Search Results (180)

Iron is an essential micronutrient integral to ocular physiology, supporting biochemical processes such as mitochondrial respiration, DNA synthesis and phototransduction. Disruptions in systemic or local iron homeostasis, whether due to overload or deficiency, have been increasingly implicated in the pathogenesis of a broad range of anterior and posterior segment ocular disorders. Iron deficiency may compromise retinal bioenergetics, impair cellular repair, and increase susceptibility to oxidative stress, while iron overload facilitates the generation of reactive oxygen species, contributing to lipid peroxidation, mitochondrial dysfunction, and ferroptosis. Dysregulated iron metabolism has been associated with several ocular pathologies, including age-related macular degeneration, diabetic retinopathy, glaucoma, retinal detachment, cataracts, and anemic retinopathy. The eye possesses specialized iron regulatory mechanisms involving proteins such as transferrin, ferritin, ferroportin, and hepcidin that govern iron transport, storage, and export across ocular barriers. Aberrations in these pathways are now recognized as contributing factors in disease progression. This narrative review explores the complex dual role of iron overload and deficiency in ocular diseases. It highlights the molecular mechanisms underlying iron-mediated pathologies in both the posterior and anterior segments of the eye, along with the clinical manifestations of iron imbalance. Current therapeutic approaches are discussed, including oral and parenteral iron supplementation for deficiency and emerging chelation-based or antioxidant strategies to address iron overload, while highlighting their limitations. Key challenges remain in developing targeted ocular delivery systems that optimize bioavailability and minimize systemic toxicity. Hence, maintaining iron homeostasis is critical for visual function, and further research is needed to refine therapeutic interventions and clarify the mechanistic role of iron in ocular health and disease. Full article

Background/Objectives: Age-related macular degeneration (AMD) is the leading cause of visual impairment among the elderly. Optical coherence tomography angiography (OCTA) is a non-invasive imaging modality that enables detailed visualisation of retinal vascular layers. However, clinical assessment of OCTA images is often challenging due to high data volume, pattern variability, and subtle abnormalities. This study aimed to develop automated algorithms to detect and quantify AMD in OCTA images, thereby reducing ophthalmologists’ workload and enhancing diagnostic accuracy. Methods: Two texture-based algorithms were developed to classify OCTA images without relying on segmentation. The first algorithm used whole local texture features, while the second applied principal component analysis ($PCA$) to decorrelate and reduce texture features. Local texture descriptors, including rotation-invariant uniform local binary patterns ($LB{P}^{2riu}$), local binary patterns ($LBP$), and binary robust independent elementary features ($BRIEF$), were combined with machine learning classifiers such as support vector machine (SVM) and K-nearest neighbour (KNN). OCTA datasets from Manchester Royal Eye Hospital and Moorfields Eye Hospital, covering healthy, dry AMD, and wet AMD eyes, were used for evaluation. Results: The first algorithm achieved a mean area under the receiver operating characteristic curve (AUC) of $1.00\pm 0.00$ for distinguishing healthy eyes from wet AMD. The second algorithm showed superior performance in differentiating dry AMD from wet AMD (AUC $0.85\pm 0.02$). Conclusions: The proposed algorithms demonstrate strong potential for rapid and accurate AMD diagnosis in OCTA workflows. By reducing manual image evaluation and associated variability, they may support improved clinical decision-making and patient care. Full article

Purpose: To systematically review the evidence regarding the characteristics of Optical Coherence Tomography Angiography (OCTA) in acute retinal arterial occlusion (RAO), with a particular focus on vascular alterations across the superficial and deep capillary plexuses, choroid, and peripapillary regions. Methods: A comprehensive literature search was performed across PubMed, Web of Science, Scopus, EMBASE, Google Scholar, and the Cochrane Database up to April 2025. The search terms included “Optical coherence tomography angiography,” “OCTA,” “Retinal arterial occlusion,” “Central retinal artery occlusion,” and “Branch retinal artery occlusion.” Studies were included if they evaluated the role of OCTA in diagnosing or assessing acute RAO. Case reports, conference abstracts, and non-English articles were excluded. Two reviewers independently conducted the study selection and data extraction. The methodological quality of the included studies was assessed using the Risk of Bias in Non-randomized Studies of Interventions (ROBINS-I) tool. Results: The initial search yielded 457 articles, from which 10 studies were ultimately included in the final analysis after a rigorous screening process excluding duplicates, non-English publications, and ineligible articles based on title, abstract, or full-text review. The included studies consistently demonstrated that OCTA is a valuable, noninvasive modality for evaluating microvascular changes in RAO. Key OCTA findings in acute RAO include significant perfusion deficits and reduced vessel density in both the superficial capillary plexus (SCP) and deep capillary plexus (DCP). Several studies noted more pronounced involvement of the SCP compared to the DCP. OCTA parameters, such as vessel density in the macular region, have been found to correlate with visual acuity, suggesting a prognostic value. While findings regarding the foveal avascular zone (FAZ) were mixed, the peripapillary area frequently showed reduced vessel density. Conclusion: Acute RAO is an ocular emergency that causes microvascular ischemic changes detectable by OCTA. This review establishes OCTA as a significant noninvasive tool for diagnosing, monitoring, and prognosticating RAO. It effectively visualizes perfusion deficits that correlate with clinical outcomes. However, limitations such as susceptibility to motion artifacts, segmentation errors, and the lack of standardized normative data must be considered. Future standardization of OCTA protocols and analysis is essential to enhance its clinical application in managing RAO. Full article

Background/objectives: Optic nerve bending and chiasmal compression impair vision in patients with sellar lesions; however, their effect on optic nerve head (ONH) blood flow remains unclear. This study used laser speckle flowgraphy to examine the relationship between clinical features and ONH blood flow in patients with optic nerve bending and chiasmal compression. Methods: This retrospective study included 32 eyes (16 eyes with and 16 without optic nerve bending on the contralateral side) from 16 patients with sellar lesions. The best-corrected visual acuity (BCVA), simple visual field impairment score (SVFIS), optic nerve head mean blur rate (ONH-MBR), and six-segmented macular ganglion cell layer + inner plexiform layer (GCL + IPL) thickness were examined. Results: Preoperative BCVA and SVFIS in eyes with optic nerve bending were significantly worse than those in eyes without bending, and significantly correlated with the optic nerve-canal bending angle (ONCBA). After tumor resection, BCVA and SVFIS significantly improved in both groups. Preoperative ONH-MBR was significantly lower in bending eyes but increased significantly post-treatment in both groups. Preoperative ONH-MBR correlated with ONCBA, while postoperative ONH-MBR correlated with nasal GCL + IPL thickness. Conclusions: Optic nerve bending and chiasmal compression showed reduced blood flow to the ONH. These changes in blood flow may be associated with GCL + IPL thickness and optic nerve bending angle. Full article

RNA-seq analysis of the highly differentiated human retinal pigment epithelial (RPE) cell-line ARPE-19, cultured on transwells for ≥4 months, yielded 44,909 genes showing 83.35% alignment with the human reference genome. These included mRNA transcripts of RPE-specific genes and those involved in retinopathies. Monolayers were fed photoreceptor outer segments (POS), designed to be synchronously internalised, mimicking homeostatic RPE activity. Cells were subsequently fixed at 4, 6, 24 and 48 h when POS were previously shown to maximally co-localise with Rab5, Rab7, LAMP/lysosomes and LC3b/autophagic compartments. A comprehensive analysis of differentially expressed genes involved in proteolysis revealed a pattern of gene orchestration consistent with POS breakdown in the autophagy-lysosomal pathway. At 4 h, these included elevated upstream signalling events promoting early stages of cargo transport and endosome maturation compared to RPE without POS exposure. This transcriptional landscape altered from 6 h, transitioning to promoting cargo degradation in autolysosomes by 24–48 h. Longitudinal scrutiny of mRNA transcripts revealed nuanced differences even within linked gene networks. POS exposure also initiated transcriptional upregulation in ubiquitin proteasome and chaperone-mediated systems within 4–6 h, providing evidence of cross-talk with other proteolytic processes. These findings show detailed evidence of transcriptome-level responses to cargo trafficking and processing in RPE cells. 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

Background/Objectives: To investigate the effect of ellipsoid zone (EZ) integrity and retinal fluid on best-corrected visual acuity (BCVA) in neovascular, age-related macular degeneration. Methods: This was a post hoc treatment-agnostic analysis of the phase 3 HAWK trial. Intraretinal fluid (IRF), subretinal fluid (SRF), and ellipsoid zone (EZ) integrity were quantified over 48 weeks. EZ integrity maintenance was defined as EZ-RPE central subfield thickness (CST) >20 µm; partial EZ attenuation was EZ-RPE CST >0 and ≤20 µm; total EZ attenuation was EZ-RPE CST = 0 µm. Results: During treatment, BCVA in eyes with no fluid (66.5 to 70.2 letters) was greater than in eyes with IRF (59.5 to 62.4 letters) but comparable to BCVA in eyes with SRF (64.9 to 68.8 letters). In eyes with no fluid, BCVA was consistently greater in eyes with EZ integrity maintained (73.4 to 78.4 letters) than in eyes with EZ partial attenuation (65.3 to 66.5 letters) or with EZ total attenuation (55.8 to 59.8 letters). Conclusions: Eyes without fluid with EZ preservation achieved the highest overall BCVA, especially when compared to eyes without fluid and a lack of EZ preservation and to eyes with SRF. Achieving a “dry” status with preservation of EZ integrity is important in optimizing visual outcomes. Full article

Objective: To conduct a comparative analysis of layer-by-layer macular thickness, peripapillary retinal nerve fiber layer (pRNFL), and minimum rim width (MRW) between the eyes of patients with prostate cancer undergoing treatment with androgen receptor pathway inhibitors (ARPIs) and those of age- and sex-matched healthy controls, with the aim of assessing the potential effects of ARPIs on retinal structure. Methods: In this prospective cross-sectional study, 80 eyes of 80 patients with ARPI-treated metastatic prostate cancer and 80 eyes of 80 age-matched healthy controls were evaluated using Heidelberg Spectralis optical coherence tomography (OCT). Layer-by-layer macular thickness, pRNFL, and MRW were measured and compared between groups. Results: Thickness in most segments of retinal layers and pRNFL, as well as all MRW values, were significantly lower in the ARPI-treated group than in the controls (p < 0.05). No significant differences were observed between groups in terms of age, visual acuity, intraocular pressure, central corneal thickness, or lens status. Conclusions: This study is the first to evaluate layer-by-layer macular thickness in patients with metastatic prostate cancer treated with ARPIs, revealing significant thinning in nearly all macular layers, pRNFL, and MRW. These findings suggest that ARPI therapy may induce neurodegenerative changes in retinal and optic nerve structures. Therefore, further research is warranted to assess the ocular safety of these therapeutic agents. Full article

Background/Objectives: Inherited retinal diseases (IRDs) are a heterogeneous group of rare eye disorders characterized by progressive photoreceptor degeneration, leading to severe visual impairment or even blindness. This study aims to investigate the prevalence, types, and clinical significance of ophthalmic comorbidities in Portuguese patients with IRDs. Methods: This nationwide Portuguese population-based retrospective study was based on the IRD-PT registry (retina.com.pt). Statistical analysis was conducted using Microsoft^® Excel^® for Microsoft 365 and IBM SPSS Statistics version 29.0.2.0. Informed consent was obtained from all participants. Results: A total of 1531 patients (1254 families) from six centers were enrolled. The cohort consisted of 51% males, with a mean age of 45.8 ± 19.3 years and a mean age at diagnosis of 39.4 ± 19.5 years. Overall, ocular comorbidities were reported in 644 patients (42.1%). In 176 individuals (11.5%), multiple concurrent comorbidities were found. Cataract was the most common comorbidity (21.3%), followed by amblyopia (6.3%) and high myopia (5.9%). Statistically significant associations with ocular comorbidities were observed in isolated progressive IRDs. Specifically, AR RP was associated with cataract (p < 0.001), and gene analysis revealed several significant associations. CRB1 was statistically linked to epiretinal membrane (ERM) (p = 0.003), EYS with cataract (p = 0.001), PROM1 with choroidal neovascularization (CNV) (p = 0.0026), and USH2A with macular hole (p = 0.01). Patients with the RPE65 mutation in Leber congenital amaurosis were associated with ERM (p = 0.019). There was also a significant association between X-linked RP and high myopia (p < 0.001) and CNV in Best disease (p < 0.001); in syndromic IRDs, cataract, cystoid macular edema, and ERM were observed in Usher syndrome, p = 0.002, p = 0.002, and p = 0.005, respectively, and the MYO7A gene was linked to cataract (p = 0.041) and strabismus (p = 0.013); pseudoxanthoma elasticum was significantly associated with CNV (p = 0.002); and foveal hypoplasia was associated with anterior segment dysgenesis (p < 0.001). Conclusions: This study enhances the current understanding of ocular comorbidities in IRDs in Portuguese patients. Common findings were cataract, refractive error, and CME. Stationary IRDs and pattern dystrophies showed fewer concomitant comorbidities, supporting their classification as non-progressive or benign conditions. The significance of registries like IRD-PT cannot be overstated, particularly in the context of rare diseases. These databases serve multiple crucial functions in enabling detailed documentation of disease characteristics and long-term monitoring of disease progression. Full article

Background: Topical statin therapy holds promise for ocular diseases, such as age-related macular degeneration, but the effective delivery to the posterior segment is limited by poor aqueous solubility, chemical instability, and ocular barriers. Cyclodextrins (CDs) can enhance statin solubility and stability; however, the behavior of CD–statin complexes in aqueous eye drops—particularly their influence on the equilibrium between the inactive lactone (ring closed) and active hydroxyacid forms (ring open)—remains unclear. This study aimed to (i) investigate how 5% and 10% (w/v) concentrations of selected CDs affect the lactone/acid equilibrium of simvastatin and atorvastatin and (ii) define formulation parameters (statin form, CD type and concentration, and pH range) for stable eye drop development. Methods: Simvastatin or atorvastatin was added to buffered solutions (pH 2.0 to pH 9.5) of RMβCD, HPβCD, γ-CD, or SBEβCD at 0%, 5%, and 10% (w/v), incubated at 23 ± 1 °C, and sampled over time for UPLC quantification of lactone and hydroxyacid forms, and rate constants for the forward and reverse reaction were calculated. Phase solubility studies were also conducted to further characterize equilibrium behavior in aqueous CD systems. Results: The lactone form was most stable at a pH of 4.5, while the hydroxyacid form prevailed at a pH ≥ 7. γ-CD and HPβCD accelerated lactone hydrolysis for both statins, whereas RMβCD exerted a stabilizing effect. Increasing the CD concentration from 5% to 10% provided minimal additional stabilization. Conclusions: These findings highlight that the precise control of the pH, an appropriate cyclodextrin choice, and the selection of the statin form are critical to developing chemically stable eye drops. Full article

Geographic atrophy (GA) is a progressive retinal disease associated with late-stage age-related macular degeneration (AMD), a significant cause of visual impairment in senior adults. GA lesion segmentation is important for disease monitoring in clinical trials and routine ophthalmic practice; however, its manual delineation is time-consuming, laborious, and subject to inter-grader variability. The use of artificial intelligence (AI) is rapidly expanding within the medical field and could potentially improve accuracy while reducing the workload by facilitating this task. This systematic review evaluates the performance of AI algorithms for GA segmentation and highlights their key limitations from the literature. Five databases and two registries were searched from inception until 23 March 2024, following the PRISMA methodology. Twenty-four studies met the prespecified eligibility criteria, and fifteen were included in this meta-analysis. The pooled Dice similarity coefficient (DSC) was 0.91 (95% CI 0.88–0.95), signifying a high agreement between the reference standards and model predictions. The risk of bias and reporting quality were assessed using QUADAS-2 and CLAIM tools. This review provides a comprehensive evaluation of AI applications for GA segmentation and identifies areas for improvement. The findings support the potential of AI to enhance clinical workflows and highlight pathways for improved future models that could bridge the gap between research settings and real-world clinical practice. Full article

Background/Objectives: Exudative age-related macular degeneration (AMD) is a disease of choroidal neovascularization that causes blindness. Current treatments to preserve vision in this prevalent and blinding condition are repeat intraocular injections of anti-vascular endothelial growth factor medicines for a patient’s lifetime to preserve and prevent vision loss leading to blindness. Rifampicin, a small-molecule antibiotic, has previously been reported to exhibit anti-angiogenic properties and a topical safety profile that is well-tolerated. Based on this evidence, we investigated the feasibility of formulating rifamycin as an ophthalmic drop capable of delivering therapeutic concentrations to the posterior segment of the eye. Methods: Inhibition of neovascularization by administration of rifampicin was analyzed in the rat oxygen-induced retinopathy (OIR) and mouse laser-induced choroidal neovascularization (CNV) models. Pharmacokinetic (PK) studies were conducted in mice, rats, and rabbits by dosing various formulations containing rifampicin, and the compound was quantified by LC/MS analysis. Results: Results from dose escalation studies in the mouse laser-induced CNV model suggested the minimum effective dose of rifampicin required for inhibiting neovascularization in subretinal tissues to be 0.7 mg/kg, which is substantially lower than the 20 mg/kg dosage approved for infectious disease treatments. The previous studies did not report the minimum effective dose in the anti-angiogenesis effects. The effective area under the concentration-time curve (AUC) in the sub-retina was evaluated as 0.27 h·ng/mg. In rabbits, rifampicin was delivered to the sub-retina by a single topical application of various formulations in a dose-dependent manner. The topical application of the formulations containing 1% rifampicin, which was well-tolerated in clinical trials previously reported for ocular trachoma, achieved subretinal delivery approximately 2–32 times greater than the effective AUC. Plasma exposure of the compound by the topical application was evaluated to range approximately 0.5–10 ng/mL. Conclusions: Rifampicin was delivered to the sub-retina in rabbits with an efficiency greater than the effective dose required for inhibiting neovascularization. Limited amounts of plasma exposure by the topical application were detected. These results suggested the therapeutic potential of the rifampicin formulations for the topical treatment of exudative macular degeneration. Full article

Background/Objectives: Chronic macular edema (CME) is a common complication of diabetic retinopathy or non-infectious uveitis affecting the posterior segment (NIU-PS). Alongside anti-VEGF therapy, glucocorticoids are frequently used to manage CME. Given the heterogeneous nature of patients’ medical history, their social conditions, and disease manifestations, individualized treatment is essential for optimal outcomes. This study assesses the effectiveness of intravitreal fluocinolone acetonide (FA) (Iluvien^®) in treating persistent and recurrent macular edema in clinical practice at the University Hospital of Erlangen–Nuremberg, Germany. Methods: A total of 46 eyes with diabetic macular edema (DME) (21 eyes) and NIU-PS (25 eyes) were retrospectively analyzed over a follow-up period of up to 36 months. Since persistent retinal thickness fluctuations are linked to long-term retinal damage and functional decline, this study analyzed central retinal thickness (CRT)—including its fluctuations measured as CRT amplitude—alongside BCVA as the primary outcomes. Results: After an initial decrease in CRT in the first year after FA treatment, the maximum CRT amplitude significantly decreased in the following years. For patients with DME, CRT amplitude reduced from 271.4 µm to 91.57 µm in the first year (p = 0.0056) and 106.0 µm in the second year (p = 0.0109). For patients with NIU-PS, CRT amplitude decreased from 185.2 µm to 87.7 µm in the first year (p = 0.0131) and 97.3 µm in the second year (p = 0.0375). Mean BCVA remained stable in both cohorts. Conclusions: Intravitreal FA proved to be effective in reducing and stabilizing CRT in patients with chronic DME and NIU-PS without losing visual acuity, reducing treatment burden. Full article

Retinal thickness analysis using optical coherence tomography (OCT) has become an indispensable tool in retinal disease management, providing high-resolution quantitative data for diagnosis, monitoring, and treatment planning. This analysis has been found to be particularly useful for both diagnostic and monitoring purposes across a wide range of retinal diseases, enabling precise disease characterization and treatment evaluation. This paper explores its applications across major retinal conditions, including age-related macular degeneration, diabetic retinopathy, retinal vein occlusion, and inherited retinal diseases. Emerging roles in other diseases such as neurodegenerative diseases and retinal drug toxicity are also highlighted. Despite challenges such as variability in measurements, segmentation errors, and interpretation difficulties, advancements in artificial intelligence and machine learning have significantly improved accuracy and efficiency. The integration of retinal thickness analysis with telemedicine platforms and standardized protocols further underscores its potential in delivering personalized care and enabling the early detection of ocular and systemic diseases. Retinal thickness analysis continues to play a pivotal and growing role in both clinical practice and research, bridging the gap between ophthalmology and broader medical fields. Full article

Optical coherence tomography angiography (OCTA) is a noninvasive imaging technique used to visualize retinal blood flow and identify changes in vascular density and enlargement or distortion of the foveal avascular zone (FAZ), which are indicators of various eye diseases. Although several automated FAZ detection and segmentation algorithms have been developed for use with OCTA, their performance can vary significantly due to differences in data accessibility of OCTA in different retinal pathologies, and differences in image quality in different subjects and/or different OCTA devices. For example, data from subjects with direct macular damage, such as in age-related macular degeneration (AMD), are more readily available in eye clinics, while data on macular damage due to systemic diseases like Alzheimer’s disease are often less accessible; data from healthy subjects may have better OCTA quality than subjects with ophthalmic pathologies. Typically, segmentation algorithms make use of convolutional neural networks and, more recently, vision transformers, which make use of both long-range context and fine-grained detail. However, transformers are known to be data-hungry, and may overfit small datasets, such as those common for FAZ segmentation in OCTA, to which there is limited access in clinical practice. To improve model generalization in low-data or imbalanced settings, we propose a multi-condition transformer-based architecture that uses four teacher encoders to distill knowledge into a shared base model, enabling the transfer of learned features across multiple datasets. These include intra-modality distillation using OCTA datasets from four ocular conditions: healthy aging eyes, Alzheimer’s disease, AMD, and diabetic retinopathy; and inter-modality distillation incorporating color fundus photographs of subjects undergoing laser photocoagulation therapy. Our multi-condition model achieved a mean Dice Index of 83.8% with pretraining, outperforming single-condition models (mean of 83.1%) across all conditions. Pretraining on color fundus photocoagulation images improved the average Dice Index by a small margin on all conditions except AMD (1.1% on single-condition models, and 0.1% on multi-condition models). Our architecture demonstrates potential for broader applications in detecting and analyzing ophthalmic and systemic diseases across diverse imaging datasets and settings. Full article