Search Results (490)

Retinal vessel segmentation in fundus images is critical for diagnosing microvascular and ophthalmologic diseases. However, the task remains challenging due to significant vessel width variation and low vessel-to-background contrast. To address these limitations, we propose WDM-UNet, a novel spatial-wavelet dual-domain fusion architecture that integrates spatial and wavelet-domain representations to simultaneously enhance the local detail and global context. The encoder combines a Deformable Convolution Encoder (DCE), which adaptively models complex vascular structures through dynamic receptive fields, and a Wavelet Convolution Encoder (WCE), which captures the semantic and structural contexts through low-frequency components and hierarchical wavelet convolution. These features are further refined by a Gated Fusion Transformer (GFT), which employs gated attention to enhance multi-scale feature integration. In the decoder, depthwise separable convolutions are used to reduce the computational overhead without compromising the representational capacity. To preserve fine structural details and facilitate contextual information flow across layers, the model incorporates skip connections with a hierarchical fusion strategy, enabling the effective integration of shallow and deep features. We evaluated WDM-UNet in three public datasets: DRIVE, STARE, and CHASE_DB1. The quantitative evaluations demonstrate that WDM-UNet consistently outperforms state-of-the-art methods, achieving 96.92% accuracy, 83.61% sensitivity, and an 82.87% F1-score in the DRIVE dataset, with superior performance across all the benchmark datasets in both segmentation accuracy and robustness, particularly in complex vascular scenarios. Full article

Multiple sclerosis (MS), a chronic disease of the central nervous system, is known to cause structural and vascular changes in the retina. Although optical coherence tomography (OCT) and fundus photography can detect retinal thinning and circulatory abnormalities, these findings are not specific to MS. This study explores the potential of Infrared Scanning-Laser-Ophthalmoscopy (IR-SLO) imaging to uncover vascular morphological features that may serve as MS-specific biomarkers. Using an age-matched, subject-wise stratified k-fold cross-validation approach, a deep learning model originally designed for color fundus images was adapted to segment optic disc, optic cup, and retinal vessels in IR-SLO images, achieving Dice coefficients of 91%, 94.5%, and 97%, respectively. This process included tailored pre- and post-processing steps to optimize segmentation accuracy. Subsequently, clinically relevant features were extracted. Statistical analyses followed by SHapley Additive exPlanations (SHAP) identified vessel fractal dimension, vessel density in zones B and C (circular regions extending 0.5–1 and 0.5–2 optic disc diameters from the optic disc margin, respectively), along with vessel intensity and width, as key differentiators between MS patients and healthy controls. These findings suggest that IR-SLO can non-invasively detect retinal vascular biomarkers that may serve as additional or alternative diagnostic markers for MS diagnosis, complementing current invasive procedures. Full article

Obstructive sleep apnea (OSA) is a common condition associated with intermittent hypoxia, systemic inflammation, and vascular dysfunction; mechanisms implicated in retinal disease pathogenesis. This real-world retrospective cohort study used data from the TriNetX Research Network to assess whether continuous positive airway pressure (CPAP) therapy reduces retinal disease incidence among adults with OSA and BMI between 25.0 and 30.0 kg/m². After 1:1 propensity score matching, 101,754 patients were included in the analysis. Retinal outcomes included diabetic retinopathy (DR), age-related macular degeneration (AMD), retinal vein occlusion (RVO), and central serous chorioretinopathy (CSC). CPAP use was associated with a modest but statistically significant reduction in DR (3.2% vs. 3.4%, RR: 0.922, p = 0.016) and AMD (2.1% vs. 2.3%, RR: 0.906, p = 0.018), while no significant differences were found for RVO or CSC. These findings support prior evidence linking CPAP to improved retinal microvascular health and suggest a protective effect against specific retinal complications. Limitations include a lack of data on CPAP adherence, OSA severity, and imaging confirmation. Still, this study highlights the importance of interdisciplinary care between sleep and eye health, and the need for further prospective studies to validate CPAP’s role in preventing retinal disease progression in OSA patients. Full article

Background: Radiation maculopathy (RM) is a delayed, sight-threatening complication of ocular radiotherapy. Traditionally regarded as a pure microvascular disease, emerging evidence points to the central role played by retinal neuroinflammation, driven by microglial activation and cytokine dysregulation affecting both the retina and the choroid. Hyperreflective retinal foci, neuroinflammatory in origin (I-HRF), visualized through advanced imaging modalities such as spectral domain optical coherence tomography (OCT), have been identified as early and critical biomarkers of both preclinical and clinical retinal neuroinflammation. Materials and Methods: This review synthesizes findings from experimental and clinical studies to explore the pathophysiology of neuroinflammation and the associated imaging parameters in RM. Results: The integration of experimental and clinical evidence specifically underscores the significance of I-HRF as an early indicator of neuroinflammation in RM. OCT enables the identification and quantification of these biomarkers, which are linked to microglial activation and cytokine dysregulation. Conclusions: The pathophysiology of RM has evolved from a predominantly vascular condition to one strongly secondary to neuroinflammatory mechanisms involving the retina and choroid. In particular, I-HRF, as early biomarkers, offers the potential for preclinical diagnosis and therapeutic intervention, paving the way for improved management of this sight-threatening complication. Full article

Chronic kidney disease (CKD)-associated anemia is a global health concern and is linked to vascular and ocular complications. Hypoxia-inducible factor (HIF) stabilizers, or HIF prolyl hydroxylase inhibitors (PHIs), are promising candidates for the treatment of CKD-associated anemia. Since hypoxia and angiogenesis are involved in eye diseases, this study examined the effects of HIF-PHIs on metabolism and gene expression in retinal pigment epithelium (RPE) cells. Results revealed that PHIs differentially induced angiogenic (VEGFA, ANG) and glycolytic (PDK1, GLUT1) gene expression, with Roxadustat causing the strongest transcriptional changes. However, Roxadustat-induced angiogenic signals did not promote endothelial tube formation. Moreover, it did not induce oxidative stress, inflammation, or significant antioxidant gene responses in ARPE-19 cells. Roxadustat also reduced the inflammatory cytokine response to tumor necrosis factor-α, including IL-6, IL-8, and MCP-1, and did not exacerbate VEGF expression under high-glucose conditions. Overall, Roxadustat triggered complex gene expression changes without promoting inflammation or oxidative stress in RPE cells. Despite these findings, ophthalmologic monitoring is advised during PHI treatment in CKD patients receiving HIF-PHIs. Full article

Background/Objectives: This study aimed to prospectively assess the incidence of retinal embolization and to evaluate the vascular and structural changes in the retina and choroid in 52 patients with asymptomatic severe carotid artery disease who underwent carotid artery revascularization. Methods: In our study, 35 patients underwent carotid endarterectomy (CEA) and 17 underwent carotid artery stenting (CAS). Biomicroscopy, fundoscopy, optical coherence tomography (OCT), and OCT-angiography (OCTA) were performed at baseline and 1 month after revascularization. Results: The subfoveal choroidal thickness (SFCT), peripapillary choroidal thickness inferior to the optic nerve head (ppCTi), total overall average retinal vascular density (rVDtot), and total overall average choriocapillaris vascular density (ccVDtot) of the eyes ipsilateral to the operated carotid artery increased significantly after revascularization, whereas a statistically significant increase was also found in the SFCT, rVDtot, and ccVDtot of the contralateral eyes in the overall cohort. Comparing the two study groups, we found that the SFCT, superior and inferior peripapillary choroidal thicknesses (ppCTs, ppCTi), rVDtot, and ccVDtot increased in both groups after revascularization, but significantly only in the CEA group. Furthermore, the temporal choriocapillaris vascular density (ccVDt) increased significantly after revascularization in both groups to a similar degree. Conclusions: Carotid artery revascularization led to a statistically significant increase in retinal and choroidal vascular densities, which indicates significantly improved ocular perfusion. The analysis of the findings of the two study groups suggests the superiority of CEA in terms of improving ocular perfusion in asymptomatic severe carotid artery disease. The rate of retinal embolization was similar in both surgical groups. Full article

Retinal ischemia is implicated in ocular diseases involving aberrant neovessel proliferation that characterizes proliferative retinopathies. Their therapy still remains confined to the intravitreal administration of anti-vascular endothelial growth factor (VEGF) medication, which is limited by side effects and progressive reduction in efficacy. Mimicking neovascular diseases in rodents, although of great help for translating fundamental mechanistic findings and assessing therapeutic potential in humans, is limited by the rodent’s short life span, which prevents retinal vessel proliferation over time. However, the oxygen-induced retinopathy (OIR) model, which mimics retinopathy of prematurity, seems to meet some criteria that are common to proliferative retinopathies. The present review provides insight into preclinical models and their suitability to mimic proliferative retinopathies. Further considerations will be applied to emerging approaches and advanced methodologies for the management of proliferative retinopathies, leading to the identification of new therapeutic targets, including our contribution in the field. Major emphasis is given to the possibility of using systemic therapies either alone or in combination with intravitreal anti-VEGF administration to maximize clinical benefits by combining drugs with different modes of action. This review is concluded by an in-depth discussion on future advancements and a critical view of preclinical finding translatability. Despite the major effort of preclinical and clinical research to develop novel therapies, the blockade of VEGF activity still remains the only treatment for proliferative retinopathies for more than twenty years since its first therapeutic application. Full article

Degenerative retinal diseases, such as age-related macular degeneration (AMD), diabetic retinopathy (DR), and retinitis pigmentosa (RP), are the leading causes of vision loss worldwide. Inflammation plays a crucial role in the pathogenesis of these diseases, with cytokines acting as key mediators of neuroinflammation, vascular dysfunction, and cellular degeneration. This review explores the complex role of cytokines in degenerative retinal diseases, highlighting their involvement in disease progression, cellular interactions, and potential therapeutic strategies. Understanding the cytokine network within the retina may provide novel insights into targeted interventions for these debilitating conditions. Full article

Mitochondria are dynamic in nature and depending on the energy demand they fuse and divide. This fusion-fission process is impaired in diabetic retinopathy and the promoter DNA of Mfn2, a fusion gene, is hypermethylated and its expression is downregulated. Long noncoding RNAs (RNAs with >200 nucleotides that do not encode proteins) can regulate gene expression by interacting with DNA, RNA, and proteins. Several LncRNAs are aberrantly expressed in diabetes, and among them, MALAT1 is upregulated in the retina, altering the expression of the genes associated with inflammation. Our aim was to investigate MALAT1’s role in mitochondrial dynamics in diabetic retinopathy. Using MALAT1-siRNA-transfected human retinal endothelial cells (HRECs) and human retinal Muller cells (RMCs) incubated in 20 mM D-glucose, Mfn2 expression and activity and its promoter DNA methylation were quantified. Mitochondrial integrity was evaluated by analyzing their fragmentation, ultrastructure, membrane potential, and oxygen consumption rate. Compared to normal glucose, high glucose upregulated MALAT1 expression and downregulated Mfn2 expression and activity in both HRECs and RMCs. MALAT1-siRNA ameliorated the glucose-induced increase in Mfn2 promoter DNA hypermethylation and its activity. MALAT1-siRNA also protected against mitochondrial fragmentation, structural damage, and reductions in the oxygen consumption rate. In conclusion, the upregulation of MALAT1 in diabetes facilitates Mfn2 promoter DNA hypermethylation in retinal vascular and nonvascular cells, leading to its suppression and the accumulation of the fragmented/damaged mitochondria. Thus, the regulation of MALAT1 has the potential to protect mitochondria and provide a possible new target to inhibit/prevent the blinding disease in diabetic patients. Full article

Background/Objectives: This study investigates the macular microvasculature in a large cohort of primary Sjögren’s disease (SjD) patients using optical coherence tomography angiography (OCTA), focusing on how disease duration, activity, and hydroxychloroquine (HCQ) treatment influence retinal microcirculation. Methods: A total of 106 eyes (53 SjD patients) and 70 eyes (35 age- and gender-matched healthy controls (HCs)) were examined. The vessel area density (VAD, %) and foveal avascular zone (FAZ, mm2) were measured in three retinal layers: Superficial Vascular Plexus (SVP), Intermediate Capillary Plexus (ICP), and Deep Capillary Plexus (DCP), respectively, in three peri-macular circular sectors (c1, c2, c3) each. Results: The VAD was significantly lower in c1 of the DCP in SjD compared to HCs (29.14 ± 7.07 vs. 31.78 ± 9.55, p = 0.038). The FAZ was significantly larger in SjD in both SVP (0.41 ± 0.13 vs. 0.34, 0.11, p < 0.001; Cohen’s |d| = 0.55) and DCP (0.45 ± 0.15 vs. 0.4 ± 0.14, p = 0.014; Cohen’s |d| ± 0.38). Significant correlations were observed between the FAZ size and reductions in the VAD in the SVP and DCP (p = 0.010, Cohen’s |d| = 0.2; p < 0.001, Cohen’s |d| ± 0.26) and across all layers combined (p = 0.019, Cohen’s |d| = −0.18). Conclusions: There was a negative correlation between the VAD in the DCP and disease duration (ρ = −0.28, p = 0.040). No significant correlation was identified between the duration of HCQ intake and the VAD or FAZ. Our findings indicate microvascular alterations in the DCP of SjD, characterized by a reduced VAD and an enlarged FAZ, which may be attributable to inflammatory or arteriosclerotic factors. OCTA may prove to be a valuable tool for the stratification of vascular risk in SjD. Full article

Background/Objectives: The INK4 locus at chromosome 9p21.3, encoding CDKN2A, CDKN2B and the long non-coding RNA CDKN2B-AS1 (ANRIL), has been implicated in multiple diseases, including glaucoma and cardiovascular disease. ANRIL plays a critical role in gene regulation, inflammation and cell proliferation, contributing to disease susceptibility through shared molecular mechanisms. This study aims to identify SNPs within the INK4 locus associated with both glaucoma and CVD using the Open Targets Genetics platform and assess their pleiotropic effects. Methods: We utilised the Open Targets Genetics platform to identify SNPs at the INK4 locus associated with glaucoma and CVD. For each SNP, we recorded its genomic location, statistical significance and associated phenotypes. We further analysed the SNPs using the Genome Aggregation Database (gnomAD) to confirm their genomic position. Phenotypic associations were assessed using PheWAS data. Results: We identified 20 GWAS SNPs significantly associated with both glaucoma and CVD. All SNPs were located within intronic regions of the long non-coding RNA ANRIL. Certain SNPs such as rs4977756, rs1333037 and rs1063192 have known pleiotropic effects, influencing retinal ganglion cell survival in glaucoma and vascular smooth muscle cell proliferation in CVD. These SNPs influence shared biological pathways, including inflammation, oxidative stress and epigenetic regulation, and may exert either protective or pathogenic effects. Certain SNPs such as rs7853090 and rs1434537531 remain underexplored, emphasising the need for further research. Conclusions: This study highlights the pleiotropic role of ANRIL in glaucoma and CVD, driven by shared genetic and molecular pathways. While SNPs within ANRIL provide valuable insights into disease mechanisms, these conditions remain complex, influenced by multiple genetic and environmental factors. Targeting ANRIL therapeutically poses challenges due to its non-coding nature, but emerging RNA-based therapies, including antisense oligonucleotides and small-molecule modulators, hold promise. Further research into underexplored SNPs and ANRIL’s regulatory mechanisms is essential for advancing therapeutic development and understanding these multifactorial diseases. Full article

Age-related macular degeneration (AMD) is a progressive retinal disorder and a leading cause of irreversible blindness among elderly individuals, impacting millions of people globally. This review synthesizes the current understanding of the cellular and molecular signaling mechanisms driving AMD, with a focus on the distinct pathophysiological features of dry and wet AMD subtypes. Key mechanisms include oxidative stress, inflammation, lipid metabolism dysregulation, and immune dysregulation, all of which converge on the retinal pigment epithelium (RPE) as a central player in disease initiation and progression. In dry AMD, oxidative damage, mitochondrial dysfunction, and lipofuscin accumulation impair RPE function, contributing to drusen formation and geographic atrophy. In wet AMD, vascular endothelial growth factor-mediated angiogenesis, coupled with inflammation and endothelial metabolic reprogramming, drives choroidal neovascularization. This article integrates findings from multiomics approaches and highlights the potential of artificial intelligence in elucidating AMD pathogenesis and advancing personalized therapies. Future research directions emphasize targeting these molecular pathways to develop innovative treatments, offering hope for improved management of this debilitating condition. Full article

Pericytes, specialized mural cells surrounding microvessels, play a crucial role in maintaining vascular homeostasis and function across various organs, including the eye. These versatile cells regulate blood flow, support the integrity of the blood–retinal barrier, and contribute to angiogenesis. Recent advancements in molecular and cellular biology have revealed the heterogeneity of pericytes and their critical involvement in ocular physiology and pathology. This review provides a comprehensive analysis of pericyte functions in ocular health and their implications in diseases such as diabetic retinopathy, age-related macular degeneration, glaucoma, and retinal vein occlusion. Pericyte dysfunction is implicated in vascular instability, neurovascular coupling failure, inflammation, and pathological neovascularization, contributing to vision-threatening disorders. The review further explores recent findings on pericyte-targeted therapies, including pharmacological agents, gene therapy, and cell-based approaches, aiming to restore pericyte function and preserve ocular health. Full article

Background/Objectives: Fruits and vegetables (F&Vs) are major dietary sources of phytochemicals, crucial for preventing non-communicable diseases. However, barriers such as preparation inconvenience and a short shelf life hinder their consumption. F&V-coated foods have emerged as an alternative. This human nutrition intervention study assessed the effects of a blended F&Vs mixture versus an F&V-coated food on phytochemical absorption and chronic disease risk markers. It also explored how genetic variation influences physiological responses to these F&V products. Methods: In this randomized-controlled trial, participants were assigned to one of three dietary interventions: a blended F&V mixture (“F&V Blend”), a rice-based cereal product coated with this blend (“Coated Pearl”), or the same product without the F&V mixture (“Uncoated Pearl”). The four-week study included a two-week run-in and a two-week intervention phase, each followed by a test day. Measurements included DNA damage resistance (comet assay), plasma antioxidant status (Trolox capacity and superoxide levels), microvasculature health (retinal analysis), and plasma phytochemical concentrations (colorimetric analyses or HPLC). To assess group differences, a linear mixed model was used. Fifteen polymorphic genes related to phytochemical metabolism and oxidative stress were tested using TaqMan and PCR, with outcomes analyzed via ANOVA. Results: The F&V Blend and Coated Pearl products increased plasma carotenoid levels versus the Uncoated Pearl product. Only the F&V Blend improved retinal dilation and DNA resistance. Surprisingly, the Uncoated Pearl product enhanced antioxidant capacity, lowered superoxide levels, and improved retinal microvasculature. Genotype effects were minimal, except for HNF1A, where wildtypes in the Uncoated Pearl group showed a higher antioxidant capacity. Conclusions: Fresh F&Vs were more effective than coated alternatives in improving vascular health and DNA protection. Full article

Rising morbidity and mortality from cardiovascular disease (CVD) have increased interest in precision and preventive management to reduce long-term sequelae. While retinal imaging has traditionally been recognized for identifying vascular changes in systemic conditions such as hypertension and type 2 diabetes mellitus, a new ophthalmologic field, cardiac-oculomics, has associated retinal biomarker changes with other cardiovascular diseases with retinal manifestations. Several imaging modalities visualize the retina, including color fundus photography (CFP), optical coherence tomography (OCT), and OCT angiography (OCTA), which visualize the retinal surface, the individual retinal layers, and the microvasculature within those layers, respectively. In these modalities, imaging-derived biomarkers can present due to CVD and have been linked to the presence, progression, or risk of developing a range of CVD, including hypertension, carotid artery disease, valvular heart disease, cerebral infarction, atrial fibrillation, and heart failure. Promising artificial intelligence (AI) models have been developed to complement existing risk-prediction tools, but standardization and clinical trials are needed for clinical adoption. Beyond risk estimation, there is growing interest in assessing real-time cardiovascular status to track vascular changes following pharmacotherapy, surgery, or acute decompensation. This review offers an up-to-date assessment of the cardiac-oculomics literature and aims to raise awareness among cardiologists and encourage interdepartmental collaboration. Full article