Search Results (822)

The retina is highly sensitive to oxygen and blood supply, and hypoxia plays a key role in retinal diseases such as diabetic retinopathy (DR) and age-related macular degeneration (AMD). Müller glial cells, which are essential for retinal homeostasis, respond to injury and hypoxia with reactive gliosis, characterized by the upregulation of the glial fibrillary acidic protein (GFAP) and vimentin, cellular hypertrophy, and extracellular matrix changes, which can impair retinal function and repair. The retinal pigment epithelium (RPE) supports photoreceptors, forms part of the blood–retinal barrier, and protects against oxidative stress; its dysfunction contributes to retinal degenerative diseases such as AMD, retinitis pigmentosa (RP), and Stargardt disease (SD). Extracellular vesicles (EVs) play a crucial role in intercellular communication, protein homeostasis, and immune modulation, and have emerged as promising diagnostic and therapeutic tools. Understanding the role of extracellular vesicles’ (EVs’) signaling machinery of glial cells and the retinal pigment epithelium (RPE) is critical for developing effective treatments for retinal degeneration. In this study, we investigated the bidirectional EV-mediated crosstalk between RPE and Müller cells under hypoxic conditions and its impact on cellular metabolism and retinal cell integrity. Our findings demonstrate that RPE-derived extracellular vesicles (RPE EVs) induce time-dependent metabolic reprogramming in Müller cells. Short-term exposure (24 h) promotes pathways supporting neurotransmitter cycling, calcium and mineral absorption, and glutamate metabolism, while prolonged exposure (72 h) shifts Müller cell metabolism toward enhanced mitochondrial function and ATP production. Conversely, Müller cell-derived EVs under hypoxia influenced RPE metabolic pathways, enhancing fatty acid metabolism, intracellular vesicular trafficking, and the biosynthesis of mitochondrial co-factors such as ubiquinone. Proteomic analysis revealed significant modulation of key regulatory proteins. In Müller cells, hypoxic RPE-EV exposure led to reduced expression of Dyskerin Pseudouridine Synthase 1 (DKc1), Eukaryotic Translation Termination Factor 1 (ETF1), and Protein Ser/Thr phosphatases (PPP2R1B), suggesting alterations in RNA processing, translational fidelity, and signaling. RPE cells exposed to hypoxic Müller cell EVs exhibited elevated Ribosome-binding protein 1 (RRBP1), RAC1/2, and Guanine Nucleotide-Binding Protein G(i) Subunit Alpha-1 (GNAI1), supporting enhanced endoplasmic reticulum (ER) function and cytoskeletal remodeling. Functional assays also revealed the compromised barrier integrity of the outer blood–retinal barrier (oBRB) under hypoxic co-culture conditions. These results underscore the adaptive but time-sensitive nature of retinal cell communication via EVs in response to hypoxia. Targeting this crosstalk may offer novel therapeutic strategies to preserve retinal structure and function in ischemic retinopathies. Full article

Age-related macular degeneration (AMD) is one of the leading causes of irreversible vision loss among the elderly, and is influenced by a combination of genetic and environmental risk factors. While genetic associations in AMD are well-established, the molecular mechanisms underlying disease onset and progression remain poorly understood. A growing body of evidence suggests that epigenetic modifications may serve as a potential missing link regulating gene–environment interactions. This review incorporates recent findings on DNA methylation, including both hypermethylation and hypomethylation patterns affecting genes such as silent mating type information regulation 2 homolog 1 (SIRT1), glutathione S-transferase isoform (GSTM), and SKI proto-oncogene (SKI), which may influence key pathophysiological drivers of AMD. We also examine histone modification patterns, chromatin accessibility, the status of long non-coding RNAs (lncRNAs) in AMD pathogenesis and in regulating pathways pertinent to the pathophysiology of the disease. While the field of ocular epigenetics remains in its infancy, accumulating evidence to date points to a burgeoning role for epigenetic regulation in AMD, pre-clinical studies have yielded promising findings for the prospect of epigenetics as a future therapeutic avenue. Full article

Age-related macular degeneration (AMD) is the leading cause of blindness in developed countries. Predicting its progression is crucial for preventing late-stage AMD, as it is an irreversible retinal disease. Both genetic factors and retinal images are instrumental in diagnosing and predicting AMD progression. Previous studies have explored automated diagnosis using single fundus images and genetic variants, but they often fail to utilize the valuable longitudinal data from multiple visits. Longitudinal retinal images offer a dynamic view of disease progression, yet standard Long Short-Term Memory (LSTM) models assume consistent time intervals between training and testing, limiting their effectiveness in real-world settings. To address this limitation, we propose time-varied Long Short-Term Memory (TV-LSTM), which accommodates irregular time intervals in longitudinal data. Our innovative approach enables the integration of both longitudinal fundus images and AMD-associated genetic variants for more precise progression prediction. Our TV-LSTM model achieved an AUC-ROC of 0.9479 and an AUC-PR of 0.8591 for predicting late AMD within two years, using data from four visits with varying time intervals. 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

Recent findings highlight that Reelin, a glycoprotein involved in neural development, synaptic plasticity, and neuroinflammation, plays some specific roles in neurodegenerative disorders associated with aging, such as age-related macular degeneration (AMD) and Alzheimer’s disease (AD). Reelin modulates synaptic function and guarantees homeostasis in neuronal-associated organs/tissues (brain and retina). The expression of Reelin is dysregulated in these neurological disorders, showing common pathways depending on chronic neurogenic inflammation and/or dysregulation of the extracellular matrix in which Reelin plays outstanding roles. Recently, the relationship between AMD and AD has gained increasing attention as they share many common risk factors (aging, genetic/epigenetic background, smoking, and malnutrition) and histopathological lesions, supporting certain pathophysiological crosstalk between these two diseases, especially regarding neuroinflammation, oxidative stress, and vascular complications. Outside the nervous system, Reelin is largely produced at the gastrointestinal epithelial level, in close association with innervated regions. The expression of Reelin receptors inside the gut suggests interesting aspects in the field of the gut–brain–eye axis, as dysregulation of the intestinal microbiota has been frequently described in neurodegenerative and behavioral disorders (AD, autism, and anxiety and/or depression), most probably linked to inflammatory, neurogenic mediators, including Reelin. Herein we examined previous and recent findings on Reelin and neurodegenerative disorders, offering findings on Reelin’s potential relation with the gut–brain and gut–brain–eye axes and providing novel attractive hypotheses on the gut–brain–eye link through neuromodulator and microbiota interplay. Neurodegenerative disorders will represent the ground for a future starting point for linking the common neurodegenerative biomarkers (β-amyloid and tau) and the new proteins probably engaged in counteracting neurodegeneration and synaptic loss. Full article

Herpes simplex virus type 1 (HSV-1) is associated with eye infections. Specifically, the acute consequences of eye infections have been extensively studied. This review gathers information on possible collateral damage caused by HSV-1 in the retina, such as age-related macular degeneration (AMD), a neurodegenerative disease. The synthesis and accumulation of Amyloid-β peptide (Aβ) is a key hallmark in these types of pathologies. AMD is a disease of multifactorial origin, and viral infections play an important role in its development. It is known that once this virus has entered the eye, it can infect adjacent cells, thus having the ability to infect almost any cell type with great tropism. In the retina, retinal pigment epithelial (RPE) cells are primarily involved in AMD. This work reviews publications that show that RPE can produce Aβ, and once they are infected by HSV-1, the release is promoted. Also, all the information available in the literature that explains how these events may be interconnected has been compiled. This information is valuable when planning new treatments for multifactorial neurodegenerative diseases. Full article

The retinal pigment epithelium (RPE), a monolayer of pigmented cells, is critical for visual function through its interaction with the neural retina. In healthy eyes, RPE cells exhibit a uniform hexagonal arrangement, but under stress or disease, such as age-related macular degeneration (AMD), dysmorphic traits like cell enlargement and apparent multinucleation emerge. Multinucleation has been hypothesized to result from cellular fusion, a compensatory mechanism to maintain cell-to-cell contact and barrier function, as well as conserve resources in unhealthy tissue. However, traditional two-dimensional (2D) imaging using apical border markers alone may misrepresent multinucleation due to the lack of lateral markers. We present high-resolution confocal images enabling three-dimensional (3D) visualization of apical (ZO-1) and lateral (α-catenin) markers alongside nuclei. In two RPE damage models, we find that seemingly multinucleated cells are often single cells with displaced neighboring nuclei and lateral membranes. This emphasizes the need for 3D analyses to avoid misidentifying multinucleation and underlying fusion mechanisms. Lastly, images from the NaIO₃ oxidative damage model reveal variability in RPE damage, with elongated, dysmorphic cells showing increased ZsGreen reporter protein expression driven by EMT-linked CAG promoter activity, while more regular RPE cells displayed somewhat reduced green signal more typical of epithelial phenotypes. Full article

Visual field (VF) testing remains a cornerstone in assessing retinal function by measuring how well different parts of the retina detect light. It is essential for early detection, monitoring, and management of many retinal diseases. By mapping retinal sensitivity, VF exams can reveal functional loss before structural changes become visible. This review summarizes how VF testing is applied across key conditions: hydroxychloroquine (HCQ) retinopathy, age-related macular degeneration (AMD), diabetic retinopathy (DR) and macular edema (DME), and inherited disorders including inherited dystrophies such as retinitis pigmentosa (RP). Traditional methods like the Goldmann kinetic perimetry and simple tools such as the Amsler grid help identify large or central VF defects. Automated perimetry (e.g., Humphrey Field Analyzer) provides detailed, quantitative data critical for detecting subtle paracentral scotomas in HCQ retinopathy and central vision loss in AMD. Frequency-doubling technology (FDT) reveals early neural deficits in DR before blood vessel changes appear. Microperimetry offers precise, localized sensitivity maps for macular diseases. Despite its value, VF testing faces challenges including patient fatigue, variability in responses, and interpretation of unreliable results. Recent advances in artificial intelligence, virtual reality perimetry, and home-based perimetry systems are improving test accuracy, accessibility, and patient engagement. Integrating VF exams with these emerging technologies promises more personalized care, earlier intervention, and better long-term outcomes for patients with retinal disease. Full article

Age-related ocular conditions like macular degeneration (AMD), diabetic retinopathy (DR), and glaucoma are leading causes of irreversible vision loss globally. Optical coherence tomography (OCT) provides essential non-invasive visualization of retinal structures for early diagnosis, but manual analysis of these images is labor-intensive and prone to variability. Deep learning (DL) techniques have emerged as powerful tools for automating the segmentation of the retinal layer in OCT scans, potentially improving diagnostic efficiency and consistency. This review systematically evaluates the state of the art in DL-based retinal layer segmentation using the PRISMA methodology. We analyze various architectures (including CNNs, U-Net variants, GANs, and transformers), examine the characteristics and availability of datasets, discuss common preprocessing and data augmentation strategies, identify frequently targeted retinal layers, and compare performance evaluation metrics across studies. Our synthesis highlights significant progress, particularly with U-Net-based models, which often achieve Dice scores exceeding 0.90 for well-defined layers, such as the retinal pigment epithelium (RPE). However, it also identifies ongoing challenges, including dataset heterogeneity, inconsistent evaluation protocols, difficulties in segmenting specific layers (e.g., OPL, RNFL), and the need for improved clinical integration. This review provides a comprehensive overview of current strengths, limitations, and future directions to guide research towards more robust and clinically applicable automated segmentation tools for enhanced ocular disease diagnosis. Full article

Gene therapy has emerged as a promising treatment for several eye diseases since it may restore vision and stop blindness. Many eye diseases, including retinitis pigmentosa and macular degeneration, have historically been rather difficult to treat and usually cause permanent vision loss. However, thanks to advances in gene therapy, many disorders can now be effectively targeted and genetically changed, providing a safer, more direct, maybe even curative approach. By introducing, altering, or repairing specific genes inside the eye, gene therapy seeks to fix the defective genes causing these disorders, thereby improving general eye health and visual ability. Voretigene neparvovec is one FDA- and EMA-approved treatment for RPE65 mutations. Retinitis pigmentosa, age-related macular degeneration, X-linked retinoschisis, choroideremia, and Stargardt disease are among the several eye disorders still under clinical trials, and experimental treatment is in progress. As research on gene therapy develops, it opens the path for groundbreaking treatments that could fundamentally change the ophthalmic care scene. Full article

Background: Optical Coherence Tomography has become a common imaging technique that enables a non-invasive and detailed visualization of the retina and allows for the identification of various diseases. Through the advancement of technology, the volume and complexity of OCT data have rendered manual analysis infeasible, creating the need for automated means of detection. Methods: This study investigates the ability of state-of-the-art object detection models, including the latest YOLO versions (from v8 to v12), YOLO-World, YOLOE, and RT-DETR, to accurately detect pathological biomarkers in two retinal OCT datasets. The AROI dataset focuses on fluid detection in Age-related Macular Degeneration, while the OCT5k dataset contains a wide range of retinal pathologies. Results: The experiments performed show that YOLOv12 offers the best balance between detection accuracy and computational efficiency, while YOLOE manages to consistently outperform all other models across both datasets and most classes, particularly in detecting pathologies that cover a smaller area. Conclusions: This work provides a comprehensive benchmark of the capabilities of state-of-the-art object detection for medical applications, specifically for identifying retinal pathologies from OCT scans, offering insights and a starting point for the development of future automated solutions for analysis in a clinical setting. Full article

Ocular diseases can significantly affect vision and overall quality of life, with diagnosis often being time-consuming and dependent on expert interpretation. While previous computer-aided diagnostic systems have focused primarily on medical imaging, this paper proposes VisionTrack, a multi-modal AI system for predicting multiple retinal diseases, including Diabetic Retinopathy (DR), Age-related Macular Degeneration (AMD), Diabetic Macular Edema (DME), drusen, Central Serous Retinopathy (CSR), and Macular Hole (MH), as well as normal cases. The proposed framework integrates a Convolutional Neural Network (CNN) for image-based feature extraction, a Graph Neural Network (GNN) to model complex relationships among clinical risk factors, and a Large Language Model (LLM) to process patient medical reports. By leveraging diverse data sources, VisionTrack improves prediction accuracy and offers a more comprehensive assessment of retinal health. Experimental results demonstrate the effectiveness of this hybrid system, highlighting its potential for early detection, risk assessment, and personalized ophthalmic care. Experiments were conducted using two publicly available datasets, RetinalOCT and RFMID, which provide diverse retinal imaging modalities: OCT images and fundus images, respectively. The proposed multi-modal AI system demonstrated strong performance in multi-label disease prediction. On the RetinalOCT dataset, the model achieved an accuracy of 0.980, F1-score of 0.979, recall of 0.978, and precision of 0.979. Similarly, on the RFMID dataset, it reached an accuracy of 0.989, F1-score of 0.881, recall of 0.866, and precision of 0.897. These results confirm the robustness, reliability, and generalization capability of the proposed approach across different imaging modalities. 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

This study aims to evaluate the real-world efficacy and safety of aflibercept 8 mg intravitreal injections (IVTs) in pretreated patients with neovascular age-related macular degeneration (nAMD) throughout the first three IVTs. Background: Established anti-vascular-endothelial-growth-factor (anti-VEGF) therapies positively impact the progression of nAMD but require frequent administration, thus burdening patients and the healthcare system. Pivotal trials of the recently approved aflibercept 8 mg have demonstrated extended dosing intervals with comparable safety to standard treatments. However, real-world data is still scarce. Methods: A retrospective, single-center single-arm analysis was conducted on 22 eyes from 18 pretreated nAMD patients. Eyes were switched from other anti-VEGF agents to aflibercept 8 mg injections continuing a treat-and-extend regimen (no loading dose after switching). Treatment intervals and structural (central subfield thickness (CST); disease activity) and functional (best corrected visual acuity (BCVA)) outcomes were assessed at baseline (date of first aflibercept 8 mg injection) and at follow-up examinations until follow-up 3. Safety data, including intraocular pressure changes, were recorded. Results: Over a median follow-up of 16.6 weeks (IQR 15.1–27.0), patients switched to aflibercept 8 mg showed prolonged intervals between injections (5.5 weeks vs. 7 weeks, p < 0.001, Wilcoxon signed-rank test), reduced disease activity, stable CST, and stable BCVA. One patient experienced transient intraocular pressure elevation, which resolved without intervention. No other adverse events were observed. Conclusions: Treatment with aflibercept 8 mg appears to provide effective disease control with prolonged treatment intervals in switched nAMD patients in routine clinical practice. These findings further indicate the potential for reducing treatment burden. Full article

Pupil cycle time (PCT) estimates the dynamics of a biofeedback loop established between pupil size and stimulus luminance, size or colour. The PCT is useful for probing the functional integrity of the retinopupillary circuits, and is therefore potentially applicable for assessing the effects of damage due to retinopathies or neuropathies. In previous studies, PCT was measured by manually counting the number of pupil oscillations during a fixed period to calculate the PCT. This method is scarce, requires a good expertise and cannot be used to estimate several PCT parameters, such as the oscillation amplitude or variability. We have developed a computerised setup based on eye-tracking that expands the possibilities of characterising PCT along several dimensions: oscillation frequency and regularity, amplitude and variability, which can be used with a large palette of stimuli (different colours, sizes, shapes or locations), and further allows measuring blinking frequency and eye movements. We used this method to characterise the PCT in young control participants as well as in patients with several pathologies, including age-related macular degeneration (AMD), diabetic retinopathy (DR), retinitis pigmentosa (RP), Stargardt disease (SD), and Leber hereditary optic neuropathy (LHON). We found that PCT is very regular and stable in young healthy participants, with little inter-individual variability. In contrast, several PCT features are altered in older healthy participants as well as in ocular diseases, including slower dynamics, irregular oscillations, and reduced oscillation amplitude. The distinction between patients and healthy participants based on the calculation of the area under the curve of the receiver operating characteristics (AUC of ROC) were dependent on the pathologies and stimuli (0.7 < AUC < 1). PCT nevertheless provides relevant complementary information to assess the physiopathology of ocular diseases and to probe the functioning of retino-pupillary circuits. Full article