Search Results (171)

The eye, a complex organ essential for visual perception, is composed of diverse cell populations with specialized functions; however, the complex interplay between these cellular components and their underlying molecular mechanisms remains largely elusive. Traditional biotechnologies, such as bulk RNA sequencing and in vitro models, are limited in capturing cellular heterogeneity or accurately mimicking the complexity of human ophthalmic diseases. The advent of single-cell RNA sequencing (scRNA-seq) has revolutionized ocular research by enabling high-resolution analysis at the single-cell level, uncovering cellular heterogeneity, and identifying disease-specific gene profiles. In this review, we provide a review of scRNA-seq application advancement in ocular physiology and pathology, highlighting its role in elucidating the molecular mechanisms of various ocular diseases, including myopia, ocular surface and corneal diseases, glaucoma, uveitis, retinal diseases, and ocular tumors. By providing novel insights into cellular diversity, gene expression dynamics, and cell–cell interactions, scRNA-seq has facilitated the identification of novel biomarkers and therapeutic targets, and the further integration of scRNA-seq with other omics technologies holds promise for deepening our understanding of ocular health and diseases. Full article

The cornea, the transparent anterior window of the eye, critically refracts light and protects intraocular structures. Corneal pathologies, including trauma, infection, chemical injury, metabolic diseases, genetic conditions, and age-related degeneration, can lead to significant visual impairment. While penetrating keratoplasty or full-thickness corneal transplantation remains a standard and effective intervention for severe corneal dysfunction, limitations in donor tissue availability and the risk of immunogenic graft rejection necessitate alternative therapeutic strategies. Furthermore, for cases of isolated epithelial disfunction, a full-thickness cornea graft may not be required or effective. This review examines the potential of corneal epithelial constructs derived from autologous stem cells with functional barrier properties for corneal reconstruction and in vitro pharmacotoxicity testing. In this review, we delineate the current limitations of corneal transplantation, the advantages of stem cell-based approaches, and recent advances in generating engineered corneal epithelium. Finally, we address remaining technical challenges and propose future research directions aimed at clinical translation. Full article

Background/Objectives: Tacrolimus, an immunosuppressant, is increasingly used topically in ophthalmology, particularly for conditions like vernal keratoconjunctivitis and post-keratoplasty rejection prophylaxis. This systematic review aims to evaluate the efficacy and safety of topical tacrolimus in these ocular conditions. Methods: A thorough search was conducted in PubMed and Cochrane Library for relevant studies published up to 16 March 2025. Studies were eligible for inclusion if they were randomized controlled trials investigating topical tacrolimus in human ocular disease, were published in English, and reported clearly defined outcomes. Exclusion criteria included non-randomized studies, animal studies, systemic treatments, non-English publications, and studies lacking clearly reported outcomes. Data regarding study design, patient demographics, intervention details, and outcomes were extracted and analyzed. The Cochrane risk-of-bias tool (RoB 2.0) was used to assess the risk of bias. Results: A total of 10 studies met the inclusion criteria, were retrieved, and were categorized as not highly biased after the risk-of-bias assessment. These studies were included in the systematic review, where a qualitative analysis took place. Our analysis revealed that the topical use of tacrolimus showed promising results, as it improved clinical signs and symptoms in most patients. In half of the studies, tacrolimus demonstrated superior efficacy compared to the control group, while in the remaining studies, it showed equivalent efficacy. Adverse effects, such as a burning sensation, were noted in 7/10 studies but were generally mild. The methodologies were somewhat heterogeneous, and some studies had small sample sizes. Conclusions: Topical tacrolimus shows promising effects in managing various ocular surface diseases. While randomized controlled trials provide evidence, further research with larger sample sizes is necessary to solidify its efficacy and safety profile compared to other immunosuppressants. Full article

This study aimed to comprehensively review surgical interventions for ocular surface diseases (OSDs), including dry eye syndrome (DES), exposure keratopathy, Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and ocular graft versus host disease (oGVHD), and to highlight the indications, contraindications, outcomes, and complications of various oculoplastic procedures used in their management. A narrative review was performed based on expert-guided selection of relevant studies retrieved from PubMed, Scopus, and Web of Science. Relevant keywords included “ocular surface disease”, “dry eye syndrome”, “exposure keratopathy”, “thyroid eye disease (TED)”, “neurotrophic keratopathy (NK)”, “Stevens-Johnson syndrome”, “toxic epidermal necrolysis”, “punctal occlusion”, “tarsorrhaphy”, “botulinum toxin”, “eyelid loading”, “retractor weakening”, “corneal neurotization (CN)”, “amniotic membrane transplantation (AMT)”, “conjunctival flap”, “ocular graft versus host disease”, and “salivary gland transplantation (SGT)”. Studies addressing surgical approaches for OSDs were included. In conclusion, surgical options for OSDs offer significant benefits when non-invasive treatments fail. Surgical techniques such as punctal occlusion, eyelid fissure narrowing, AMT, and conjunctival flap procedures help stabilize the ocular surface and alleviate symptoms. Advanced methods like CN and SGT target the underlying pathology in refractory cases such as oGVHD. The outcomes vary depending on the disease severity and surgical approach. Each procedure carries specific risks and requires individualized patient selection. Therefore, a tailored approach based on clinical condition, anatomical involvement, and patient factors is essential to achieve optimal results. Ongoing innovations in reconstructive surgery and regenerative medicine are expected to further improve outcomes for patients with OSDs. Full article

Background/Objectives: Post-keratoplasty astigmatism can limit visual recovery even after successful corneal transplantation. Femtosecond laser-assisted arcuate keratotomy (FSAK) has emerged as a method to reduce high residual astigmatism and enhance visual outcomes. This study aimed to evaluate the outcome of FSAK in treating astigmatism following keratoplasty. Methods: This retrospective study included 32 eyes from 31 patients who underwent FSAK after keratoplasty. Inclusion required complete suture removal, regular corneal topography, and the absence of additional ocular pathology or prior intraocular surgery. Data collected included uncorrected (UCVA) and best-spectacle-corrected visual acuity (BSCVA), manifest refraction, and tomographic parameters. The primary outcomes were changes in visual, refractive, and tomographic measures across the entire cohort, with further subgroup analysis between penetrating keratoplasty (PKP) and lamellar keratoplasty (LKP) eyes. Secondary outcomes were documentation of complications. Results: UCVA improved significantly from 0.92 ± 0.33 to 0.58 ± 0.39 LogMAR (p < 0.001). BSCVA showed a non-significant trend toward improvement from 0.32 ± 0.21 to 0.26 ± 0.22 LogMAR (p = 0.158). The manifest cylinder reduced significantly from −6.15 ± 2.75 D to −4.49 ± 2.92 D (p = 0.037). Corneal topography revealed significant postoperative steepening in keratometric values. While overall outcomes were comparable between the subgroups, LKP eyes demonstrated a greater myopic shift and a higher rate of overcorrection, whereas PKP eyes tended toward undercorrection. Conclusions: FSAK appears to be an effective approach for reducing post-keratoplasty astigmatism and improving uncorrected visual acuity. Given the biomechanical differences between graft types, individualized treatment planning based on graft characteristics may enhance surgical predictability and optimize outcomes. Full article

The therapeutic potential of exosomes (Exos), a subpopulation of extracellular vesicles (EVs) secreted by various cell types, has been broadly emphasized. Exos are endosome-derived membrane-bound vesicles 50–150 nm in size. Exos can be general or cell type-specific. Their contents enable them to function as multi-signaling and vectorized vehicles. Exos are important for maintaining cellular homeostasis. They are released into extracellular spaces, leading to uptake by neighboring or distant cells and delivering their contents to modulate cell signaling. Exos influence tissue responses to injury, infection, and disease by fusion with the target cells and transferring their cargo, including cytokines, growth and angiogenic factors, signaling molecules, lipids, DNA, mRNAs, and non-coding RNAs. They are implicated in various physiological and pathological conditions, including ocular surface events, such as corneal scarring, wound healing, and inflammation. Their biocompatibility, stability, low immunogenicity, and easy detectability in bodily fluids (blood, tears, saliva, and urine) make them promising tools for diagnosing and treating ocular diseases. The potential to engineer specific Exo cargos makes them outstanding therapeutic delivery vehicles. The objective of this review is to provide novel insights into the functions of Exo cargos and their applications as biomarkers and therapeutics, or targets in the cornea. Full article

Background/Objectives: Chronic neuropathic ocular pain (NOP) can manifest concurrently with dry eye (DE) symptoms following ocular surgical procedures. Due to its low prevalence, NOP remains an underrecognized and underdiagnosed postoperative complication, leading to suboptimal management. This study evaluated the long-term evolution of symptoms, signs, and tear biomarkers in patients with NOP and DE after corneal refractive surgery (RS). Methods: Patients with chronic NOP and persistent DE-related symptoms after corneal RS were assessed in two visits (V1 and V2), at least two years apart. Symptoms (DE, pain, anxiety, and depression) were measured with specific questionnaires. Clinical examination included a slit-lamp ocular surface evaluation, corneal sensitivity measurement, and subbasal corneal nerve plexus evaluation. Basal tear samples were collected, and a 20-plex cytokine panel and Substance P (SP) were assayed. Results: Twenty-three patients (35.57 ± 8.43 years) were included, with a mean time between visits of 4.83 ± 1.10 years. DE symptoms, measured with the Ocular Surface Disease Index questionnaire, improved at V2 (p < 0.001), along with a reduction in anxiety and depression levels, measured with the Hospital Anxiety and Depression Scale (p = 0.027). Corneal staining also decreased (p < 0.001), while subbasal nerve plexus parameters and corneal sensitivity remained unchanged. Tear analysis revealed increased concentrations of fractalkine/CX3CL1 (p = 0.039), interleukin (IL)-1 receptor antagonist (Ra) (p = 0.025), IL-10 (p = 0.002), and SP (p < 0.001). Conclusions: Symptom improvement may result from better control of underlying pathologies or natural disease progression. However, the increased levels of SP and fractalkine/CX3CL1 suggest sustained neurogenic inflammation, while elevated IL-1Ra and IL-10 indicate a potential compensatory anti-inflammatory response. Full article

Although approached through many concepts, the pleiotropic healing issue, specifically, maintaining/reestablishing tissue integrity, remains a central challenge in pharmacology, particularly when the process is misdirected or not properly controlled. Robert and Szabo’s concept of cytoprotection holds that innate cell (epithelial (Robert), endothelial (Szabo)) integrity and protection/maintenance/reestablishment in the stomach is translated to other organ therapy (cytoprotection → organoprotection) via the cytoprotection agent’s effect. Therefore, we defend stable gastric pentadecapeptide BPC 157 therapy’s efficacy and pleiotropic beneficial effects, along with its high safety (LD1 not achieved), against speculation of its negative impact, speculation of angiogenesis toward tumorigenesis, increased NO and eNOS, damaging free radical formation, and neurodegenerative diseases (Parkinson’s disease and Alzheimer’s disease). Contrarily, in wound healing and general healing capabilities, as reviewed, as a cytoprotective agent and native cytoprotection mediator, BPC 157 controls angiogenesis and the NO-system’s healing functions and counteracts the pathological presentation of neurodegenerative diseases in acknowledged animal models (i.e., Parkinson’s disease and Alzheimer’s disease), and it presents prominent anti-tumor potential in vivo and in vitro. BPC 157 resolved cornea transparency maintenance, cornea healing “angiogenic privilege” (vs. angiogenesis/neovascularization/tumorigenesis), and it does not produce corneal neovascularization but rather opposes it. Per Folkman’s concept, it demonstrates an anti-tumor effect in vivo and in vitro. BPC 157 exhibits a distinctive effect on the NO-level (increase vs. decrease), always combined with the counteraction of free radical formation, and, in mice and rats, BPC 157 therapy counteracts Parkinson’s disease-like and Alzheimer’s disease-like disturbances. Thus, BPC 157 therapy means targeting angiogenesis and NO’s cytotoxic and damaging actions but maintaining, promoting, or recovering their essential protective functions. Full article

Background: Cabozantinib is a Vascular Endothelial Growth Factor Receptor Tyrosine Kinase Inhibitor (VEGFR-TKI). These drugs are employed as therapy for several malignancies. In detail, Cabozantinib has demonstrated its efficacy against several malignancies. On the other hand, Cabozantinib and other VEGFR-TKIs can be responsible for various adverse events (AEs), in particular hepatic and dermatological AEs. Methods: To date, limited data are available in the literature regarding ocular AEs due to therapy with these drugs. In this regard, one case of corneal perforation during treatment with a VEGFR-TKI, Regorafenib, has been reported, while there are no data about Cabozantinib. In this paper, we present another clinical case of corneal perforation in a patient affected by advanced RCC and treated with Cabozantinib as a second-line therapy. The patient started Cabozantinib at the dosage of 60 mg/die although it was necessary to apply some dose reductions because of grade 2 AEs (according to CTCAE v6.0), such as asthenia, diarrhea, dysgeusia, and loss of appetite. Results: After approximately 15 months of treatment, the patient began to experience pain and vision loss in the right eye. A diagnosis of corneal perforation was made, followed by medical and surgical treatment. As regards the etiology of this pathology, all other possible causes were excluded, including a history of ocular disease, contact trauma, exposure to damaging agents (e.g., chemical agents and prolonged use of drugs such as topical NSAIDs), infections, or dry eye. Therefore, we hypothesized a correlation with Cabozantinib’s mechanisms of action and paused its administration. Conclusions: Cabozantinib may alter the ocular environment due to a lack of or imbalance in growth factors in the tear film, with a reduction in corneal epithelium proliferation. This condition might cause dry eye and a delay in corneal healing. Therefore, particular importance should be placed on ophthalmologic surveillance during treatment with these drugs in patients who develop ocular symptoms. Further in vitro and in vivo studies are necessary to deepen the knowledge about VEGFR-TKI-mediated ocular AEs. Full article

The cornea, a highly innervated and avascular ocular tissue, relies on intricate neuro-immune interactions to maintain homeostasis. Among key neuromediators, substance P (SP)—a neuropeptide belonging to the tachykinin family—plays a dual role in corneal physiology and pathology. This review synthesizes current knowledge on SP’s involvement in corneal innervation, epithelial homeostasis, immune regulation, neovascularization, and wound healing, while highlighting its dichotomous effects in both promoting tissue repair and exacerbating inflammation. SP, primarily signaling through the neurokinin-1 receptor (NK1R), influences corneal epithelial proliferation, barrier function, and wound healing by modulating cytokines, chemokines, and growth factors. However, its overexpression is linked to pain sensitization, inflammatory keratitis, and corneal neovascularization, driven by interactions with immune cells (e.g., mast cells, neutrophils) and pro-angiogenic factors (e.g., VEGF). Clinical studies demonstrate altered SP levels in dry eye disease, neurotrophic keratitis, and post-refractive surgery, correlating with nerve damage and ocular surface dysfunction. Emerging therapies targeting SP pathways- such as NK1R antagonists (e.g., fosaprepitant) and SP-IGF-1 combinations-show promise for treating neurotrophic ulcers but face challenges due to SP’s context-dependent actions. Future research should clarify the roles of NK2R/NK3R receptors and optimize SP-based interventions to balance its reparative and inflammatory effects. Understanding SP’s multifaceted mechanisms could advance the development of therapies for corneal diseases, particularly those involving sensory neuropathy and immune dysregulation. Full article

Background: Sjögren’s syndrome (SS) is a systemic autoimmune condition marked by significant dry eye disease (DED), leading to considerable corneal changes. These modifications, encompassing punctate epithelial erosions, chronic epithelial abnormalities, and corneal ulcers, significantly impact eyesight and quality of life. Progress in comprehending the corneal pathophysiology associated with SS has prompted innovative diagnostic and treatment approaches. Aim: This narrative review aims to examine developing trends in the pathogenesis, diagnostic methods, and treatment strategies for Sjögren’s syndrome-associated corneal changes. Methods: The study was based on a narrative review of the current literature available on PubMed and Cochrane from Jan 2000 to December 2024. Results: Corneal changes associated with Sjögren’s syndrome result from a multifactorial interaction of ocular surface inflammation, tear film instability, and epithelium degradation. Recent research underscores the significance of immune-mediated pathways, such as T-cell-induced inflammation and cytokine dysregulation, as crucial factors in corneal disease. Innovations in diagnostic instruments, including in vivo confocal microscopy and tear proteomics, provide earlier and more accurate identification of subclinical alterations in the corneal epithelium and stroma. Therapeutic developments concentrate on meeting the specific requirements of SS-related DED. Biological treatments, especially tailored inhibitors of interleukin-6 and tumor necrosis factor-alpha, show potential in mitigating inflammation and facilitating epithelial repair. Moreover, regenerative approaches, such as autologous serum tears and mesenchymal stem cell therapies, provide innovative methods to repair ocular surface integrity. Advanced drug delivery technologies, including nanoparticle-loaded eye drops, enhance bioavailability and therapeutic efficacy. Conclusion: Recent developments in comprehending SS-related corneal changes have transformed the management approach to precision medicine. The combination of improved diagnostics and innovative therapy approaches offers potential for reducing disease progression, maintaining corneal health, and enhancing patient outcomes. Subsequent investigations ought to concentrate on enhancing these tactics and examining their long-term safety and effectiveness. Clinicians and researchers must adopt these developments to successfully tackle the difficulties of SS-related corneal illness, providing hope for improved care and higher quality of life for those affected. Full article

Objective: The aim of this study was to assess the safety and preliminary efficacy of repetitive magnetic stimulation (RMS) as a treatment intervention for dry eye disease (DED), focusing on symptom reduction. Methodology: This investigation involved 22 adult participants (85% females, aged between 22 and 79 years) diagnosed with moderate-to-severe DED. These individuals were subjected to RMS treatment targeting one or both eyes using the VIVEYE-Ocular Magnetic Neurostimulation System version 1.0 (Epitech-Mag LTD; National Institute of Health (NIH) clinical trials registry #NCT03012698). A placebo-controlled group was also included for comparative analysis, with all subjects being monitored over a three-month period. The evaluation of safety encompassed monitoring changes in best corrected visual acuity, ocular pathology, and the reporting of adverse events. Participant tolerance was gauged through questionnaires, measurements of intraocular pressure (IOP), Schirmer’s test, and vital signs. The efficacy of the treatment was assessed by comparing pre- and post-treatment scores for fluorescein staining (according to National Eye Institute (NEI) grading) and patient-reported outcomes. Results: No statistically significant changes were found in visual acuity, IOP, or Schirmer’s test results between the RMS-treated and control groups (p < 0.05), indicating that RMS does not negatively impact these ocular functions. However, RMS treatment was associated with improved tear film stability (p = 0.19 vs. p = 0.04) and corneal health (p = 0.52 vs. p = 0.004), with no improvements in the control group. Initial symptom improvement was observed in both RMS-treated and placebo groups (p = 0.007 vs. p = 0.008), suggesting a potential therapeutic benefit of RMS for ocular surface conditions beyond a placebo effect. Conclusions: This study presents RMS as a promising therapeutic approach for DED, highlighting its potential to promote corneal epithelial repair, enhance tear film stability, and improve patient-reported symptoms without negatively impacting IOP, visual acuity, or tear production. This confirms the safety and suggests the efficacy of RMS therapy for dry eye conditions. Full article

Background: Myopia is a leading cause of visual impairment worldwide, and accumulating evidence suggests that biomechanics may be closely linked to its development. Understanding this relationship may help clarify the underlying mechanisms of myopia and guide treatment strategies. The aim of the study is to investigate the causal relationship between myopia and corneal biomechanics using the UK Biobank (UKB) database. Methods: Data from 11,064 eyes in the UKB, including refraction results and Ocular Response Analyzer (ORA) measurements, were analyzed. Eyes were categorized by spherical equivalent (SE) into emmetropia, mild myopia, moderate myopia, and high myopia. One-way ANOVA assessed differences in corneal biomechanical parameters across the varying myopia groups, while Quantile Regression (QR) explored the relationship between these parameters and myopia severity across the different quantiles. A Mendelian randomization (MR) analysis was employed to explore the causal relationships. Results: Significant differences in corneal biomechanical parameters and intraocular pressure (IOP) were observed across the myopia levels (p < 0.001). High myopia was associated with lower corneal hysteresis (CH), a lower corneal resistance factor (CRF), and increased IOP. The QR analysis demonstrated that lower corneal biomechanics were associated with higher degrees of myopia, with the impact of corneal biomechanics becoming more pronounced as the myopia severity increased. The MR analysis indicated that low CH (OR = 0.9943, p = 0.004) and CRF (OR = 0.9946, p = 0.002) values were risk factors for myopia, while no causal effect was found when the myopia was treated as the exposure and corneal biomechanics as the outcome. Conclusions: This study establishes a causal relationship where reduced corneal biomechanics contribute to myopia, while myopia itself does not directly affect biomechanics. Corneal biomechanics could serve as a biomarker for assessing high myopia risk. These findings offer new insights into high myopia’s pathological mechanisms and targeted prevention. Full article

Keratoconus (KC) is a progressive ocular disorder marked by structural and functional alterations of the cornea, leading to significant visual impairment. Recent studies indicate that these corneal changes are linked to molecular and cellular mechanisms that disrupt and degrade the extracellular matrix. This degradation is influenced by proteinases that contribute to a loss of homeostasis and an imbalance in the antioxidant/oxidative state within the cornea, fostering oxidative stress, inflammation, and apoptosis. Although these biological processes have been identified primarily through molecular biology research, omics technologies have significantly advanced our understanding of the physiological and pathological phenomena associated with KC. Omics studies encompassing genomics, transcriptomics, proteomics, epigenomics, and metabolomics, have emerged as critical tools in elucidating the complex biological landscape of various diseases, including ocular conditions. The integrative application of these studies has demonstrated their potential in personalizing medicine across diverse fields such as oncology, neurology, and ophthalmology. This review aims to describe findings from omics research applied to keratoconus, highlighting the genomic, transcriptomic, proteomic, epigenomic, and metabolomic aspects derived from ocular and other biological samples. Notably, the molecular insights gained from these studies hold promise for identifying biomarkers of keratoconus, which could enhance diagnostic accuracy and therapeutic strategies. The exploration of these biomarkers may facilitate improved management and treatment options for patients, contributing to personalized care in keratoconus management. Full article

Fuchs Endothelial Corneal Dystrophy (FECD) is a corneal endothelial disease that causes microenvironment alterations and endothelial cell loss, which leads to vision impairment. It has a high global prevalence, especially in elderly populations. FECD is also one of the leading indications of corneal transplantation globally. Currently, there is no clearly defined canonical pathway for this disease, and it has been proposed that the combinatorial effects of genetic mutations and exogenous factors cause FECD. Clinical studies and observations have provided valuable knowledge and understanding of FECD, while preclinical studies are essential for gaining insights into disease progression and mechanisms for the development and testing of regenerative medicine therapies. In this review, we first introduce the proposed genetic and molecular pathologies of FECD. Notably, we discuss the impact of abnormal extracellular matrix deposition (guttata), endothelial-to-mesenchymal transition, cell senescence, and oxidative stress on the pathology and etiology of FECD. We review and summarize the in vitro cell models, ex vivo tissues, and in vivo animal models used to study FECD. The benefits and challenges of each model are also discussed. Full article