Search Results (319)

Background: Chemical eye burns are a serious ophthalmic emergency that can lead to permanent vision loss in severe cases. This study aims to evaluate structural changes in the posterior segment of the eye in individuals who have experienced chemical burns. Methods: The study included 64 eyes from 54 patients with chemical burns (chemical burn group) and 87 healthy eyes from 87 subjects (control group), matched by age and sex. Patients had confirmed burns with limbal ischemia, no glaucoma, normal intraocular pressure, and no major ocular or systemic diseases. Burned eyes were examined during the acute phase and again at 3 months, with some followed up at 6 months if significant retinal asymmetry was detected. Retinal nerve fiber layer (RNFL) thickness was assessed in four quadrants, and ganglion cell complex (GCL++) thickness was analyzed using automated segmentation of optical coherence tomography (OCT) maps. Results: This study compared measurements between the burn group, the control group, and timepoints. OCT analysis revealed no significant difference in total RNFL thickness between burn patients and controls (mean difference: −1.14 µm, 95% CI: −3.92 to 1.64). Similarly, GCL++ thickness did not differ significantly between groups (mean difference: −0.97 µm, 95% CI: −3.31 to 1.37). At 6-month follow-up, a non-significant decline in both RNFL and GCL++ thicknesses was observed. Logistic regression identified higher Dua grade as an independent predictor of RNFL thinning (OR: 4.816, 95% CI: 1.103–21.030; p = 0.037). Patients with severe ocular chemical burns (Dua grade ≥ 3) demonstrated reduced RNFL thickness in all quadrants compared to healthy controls. The most pronounced reductions were observed in the nasal and superior quadrants (p = 0.007 and p = 0.069, respectively); however, after applying Bonferroni correction for multiple comparisons, only the difference in the nasal quadrant remained statistically significant (adjusted p = 0.035). Conclusions: Although overall RNFL and GCL++ thicknesses did not differ significantly between burn patients and healthy controls, patients with severe ocular chemical burns (Dua grade ≥ 3) showed a significant reduction in RNFL thickness, in the nasal quadrant. Higher Dua grade was identified as an independent predictor of RNFL thinning. These findings suggest a potential association between burn severity and posterior segment changes, highlighting the need for further longitudinal studies with larger cohorts. Full article

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), is known to affect multiple organ systems, including the respiratory tract and nervous and ocular systems. This retrospective study aimed to characterize the spatiotemporal distribution of viral antigen and associated pathological changes in the nose, lungs, brain, and eyes of K18-hACE2 mice intranasally infected with SARS-CoV-2. Using histology and immunohistochemistry, tissues were examined at 3, 6, and 7/8 days post-infection (dpi). In addition, lung and brain tissues were analyzed by means of RT-qPCR to determine viral RNA titers. Viral antigen was most pronounced in the nose, brain, and lung at 3, 6, and 7/8 dpi, respectively, whereas viral antigen was detected at 6 and 7/8 dpi in the retina. Quantitative PCR confirmed increasing viral RNA levels in both lung and brain, peaking at 7/8 dpi. Nasal and lung inflammation mirrored viral antigen distribution and localization. In the brain, the predominantly basal viral spread correlated with lymphohistiocytic meningoencephalitis, neuronal vacuolation, and altered neurofilament immunoreactivity. Retinal ganglion cells showed viral antigen expression without associated lesions. Microglial activation was evident in both the optic chiasm and the brain. These findings highlight the K18-hACE2 model’s utility for studying extrapulmonary SARS-CoV-2 pathogenesis. Understanding the temporal and spatial dynamics of viral spread enhances insights into SARS-CoV-2 neurotropism and its clinical manifestations. Full article

Dominant Optic Atrophy (DOA) is the most common inherited optic neuropathy and presents as gradual visual loss caused by the loss of retinal ganglion cells (RGCs). Over 60% of DOA cases are caused by pathogenic variants in the OPA1 gene, which encodes a mitochondrial GTPase essential in mitochondrial fusion. Currently, there are no treatments for DOA. Here, we tested the therapeutic potential of an approach to DOA using CRISPR activation (CRISPRa). Homology directed repair was used to introduce a common OPA1 pathogenic variant (c.2708_2711TTAGdel) into HEK293T cells as an in vitro model of DOA. Heterozygous c.2708_2711TTAGdel cells had reduced levels of OPA1 mRNA transcript, OPA1 protein, and mitochondrial network alterations. The effect of inactivated Cas9 fused to an activator (dCas9–VPR) was tested with a range of guide RNAs (gRNA) targeted to the promotor region of OPA1. gRNA3 and dCas9–VPR increased OPA1 expression at the RNA and protein level towards control levels. Importantly, the correct ratio of OPA1 isoform transcripts was maintained by CRISPRa. CRISPRa-treated cells showed an improvement in mitochondrial networks compared to untreated cells, indicating partial rescue of a disease-associated phenotype. Collectively, these data support the potential application of CRISPRa as a therapeutic intervention in DOA. Full article

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

Purpose: To investigate the role of the kynurenine pathway (KP) in ocular diseases by evaluating the activity of key enzymes—kynurenine aminotransferase (KAT) and kynurenine monooxygenase (KMO)—and the 3-hydroxykynurenine to kynurenic acid (3-HK/KYNA) ratio in relation to cataract severity, diabetes, glaucoma, and pseudoexfoliation syndrome (PEXS). Methods: Tryptophan metabolite levels were measured in patients undergoing cataract surgery and stratified by SPONCS grading and comorbid conditions. KAT and KMO activities were estimated using metabolite ratios (KYNA/KYN and 3-HK/KYN, respectively). Statistical analyses included Kruskal–Wallis tests with post hoc comparisons and Mann–Whitney U tests. Results: KAT activity declined significantly with increasing SPONCS grade (p = 0.014), suggesting a progressive loss of KYNA production and antioxidative capacity in advanced cataracts. Diabetic patients exhibited higher KMO activity (p = 0.039) and elevated 3-HK/KYNA ratios (p = 0.013), indicating a metabolic shift toward oxidative stress and neurotoxicity. Similarly, glaucoma patients had significantly increased KMO activity (p = 0.032), consistent with enhanced 3-HK-mediated retinal ganglion cell damage. In contrast, PEXS showed no significant alterations in KP markers. Conclusions: The kynurenine pathway is differentially modulated in ocular diseases. A decline in KAT activity correlates with cataract severity, while upregulation of KMO is prominent in diabetes and glaucoma, revealing disease-specific metabolic dysregulation. Targeting KMO to reduce toxic metabolite accumulation or enhancing KYNA synthesis may offer novel therapeutic avenues. These findings also support the potential of KP metabolites as biomarkers for disease monitoring and progression. Full article

Recent evidence suggests that SARS-CoV-2 may induce subtle anatomical changes in the retina, detectable through advanced imaging techniques. This retrospective case–control study utilized optical coherence tomography (OCT) to assess medium-term retinal alterations in 55 healthcare workers, including 25 individuals with PCR-confirmed COVID-19 and 30 non-COVID-19 controls, all of whom had worked in COVID-19 clinical settings. Comprehensive ophthalmological examinations, including OCT imaging, were conducted six months after infection. The analysis considered demographic variables, comorbidities, COVID-19 severity, risk factors, and treatments received. Central macular thickness (CMT) was significantly increased in the post-COVID-19 group (p < 0.05), with a weak but statistically significant positive correlation between CMT and disease severity (r = 0.245, p < 0.05), suggesting potential post-inflammatory retinal responses. No significant differences were observed in retinal nerve fiber layer (RNFL) or ganglion cell complex (GCL + IPL) thickness. However, mild negative trends in inferior RNFL and average GCL+IPL thickness may indicate early neurodegenerative changes. Notably, patients with comorbidities exhibited a significant reduction in superior and inferior RNFL thickness, pointing to possible long-term neurovascular impairment. These findings underscore the value of OCT imaging in identifying subclinical retinal alterations following COVID-19 and highlight the need for continued surveillance in recovered patients, particularly those with pre-existing systemic conditions. Full article

Purpose: To analyze the retinal and choriocapillaris changes in diabetic patients with no or with early signs of diabetic retinopathy using high-definition (HD) angio optical coherence tomography angiography (OCTA) software and spectral-domain (SD) OCT. Methods: A total of 112 eyes (54 eyes from 27 diabetic patients and 58 eyes from 29 control subjects) were included in this retrospective cross-sectional study of healthy and diabetic adults. Retinal microvascular changes were assessed by using HD-OCTA software to calculate vascular density (VD) and foveal avascular zone (FAZ). SD-OCT was used to assess retinal thickness and volume in parafovea as well as ganglion cell complex (GCC) parameters. Results: The VD-whole image was significantly higher in the healthy control group (MW z = 1109.5, p = 0.012; t = 2.611, p = 0.010). Also, VD-parafovea was significantly higher in the healthy subjects (MW z = 1053.5, p = 0.004; t = 3.207, p = 0.002). GCC focal loss volume (FLV) was significantly decreased in diabetic patients (p = 0.051). Non-flow FAZ did not show a statistically significant difference between groups, although the FAZ was larger in the diabetic patients. Conclusions: Diabetic patients with no or early signs of diabetic retinopathy have decreased VD compared to healthy individuals. They also present retinal changes at the GCC that are correlated with initial neurodegeneration. HD-OCTA and SD-OCT can detect vascular changes and structural signs of retinal neurodegeneration before clinically apparent diabetic retinopathy. Potentially, these methods may offer new biomarkers for monitoring disease progression and visual prognosis. Full article

Background/Objectives: Certain aspects of retinal thickness assessed by optical coherence tomography (OCT) in patients with Parkinson’s disease (PD) require additional clarification. It is supposed that attributing reduced retinal thickness in PD to dopaminergic loss may not be acceptable as it also happens in diseases where dopaminergic loss does not occur. The objective of our study is to compare the ganglion cell/inner plexiform layer (GCIPL), peripapillary retinal nerve fiber layer (pRNFL), and macular thickness of PD and dopa responsive dystonia (DRD) patients with healthy controls (HC), to investigate whether DRD patients, as a distinctive model of genetically induced dopamine deficiency, have reduced retinal thickness in comparison with PD, and to analyze correlation between retinal thickness and various PD clinical parameters. Methods: We analyzed 86 patients with PD, 10 patients with DRD, and 96 age- and sex-matched HC. Results: GCIPL, pRNFL, and central macula thickness (CMT) are statistically significantly thinner in PD patients compared to HC (p < 0.001, all). GCIPL and CMT are also statistically significantly thinner in DRD patients compared to HC (p = 0.012, p = 0.001, respectively). GCIPL thickness correlates positively with the daily dose of levodopa (r = 0.244, p < 0.01). The thickness of GCIPL and pRNFL correlate negatively with current age (r = −0.219; p < 0.01 and r = −0.358; p < 0.05, respectively). All retinal parameters are statistically significantly thinner in females than in males (p < 0.05). Conclusions: Patients with PD and DRD did not differ in GCIPL and pRNFL thickness when compared to one another. These results, supported by positive correlation of levodopa dose and GCIPL thickness in PD patients, emphasize the importance of dopamine in maintaining retinal thickness. Full article

Background/Objectives: This study aimed to analyze optic nerve parameters, retinal nerve fiber layer thickness (RNFLT), ganglion cell layer thickness (GCLT), and subfoveal choroidal thickness (ChT) in patients who have recovered from coronavirus disease 2019 (COVID-19). Methods: This comparative study included 78 recovered COVID-19 patients (16 men, 62 women) and 56 age- and sex-matched healthy controls (18 men, 38 women). COVID-19 was confirmed in all patients, either through the detection of viral RNA in nasopharyngeal swabs via reverse transcriptase polymerase chain reaction or by serological testing for SARS-CoV-2 antibodies. Spectral-domain optical coherence tomography (SD-OCT) was used to assess optic nerve parameters, RNFLT, GCLT, and ChT. Results: The mean age was 35.0 ± 8.3 years in the COVID-19 group and 31.5 ± 8.3 years in the control group, with no statistically significant differences in age or sex distribution between groups (p = 0.41 and p = 0.16, respectively). Optic nerve parameters and RNFLT (overall and across the four peripapillary quadrants) did not differ significantly between the COVID-19 and control groups. However, the mean ganglion cell–inner plexiform layer (GC-IPL) thickness was significantly reduced in all quadrants in the COVID-19 group compared to the controls. No significant difference was observed in mean subfoveal ChT between groups. Conclusions: A significant reduction in ganglion GCLT was observed in recovered COVID-19 patients compared to healthy controls, suggesting a potential neurodegenerative effect of the disease on the optic nerve. Full article

(1) Background: Glaucoma is a multifactorial group of diseases characterized by progressive optic neuropathy. Intraocular pressure (IOP) is the only successfully modifiable risk factor for all forms of glaucoma. However, recent research has highlighted the reduction of oxidative stress and neuroinflammation as promising therapeutic targets. In this study, we evaluated the antiglaucomatous effects of a combined herbal extract applied as eye drops in a rat model of glaucoma. (2) Methods: Sprague Dawley rats were divided into four groups: healthy controls, glaucomatous animals treated with preservative-free artificial tears, and healthy and glaucomatous groups receiving combined herbal-based eye drops for 8 weeks. Glaucoma was induced through injection of microbeads into the anterior chamber at week 1 and week 3. Before the first injection and at weeks 4 and 8, rats underwent optical coherence tomography (OCT) and electroretinogram (ERG) recordings. Retinal analyses were conducted to assess retinal ganglion cell (RGC) count, vessel density, and markers of neural pathways, oxidative stress, and inflammation. (3) Results: The combination of herbal extracts showed beneficial effects on IOP elevation, and significantly improved ERG responses. Neuroprotective effects were assessed using OCT, immunohistochemistry, and proteomics. Most parameters in herbal eye drop-treated rats were not statistically different from those in healthy controls. (4) Conclusions: Topical administration of plant-based compounds may serve as an effective supportive therapy for ocular hypertension and retinal neuroprotection. Full article

Background/Objectives: This prospective study evaluates the relationship between the ganglion cell–inner plexiform layer (GCIPL), retinal nerve fiber layer (RNFL), and photopic negative response (PhNR) in patients with newly diagnosed pituitary macroadenomas over 12 months. Methods: A total of 40 patients (80 eyes) were included, divided into a treatment group of 27 patients (54 eyes), receiving pharmacological and/or surgical intervention, and an observation group of 13 patients (26 eyes), with non-functional pituitary adenomas (NFPAs) that did not require treatment. Results: Key findings indicate a significant improvement in best corrected visual acuity (BCVA) after 12 months in the treatment group (p = 0.02) and a significant reduction in RNFL thickness in multiple quadrants (p < 0.01). Moreover, PhNR amplitude and W-ratio significantly increased in the treatment group (p < 0.0001). In the observation group, only GCIPL Inferior (p = 0.0470) and PhNR W-ratio (p = 0.0015) showed significant differences. Between-group comparisons showed significant differences in RNFL Nasal quadrant at baseline (p = 0.0017) and after 12 months (p = 0.0150). PhNR amplitude and W-ratio also differed significantly between groups at 12 months (p = 0.0012 and p = 0.0016, respectively). Correlations between OCT and ERG parameters were weak at baseline and diminished over time. Conclusions: These findings suggest that GCIPL, RNFL, and PhNR analyses may be useful for monitoring disease progression and guiding treatment decisions in patients with pituitary macroadenomas. Full article

Retinal degeneration, characterized by the progressive loss of photoreceptors, retinal pigment epithelium cells, and/or ganglion cells, is a leading cause of vision impairment. These diseases are generally classified as inherited (e.g., retinitis pigmentosa, Stargardt disease) or acquired (e.g., age-related macular degeneration, diabetic retinopathy, glaucoma) ocular disorders that can lead to blindness. Available treatment options focus on managing symptoms or slowing disease progression and do not address the underlying causes of these diseases. However, recent advancements in regenerative medicine offer alternative solutions for repairing or protecting degenerated retinal tissue. Stem and progenitor cell therapies have shown great potential to differentiate into various retinal cell types and can be combined with gene editing, extracellular vesicles and exosomes, and bioactive molecules to modulate degenerative cellular pathways. Additionally, gene therapy and neuroprotective molecules play a crucial role in enhancing the efficacy of regenerative approaches. These innovative strategies hold the potential to halt the progression of retinal degenerative disorders, repair or replace damaged cells, and improve visual function, ultimately leading to a better quality of life for those affected. Full article

Mitochondria are vital organelles responsible for ATP production and metabolic regulation, essential for energy-intensive cells such as retinal ganglion cells. Dysfunction in mitochondrial oxidative phosphorylation or mitochondrial DNA (mtDNA) pathogenic variants can disrupt ATP synthesis, cause oxidative stress, and lead to cell death. This has profound implications for tissues such as the retina, optic nerve, and retinal pigment epithelium, which are dependent on robust mitochondrial function. In this review, we provide a comprehensive compilation of pathogenic variants in the mtDNA associated with various ophthalmic diseases, including Leber’s hereditary optic neuropathy, chronic progressive external ophthalmoplegia, Leigh syndrome, mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes, among others. We highlight the genetic variants implicated in these conditions, their pathogenic roles, and the phenotypic consequences of mitochondrial dysfunction in ocular tissues. In addition to well-established mutations, we also discuss the emerging evidence of the role of mtDNA’s variants in complex multifactorial diseases, such as non-arteritic anterior ischemic optic neuropathy, primary open-angle glaucoma, and age-related macular degeneration. The review aims to serve as a valuable resource for clinicians and researchers, providing a detailed overview of mtDNA pathogenic variants and their clinical significance in the context of mitochondrial-related eye diseases. Full article

Background/Objectives: Leber hereditary optic neuropathy (LHON) is often misdiagnosed in its early stages as idiopathic single isolated optic neuritis (SION) or multiple-sclerosis-associated optic neuritis (MS-ON) due to the young age of the patients, the subacute vision loss, and the central visual field defect. The aim of this retrospective study was to evaluate changes in the peripapillary RNFL and GCLT over time in patients with early LHON, MS-ON, and SION in order to differentiate Leber hereditary optic neuropathy (LHON) from optic neuritis (ON) in the early stages of the disease. Methods: Patients with LHON and ON (either idiopathic single isolated optic neuritis (SION) or ON as the first symptom of relapsing–remitting multiple sclerosis (MS-ON) were included. Optical coherence tomography (OCT) scans were reviewed. The inclusion criteria were at least one follow-up OCT examination and a definite diagnosis after examination. Changes in the peripapillary retinal nerve fibre layer (RNFL) and macular ganglion cell layer thickness (GCLT) in both groups were evaluated over time and compared with normative data. The analysis focused on the early phase (0–45 days) after symptom onset. Results: Nine LHON patients with early OCT scans and twenty patients with ON were included. Quantitative OCT analysis showed greater RNFL swelling in LHON compared to ON during the first 60 days after symptom onset. Between day 61 and day 120, subnormal RNFL values were observed in both groups compared to controls. Thereafter, the RNFL decreased continuously and severely in the LHON group. The RNFL of ON patients did not show a clear progression after day 120. The GCLT in five LHON eyes showed a strong and solid decrease from day 0 to day 45, which was stronger than the moderate atrophy measured in ON eyes. Continuous GCL atrophy was measured until day 121 in LHON, after which a floor effect was reached. The GCLT in the inner nasal and inner inferior sectors was significantly smaller in LHON compared to ON patients on days 0–45. Conclusions: Thinning of the GCLT occurs at an early stage in LHON patients. Thus, GCLT may become a diagnostic tool to differentiate LHON from ON in the early phase of disease. Full article

The CYP1B1 gene encodes a cytochrome p450 monooxygenase enzyme, and over 150 variants have been associated with a spectrum of eye diseases, including primary congenital glaucoma, anterior segment dysgenesis, juvenile open-angle glaucoma, and primary open-angle glaucoma. Clinical genetics has yielded insights into the functions of the various CYP1B1 gene domains; however, animal studies are required to investigate the molecular role of CYP1B1 in the eye. While both zebrafish and mice express CYP1B1 in the developing eye, embryonic studies have shown disparate species-specific functions. In zebrafish, CYP1B1 regulates ocular fissure closure such that overexpression causes a remarkable phenotype consisting of the absence of the posterior eye wall. Adult CYP1B1 null zebrafish lack an ocular phenotype but show mild craniofacial abnormalities. In contrast, CYP1B1^−/− mice display post-natal mild to severe trabecular meshwork degeneration due to increased oxidative stress damage. Interestingly, the retinal ganglion cells in CYP1B1 null mice may be more susceptible to damage secondary to increased intraocular pressure. Future studies, including detailed genotype–phenotype information and animal work elucidating the regulation, substrates, and downstream effects of CYP1B1, will yield important insights for developing molecularly targeted therapies that will aim to prevent vision loss in CYP1B1-related eye diseases. Full article