Search Results (131)

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

Background: Syndromic inherited retinal diseases (IRDs) are a clinically and genetically heterogeneous group of disorders, involving the retina and additional organs. Over 80 forms of syndromic IRD have been described. Methods: We aimed to phenotypically and genotypically characterize a cohort of 171 individuals from 140 Israeli families with syndromic IRD. Ophthalmic examination included best corrected visual acuity, fundus examination, visual field testing, retinal imaging and electrophysiological evaluation. Most participants were also evaluated by specialists in fields relevant to their extra-retinal symptoms. Genetic analyses included haplotype analysis, homozygosity mapping, Sanger sequencing and next-generation sequencing. Results: In total, 51% of the families in the cohort were consanguineous. The largest ethnic group was Muslim Arabs. The most common phenotype was Usher syndrome (USH). The most common causative gene was USH2A. In 29% of the families, genetic analysis led to a revised or modified clinical diagnosis. This included confirmation of an atypical USH diagnosis for individuals with late-onset retinitis pigmentosa (RP) and/or hearing loss (HL); diagnosis of Heimler syndrome in individuals with biallelic pathogenic variants in PEX6 and an original diagnosis of USH or nonsyndromic RP; and diagnosis of a mild form of Leber congenital amaurosis with early-onset deafness (LCAEOD) in an individual with a heterozygous pathogenic variant in TUBB4B and an original diagnosis of USH. Novel genotype–phenotype correlations included biallelic pathogenic variants in KATNIP, previously associated with Joubert syndrome (JBTS), in an individual who presented with kidney disease and IRD, but no other features of JBTS. Conclusions: Syndromic IRDs are a highly heterogeneous group of disorders. The rarity of some of these syndromes on one hand, and the co-occurrence of several syndromic and nonsyndromic conditions in some individuals, on the other hand, complicates the diagnostic process. Genetic analysis is the ultimate way to obtain an accurate clinical diagnosis in these individuals. 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

Pregnancy orchestrates profound neurological, hormonal, and anatomical transformations in the maternal brain, preparing it for caregiving and infant bonding. Neuroimaging reveals structural changes such as gray matter reductions and white matter reorganization during pregnancy, followed by partial recovery postpartum. These adaptations are modulated by fluctuating levels of estradiol, progesterone, prolactin, and oxytocin, which coordinate neuroplasticity and behavioral readiness. At the molecular and cellular levels, pregnancy hormones drive synaptic remodeling, neurogenesis, and glial activity. Together, these changes support maternal motivation, attachment, and responsiveness, highlighting the maternal brain’s dynamic plasticity across gestation and the postpartum period. Also, pregnancy induces profound physiological changes, particularly in vascular, hormonal, and neurologic systems, to support maternal and fetal health. While these adaptations are essential, they can predispose pregnant individuals to various neurologic and ophthalmic pathologies. This review explores how pregnancy-related changes—including hypercoagulability, pituitary enlargement, hormonal fluctuations, and immunological modulation—contribute to conditions such as stroke, idiopathic intracranial hypertension, preeclampsia-associated visual disturbances, and demyelinating disorders like neuromyelitis optica spectrum disorder and multiple sclerosis. Additionally, ocular manifestations of systemic diseases like diabetic retinopathy and thyroid orbitopathy are discussed. Understanding these complex interactions is critical for prompt recognition, accurate diagnosis, and appropriate management of vision-threatening and neurologically significant complications during pregnancy. Nevertheless, many aspects of physiological and pathological changes during and after pregnancy remain unknown and warrant further investigation. Full article

Dark adaptometry is a non-invasive functional test that assesses the retina’s ability to recover sensitivity in low-light conditions following photobleaching. This review explores the physiological mechanisms underlying dark adaptation (DA), including photopigment regeneration and the critical role of the retinal pigment epithelium in the visual cycle. We detail clinical protocols for dark adaptometry using modern instruments such as the AdaptDx, highlighting methodological advances that improve testing efficiency and reproducibility. The clinical utility of dark adaptometry is examined across a range of inherited and acquired retinal disorders, including age-related macular degeneration (AMD), retinitis pigmentosa (RP), Stargardt disease, diabetic retinopathy (DR), cone–rod dystrophy (CRD), vitamin A deficiency, and congenital stationary night blindness (CSNB). Dark adaptometry has emerged as a sensitive biomarker capable of detecting functional deficits before structural changes are evident, making it a valuable tool for early diagnosis and monitoring disease progression. However, limitations such as age-related variability, patient compliance, and lack of standardization remain challenges to broader clinical adoption. Continued refinement of dark adaptometry protocols and instrumentation is essential to maximize its diagnostic potential in ophthalmic practice. Full article

For plant-derived raw materials, there are very few studies regarding the effect of intraocular administration on intraocular pressure (IOP) and associated blood flow. Traditional folk medicine uses many natural resources for eye disorders. However, in the main, these exhibit an anti-inflammatory and moisturizing effect. The intraocular pressure reduction and neuroprotective effects are known, but only for orally administered products. In the work presented here, the effect of eight natural iridoids in concentrations of 0.1 and 0.5% in saline on IOP and blood flow in iris vessels was studied in white New Zealand rabbits. No ocular adverse effects were observed during the whole experiment. We demonstrated, for the first time, significant reductions in IOP for five of the eight iridoids tested at a concentration of 0.5%. These were verbenalin, aucubin, oleuropein, gentiopicroside, and secologanin. The highest effect of IOP lowering, a nearly 1.5 mmHg difference from baseline, was observed for verbenalin 2 h after administration. An increase in vascular inflow was observed only with the administration of aucubin, catalpol, and gentiopicroside at 2 and 3 h after administration of the 0.5% solution. This effect was contrary to the result for the reference—timolol—which significantly reduced flow by more than 100 flux during the first hours of the experiment. In summary, selected iridoids could be considered, after further investigation, as natural components for ophthalmic formulation in the prevention of eye diseases. Full article

Introduction/Objectives: Chronic progressive external ophthalmoplegia (CPEO) is commonly associated with mtDNA deletions. Multiple deletions result mostly due to nuclear DNA defects that lead to an autosomal mode of inheritance, whereas single mtDNA deletions are mostly sporadic events with low inheritance risk. The study focused on assessing the clinical ophthalmic outcomes and their effects on patients with mitochondrial DNA disorders. Methods: A retrospective analysis of clinical characteristics in a cohort of CPEO patients (n = 36; 11 males, 25 females; mean age of onset: 41.2 years (±SD)) was performed. The underlying genetic defects, as well as histological features and their correlation with the clinical features, were evaluated. Results: Ptosis (56% of patients) was a frequently identified clinical symptom. Single mtDNA deletions were reported in all patients, and the ‘common’ 4977 bp deletion (CD) was detected in 11 patients (30.6%). The incidence of the common deletion was higher (36.36%) in older patients (≥51 years) as compared to younger patients (18.18%). The mean age of onset in patients harboring CD was 27 years (±11.9). Furthermore, a tendency to increase the frequency of COX-deficient fibers with increasing age was observed in patients harboring the CD. Conclusions: The present study shows that CD is typically associated with elderly patients with CPEO. Moreover, ptosis and the presence of a single deletion in patients with mitochondrialopathy seem to be preliminary diagnostic criteria. Full article

Oculomics is an emerging field that leverages ophthalmic imaging data to identify biomarkers of systemic disease, facilitating early diagnosis and risk stratification. Despite its growing recognition, gaps remain in the literature regarding the clinical applications of oculomics. Various systemic diseases—including metabolic disorders (e.g., diabetes mellitus), infectious diseases (e.g., COVID-19), neurodegenerative diseases (e.g., dementia), hematologic disorders (e.g., thalassemia), autoimmune conditions (e.g., rheumatoid arthritis), and genetic syndromes (e.g., Fabry disease)—exhibit ocular manifestations detectable through in vivo confocal microscopy and anterior segment optical coherence tomography, among other imaging modalities. Increasing evidence supports the role of corneal imaging in identifying systemic disease biomarkers, a process further enhanced by artificial intelligence-driven analyses. This review synthesizes the current findings on corneal biomarkers of systemic disease, their ophthalmic imaging correlates, and the expanding role of corneal oculomics in translational medicine. Additionally, we explore future directions for integrating oculomics into clinical practice and biomedical research. Full article

Fat embolism syndrome (FES) is a rare multisystem disorder caused by the dispersion of fat emboli in the systemic circulation. FES typically occurs after orthopedic trauma and classically manifests as a triad of respiratory failure, neurologic impairment, and petechial rash. Ophthalmic involvement is uncommon in the absence of cardiac or pulmonary arteriovenous shunts and presents with diffuse retinal hemorrhages and accompanying visual disturbances. We report a case of FES and Purtscher-like retinopathy following the surgical repair of a comminuted femur fracture in a previously healthy 19-year-old male without a known predisposing cause and document the course of successful recovery. Full article

Retinal dysplasia is a genetically heterogeneous ocular disorder in dogs, characterized by abnormal retinal development, resulting in a range of visual impairments from mild to complete blindness. The objective of this study was to investigate the prevalence and genetic basis of retinal dysplasia in the Czechoslovakian Wolfdog breed. An ophthalmic examination was conducted on a cohort of 117 Czechoslovakian Wolfdogs, which revealed a prevalence of multifocal retinal dysplasia of 5.13%. A genome-wide case–control association study was conducted on a subset of 36 adult dogs to explore the underlying genetic architecture of multifocal retinal dysplasia in this breed. The GWAS identified a suggestive association with a locus on canine chromosome CFA37. The strongest association signal for SNP marker BICF2G630130992 (p = 1.29 × 10⁻⁶) was identified in the first intron of the CYP27A1 gene, which encodes a cytochrome P450 enzyme involved in vitamin D metabolism and potentially retinal function. The region of CFA37 contains several other genes that have been previously implicated in ocular development and disease. Further studies utilizing next-generation sequencing and functional analyses are required to validate these findings, identify the causative variants, and fully elucidate the genetic architecture of retinal dysplasia in this breed. Full article

Rho-associated kinase (ROCK) inhibitors have gained popularity as novel treatment options in the management of glaucoma and corneal endothelial disorders. Among the various ocular side effects, reticular corneal epithelial edema has been most frequently reported, mainly after treatment with netarsudil. To explain the potential mechanisms, we comparatively analyzed the effects of ripasudil and netarsudil on corneal endothelial and epithelial function in vitro. Primary human corneal endothelial and epithelial cells were incubated with netarsudil dihydrochloride and ripasudil hydrochloride dihydrate for up to 7 days. Gene and protein expression analyses were performed by real-time PCR and immunocytochemistry. Functional assays assessed the cell migration, proliferation, viability, Na⁺/K⁺-ATPase activity, transcellular electrical resistance, and FITC–dextran permeability. Reticular bullous corneal epithelial edema was observed in a patient following netarsudil 0.02%/latanoprost 0.005% ophthalmic solution (Roclanda^®) for elevated intraocular pressure. In the subsequent laboratory analyses, both netarsudil and ripasudil were found to improve the corneal endothelial pump and barrier function, but they showed differential effects on corneal epithelial cells. Whereas ripasudil improved the epithelial barrier function by upregulating major components of the tight and adherens junctions and reducing paracellular permeability, netarsudil had no or even adverse effects on the epithelial barrier properties by downregulating the expression levels of cell-junction-associated genes. The expression changes normalized after discontinuation of ROCK inhibitors. The findings support the concept that ROCK inhibitors can act as a double-edged sword by having beneficial effects on corneal endothelial cells and adverse effects on epithelial cells. Full article

Purpose: Our purpose was to review the current literature regarding ophthalmologic indications for cesarean section (CS). Methods: A literature search was conducted using MEDLINE, Embase, and the Cochrane Library from inception through October 2024. The databases were searched using the following keywords: “Caesarean section” OR “Caesarean section” OR “delivery” OR “pregnancy” AND “eyes” OR “eye disorders” OR “ocular disease” OR “diabetic retinopathy” OR “myopia” OR “retinal detachment” OR “glaucoma” OR “keratoconus”. Studies were considered eligible if they described pregnancy management in women affected by an eye disorder, with insight into the mode of delivery. Results: A total of 8383 results were identified, including only 1 specific guideline and no randomized controlled trials. After a manual review, 38 manuscripts were selected for inclusion. Based on the available evidence, an elective CS may be considered on a case-by-case basis in the presence of specific ophthalmic conditions, such as high-grade myopia with subretinal neovascularization, proliferative diabetic retinopathy, advanced glaucoma, or advanced keratoconus. These conditions are rare among women of childbearing age. Conclusions: Currently, only a limited number of highly specific ophthalmic conditions may benefit from an elective CS. Considering the potential short- and long-term implications of a CS, and in line with the current World Health Organization recommendations, this surgical procedure should be reserved for cases with a clear indication. Given the paucity of data in the available literature, further prospective randomized controlled trials are necessary to enhance the quality of evidence. Full article

Background/Objectives: Aniridia is a rare congenital disorder characterized by structural and functional abnormalities in ocular development due to PAX6 haploinsufficiency, leading to complications such as aniridia-associated keratopathy (AAK). Meibomian gland dysfunction (MGD), a prevalent yet underexplored condition in aniridia, exacerbates tear film instability and chronic ocular surface inflammation, contributing to AAK progression. This study investigates the relationship between MGD severity and AAK in individuals with aniridia. Methods: This prospective randomized study included 113 participants (53 with aniridia and 60 controls). Comprehensive ophthalmic evaluations, including noninvasive meibography, were performed. The MGD severity was assessed using a standardized meiboscore scale, while the AAK severity was classified according to established clinical grading criteria. Statistical analyses, including Spearman’s correlation and chi-squared tests, were used to evaluate the relationships among MGD, AAK, and visual acuity. Results: MGD was significantly more prevalent and severe in the aniridia group compared to controls (p < 0.00001). A strong positive correlation was observed between MGD severity and AAK grade (r = 0.72, p < 0.00001), with both conditions associated with reduced best-corrected visual acuity (BCVA; r = −0.80 and −0.86, respectively, p < 0.0001). Age was positively correlated with MGD (r = 0.47, p = 0.0004) and AAK (r = 0.34, p = 0.0123), with gender-specific trends observed in females. Conclusions: MGD significantly contributes to AAK progression and visual impairment in aniridia. Meibography offers valuable insights into MGD severity, supporting early diagnosis and targeted interventions. Addressing MGD through tailored therapies could mitigate AAK progression and improve visual outcomes in this challenging condition. Full article

The abnormal growth of irregular new blood vessels into the subretinal or intraretinal space is known as macular neovascularization (MNV). People over 50 are often affected by this disorder, which is typically brought on by age-related macular degeneration. In addition, MNV can be found in people under 50 years of age, who may present primary ophthalmic diseases such as pathological myopia, angioid streaks, traumatic choroidal rupture, or suspected ocular histoplasmosis syndrome. However, it is important to consider a specific set of young individuals who may develop MNV even in the absence of pathological myopia or other identifiable inflammatory, peripapillary, post-traumatic, or degenerative fundus abnormalities. This latter condition is classified as idiopathic MNV. After a literature review focused on young patients affected by one of these two clinical entities, we report the case of a Caucasian young woman suffering for four years from an idiopathic and quiescent MNV that started exuding after childbirth, probably due to the induction with oxytocin, and was treated with intravitreal Aflibercept 2 mg injections. Full article

Advancements in neuroimaging, particularly diffusion magnetic resonance imaging (MRI) techniques and molecular imaging with positron emission tomography (PET), have significantly enhanced the early detection of biomarkers in neurodegenerative and neuro-ophthalmic disorders. These include Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, neuromyelitis optica, and myelin oligodendrocyte glycoprotein antibody disease. This review highlights the transformative role of advanced diffusion MRI techniques—Neurite Orientation Dispersion and Density Imaging and Diffusion Kurtosis Imaging—in identifying subtle microstructural changes in the brain and visual pathways that precede clinical symptoms. When integrated with artificial intelligence (AI) algorithms, these techniques achieve unprecedented diagnostic precision, facilitating early detection of neurodegeneration and inflammation. Additionally, next-generation PET tracers targeting misfolded proteins, such as tau and alpha-synuclein, along with inflammatory markers, enhance the visualization and quantification of pathological processes in vivo. Deep learning models, including convolutional neural networks and multimodal transformers, further improve diagnostic accuracy by integrating multimodal imaging data and predicting disease progression. Despite challenges such as technical variability, data privacy concerns, and regulatory barriers, the potential of AI-enhanced neuroimaging to revolutionize early diagnosis and personalized treatment in neurodegenerative and neuro-ophthalmic disorders is immense. This review underscores the importance of ongoing efforts to validate, standardize, and implement these technologies to maximize their clinical impact. Full article