Search Results (35)

Corneal diseases are a leading cause of blindness worldwide, although their early detection remains challenging due to subtle clinical presentations. Recent advances in artificial intelligence (AI) have shown promising diagnostic performance for anterior segment disorders. This narrative review summarizes current applications of AI in the detection of corneal conditions—including keratoconus (KC), dry eye disease (DED), infectious keratitis (IK), pterygium, Fuchs endothelial corneal dystrophy (FECD), and corneal transplantation. Many AI models report high accuracy on test datasets, comparable to, and in some studies exceeding, that of junior ophthalmologists. In addition to detection, AI systems can automate image labeling and support education and patient home monitoring. These findings highlight the potential of AI to improve early management and standardized classification of corneal diseases, supporting clinical practice and patient self-care. Full article

Late-onset Fuchs endothelial corneal dystrophy (FECD) is a hereditary, progressive, bilateral and irreversible disorder that is characterized by thickening of Descemet’s membrane, microscopic collagenous protuberances known as guttae, and accelerated loss of corneal endothelial cells. Patients initially complain of blurred vision, and as the disease progresses, painful epithelial edema develops. Untreated cases of FECD often result in blindness, and then, the only treatment is corneal transplantation. DNA polymorphisms in many genes have been implicated, among them TCF4 on chromosome 18q, encoding a transcription factor protein E2-2, which is involved in regulating cellular growth and differentiation in the cornea. In our previous published study, we confirmed the association of an intronic TCF4 SNP (rs613872) with the disease in our population. The purpose of this present study is to further investigate another intronic point of interest in the same gene, the CTG18.1 trinucleotide repeat expansion. DNA was isolated from EDTA blood from a well-ascertained group of 36 Greek patients with FECD (Krachmer scale ≥ 2) and 58 healthy individuals, age- and sex-matched after obtaining their informed consent. STR-PCR and triplet-repeat primed PCR (TP-PCR) were performed, followed by gel electrophoresis and fragment analysis on an ABI SeqStudio genetic analyzer. Our real-time qPCR genotyping method was used for the SNP in the LightCycler (Roche). Statistical analysis of both genetic results was performed with SPSS and SNPStats. Full article

Disorders of the cornea are responsible for a significant portion of preventable blindness worldwide. Various types of corneal transplantation procedures have successfully restored vision in many individuals; however, they carry the risk of graft failure due to immune rejection, endothelial cell dysfunction, infections and limbal stem cell deficiency. Thus, regenerative therapies of the cornea serve as promising alternatives or adjunct therapies. With improved understanding of limbal stem cell function and advancement in limbal stem cell culture technologies, major progress has been made in the in vivo and ex vivo cell-based therapies for treatment of corneal diseases. In this review, we summarize the recent developments achieved in cell-based therapeutics to target corneal epithelial, stromal, and endothelial cell disorders. Full article

Corneal nerves play a crucial role in maintaining ocular surface homeostasis by supporting the functional integrity of corneal epithelial, stromal, and endothelial cells; modulating tear secretion; and facilitating sensory responses essential for overall ocular health. With advancing age, these highly specialized peripheral sensory fibers undergo progressive attrition and morphologic distortion driven by the canonical hallmarks of aging including genomic instability, impaired proteostasis, mitochondrial dysfunction, and chronic low-grade inflammation. The resulting neuro-immune dysregulation reduces trophic support, delays wound healing, and predisposes older adults to dry-eye disease, neurotrophic keratopathy, and postsurgical hypoesthesia. Age-exacerbating cofactors including diabetes, dyslipidemia, neurodegenerative disorders, topical preservatives, chronic contact-lens wear, herpes zoster ophthalmicus, and ocular-surface hypoxia further accelerate sub-basal nerve rarefaction and functional decline. This review provides an overview of age-related physiological alterations in ocular surface nerves, with a particular emphasis on corneal innervation. It also discusses risk factors that speed up these changes. Given the inherently limited regenerative capacity of corneal nerves and their inability to fully restore to baseline conditions following injury or degeneration, it is critical to identify and develop effective strategies aimed at mitigating or delaying physiological nerve degeneration and promoting nerve regeneration. This review also brings up emerging therapeutic strategies, including regenerative medicine, neuroprotective agents, and lifestyle interventions aimed at mitigating age-related corneal nerve degeneration. Full article

Background: In vivo confocal microscopy (IVCM) provides high-resolution corneal imaging that may enhance preoperative and postoperative assessment in refractive surgery. This pilot study aimed to evaluate the diagnostic utility of IVCM in identifying subclinical corneal abnormalities that could influence surgical qualification and outcomes. Methods: A total of 7 patients (3 males, 4 females; mean age 48.8 ± 14.5 years) undergoing qualification or follow-up for refractive surgery were prospectively examined between May 2021 and March 2025. Each participant underwent a comprehensive ophthalmic evaluation, including slit-lamp biomicroscopy, corneal topography, anterior segment optical coherence tomography (AS-OCT), and IVCM using the Heidelberg Retina Tomograph II with Rostock Cornea Module. Patients with prior ocular surgery, active infection, or systemic corneal disease were excluded. Results: IVCM revealed subtle epithelial, stromal, and endothelial abnormalities undetectable by conventional methods. Findings such as Thygeson’s keratitis, pre-Descemet’s dystrophy, and subclinical herpes simplex keratitis led to modifications of surgical plans or disqualification in selected cases. The technique also aided postoperative evaluation of epithelial–stromal interface disorders. Conclusions: IVCM proved to be a valuable adjunct in detecting subclinical corneal pathology, refining patient selection, and improving safety in refractive surgery. Larger multicenter studies are warranted to validate its clinical role and define standardized indications for preoperative screening. Full article

Background/Objectives: Although methylphenidate is a first-line pharmacological agent in the treatment of Attention-Deficit/Hyperactivity Disorder (ADHD), its long-term effects on ocular tissues, particularly the corneal endothelium, remain poorly understood. Given the cornea’s metabolic sensitivity, subclinical changes may occur even in the absence of overt ophthalmologic symptoms. This study aims to evaluate the impact of six-month methylphenidate treatment on corneal endothelial morphology and intraocular pressure (IOP) in pediatric patients with ADHD. Methods: This prospective observational study included 100 treatment-naive children with ADHD and 100 age- and sex-matched healthy controls. All participants underwent comprehensive ophthalmologic assessment at baseline. In the ADHD group, follow-up evaluations were performed after six months of methylphenidate therapy. Endothelial cell density (ECD), average cell area (AVE), standard deviation (SD), coefficient of variation (CV), hexagonality index (6A), central corneal thickness (CCT), and IOP were measured using specular microscopy and corneal topography. ADHD symptom severity was evaluated using the Turgay DSM-IV-Based Rating Scale. Results: Significant reductions in ECD and increases in CCT, CV, AVE, and SD were observed following treatment (p < 0.001). IOP also showed a statistically significant increase while remaining within normal physiological limits. Weak but significant correlations were found between inattention scores and ECD (r = 0.222), and between inattention and corneal volume (r = −0.248). Conclusions: Chronic methylphenidate use may be associated with measurable changes in corneal endothelial microstructure and IOP in children with ADHD. These findings highlight the need for routine ophthalmologic monitoring during stimulant therapy and underscore the importance of further large-scale, long-term studies exploring the neuro-ophthalmologic implications of pediatric psychopharmacological treatment. Full article

Diabetes mellitus (DM) is a chronic metabolic disorder that can induce systemic and ocular complications. Among the latter, an increase in central corneal thickness (CCT) has been reported, potentially affecting endothelial function and increasing the risk of ocular disease. This study aimed to determine the impact of DM on CCT and to assess its correlation with diabetes duration and glycosylated hemoglobin (HbA1c) levels. A systematic literature search was conducted in Web of Science (1980–2025) following a PICO-based strategy. Observational studies evaluating CCT in diabetic patients were included. Data were analyzed using a random-effects model. Statistical heterogeneity was assessed with χ² test, p values, and I² index. Publication bias was evaluated using Begg’s funnel plot and Egger’s regression test. Twenty-nine studies were included in the meta-analysis. Diabetic patients showed significantly higher CCT values compared to controls, particularly in those with long-standing DM (p < 0.001) and poor glycemic control (HbA1c, p < 0.001). Egger’s regression suggested an association between increasing CCT, disease duration, and HbA1c levels, while funnel plot asymmetry indicated potential publication bias. CCT appears to increase in patients with long-term DM and inadequate glycemic control. These findings highlight the relevance of CCT assessment as a potential indicator of corneal changes in diabetic patients. Full article

Corneal sensitivity is an important indicator of corneal health and innervation. Corneal hypoesthesia may be an early indicator of corneal diseases such as neurotrophic keratopathy. Various instruments have been used to measure corneal sensitivity, the first being the Cochet–Bonnet aesthesiometer. Over the years, new devices employing different stimuli have been developed, such as the gas-based Belmonte aesthesiometer, the Swiss liquid-jet aesthesiometer, and the most recently released corneal Brill aesthesiometer. In this review, the progress and advancement of aesthesiometers since their introduction is described. The mechanism, advantages, and disadvantages of these aesthesiometers are discussed and compared. We also report the relationship between corneal sensitivity and corneal innervation in various conditions, including diabetes mellitus, Fuchs’ endothelial dystrophy, dry eye disease, glaucoma, keratoconus, herpes simplex keratitis, post-refractive surgery, and ocular graft-versus-host disease. Through this review, we aim to highlight the importance of the assessment of corneal sensitivity and innervation in the diagnosis, treatment, and monitoring of anterior and posterior segment ocular disorders. Full article

Background and Clinical Significance: Brittle cornea syndrome (BCS) is a rare, autosomal recessive connective tissue disorder characterized by extreme corneal thinning, high myopia, and increased risk of spontaneous or trauma-induced ocular rupture. It is primarily caused by mutations in the ZNF469 or PRDM5 genes, which regulate extracellular matrix integrity. Early recognition and diagnosis of BCS are crucial to prevent severe visual impairment. This report presents two genetically confirmed cases of BCS in Albanian siblings, emphasizing the diagnostic value of whole-exome sequencing and individualized surgical management strategies. Case Presentation: Two siblings—a 28-year-old male and a 25-year-old female—presented with progressive visual deterioration and marked corneal thinning (<200 µm). Both had a history of spontaneous ocular rupture following minor trauma in the contralateral eye. Detailed ophthalmologic evaluation revealed keratoglobus, high myopia, and irregular astigmatism. Genetic testing identified the homozygous pathogenic variant c.974delG (p.Cys325LeufsX2) in the PRDM5 gene in both cases. The male underwent penetrating keratoplasty (PKP), achieving a best-corrected visual acuity (BCVA) of 20/30. The female initially underwent deep anterior lamellar keratoplasty (DALK), which was converted to PKP intraoperatively due to central endothelial perforation, resulting in a BCVA of 20/25. Both patients remained complication-free over a 7-year follow-up period. Conclusions: These cases highlight the importance of early genetic diagnosis and a tailored surgical approach in managing BCS. Long-term monitoring and protective strategies are essential to prevent complications. Incorporating genetic testing into clinical practice can enhance diagnostic accuracy and guide personalized treatment plans in patients with hereditary corneal dystrophies. Full article

Fuchs endothelial corneal dystrophy (FECD) is the most common corneal endothelial dystrophy. It is characterized by the progressive loss of corneal endothelial cells (CECs), guttae formation on the Descemet membrane, and corneal edema, leading to visual impairment. Corneal transplantation remains the standard treatment, but it has limitations such as donor shortages, infection risk, and graft rejection. Rho-kinase (ROCK) inhibitors have emerged as a promising pharmacological alternative. These agents promote CEC proliferation, migration, and adhesion while inhibiting apoptosis and enhancing corneal endothelial wound healing. Several studies have demonstrated the efficacy of ROCK inhibitors in improving corneal clarity and endothelial function, particularly when used as an adjunct to Descemet Stripping Only (DSO) surgery. Additionally, they show potential in preventing corneal edema in FECD patients undergoing cataract surgery. The methodology involved a literature search through the PubMed and Medline databases using relevant keywords. Only peer-reviewed articles in English were included, with additional references from selected articles reviewed to ensure comprehensive coverage. ROCK inhibitors offer a novel pharmacological approach to managing FECD. They have shown potential in promoting endothelial cell regeneration and improving corneal functIion. Despite promising results, further research is required to determine ROCK inhibitors’ long-term safety, optimal dosing, and efficacy in surgical and non-surgical FECD patients. Their potential to delay or prevent corneal transplantation represents a significant advancement in FECD management. Full article

Fuchs endothelial corneal dystrophy (FECD) is a progressive disorder characterized by endothelial cell loss and excessive extracellular matrix (ECM) accumulation leading to corneal dysfunction. Emricasan, a pan-caspase inhibitor, was investigated for its therapeutic potential in suppressing these pathological changes. Patient-derived FECD cells and stress-induced cell models were treated with emricasan to assess its effects on apoptosis and ECM production. Caspase-specific knockdown experiments were performed to identify key mediators. Col8a2^Q455K/Q455K mice, model mice of early-onset FECD, received twice-daily administration of 0.1% emricasan eye drops from 8 to 28 weeks of age. Endothelial cell density, hexagonality, cell size variation, and guttae area were evaluated by contact specular microscopy, while transcriptomic changes were analyzed via RNA sequencing. Emricasan effectively reduced apoptosis and ECM production in vitro by selectively inhibiting caspase-7 without affecting canonical TGF-β signaling. In vivo, emricasan-treated mice exhibited significantly higher endothelial cell density, improved hexagonality, and reduced variation in cell size compared with controls. Transcriptome analysis revealed distinct gene expression changes in the corneal endothelium following emricasan treatment. These findings suggest that emricasan exerts dual protective effects by inhibiting caspase-7-mediated ECM accumulation and broadly suppressing apoptosis, highlighting its potential as a pharmacological therapy for FECD. Full article

Cornea vascularisation is a significant cause of ocular morbidity. Disease or injury often triggers the development of new blood vessels in the cornea, compromising its clarity and impairing vision. Common causes of corneal neovascularisation include infections, chemical burns, and local and systemic inflammatory disorders. Topical corticosteroid eye drops remain the standard therapy; however, extended use of corticosteroids has been known to cause side-effects including cataracts and raised intraocular pressure. As such, an alternative therapy has been actively sought. Vascular endothelial growth factor (VEGF) is a major angiogenic factor implicated in neovascularisation. The success of anti-VEGF agents in managing leaking blood vessels in neovascular age-related macular degeneration provides an opportunity to explore its use in the treatment of corneal neovascularisation. The therapeutic potential of anti-VEGF agents has been evaluated in experimental models of corneal neovascularisation and clinical trials with variable results. Here, we review the study results and discuss the development of new strategies that may improve treatment outcomes for corneal neovascularisation. 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

Fuchs endothelial corneal dystrophy (FECD) is a progressive and debilitating disorder of the corneal endothelium (CE) that affects approximately 4% of individuals over the age of 40. Despite the burden of the disease, the pathogenesis of FECD remains poorly understood, and treatment options are limited, highlighting the need for deeper investigation into its underlying molecular mechanisms. Over the past decade, studies have indicated independent contributions of endoplasmic reticulum (ER) and mitochondrial stress to the pathogenesis of FECD. However, there are limited studies suggesting ER-mitochondria crosstalk in FECD. Recently, our lab established the role of chronic ER stress in inducing mitochondrial dysfunction for corneal endothelial cells (CEnCs), indicating the existence of ER-mitochondria crosstalk in FECD. This paper aims to provide a comprehensive overview of the current understanding of how ER and mitochondrial stress contribute to FECD pathogenesis. The paper also reviews the literature on the mechanisms of ER-mitochondria crosstalk in other diseases relevant to FECD. Full article

Limbal mesenchymal stromal cells (LMSCs) reside in the limbal niche, supporting corneal integrity and facilitating regeneration. While mesenchymal stem/stromal cells (MSCs) are used in regenerative therapies, there is limited knowledge about LMSC subpopulations and their characteristics. This study characterized human LMSC subpopulations through the flow cytometric assessment of fifteen cell surface markers, including MSC, wound healing, immune regulation, ASC, endothelial, and differentiation markers. Primary LMSCs were established from remnant human corneal transplant specimens and passaged eight times to observe changes during subculture. The results showed the consistent expression of typical MSC markers and distinct subpopulations with the passage-dependent expression of wound healing, immune regulation, and differentiation markers. High CD166 and CD248 expressions indicated a crucial role in ocular surface repair. CD29 expression suggested an immunoregulatory role. Comparable pigment-epithelial-derived factor (PEDF) expression supported anti-inflammatory and anti-angiogenic roles. Sustained CD201 expression indicated maintained differentiation capability, while VEGFR2 expression suggested potential endothelial differentiation. LMSCs showed higher VEGF expression than fibroblasts and endothelial cells, suggesting a potential contribution to ocular surface regeneration through the modulation of angiogenesis and inflammation. These findings highlight the heterogeneity and multipotent potential of LMSC subpopulations during in vitro expansion, informing the development of standardized protocols for regenerative therapies and improving treatments for ocular surface disorders. Full article