Search Results (542)

The genus Alternaria comprises several species of dematiaceous hyphomycetes known to cause opportunistic infections in humans. Over the past two decades, fungal infections have emerged as a significant cause of morbidity and mortality, particularly among immunocompromised individuals. Such infections often occur following disruption of the skin or corneal epithelial barrier, especially in patients with pre-existing ocular conditions or compromised immune status. This case report describes a rare instance of fungal keratitis (FK) caused by Alternaria citri in a 71-year-old male who presented with an acute onset of eye infection. The patient showed a favorable response to treatment with voriconazole. Full article

Background and Objectives: Dry eye disease (DED) is a multifactorial ocular surface disease that markedly diminishes quality of life. Although diabetes mellitus is well-known for its retinal consequences, anterior segment symptoms including dry eye disease are often overlooked. Chronic hyperglycemia causes metabolic, neurovascular, and immunological changes that undermine tear film stability, corneal innervation, and ocular surface integrity. This review seeks to consolidate existing knowledge regarding the concealed impacts of diabetes on ocular surface homeostasis, highlighting processes, diagnostic difficulties, and treatment prospects. Materials and Methods: A narrative review of the literature was performed by searching PubMed for publications from January 2020 to July 2025 using the terms “diabetic dry eye,” “hyperglycemia AND ocular surface,” “tear proteomics AND diabetes,” “corneal nerves AND diabetes,” and “neurotrophic keratitis.” Eligible studies were experimental research, clinical trials, and translational investigations concerning tear film function, corneal neuropathy, inflammatory indicators, or lacrimal gland dysfunction in diabetes. The exclusion criteria were non-English language, lack of primary data, and inadequate methodological description. Results: Hyperglycemia compromises lacrimal gland functionality, modifies lipid secretion from Meibomian glands, and diminishes corneal nerve density, resulting in neurotrophic deficits. Inflammatory cytokines and oxidative stress compromise epithelial integrity, but proteome alterations in tears serve as sensitive indicators of disease. Diagnosis is impeded by corneal hypoesthesia, resulting in a disconnection between symptoms and findings. Progress in imaging, proteomics, and artificial intelligence may facilitate earlier detection and improved risk assessment. Novel therapeutics, such as neurotrophic drugs, antioxidants, and customized anti-inflammatory approaches, show promise but remain under clinical evaluation. Conclusions: Diabetes-related dry eye disease is a multifaceted and underappreciated condition influenced by systemic metabolic dysfunction. The ocular surface may act as an initial indicator for systemic disease load. Narrative synthesis emphasizes the necessity for customized diagnostic instruments, individualized treatment approaches, and collaborative management. Reconceptualizing diabetic dry eye disease within the context of systemic metabolic care presents prospects for precision medicine strategies that enhance both ocular and systemic results. Full article

Background and Objectives: Corneal ulcers in patients with lagophthalmos due to facial nerve palsy pose a significant therapeutic challenge. Topical insulin has emerged as a promising adjuvant therapy for enhancing corneal re-epithelialization. The aim of this study is to evaluate the efficacy of insulin drops compared with lipid-based artificial tears, and to compare the corneal healing rate in achieving complete epithelialization within 30 days in diabetic patients. Materials and Methods: This retrospective case–control study included 32 patients with facial nerve palsy and lagophthalmos who developed an exposed corneal ulcer, of whom 20 received topical insulin and 12 received lipid-based artificial tears. The primary outcome was complete epithelialization at day 30. Additional variables included age, sex, and baseline defect characteristics. Results: By day 30, complete epithelialization was achieved in 18 of 20 patients (90%) in the insulin group compared with 5 of 12 (41.7%) in the control group. Binary logistic regression analysis confirmed significantly higher odds of healing with insulin treatment (OR = 10.8; 95% CI 1.8–63.9). No systemic adverse events or signs of hypoglycemia were observed. Conclusions: Topical insulin significantly accelerates corneal epithelialization in patients with facial nerve palsy and exposed ulcers, offering safe and effective adjuvant therapy for a high-risk population. Despite promising results, the study’s limitations—including small sample size, single-center design, and retrospective nature—highlight the need for larger, multicenter prospective studies to confirm efficacy, optimize dosing, and further evaluate long-term safety. Full article

Human allogeneic umbilical cord blood serum stands out as a potent adjunct to conventional therapies for ocular surface disorders related to severe Dry Eye Disease. By expediting ocular surface regeneration and fostering epithelial integrity, umbilical cord blood serum not only enhances subjective patient experiences but also improves objective clinical indicators. This makes it particularly useful in patients with corneal ulcers through ocular surface regeneration and anti-inflammatory activity. This retrospective, interventional, non-randomized clinical study aims to explore the efficacy of allogenic umbilical cord blood serum in patients who had previously received other treatments unsuccessfully. This study was a retrospective, non-comparative, interventional clinical study involving 55 patients (35 females and 20 males) aged 18–82 years with severe Dry Eye Disease who were unresponsive to standard treatments. The study was conducted at Eye Center “G.B. Morgagni-DSV”, Catania, Italy. Patients were categorized based on the etiology of severe Dry Eye Disease into four groups: group I consisted of 26 patients with filamentary keratitis and corneal ulcers associated with rheumatologic diseases such as Sjogren’s syndrome and systemic sclerosis; group II comprised 15 patients with graft-versus-host disease; group III consisted of 10 patients with corneal neurotrophic ulcers; group IV included four patients with Steven–Johnson syndrome. Outcomes evaluated before and after treatment were OSDI (Ocular Surface Disease Index) and SANDE (Symptom Assessment in Dry Eye) Questionnaires, VAS (Visual Analog Scale), Slit-Lamp Examination, Esthesiometry, Lissamine Green Staining, NIBUT (Non-Invasive Break-Up Time) and BUT, Fluorescein Staining with Photography and Oxford Classification, Schirmer Test, Best-Corrected Visual Acuity (BCVA), Meibography. We observed a significant improvement in SANDE, VAS and OSDI questionnaires, Schirmer Test, BUT, BCVA, and Oxford classification after treatment with allogeneic cord blood serum eyedrops. Clinical variables, such as corneal inflammation, conjunctivalization, corneal neovascularization, or pain, were also considered individually. Nevertheless, pain and inflammation reduced markedly over time until completely healed in all cases. Our study highlights the remarkable efficacy of allogeneic cord blood serum eyedrops in patients with severe Dry Eye Disease who have shown absent or inadequate response to usual treatments for dry eye. This underscores the need for further comprehensive investigations in this field. 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

Corneal transplantation is often considered the last resort for severe corneal epithelial disorders, especially limbal stem cell deficiency (LSCD). Tissue engineering offers novel strategies to mitigate the shortage of corneal transplant donors. However, low cell viability and compromised functionality in tissue engineering represent a major challenge. In this review, we describe the key characteristics required for corneal epithelium bioscaffolds. We summarize the research progress centered on optimizing cell activity and functionality in the past 10 years from four key perspectives: the sourcing of cells, seed cell pretreatments, biomaterial optimization, and engineered culture system innovation. The sources, isolation, and induction methods of seed cells are described, and the advantages and disadvantages of existing clinical treatment methods are compared. Furthermore, we compare existing clinical therapies and summarize promising seed cell pretreatment strategies for the first time. Several innovative engineered cell culture systems are exhibited as well. We demonstrated how to preserve cell viability through bioscaffold stiffness modulation, topographic design, and application of innovative fabrication techniques. Finally, we propose a personalized and precise regeneration strategy based on high-resolution images, digital modeling, bioprinting, and machine learning. Full article

Background/objectives: The continuous necessity to support biostrumental data with biolomecular data collected using non-invasive tools is influencing the world of ocular surface devices. The ocular imprint still represents a non-invasive and safety technique for collecting corneal and conjunctival epithelia in an easy way, as performed in human and veterinary clinics. Although used in clinical practice since 1977, operators might benefit from improvements in these techniques, especially in terms of handling and management. Methods: Herein, by reporting the design and characteristics of a patent of ocular surface sampling (the SurfAL pen and periocular-assisted SurfAL pen; PCT WO2016IB51474 20160316), we performed a validation and analysis of its value compared to gold standards. The level-headedness and advantages of this device were verified in 15 sclerocorneal specimens (sampling advantages) and tested in 25 volunteers (handling and operator efficiency, as well as frequency of discomfort in volunteers). Morphological as well as biomolecular analyses were used to compare SurfAL devices with conventional ones. Results: The easy management of SurfAL pens and the good detection of epithelial/goblet cells were confirmed. The SurfAL pen was found to be smart and suitable for routine analysis, as confirmed by quick and reproducible onsite sampling. Periocular-assisted SurfAL pen was comparable in terms of sampling quality but less comparable in terms of subject confidence due to its geometry. Conclusions: This study suggests that the SurfAL pen and periocular-assisted SurfAL pen might represent an additional and hands-on way of sampling ocular surface cells and improve the diagnostic route in ophthalmology. Full article

A corneal abrasion results from the disruption or loss of cells in the corneal epithelium. If inadequately treated, it can compromise visual clarity. The wound healing process of a corneal abrasion involves epithelial migration, proliferation and adhesion. Clitoria ternatea flower extract (CTE) is rich in flavonoids, anthocyanins and other bioactive compounds. It has antioxidant, anti-inflammatory and wound-healing properties. This study explores the potential of CTE to be used as a natural supplement to improve corneal wound healing. Phytochemical profiling via LC–MS identified a total of 51 distinct bioactive constituents. The anthocyanin content, quantified in terms of cyanidin-3-glucoside equivalent, was quantified at 33.06 mg per gram of extract. The extract exhibited 33.8% DPPH radical scavenging activity and a total polyphenol content equivalent to 24.14 mg/g gallic acid. Human telomerase-immortalized corneal epithelial (hTCEpi) cells maintained in keratinocyte basal medium were utilized to determine cytotoxicity and wound-healing effects. The optimal extract concentration of 0.08 mg/mL, quantified via MTT assay, resulting in enhanced cell viability. Scratch assays demonstrated a higher percentage of wound closure in the CTE-treated group at 6 and 12 h relative to the untreated group, with statistical significance (p < 0.05). The gene expressions of CK3 and Cx43, quantified via qRT-PCR, showed no significant differences between groups. However, within the CTE-treated group, CK3 expression increased at 12 h relative to 0 h and 6 h, and Cx43 expression rose significantly at 12 h compared with 0 h (p < 0.05). Immunofluorescence confirmed positive protein expression of both markers. These findings suggest that CTE possesses potent antioxidant properties and promotes corneal epithelial wound healing through upregulation of CK3 and Cx43 in vitro. Full article

Background: The increasing prevalence of high-fat diets is associated with a rise in metabolic and neurodegenerative diseases. The retina and retinal pigment epithelium are metabolically active tissues exposed to oxidative stress, making them particularly vulnerable to lipid excess. Materials and Methods: A systematic literature review was conducted covering years until 2025 inclusive. Results: High-fat diets lead to cholesterol accumulation and lipid metabolism disturbances in the retina, retinal pigment epithelium, and ocular vessels. They activate inflammatory and oxidative stress pathways, resulting in structural and functional damage. Omega-3 deficiency exacerbates inflammation, while supplementation improves the tear film stability, corneal epithelial function, intraocular pressure regulation, and exerts neuroprotective effects. Conclusions: High-fat diets represent a significant risk factor for ocular diseases by disrupting lipid metabolism, enhancing inflammation, and inducing oxidative stress. Omega-3 fatty acid supplementation reduces inflammation and supports ocular functions. Full article

Regulated proteolysis via autophagy is essential for cellular homeostasis, yet the specific role of autophagy-related gene 7 (ATG7) in corneal epithelial maintenance remains unclear. Using a conditional knockout mouse model (Atg7^f/f K14Cre^+/−), we investigated the impact of ATG7 deficiency on corneal epithelial autophagy, morphology, and vascular dynamics. Loss of ATG7 disrupted autophagosome formation, evidenced by increased LC3B expression but reduced LC3B-positive puncta and absence of autophagosomes ultrastructurally. Although gross corneal morphology was preserved, ATG7 deficiency led to thickened epithelium and increased peripheral lymphatic vessel sprouting, indicating a pro-inflammatory and pro-lymphangiogenic microenvironment. Proteomic analysis revealed upregulation of RAB8, TM9S3, and RETR3, suggesting activation of compensatory pathways such as exophagy, reticulophagy, and Golgiphagy. Inflammatory and angiogenic components were downregulated, suggesting a moderate loss of inhibitory capacity based on the lymphatic phenotypes observed. At the same time, while these two compensatory changes occur, other proteins that positively regulate lysosome formation are reduced, resulting in a phenotype linked to deficient autophagy. These findings demonstrate that ATG7-mediated autophagy maintains corneal epithelial homeostasis and immune privilege, with implications for understanding corneal inflammation and lymphangiogenesis in ocular surface diseases. Full article

Background: Contact lens-assisted corneal cross-linking can be used to treat keratoconus in patients with thin corneas under measuring less than 400 µm. This study compares the long-term clinical and tomographic outcomes between accelerated corneal cross-linking (A-CXL) and accelerated contact lens-assisted corneal cross-linking (A-CACXL). Methods: Patients who underwent either A-CXL or A-CACXL protocol due to progressive keratoconus were enrolled in this retrospective cohort study conducted between January 2015 and December 2018. The control group (patients with minimum corneal thickness of at least 400 µm, comprising 32 eyes of from 32 patients) was treated with A-CXL, whereas the treatment group (patients that had minimum corneal thickness after epithelial removal below 400 µm; 30 eyes of from 30 patients) underwent the A-CACXL protocol. Clinical and tomographic data were obtained from a 3-year follow-up period. Results: At 3 years, both groups represented a significant gain in best-corrected visual acuity (from 0.32 to 0.18 LogMAR units for A-CXL, p = 0.001; from 0.51 to 0.33 LogMAR units for A-CACXL, p = 0.037). Furthermore, postoperative tomographic parameters (Kmax, Kmean, or corneal astigmatism) were comparable between the two protocols. Progression of keratoconus was halted among 87% of eyes in the A-CXL group and among 73% of eyes in the A-CACXL group (p = 0.2). Conclusions: A-CACXL treatment is an effective and safe option for patients with keratoconus and thin corneas, yielding long term outcomes comparable to those of A-CXL treatment for patients with a minimum corneal thickness of 400 µm following a 3-year follow-up. Full article

Background: This study aimed to evaluate the influence of scleral contact lens (SCL) wear on optical coherence tomography (OCT) scan quality and structural measurements in patients with keratoconus. Methods: This retrospective observational study included 28 eyes of 28 keratoconus patients. All participants underwent a comprehensive ophthalmologic evaluation, including corneal topography and spectral-domain OCT (Optopol REVO 60). Two OCT measurement sessions were performed on the same day: one without SCLs and one after a 30–75 min adaptation period with Mini Misa^® scleral lenses. Recorded parameters included corneal and epithelial thicknesses, ganglion cell–inner plexiform layer (GCIPL) thickness, retinal nerve fiber layer (RNFL) thickness, and device-reported quality index (QI). Correlation analyses between topographic values, age, and OCT parameters were also conducted. Results: The mean age of participants was 32.96 ± 13.72 years. SCL wear significantly decreased anterior segment QI (6.76 ± 1.73 vs. 5.57 ± 2.34, p = 0.019) but improved posterior segment QI in both the ganglion (2.52 ± 1.03 vs. 5.76 ± 2.17, p < 0.001) and disc (2.82 ± 0.94 vs. 4.39 ± 1.87, p < 0.001) modules. Central corneal thickness remained stable, while central epithelial thickness decreased slightly (50.53 ± 6.66 µm vs. 47.59 ± 7.20 µm, p = 0.007). RNFL and GCIPL thicknesses showed no significant changes, except for minor sectoral variations. Steeper keratometry values correlated with lower QI in both conditions. Conclusions: SCLs enhanced posterior OCT scan quality while reducing anterior segment image clarity. These findings suggest that SCLs not only provide visual rehabilitation but also facilitate more reliable posterior segment imaging in keratoconus patients, despite mild interference with anterior segment OCT metrics. Further prospective studies are warranted to validate these results. Full article

We investigated the repeatability of the MS-39 in determining power vector components—the spherical equivalent (SEQ) and astigmatic powers (C0 and C45) and asphericity (Q)—of corneal epithelium, stroma, and endothelium in a large patient cohort. In this retrospective cross-sectional single-centre study, we evaluated a dataset containing 600 MS-39 anterior segment tomography measurements from 200 eyes (three repeat measurements each) taken prior to cataract surgery. The exported measurements included height map data for the epithelium, stroma, and endothelium surface. Model surfaces (spherocylinder (SphCyl), cylindrical conoid (CylConoid), and biconic (Biconic), all in the 3/6 mm zone) were fitted using nonlinear iterative optimisation, minimising the height difference between the measurement and model. The mean (MEAN) and standard deviation (SD) for each sequence of measurements were derived and analysed. In the 3 mm and 6 mm zone, the MEAN SEQ was 53.47/53.56/53.57 and 53.21/53.54/53.54 D for SphCyl/CylConoid/Biconic for the epithelium, −4.47/−4.51/−4.51 and −4.45/−4.50/−4.50 D for the stroma, and −6.23/−6.26/−6.26 and −6.18/−6.29/−6.30 D for the endothelium. With the three surface models and the 3/6 mm zone, the SD for SEQ/C0/C45 was in the range of 0.04 to 0.11/0.05 to 0.13/0.04 to 0.11 D for epithelium; 0.01 to 0.02/0.01 to 0.05/0.01 to 0.06 D for stroma; and 0.01 to 0.02/0.02 to 0.07/0.03 to 0.07 D for endothelium. Fitting floating model surfaces with astigmatism to map data of the corneal epithelium, stroma, and endothelium seems to be a robust and reliable method for extracting equivalent power and astigmatism using all the datapoints within a region of interest. Full article

Background: Antibody-drug conjugates (ADCs) have ushered in a new era of precision oncology by combining the targeting specificity of monoclonal antibodies with the potent cytotoxicity of chemotherapeutic drugs. However, the cellular and molecular mechanisms underlying their dose-limiting ocular toxicity remain unclear. Elahere™, the first FDA-approved ADC targeting folate receptor α (FRα), demonstrates remarkable efficacy in platinum-resistant ovarian cancer but causes keratitis and other ocular toxicities in some patients. Notably, FRα is not expressed in the corneal epithelium—the primary site of damage—highlighting the urgent need to elucidate its underlying mechanisms. The aim of this study was to identify the cell-type-specific molecular mechanisms underlying Elahere-induced ocular toxicity. Methods: Sprague-Dawley rats were treated with intravenous Elahere (20 mg/kg) or vehicle weekly for five weeks. Ocular toxicity was determined by clinical examination and histopathology. Corneal single-cell suspensions were analyzed using the BD Rhapsody single-cell RNA sequencing (scRNA-seq) platform. Bioinformatic analyses to characterize changes in corneal cell populations, gene expression, and signaling pathways included cell clustering, differential gene expression, pseudotime trajectory inference, and cell-cell interaction modeling. Results: scRNA-seq profiling of 47,606 corneal cells revealed significant damage to the ocular surface and corneal epithelia in the Elahere group. Twenty distinct cell types were identified. Elahere depleted myeloid immune cells; in particular, homeostatic gene expression was suppressed in phagocytic macrophages. Progenitor populations (limbal stem cells and basal cells) accumulated (e.g., a ~2.6-fold expansion of limbal stem cells), while terminally differentiated cells decreased in corneal epithelium, indicating differentiation blockade. Endothelial cells exhibited signs of injury and inflammation, including reduced angiogenic subtypes and heightened stress responses. Folate receptor alpha, the target of Elahere, was expressed in endothelial and stromal cells, potentially driving stromal cells toward a pro-fibrotic phenotype. Fc receptor genes were predominantly expressed in myeloid cells, suggesting a potential mechanism underlying their depletion. Conclusions: Elahere induces complex, multi-compartmental ocular toxicity characterized by initial perturbations in vascular endothelial and immune cell populations followed by the arrest of epithelial differentiation and stromal remodeling. These findings reveal a cascade of cellular disruptions and provide mechanistic insights into mitigating Elahere-associated ocular side effects. Full article