Search Results (893)

Glaucoma is a leading cause of irreversible vision loss characterized by the progressive degeneration of retinal ganglion cells (RGCs) and structural and biochemical remodeling of the optic nerve head. Although lowering intraocular pressure remains the primary clinical intervention, neurodegeneration often persists, highlighting the complexity and multiple mechanisms involved in the disease’s pathophysiology. In the healthy retina, astrocytes and Müller cells maintain structural integrity, homeostatic balance, and metabolic support. However, sustained pathological stress triggers reactive gliosis, a phenomenon with a dichotomous phenotype. Initially, the macroglial response is adaptive and neuroprotective. Persistent biomechanical and ischemic insults shift this profile into a typically deleterious one, characterized by extracellular matrix remodeling, complement system activation, and heightened neuroinflammation, factors that intensify RGC death. Mechanosensitive pathways, notably Piezo1 and various transient receptor potential (TRP) channels, emerge as critical sensors translating physical stress into these reactive cascades within interconnected multicellular networks. This review examines the crucial role of astrocytes and Müller cells in the dynamic modulation of the retinal microenvironment during glaucomatous progression. Finally, it discusses the therapeutic potential of macroglia-directed pharmacological or gene therapies to reprogram the retinal environment. 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

Neurodegenerative diseases represent a major and growing global health burden characterized by progressive neuronal dysfunction, axonal degeneration, and irreversible neural tissue loss. Increasing evidence identifies oxidative stress as one of several interacting pathogenic mechanisms in Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, and several optic neuropathies. Interest has increasingly focused on the brain-retina axis, as the retina and optic nerve share structural, metabolic, and molecular features with the central nervous system and may provide accessible insights into neurodegeneration. This scoping review mapped current evidence on oxidative stress in neurodegeneration, emphasizing cranial nerve involvement, optic nerve vulnerability, retinal ganglion cell degeneration, visual dysfunction, oxidative biomarkers, and emerging therapeutic strategies. The review followed established methodological frameworks and PRISMA-ScR recommendations; no formal risk-of-bias appraisal was undertaken, consistent with scoping-review methodology. The literature shows that oxidative stress interacts with mitochondrial dysfunction, neuroinflammation, impaired mitophagy, ferroptosis, and altered bioenergetics, contributing to neuronal injury in cerebral and retinal disorders. Retinal ganglion cells appear particularly vulnerable because of their high metabolic demands and reliance on oxidative phosphorylation. Glaucoma and other optic neuropathies share molecular signatures with central neurodegenerative diseases. Retinal imaging and oxidative biomarkers show promise for diagnosis, monitoring, and stratification. The evidence base is nonetheless dominated by preclinical work; biomarker performance is inconsistent across matrices and assay platforms and most antioxidant clinical trials have been negative. Oxidative stress is therefore best regarded as one interacting node of a broader pathogenic network rather than a universal or predominant driver and the brain-retina continuum as a mechanistically plausible but not yet clinically validated framework for biomarker-guided neuroprotection. Full article

Ocular diseases are a significant public health problem worldwide and represent one of the leading causes of disability. The prevalence of visual impairment is steadily increasing, largely driven by the ageing population. Oxidative stress, chronic inflammation and neurodegenerative processes underlie the pathogenesis of many eye diseases, including age-related macular degeneration (AMD), diabetic retinopathy, glaucoma, and cataracts, contributing to progressive vision loss and functional impairment. Carotenoids such as lutein, zeaxanthin, meso-zeaxanthin, β-carotene, lycopene, and astaxanthin exhibit multidirectional biological effects, including antioxidant, anti-inflammatory, and neuroprotective properties. These compounds are selectively accumulated in the tissues of the eye, especially in the retina and macula, where they neutralise reactive oxygen species, modulate inflammatory pathways, stabilise mitochondrial function and support the survival and function of retinal ganglion cells and photoreceptors. The aim of our review was to provide a comprehensive review of current data regarding the mechanisms of action of carotenoids and their potential clinical significance in the prevention and treatment of retinal, optic nerve, lens, and eye surface diseases, including dry eye syndrome and Meibomian gland dysfunction. We identified results of available experimental and clinical research and outlined that an adequate supply of carotenoids in the diet or in the form of supplementation may support the protection of eye structures against oxidative and inflammatory damage, improve visual performance and potentially slow disease progression. However, high-quality prospective clinical trials are necessary to conclusively assess their therapeutic efficacy and establish evidence-based recommendations for clinical practice. Full article

Objectives: To evaluate the retinal ganglion cell (RGC) function and neural conduction along the visual pathways after treatment with Citicoline plus Nicotinamide oral solution in patients with open angle glaucoma (OAG). Methods: Thirty OAG patients (mean age ± standard deviation: 62.588 ± 6.022 years, IOP < 18 mmHg with medical therapy) were enrolled. Of these, 20 OAG patients (providing 20 eyes) were treated with Citicoline plus Nicotinamide oral solution (Kron^®, Omikron Italia) (Citicoline plus Nicotinamide group), and 10 OAG patients (providing 10 eyes) were treated with an oral placebo (Placebo group). In all participants, Humphrey 24-2 visual field (HFA 24-2), pattern electroretinogram (PERG), visual evoked potentials (VEP) and retinal nerve fiber layer thickness (RNFL-T) were assessed at baseline and at the end of the 3-month period of treatment. Results: PERG and VEP data obtained from 28 patients were included in the final analysis, while all the patients were included in the visual field and RNFL-T analyses. At baseline, both groups showed HFA 24-2 mean deviation (MD), PERG, VEP and RNFL-T values not statistically (ANOVA, p > 0.05) different. After 3 months of Citicoline plus Nicotinamide oral solution treatment, a significant (p < 0.05) increase in PERG P50-N95 and VEP N75-P100 amplitudes, and a significant (p < 0.05) shortening of VEP P100 implicit times were found. The shortening of VEP P100 implicit times was not significantly correlated (p > 0.01) with the increase in PERG P50-N95 amplitude. Conversely, in the Placebo group, no significant changes in PERG and VEP values were found. The HFA MD and RNFL-T changes were not significantly different (p > 0.05) between groups. Conclusions: In OAG patients, treatment with Citicoline plus Nicotinamide oral solution for three months induces RGC functional enhancement (increase in PERG amplitude) and improves the neural conduction along the visual pathways (shortening of VEP implicit time and increased amplitude), without significant changes in visual field or RNFL-T. Full article

Glutamate excitotoxicity is a key contributor to the pathogenesis of glaucoma, a leading cause of irreversible blindness worldwide; however, the molecular events driving progressive retinal ganglion cell (RGC) loss and axonal degeneration remain incompletely understood, and effective neuroprotective therapies are lacking. Here, we evaluated the preventive potential of K9-C-peptide, a biopolymer-conjugated human C-peptide, in a mouse model of N-methyl-D-aspartate (NMDA)-induced retinal neurodegeneration and optic nerve axonal transport impairment, and examined potential mechanisms underlying its protective effects. In NMDA-induced excitotoxic mouse retinas, intracellular Ca²⁺ elevation mediated NMDA-induced oxidative stress, including both intracellular and mitochondrial reactive oxygen species (ROS) generation and lipid peroxidation. NMDA exposure induced activation of Müller glia and microglia and upregulation of inflammatory cytokines, ultimately leading to RGC death; these effects were attenuated by prolonged intraocular delivery of ROS scavengers. K9-C-peptide significantly reduced NMDA-induced retinal degeneration, including RGC loss and retinal thinning, and preserved optic nerve axonal transport function in both whole-mount retinas and optic nerve longitudinal sections. These protective effects were associated with suppression of NMDA-induced oxidative stress, mitochondrial dysfunction, and inflammation and reactive gliosis, without altering intracellular Ca²⁺ levels. Notably, sustained intraocular delivery of human C-peptide conferred robust neuroprotection for at least 3 weeks against NMDA-induced retinal degeneration and optic nerve axonal transport impairment. These findings suggest that K9-C-peptide acts as a long-acting neuroprotective agent that mitigates oxidative stress-driven retinal damage and axonal dysfunction, highlighting its translational potential as a C-peptide-based neuroprotective strategy for retinal glutamate excitotoxicity. Full article

Glaucoma is a major global health concern, identified as the foremost cause of irreversible blindness, affecting nearly 95 million individuals. It is characterized by the progressive degeneration of retinal ganglion cells (RGCs), leading to significant vision-related disabilities and an extensive socio-economic impact. The concept that glaucoma should be viewed not solely as an ocular condition but also as a neurodegenerative disorder, sharing pathophysiological features with diseases like Alzheimer’s and Parkinson’s, is now widely accepted. This review examines the convergence of molecular mechanisms, including the roles of amyloid precursor proteins and neuroinflammation, that contribute to RGC loss. Notably, lithium, traditionally used as a mood stabilizer, has emerged as a potential neuroprotective agent for the treatment of Alzheimer’s disease. In light of the common neurodegenerative mechanisms linking glaucoma with central neurodegenerative diseases, here, we review the current evidence supporting lithium’s therapeutic potential in glaucoma, emphasizing the need for further clinical studies to determine its effectiveness in preserving optic nerve health and improving patient outcomes. Full article

Background: The latest revision of the McDonald criteria for diagnosis of multiple sclerosis (MS) establishes that the optic nerve can serve as a fifth anatomical location within the central nervous system for diagnosis. Optical coherence tomography (OCT) images can serve as evidence for this purpose. Objective: To assess the accuracy of automated artificial-intelligence-based classification of MS patients using OCT data obtained from two different centers. Methods: OCT data were collected from two centers using standardized APOSTEL-based protocols and similar equipment. Retinal layer thicknesses—mean and standard deviation (STD) values—were analyzed in four layers and in six regions per layer per eye. A support vector machine classifier with recursive feature elimination and Shapley additive explanations value analysis was applied to identify the most relevant features and maximize classification accuracy between control subject and MS patient eyes. Results: The database drawn from two hospitals comprised 112 eyes with MS without prior history of optic neuritis and 193 eyes of control subjects. The classifier achieved maximum accuracy (0.8459) using 20 input features. The mean and STD metrics had similar importance, with the most influential layers being the ganglion cell layer, inner plexiform layer, and the inner retinal layer complex. Key regions included the papillomacular bundle and the superior temporal perimacular area. Conclusions: OCT data facilitates highly accurate MS diagnosis across different centers. Artificial intelligence assessment could facilitate automated classification. These findings provide evidence of the important role of the optic nerve in MS diagnosis. Full article

Background/Objectives: This study investigates the correlation between substantia nigra (SN) hyperechogenicity, detected via transcranial sonography (TCS), and retinal thinning in patients with Parkinson’s disease (PD). Methods: In this cross-sectional study, 86 PD patients (172 eyes) underwent clinical assessment (UPDRS, Hoehn–Yahr), TCS for SN area measurement, and optical coherence tomography (OCT) for retinal nerve fiber layer (RNFL), ganglion cell-inner plexiform layer (GCIPL), and macular thickness analysis. Results: PD patients exhibited significant thinning of the GCIPL, average RNFL, and central macular thickness compared to healthy controls (p < 0.001 in all instances). Pathological SN hyperechogenicity (>0.19 cm²) was detected in 85.9% of patients with a preserved temporal bone window (71 out of 86). A significant negative correlation was found specifically between the SN echogenic area and central macular thickness (r = −0.248, p = 0.003). Patients with pathological SN findings had a significantly thinner central macula (p = 0.006) compared to those with a normal SN, while no significant correlations were observed between the SN area and RNFL or GCIPL. Conclusions: These findings demonstrate a specific correlation between SN hyperechogenicity and central macular thinning. While RNFL and GCIPL effectively differentiate PD from controls, the central macula might serve as a promising biomarker candidate reflecting SN changes. Further longitudinal studies are required to evaluate the role of these combined markers in the PD diagnostic algorithm. Full article

Background/Objectives: To evaluate long-term neuroretinal changes in patients with persistent COVID-19 (PC) versus asymptomatic controls, using optical coherence tomography (OCT) over a two-year follow-up. Methods: This prospective longitudinal study enrolled 133 participants: 94 PC patients and 39 control subjects. Participants underwent comprehensive ophthalmological assessment at baseline, at 1 year (voluntary), and at 2 years. Structural retinal changes were analysed using spectral-domain OCT with the Bruch’s Membrane Opening–Minimum Rim Width and Posterior Pole protocols. Longitudinal analyses focused on within-subject change from baseline to 2 years and on between-group comparisons of these change scores, with Bonferroni correction applied within predefined families of comparisons. Results: The most robust corrected between-group longitudinal finding was a greater decrease in the central macular sector (C0) of the inner plexiform layer (IPL) in PC patients than in control subjects. Conclusions: Although these findings suggest possible subtle inner retinal involvement in PC patients, particularly in the central IPL, the results should be interpreted cautiously because of the modest control sample, control-group heterogeneity, and the exploratory nature of the sectoral OCT analyses. OCT may be useful in research settings as a complementary tool for exploring subtle neuroretinal changes in PC patients; however, its clinical utility and role as a validated biomarker remain unproven. Full article

Progression independent of relapse activity (PIRA) and smouldering multiple sclerosis (MS) represent major unmet challenges in contemporary MS care. Disability may accumulate independently of clinical relapses, driven in part by chronic compartmentalised inflammation behind a relatively intact blood–brain barrier and incompletely captured by conventional monitoring tools. This narrative review synthesises evidence across four complementary biomarker domains for detecting smouldering MS and PIRA: advanced MRI (paramagnetic rim lesions [PRLs], slowly expanding lesions, deep grey matter atrophy, quantitative susceptibility mapping); fluid biomarkers (serum glial fibrillary acidic protein [sGFAP], serum neurofilament light chain [sNfL]); retinal optical coherence tomography (ganglion cell–inner plexiform layer thinning); and digital health metrics (wearable accelerometry, digital Symbol Digit Modalities Test). In a single prospective cohort, combined elevation of sGFAP and sNfL conferred a 4.71-fold increased hazard for PIRA (HR 4.71; 95% CI 2.05–9.77); independent data suggest sGFAP may carry selectivity for progression beyond sNfL, although this remains to be confirmed. No single domain sufficiently characterises smouldering pathology. We therefore propose a hypothesis-generating Multimodal PIRA Score (MPS) as a conceptual validation scaffold intended to structure—rather than inform—prospective multicentre evaluation against a long-horizon disability endpoint. Harmonisation of acquisition protocols, reference ranges, and digital phenotyping algorithms remains a prerequisite. Full article

Background: This study aimed to evaluate longitudinal changes in retinal layers, retinal vessel diameters, and choroidal thickness using optical coherence tomography (OCT) in patients with central retinal artery occlusion (CRAO). Methods: This retrospective study included 35 patients (70 eyes) diagnosed with unilateral CRAO between 1 January 2020 and 5 January 2024. Unaffected fellow eyes served as internal controls. OCT-based macular segmentation, retinal arterial and venous diameter measurements, and subfoveal and peripapillary choroidal thickness were assessed in the acute phase (<24 h) and at 1-month and 6-month follow-up visits. Subgroup analyses compared patients who received hyperbaric oxygen therapy (HBOT) with those who did not. Statistical analyses included t-tests, Mann–Whitney U, Wilcoxon signed-rank, and chi-square tests. Results: Retinal arterial and venous diameters showed significant narrowing during follow-up (arteries: 77.91  ±  11.77 µm to 70.74  ±  15.12 µm; veins: 130.94  ±  22.54 µm to 118.57  ±  20.61 µm; both p  <  0.05). Macular segmentation demonstrated marked thinning of the inner retinal layers, most prominently in the retinal nerve fiber layer and ganglion cell layer (40.09 ± 26.86 to 12.51 ± 4.99 µm and 61.20 ± 25.83 to 24.26 ± 12.11 µm, respectively; both p = 0.001). Subfoveal choroidal thickness progressively decreased over time (from 206.40 ± 34.91 µm to 178.86 ± 28.28 µm, p = 0.009). Peripapillary choroidal thickness increased across all quadrants at 6 months, most consistently in the inferior quadrant (p = 0.001). No significant differences in retinal or choroidal parameters were observed between HBOT-treated and non-treated patients. All cases exhibited persistent vascular occlusion without reperfusion. Conclusions: CRAO is characterized by progressive inner retinal atrophy, retinal vessel narrowing, and distinct temporal changes in choroidal morphology. The relative preservation and subsequent increase in peripapillary choroidal thickness during follow-up suggest dynamic choroidal involvement despite persistent occlusion. OCT-based macular segmentation and retinal vessel analysis provide objective biomarkers for longitudinal structural assessment in CRAO. By jointly quantifying retinal layer, retinal vascular, and choroidal remodeling, these findings may also provide reference data for future studies of structural evolution in non-reperfused CRAO. 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

Mitochondrial genetic disorders compromise oxidative phosphorylation (OXPHOS) and cellular energy supply, and the eye is among the first organs to feel the deficit. Photoreceptors and retinal ganglion cells (RGCs) sustain among the highest metabolic rates in the body, so ophthalmic features often dominate the clinical picture and arrive before systemic disease is recognized. More than half of all patients with confirmed mitochondrial disease develop sight-threatening complications. This review integrates mtDNA and nuclear genetics; ophthalmic and extraocular phenotypes; the bioenergetic and apoptotic mechanisms that drive vision loss; the clinical examination and investigations that delineate the problem; the differential diagnoses that must be excluded; the contribution of common mtDNA haplogroup variation to age-related retinal disease; and the diagnostic, therapeutic, and counseling approaches that turn a molecular result into useful care. Recurring themes are heteroplasmy, the threshold effect, and the selective vulnerability of RGCs and extraocular muscle across genetically distinct disorders. Treatment remains largely supportive, but idebenone, gene therapy, mitophagy modulation, and targeted antioxidants now offer mechanism-based intervention for several ophthalmic manifestations. Full article