Search Results (3,429)

Background and Clinical Significance: Blunt ocular trauma is a significant but often underestimated cause of visual impairment, particularly among adolescents involved in high-risk activities such as horseback riding. While most equestrian injuries affect the head and extremities, ocular trauma, especially commotio retinae, can result in severe visual complications. Case Presentation: We report the case of a 15-year-old girl who sustained blunt ocular trauma to the left eye following a fall from a horse and presented with decreased visual acuity. Multimodal imaging revealed outer retinal abnormalities on spectral-domain optical coherence tomography (OCT), including ellipsoid zone irregularities. Early-phase fluorescein angiography showed central hypofluorescence in the foveal region with surrounding mild mottled hyperfluorescence, without clear vascular abnormalities. Fundus photography demonstrated subtle macular changes. Visual acuity improved significantly following treatment, with partial resolution of macular changes, although mild outer retinal irregularities persisted on follow-up imaging. Conclusions: These findings underscore the importance of early ophthalmic evaluation and advanced retinal imaging in blunt ocular trauma. Given the high risk of visual injury during equestrian activities, especially in pediatric and adolescent populations, preventive strategies such as mandatory helmet use and rider education are essential. Implementation of standardized follow-up protocols is also recommended to monitor long-term retinal changes in patients with traumatic maculopathy. Full article

Background/Objectives: The current study was designed to identify the underlying genetic causes of congenital stationary night blindness (CSNB) in the indigenous consanguineous families from the Southern Punjab region of Pakistan, a population where the inherited retinal disorders are relatively common. Methods: A detailed questionnaire and medical examination were done to check the presence of CSNB in the affected individuals of the enrolled families. Whole-exome sequencing (WES) was performed to identify the pathogenic variants, followed by segregation analyses to confirm the segregation of the identified variants with the disease phenotype in the available affected individuals of the families. Results: We identified two novel and three known pathogenic variants in SAG, GRK1, TRPM1, SLC24A1, and GPR179, having established roles in CSNB. Two novel variants, NM_001252020.1 (p.Gly1020Arg) and NM_001004334.3 (p.Trp508Ter), were identified, and their segregation was confirmed in two families, PKIURP102 and PKIURP564, respectively. NM_002929.3 (p.Arg19Ter) and NM_001301032.1 (p.Phe538CysfsTer23) were the reported variants identified in PKIURP17 and PKIURP528 families, respectively. NM_000541.5 (p.Glu306Ter) was identified in two independent families, PKIURP552 and PKIURP565. Conclusions: Identification of five pathogenic variants in five different genes shows the genetic heterogeneity of CSNB in Pakistani patients. Our findings also expand the mutational spectrum of CSNB in the Pakistani population and may help in the identification of mutational hotspots and may help in the genetic diagnosis of CSNB in consanguineous populations. Full article

While diabetic retinal disease (DRD) has classically been viewed as a microvascular complication, emerging evidence places the photoreceptor at the center of its pathogenesis. Recognizing this central role provides a critical framework for resolving a major clinical paradox in diabetes: why the retina exhibits profound susceptibility to hyperglycemic damage, whereas closely related neural tissues like the brain are mostly spared. In this review, we synthesize the evidence for photoreceptor-driven DRD pathology by evaluating two primary mechanistic paradigms. In the first, hyperglycemia-induced damage to the blood vessels limits perfusion, creating an ischemic environment that selectively devastates tissues dependent on exceptionally high blood flow and energy delivery—specifically, the photoreceptors. In the second paradigm, hyperglycemia induces a direct shift in the metabolic profile of photoreceptors, triggering oxidative stress and dysregulated lipogenesis that subsequently place pathological strain on the local microvasculature. Regardless of whether the initial insult is vascular or neuronal, the photoreceptor remains the critical node of disease progression. Because current and investigational DRD treatments predominantly target downstream vascular consequences, exploring these dual mechanisms highlights an urgent need and a significant opportunity to develop novel therapies that target the photoreceptor to address DRD at its root. Full article

Background/Objectives: Color vision deficiency (CVD) arises from the absence or dysfunction of one or more cone photoreceptors in the retina, resulting in impaired color discrimination. Although inherited CVD cannot be cured, optical compensation strategies such as color-filtering glasses have been developed to enhance color perception. However, quantitative clinical evaluations of their corrective efficacy remain limited. This study aimed to assess the effectiveness of notch filter-based color blind glasses in improving color perception and discrimination in individuals with CVD. Methods: Notch filters were employed as color correction lenses, and clinical assessments were conducted to evaluate their impact on human color perception. Subjects underwent standardized color vision tests, including the Color Bridge test, Farnsworth-Munsell 100 Hue test, and D-15 panel test, both before and after wearing the glasses. Outcomes were quantitatively analyzed using total error score (TES), confusion angle, and confusion index (C-index) to determine changes in color discrimination performance. Results: Quantitative analysis demonstrated that wearing the notch filter glasses amplified color differences along confusion lines. In clinical trials, 83% of subjects showed improved color discrimination in the F-M 100 Hue test, with TES reductions between 6.67% and 50.00%. Furthermore, D-15 panel testing revealed that 67% of participants exhibited a decreased C-index and reduced scatter index (S-index), with specific cases shifting from deficient to normal color perception (C-index < 1.6). These results indicate that the filters effectively mitigate symptoms of color vision deficiency by increasing perceptual contrast. Conclusions: Notch filter-based color correction glasses can enhance chromatic discrimination in individuals with CVD by increasing perceptual color contrast. These findings provide practical insights for the optimization and fabrication of color vision correction eyewear utilizing spectral notch filtering strategies. Full article

Alzheimer’s disease (AD) is increasingly recognized as a multisystem neurodegenerative disorder in which sensory dysfunction accompanies cognitive decline. As an accessible extension of the central nervous system, the retina provides a valuable window for investigating early neurodegenerative processes; however, the cellular mechanisms underlying AD-associated retinal pathology remain incompletely understood. Here, using the APP/PS1 mouse model, we systematically examined structural, functional, and glial alterations in the retina across disease stages. Despite robust age-dependent amyloid plaque accumulation in visual-related brain regions, no plaque-like β-amyloid (Aβ) deposits were detected in the retina even at advanced ages. Nevertheless, young APP/PS1 mice exhibited early thinning of inner retinal layers, impaired retinal electrophysiological responses, and reduced excitatory synaptic inputs to retinal ganglion cells (RGCs), preceding overt neuronal loss. These neuronal changes were accompanied by pronounced Müller glial activation, characterized by upregulation of gliosis markers and extensive morphological remodeling. Functional analyses further revealed dynamic alterations in glial homeostasis, including early elevation followed by age-dependent decline of glutamine synthetase activity, together with increased expression and disrupted perivascular polarity of aquaporin-4. Consistently, transcriptomic profiling of young AD retinas identified coordinated dysregulation of genes involved in amino acid metabolism, transport, and oxidative stress responses. Together, our findings identify Müller glial remodeling as an early feature of AD-associated retinal pathology that coincides with synaptic vulnerability of RGCs and occurs independently of local Aβ plaque deposition, highlighting retinal glia as potential early indicators and modulators of neurodegeneration. Full article

Background/Objectives: Arterial hypertension might lead to serious organ damage and complications like hypertensive retinopathy. The retina is the only place in the human body where microscopic blood vessels can be directly investigated. This enables early diagnosis of arterial hypertension-mediated organ damage. Untreated hypertensive retinopathy leads to vision loss in its advanced stages. There are many methods of assessing changes in the arterioles; however, the most accurate is adaptive optics (RTX1™ device with AODetectArtery software, ver. 3.0., Imagine Eyes, Orsay, France). It provides a resolution of 1.6 μm, which is superior to conventional imaging techniques. Optical coherence tomography angiography can serve as an early, minimally invasive marker of microvascular damage. Across the studies analyzed, the WLR (Wall-to-Lumen Ratio) exhibited significantly higher values when comparing individuals with hypertensive retinopathy to normotensives (0.31 vs. 0.26). The main aim of this review is to present the application of adaptive optics in the early diagnosis of hypertensive retinopathy. Methods: The search strategy included 267 original studies, among which 12 were selected to be described and analyzed in this review based on criteria including original research and studies performed on humans with hypertensive retinopathy. Results: RTX1™ enables the assessment of arterial parameters such as the Wall Thickness (WT), Lumen Diameter (LD), Outer Diameter (OD), Wall-to-Lumen Ratio (WLR) and Wall Cross Sectional Area (WCSA). These parameters differ depending on the arterial hypertension. The WLR was identified to be the parameter that differs in the vast majority of analyzed studies when comparing hypertensive patients to normotensive patients. Vascular parameters were also found to change depending on different organisms’ states, treatment applications and etiological causes of disease. Furthermore, changes in retinal arterial parameters were associated with increased cardiovascular risk in observational studies. RTX1™ was also identified to provide very good intra- and interobserver variability. Conclusions: RTX1™ is a valuable tool in the examination of arterial vessels and in establishing associations between retinal vascular parameters and a patient’s clinical state. Full article

Background: Recent studies strongly suggest that low intracranial pressure (ICP) may be involved in the pathogenesis of glaucomatous optic neuropathy. As retinal ganglion cells (RGCs) are highly susceptible to mitochondrial dysfunction, mitochondrial injury may be associated with optic neuropathy related to reduced ICP. In this study, aquaporin-1 (AQP1)-null mice were used to investigate whether reduced ICP is associated with alterations in mitochondrial structure and the release of optic atrophy type 1 (OPA1) and cytochrome c from mitochondria. Methods: Intraocular pressure (IOP) and ICP were measured in AQP1-null mice, and mitochondrial structural changes were examined using transmission electron microscopy (TEM). Total OPA1 and cytochrome c protein levels were evaluated using immunocytochemistry and Western blotting. Cytosolic and mitochondrial fractions were extracted from retinal tissues, and the subcellular distribution of OPA1 and cytochrome c was further analyzed by Western blotting. Bax and Bcl-2 expression levels were also detected. Results: TEM revealed mitochondrial fission, matrix swelling, and abnormal cristae depletion in the retinas of 1-, 3-, and 6-month-old AQP1-null mice. Morphometric quantification further confirmed significantly reduced mitochondrial length across all age groups and increased mitochondrial width at 1 and 6 months in AQP1-null mice compared with wild-type controls. Decreased retinal OPA1 immunoreactivity and protein expression were observed across all age groups of AQP1-null mice compared with age-matched C57BL/6 control mice. Subcellular fractionation showed increased mitochondrial release of OPA1 (at 3 and 6 months) and cytochrome c (at 1, 3, and 6 months) in the retinas of AQP1-null mice. Altered Bax expression was also detected in the retinas of AQP1-null mice with reduced ICP at all examined ages. Conclusions: Mitochondrial ultrastructural abnormalities, including fission and cristae depletion, altered OPA1 distribution, increased mitochondrial release of OPA1 and cytochrome c, and upregulated Bax expression were observed in the retinas of AQP1-null mice with reduced ICP. These concurrent changes indicate a close association between reduced ICP and retinal mitochondrial dysfunction. Maintaining mitochondrial integrity may therefore serve as a potential protective strategy against optic nerve degeneration in patients with chronic low ICP. Full article

Porcine organotypic retinal explant cultures are widely used to study retinal neurodegeneration under controlled conditions, but the biological processes that occur in the retinal explant over time due to preparation-induced injury and culture are not well understood. Here, we generated a time-resolved transcriptomic reference for porcine neural retinal explants, which were maintained ex vivo for 10 days. Global expression profiles are strongly separated by culture time, with Day 0 clearly distinct from cultured samples and Day 7 and Day 10 showing the highest similarity, indicating a transition toward a later stabilized state. Across the time course, 3187 genes were differentially expressed relative to Day 0, with the largest shifts occurring at an early stage of culture (Day 1–Day 3). Pathway-level analyses revealed coordinated remodeling involving inflammatory signaling and metabolic/bioenergetic changes, including reduced mitochondrial and oxidative phosphorylation-related programs at later time points. Here, we provide a time-resolved transcriptomics reference dataset for cultured porcine retinal explants. These data can build a foundation to interpret data generated in this model, differentiate changes inherent to the explant culture from treatment-specific effects and select appropriate experimental windows for mechanistic studies of retinal degeneration. Full article

The retina is a complex sensory neural tissue composed of six major types of neurons and one type of glial cell. The cell fate specification of retinal cells is tightly governed by intrinsic factors and extrinsic microenvironmental cues. Among the key regulators directing retinal cell fate differentiation is a group of bHLH family transcription factors (TFs). Our previous work demonstrated that the bHLH TF Ngn3 exhibits robust potential to induce retinogenesis in both distantly related fibroblasts in vitro and late retinal progenitor cells (RPCs) in vivo. However, the underlying molecular mechanisms remain largely elusive. In this study, we combined immunohistological examination and RNA-seq and ATAC-seq analyses to investigate the cellular and molecular mechanisms governing Ngn3-driven retinogenesis in late RPCs. Our results revealed that Ngn3 overexpression promotes premature cell cycle exit in late RPCs and remodels their transcriptomic and epigenomic landscape towards a state favoring rod photoreceptor and RGC differentiation. Furthermore, cross-comparison with Ngn3-overexpressing fibroblasts in vitro revealed cell-type-specific mechanisms underlying Ngn3-mediated neuronal fate reprogramming. These findings advance our understanding of Ngn family-mediated retinal cell fate regulation and provide a mechanistic framework for optimizing Ngn3-based retinal regeneration strategies for the treatment of retinal degeneration diseases. Full article

Background and Objectives: Age-related macular degeneration (AMD) is a multifactorial retinal disease in which inflammation and blood-retinal barrier dysfunction may contribute to disease pathogenesis. Claudin-5 is a key tight-junction protein involved in endothelial barrier integrity. Hemogram-derived indices such as the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), and pan-immune-inflammation value (PIV) reflect systemic inflammatory status. This study aimed to evaluate circulating claudin-5 levels and systemic inflammatory indices in patients with wet and dry AMD and to investigate their associations with visual function. Materials and Methods: This prospective case–control study included 90 participants: 30 patients with wet AMD, 30 patients with dry AMD, and 30 healthy controls. All participants underwent detailed ophthalmologic examination, including best-corrected visual acuity (BCVA) assessment and optical coherence tomography. Serum claudin-5 levels were analyzed by enzyme-linked immunosorbent assay, and NLR, PLR, MLR, and PIV were calculated from complete blood count parameters. Group comparisons, correlation analyses, and age-adjusted analyses were performed using appropriate statistical methods. Results: Age differed significantly among the groups (p = 0.032), with the highest median age in the dry AMD group. BCVA (logMAR) also differed significantly (p < 0.001), and both AMD groups had worse visual acuity than controls. Median serum claudin-5 levels were 2.42 in controls, 3.28 in the wet AMD group, and 3.10 in the dry AMD group, with no significant between-group difference (p = 0.280). NLR, MLR, and PIV were also comparable among the groups (p = 0.310, p = 0.410, and p = 0.752, respectively). PLR differed among the groups (p = 0.019), and post hoc analysis showed higher PLR values in the dry AMD group than in the wet AMD group (p = 0.013). However, this difference was no longer statistically significant after adjustment for age (adjusted p = 0.098). Serum claudin-5 was not significantly correlated with age, BCVA, NLR, PLR, MLR, or PIV. Conclusions: Circulating claudin-5 did not differ significantly across AMD phenotypes and was not associated with age, visual function, or systemic inflammatory indices. Although PLR differed between wet and dry AMD before adjustment for age, the overall findings suggest that single-point peripheral serum measurements of claudin-5 may have limited utility in reflecting local retinal barrier-related changes in AMD. Larger longitudinal studies are needed to clarify its potential biomarker role. Full article

Purpose: Neuroinflammation and oxidative stress are increasingly recognized as central, interconnected drivers of neurodegeneration in the visual system. This review examines the pathogenic mechanisms shared across glaucoma, age-related macular degeneration (AMD), diabetic retinopathy (DR), and Alzheimer’s disease (AD), and evaluates the therapeutic rationale for targeting both pathways simultaneously. Methods: A narrative review of peer-reviewed literature was conducted using PubMed. Searches included the following MeSH terms: neuroinflammation, oxidative stress, retinal neurodegeneration, microglia, Müller glia, mitochondrial dysfunction, glaucoma, age-related macular degeneration, diabetic retinopathy, and Alzheimer’s disease. Priority was given to original research, systematic reviews, and high-impact publications from 2000 through 2025. However, seminal foundational works were included regardless of publication date. Studies were selected based on relevance to glial activation, mitochondrial dysfunction, reactive oxygen and nitrogen species, and disease-specific neuronal outcomes. Results: Across all four diseases, persistent microglial and Müller glial activation, mitochondrial electron transport chain dysfunction, and excess reactive oxygen species (ROS) and reactive nitrogen species (RNS) production form a self-amplifying feed-forward loop that accelerates neuronal injury. In glaucoma, these mechanisms drive intraocular pressure-independent retinal ganglion cell loss. In AMD and DR, lipid dysregulation, complement activation, and chronic hyperglycemia sustain oxidative-inflammatory injury to the retinal pigment epithelium, photoreceptors, and neurovasculature. In AD, retinal amyloid deposition and oxidative burden mirror cortical pathology, positioning the retina as a noninvasive biomarker site. Conclusions: Neuroinflammation and oxidative stress constitute unifying upstream mechanisms across major vision-threatening neurodegenerative diseases. Combination therapeutic strategies that simultaneously modulate glial activation and restore redox homeostasis may offer superior neuroprotective efficacy compared to approaches targeting isolated downstream mediators. Full article

Background/Objectives: Hepatic diseases frequently present with ocular manifestations that aid diagnosis, provide prognostic data, and guide therapy. Despite the clear utility of the liver–eye axis, the literature lacks reviews that categorize these manifestations by etiology. This review evaluates current evidence to identify ocular findings that serve as clinical tools for diagnosis, prognosis, and therapeutic monitoring of hepatic pathologies. Methods: A narrative review was conducted using PubMed and Google Scholar to identify English-language articles addressing ocular manifestations associated with liver disease. The primary search encompassed publications from 2000 to 2025, with inclusion of select foundational works published prior to 2000 when they represented seminal studies establishing diagnostic criteria, pathophysiological mechanisms, or natural history data not superseded by subsequent research. Search terms included combinations of liver, hepatic, hepatitis, cirrhosis, cholestasis, eye, ocular, retina, cornea, sclera, conjunctiva, ophthalmic manifestations, and specific disease names. All study designs were eligible. Society guidelines, systematic reviews, and studies from high-impact journals were prioritized. The final selection comprised 59 references representing the most authoritative sources across the spectrum of hepatic conditions. Results: A spectrum of ocular findings linked to distinct hepatic conditions was identified. Manifestations with established clinicopathologic associations were categorized into congenital and acquired etiologies. Congenital liver pathologies included metabolic disorders (Wilson disease, galactosemia, lysosomal storage disorders) and syndromic/genetic causes (Alagille syndrome, hereditary hemochromatosis). Acquired liver diseases encompassed infectious (hepatitis B/C), drug-induced and iatrogenic (interferon, immune checkpoint inhibitors), nutritional (vitamin A deficiency), neoplastic (metastatic hepatocellular carcinoma), and cirrhotic causes. Conclusions: Specific ocular signs raise clinical suspicion for underlying liver disease and warrant targeted hepatic evaluation. Recognizing these associations facilitates earlier diagnosis and improves outcomes. Systematic screening for these signs is supported in at-risk populations, and prospective validation studies should establish their sensitivity and specificity. Full article

Diabetic retinopathy (DR) is a common cause of vision loss in diabetes, and it often progresses without early symptoms. DR reflects injury of the retinal neurovascular unit (NVU), which includes neurons, Müller glia, astrocytes, endothelial cells, pericytes, and immune cells. Chronic hyperglycemia drives oxidative stress, advanced glycation end products–receptor for advanced glycation end products (AGE–RAGE) signaling, mitochondrial injury, and low-grade inflammation. These changes disrupt endothelial junctions, promote leukostasis, weaken pericyte support, increase basement membrane thickening, and lead to capillary dropout and hypoxia. Hypoxia-related signaling increases anti-vascular endothelial growth factor (VEGF) activity, which raises vascular leakage and supports neovascular disease. Glial stress and microglial activation add cytokines and reactive oxygen species, and neural dysfunction can appear early and can weaken neurovascular coupling. Modern diabetes care changes the short-term risk landscape because potent therapies can lower HbA1c quickly. Large and rapid HbA1c reductions can trigger early worsening of diabetic retinopathy (EWDR), mainly in patients with high baseline HbA1c and moderate-to-severe baseline DR. Semaglutide’s retinopathy complication signal in SUSTAIN-6 fits an EWDR-like pattern that tracks with rapid glycemic improvement in vulnerable eyes. In parallel, surgery adds acute stress, inflammation, glucose swings, hemodynamic shifts, and medication interruptions. These factors can worsen microvascular instability during recovery. Current perioperative guidelines and regulatory recommendations describe glucose targets and medication safety considerations, including preoperative interruption of SGLT2 inhibitors to reduce euglycemic ketoacidosis risk; however, the retina-specific implications of these measures remain indirect. This review summarizes current evidence linking NVU biology, EWDR risk, and perioperative diabetes-related factors. It discusses how these factors may interact in patients with diabetes and how they may influence retinal outcomes. The review is intended to synthesize current evidence and mechanistic interpretations rather than to provide formal clinical practice recommendations. Full article

The purpose of this project was to define gene expression changes associated with the acquisition and loss of resilience to diabetic retinopathy (RDR) in individual retinal cell types. A non-immune form of type 1 diabetes mellitus (DM) was induced by injecting male C57Bl6J mice with streptozotocin. Single-cell RNA sequencing was performed on retinas from mice that experienced DM for 5 or 15 days, along with retinas from age-matched, non-DM mice. The resulting data sets were analyzed to identify DM-associated differentially expressed genes and pathway enrichments after each duration of DM. We observed that acquisition of RDR, previously shown to arise after 5 days of DM was linked to altered expression of genes in a subset of retinal cells, mainly Müller cells. Pathway analysis indicated enhancement of numerous modes of protection, including reinforced neurovascular and structural homeostasis through phagocytosis, integrin signaling, and interferon-mediated defense. After 15 days of DM, when we previously showed that RDR is waning this pro-protection surge in gene expression subsided. We conclude that a duration of DM that is too short to cause diabetic retinopathy (DR) nonetheless evoked a profound change in the gene expression profile within a subset of retinal cell types. The nature and timing of this molecular shift indicated that it was not the preamble to DM-related damage that eventually develops. Rather, DM engaged numerous defense programs within Müller cells. The temporal alignment between RDR and activation of Müller cell-based defense provides a molecular foundation for the retina’s transient ability to remain healthy in the face of DM. Full article