt severity, whereas retinal OCTA findings were exploratory, suggesting that OCTA may provide objective insight into posture-related choroidal microvascular alterations. Full article

Objective: This study aimed to evaluate the predictability of baseline optical coherence tomography angiography (OCTA) metrics utilizing a specialized capillary–large vessel segmentation analysis framework in patients with diabetic macular edema (DME) undergoing anti-vascular endothelial growth factor (anti-VEGF) therapy. Methods: Forty-two treatment-naïve eyes with DME receiving three monthly loading anti-VEGF injections were included. Superficial capillary plexus (SCP) images from 3 × 3 mm OCTA scans were processed to isolate the capillary network from the large vessels via image processing. Vessel density and skeleton density were extracted for the total, large-vessel, and capillary components. Multiple linear and logistic regression models were used to identify independent predictors of post-treatment best-corrected visual acuity (BCVA) and “good visual outcome” (≥3-line improvement or final BCVA of 20/40 or better). Results: Following three monthly anti-VEGF injections, the mean BCVA significantly improved from 0.57 ± 0.36 to 0.37 ± 0.30 LogMAR (p < 0.0001), and the mean central retinal thickness decreased from 424.3 ± 117.7 μm to 316.9 ± 84.7 μm (p < 0.0001). The proportion of patients who achieved a good visual outcome was 73.8%. Baseline central retinal thickness was associated with baseline BCVA (p = 0.049) but not predictive of post-treatment BCVA (p = 0.38) or good visual outcomes (p = 0.79). Baseline capillary vessel density was identified as a significant independent predictor of post-treatment BCVA (p = 0.024), whereas total and large-vessel metrics were not. Capillary vessel density was also the only significant predictor of good visual outcomes (p = 0.044). Conclusions: Baseline capillary vessel density is a robust predictor of visual prognosis after anti-VEGF therapy in patients with DME, underscoring the importance of capillary network integrity in functional recovery. Full article