Search Results (267)

Corneal alkali burn induces severe inflammation and tissue damage, leading to loss of corneal transparency and vision impairment. In this study, we evaluated the therapeutic potential of rapamycin (RAPA) compared with cyclosporine A (CsA) in a mouse model of corneal alkali burn, focusing on nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)–mediated inflammatory signaling and its impact on corneal wound healing and repair. Notably, RAPA robustly suppressed NF-κB activation, reduced infiltration of F4/80 macrophages and MPO neutrophils, and downregulated pro-inflammatory cytokines, including TNF-α, IL-1β, and IL-6. RAPA also markedly inhibited corneal neovascularization, as evidenced by decreased VEGF expression, reduced CD31 vessel formation, and suppression of Ang-2. RAPA substantially inhibited pathological fibrotic remodeling by reducing TGF-β1 expression, attenuating myofibroblast activation (α-SMA), decreasing collagen III deposition, and modulating matrix remodeling through suppression of MMP-9. Crucially, RAPA preserved epithelial barrier integrity by maintaining occludin expression, supported proper epithelial differentiation through sustained expression of CK12, and enhanced mucin layer stability by increasing MUC1 expression. It also restored tear production, reduced apoptotic cell death (TUNEL), and decreased dysregulated epithelial proliferation (Ki67). In conclusion, RAPA showed superior efficacy compared with CsA, primarily by enhancing corneal wound healing and facilitating structural and functional outcomes in the burned cornea. These findings underscore RAPA as a promising therapeutic candidate for ocular surface repair and vision restoration in extensive corneal injury. Full article

Age-related macular degeneration (AMD) is the most common cause of blindness and vision impairment in individuals over 60 years of age in the United States (US). Despite this, current treatment options have limitations related to drug efficacy and durability. Gene therapy provides a potential solution by providing a more durable and longer- acting treatment option that can decrease treatment burden and improve long-term visual outcomes. This review presents the current treatment approaches, routes of administration, and vectors being investigated for gene therapy delivery in AMD. It also provides an update on the ongoing gene therapy clinical trials for dry and wet AMD. As these therapies advance into later-stage clinical trials, ophthalmologists need to be mindful of the many challenges pertaining to gene therapy delivery, including safety, limitations related to immunogenicity, long-term ocular and systemic side effects, and potential barriers to drug manufacturing and access. Continued efforts are required to improve precision, safety, and efficacy, including identifying the safest and most effective vectors and delivery routes, and minimizing potential adverse effects. In addition, guidelines need to be established to guide appropriate patient selection before gene therapy can be integrated into clinical practice. Full article

Background/Objectives: The corneal endothelium maintains corneal transparency through its barrier function and active pumping mechanism that regulates stromal hydration. Limited regenerative capacity makes these cells vulnerable to progressive cell loss. Although local ocular factors are well known, recent data suggest that numerous systemic diseases may contribute to endothelial dysfunction and reduce endothelial reserve before the onset of clinically apparent corneal pathology. The purpose of this narrative review is to synthesize current evidence on the impact of systemic diseases on corneal endothelial health and to highlight the underlying mechanisms and clinical implications. Methods: A narrative literature review was conducted using the PubMed, MEDLINE, and Google Scholar databases for articles published between January 2000 and December 2025. Observational studies, case series, and review articles that evaluated structural or functional changes in the corneal endothelium in association with systemic diseases were included. Results: Reviewed literature shows that several categories of systemic diseases are associated with signs of corneal endothelial stress. These changes include decreased endothelial cell density, increased cell size variability, reduced hexagonality, and, in some cases, increased central corneal thickness. Metabolic, cardiovascular, renal, autoimmune, and hypoxic conditions, as well as extracellular matrix disorders and aging, show consistent associations with these changes. Conclusions: Systemic diseases can compromise corneal endothelial integrity and reduce functional reserve even in the absence of clinically evident corneal pathology. Recognition of these associations underscores the importance of evaluating the patient’s systemic context, including a detailed medical history and corneal endothelial analysis, particularly before intraocular surgery. Full article

Introduction: Although anterior non-infectious uveitis affects the structures of the anterior segment of the eye, (inflammatory) disruption of the hemato–ocular barrier may lead to changes in the structures of the posterior segment of the eye. Objective: To evaluate functional retinal changes using multifocal electroretinography (mfERG) and their relationship with structural optical coherence tomography (OCT) parameters in patients with acute anterior non-infectious uveitis (AANU). Methods: This prospective study included 38 eyes of 19 patients diagnosed with unilateral AANU and age-matched healthy fellow eyes as controls. All subjects underwent comprehensive ophthalmological examination, including best-corrected visual acuity (BCVA), spectral-domain OCT, and mfERG testing at baseline, 3 months, and 6 months. mfERG parameters (amplitude and implicit times) were analyzed alongside central field thickness (CFT), macular volume (MV), and average macular thickness (AMT). Results: Eyes affected by AANU demonstrated a significant reduction in mfERG response amplitude in the central retinal region compared with control eyes, particularly during the acute phase. Although OCT parameters showed partial structural normalization during follow-up, functional recovery was less pronounced in selected retinal regions. Latency values showed minimal variation over time. These findings indicate a potential dissociation between electrophysiological function and structural morphology during disease resolution. Conclusions: Acute anterior uveitis is associated with measurable macular functional impairment detectable by mfERG, even when structural OCT parameters appear relatively stable. These results suggest that inflammatory processes in AAU may extend beyond the anterior segment and transiently affect retinal function. mfERG may therefore serve as a sensitive adjunct tool for detecting and monitoring subclinical macular dysfunction in AANU. Clinical Relevance: Functional retinal impairment may persist despite apparent structural recovery in acute anterior uveitis. Incorporating mfERG into clinical evaluation may improve the detection of subtle macular involvement and enhance understanding of disease dynamics beyond conventional imaging findings. Full article

Ocular fungal diseases are associated with severe infection and pain and, in advanced stages, can lead to vision loss. Current treatment options are limited to the topical application of conventional drugs, and the bioavailability of these drugs is quite limited due to ocular barriers. In this study, a dual-drug nanodelivery system was developed to improve intraocular drug delivery by combining antifungal and anti-inflammatory therapies. Posaconazole (PSC), a broad-spectrum triazole antifungal agent, and dexketoprofen trometamol (DKP), a rapidly acting nonsteroidal anti-inflammatory drug, were co-loaded onto polymeric micelles and then incorporated into electrospun poly(vinyl alcohol)/poly(vinylpyrrolidone) (PVA/PVP) nanofiber intraocular implants. DSC, XRD, FTIR, and FESEM analyses showed that both APIs were successfully converted into nanofiber form without disrupting the micelle structure. Comparative studies with DKP solution and PSC commercial oral suspension (Noxafil^® 40 mg/mL) showed that the produced micelle-loaded nanofibers provided sustained release and significantly increased ex vivo ocular permeation and penetration. In vitro antifungal activity tests demonstrated efficacy against Candida albicans, and HET-CAM toxicity tests showed that the micelle-loaded nanofibers were non-irritating and suitable for ocular application. Overall, the micelle-loaded electrospun nanofiber ocular inserts developed in this study represent a promising platform for combined antifungal and anti-inflammatory ocular therapy. Full article

Ocular neovascular diseases represent a major cause of irreversible vision loss worldwide, while the complex ocular barrier system significantly limits the efficacy of conventional treatment approaches. In this context, colloidal drug delivery systems (CDDSs) have emerged as an innovative nanomedicine strategy that demonstrates remarkable advantages in enhancing ocular drug bioavailability and treatment precision through the integration of sustained release, active targeting, and stimulus-responsive functional modules. This review systematically summarizes recent research advances in CDDSs for treating ocular neovascular diseases, with a particular focus on design strategies and mechanisms for overcoming physiological barriers and achieving lesion-specific drug delivery. Furthermore, it provides in-depth analysis of key challenges in current clinical translation. With ongoing technological advancements, CDDSs are expected to offer breakthrough solutions for treating ocular neovascular diseases, ultimately leading to significant improvements in patients’ visual prognosis and quality of life. Full article

Purpose: The objective of this study was to engineer and optimize a mucoadhesive, positively charged stearylamine-enriched liposomal platform, termed Aminosomes, to circumvent the biophysical barriers limiting the ocular bioavailability of Brimonidine Tartrate (BT), an alpha-2 adrenergic receptor agonist for glaucoma management. Methods: Aminosomes were synthesized using a tailored ethanol injection technique and optimized via a 3² × 2¹ full factorial design. Molecular integrity and crystallinity were assessed using Fourier-transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD). The mucoadhesive potential was validated through a mucin interaction assay based on zeta potential shifts. In vitro release kinetics were evaluated using the dialysis membrane diffusion technique, while the therapeutic potential and ocular safety were validated through in vivo pharmacodynamic profiling of intraocular pressure (IOP) reduction, alongside comprehensive biocompatibility assessments via Draize irritancy protocol and histopathological examination. Results: The optimized Aminosomes exhibited nanometric dimensions, monodisperse size distribution, robust positive surface charge, and superior drug loading. FTIR and XRD analyses confirmed the chemical compatibility of the formulation components, as well as the successful encapsulation of BT and its transition to an amorphous state within the lipidic matrix. The mucoadhesion test demonstrated a high binding affinity for mucin. The in vitro release profile demonstrated a sustained-release pattern (78.8% over 12 h). Non-compartmental pharmacodynamic analysis of IOP-reduction data revealed a 2.8-fold increase in AUC_0–24h, 3.5-fold extension in t_1/2, and 5.2-fold prolongation in mean residence time (MRT) relative to the standard solution. Conclusions: The optimized Aminosomes demonstrated superior mucoadhesive anchoring, enhanced and sustained therapeutic flux without inducing ocular toxicity, offering a robust strategy for enhancing the pharmacodynamics of BT. Full article

Ocular diseases pose significant therapeutic challenges due to the eye’s intricate anatomy and efficient physiological clearance mechanisms, which result in the rapid elimination of topically administered drugs and an overall bioavailability of less than 5%. Anterior segment disorders—including keratitis, glaucoma, and dry eye syndrome—account for the majority of ophthalmic conditions and are primarily managed with pharmacological agents. However, due to extremely low drug bioavailability and poor patient compliance, their therapeutic outcomes often result in a decreased disease control rate or require early surgical interventions. Nebulized drug delivery, particularly employing advanced vibrating mesh technology, has emerged as a promising strategy to overcome these limitations. By converting liquid formulations into a uniform aerosol of micron-sized (1–10 μm) droplets, this approach achieves extensive and consistent coverage of the ocular surface, increases the absorption contact area, prolongs drug residence time, and ultimately enhances drug bioavailability. Preliminary clinical evidence indicates that nebulized therapies outperform traditional eye drops by achieving higher drug concentrations in the aqueous humor and demonstrating superior pharmacodynamic profiles and patient tolerability—particularly in conditions such as dry eye syndrome and glaucoma. This review presents a comprehensive overview of the mechanistic principles, technological advancements, and translational applications of nebulization-based ocular drug delivery systems. We place special emphasis on the integration of next-generation platforms that incorporate microelectromechanical systems (MEMS) and intelligent sensing technologies, enabling precision medicine approaches tailored to individual ocular pathophysiological characteristics. By bridging biomedical engineering and clinical ophthalmology, these innovations not only optimize existing therapeutic regimens but also pave the way for non-invasive delivery of complex biologics and gene therapies—potentially reshaping the landscape of anterior segment drug delivery. Full article

Glaucoma is a leading cause of irreversible blindness, yet vision loss often progresses despite effective intraocular pressure (IOP) control, suggesting the involvement of non-hydrodynamic mechanisms. This review explores the potential synergistic interaction between viral persistence and microbial dysbiosis in pathogenesis. While acknowledging that current evidence regarding the microbiome is largely associative and derived from small cohorts or animal models, we analyze how these environmental insults may disrupt autophagic flux and induce immune dysregulation to drive chronic neuroinflammation. Furthermore, we explore theoretical therapeutic strategies targeting this distinct pathological nexus, ranging from metabolic restoration of the gut–eye axis to the repurposing of advanced nanocarriers to overcome ocular barriers. This framework lays the groundwork for next-generation, etiology-based precision management. Full article

Protein C (PC) and its activated form, activated protein C (APC), are well-established regulators of coagulation and cytoprotection. While their systemic functions are extensively characterized, their physiological roles in the retina have only recently begun to be explored. This gap persists despite the observation that congenital PC deficiency is consistently associated with severe ocular complications. Emerging evidence, including the development of a murine model of severe protein C deficiency (SPCD), indicates that APC contributes to retinal integrity and vascular homeostasis under physiological conditions. Beyond its physiological function, APC has shown therapeutic activity in several models of retinal disease. Recent findings from our group further demonstrated that intravenously administered APC and its cytoprotective analog, 3K3A-APC, can cross the blood–retina barrier via the endothelial protein C receptor (EPCR), despite their relatively large molecular weight (~62 kDa), and induce cytoprotective activities in the retina. These findings highlight the translational potential of 3K3A-APC and support its further development as a systemically delivered therapeutic approach for retinal pathologies. This review integrates current knowledge of the molecular biology of the PC/APC pathways with its emerging physiological functions in the retina, and the accumulating preclinical and early clinical evidence that supports its therapeutic relevance. Full article

Conventional topical therapy for corneal and anterior segment diseases is limited by rapid tear clearance and multilayer corneal barriers, resulting in low bioavailability and the need for frequent dosing. Artificial intelligence (AI) is emerging as a complementary approach that learns quantitative relationships between molecular structure, formulation variables, and ocular performance. In corneal drug delivery, machine learning models have been used to optimize multicomponent formulations and processing conditions; predict key quality attributes such as particle size, zeta potential, encapsulation efficiency and release kinetics; and estimate corneal permeability, retention and ocular irritation risk, thereby reducing experimental burden and guiding safer design. AI can also be coupled with mechanistic ocular pharmacokinetic/pharmacodynamic models to translate formulation attributes into predicted tissue exposure. Finally, inverse design approaches enable the discovery of new carriers and devices, illustrated by machine learning-guided peptide carriers and smart contact lens platforms that combine sensing with on-demand drug release. Despite these advances, current datasets remain small and heterogeneous, external validation and benchmarking against conventional workflows are limited, and uncertainty quantification and interpretability must be addressed to enable clinical translation. This review summarizes corneal barriers and delivery platforms, critically evaluates where AI provides measurable value across design, characterization and performance and highlights data and validation priorities needed for trustworthy AI-enabled corneal therapeutics. Full article

The blood–retinal barrier (BRB) maintains neurovascular homeostasis by regulating solute and ion exchange between the retina and circulation. This selectivity depends on tight junctions (TJs), with claudin (Cldn) proteins forming the core structure that defines paracellular permeability. Distinct Cldn isoforms show cell-specific expression, with Cldn-5 predominating in the endothelial cells of the inner BRB and Cldn-19 is the signature Cldn in the retinal pigment epithelium forming the outer BRB. Disruption of these isoforms contributes to vascular leakage, inflammation, and neuronal loss across various ocular diseases. Cldn function in vascular homeostasis is multifaceted; barrier dysfunction does not always result from Cldn loss, as excessive expression or mislocalization, particularly of Cldn-5, can also impair BRB integrity. Cldns act as dynamic signaling hubs that respond to metabolic, oxidative, and mechanical stress and are regulated through VEGF, Wnt/β-catenin, and RhoA/ROCK pathways. This review summarizes current understanding of Cldn biology in retinal vascular regulation and highlights emerging therapeutic strategies aimed at stabilizing Cldn expression and junctional localization. Small molecules and blocking antibodies that enhance localization or prevent degradation are redefining barrier repair. Key questions remain regarding isoform specificity, inter-barrier communication, and systemic safety. Integrative omics and spatial imaging may reveal disease-specific Cldn signatures and guide molecular restoration of BRB integrity. Full article

Background/Objectives: While CRISPR/Cas9 technology offers a revolutionary approach for correcting genetic ocular blindness, efficient and safe delivery remains the primary bottleneck. Traditional viral vectors, despite their efficacy, face challenges regarding cargo size limitations and potential genomic integration risks. Non-viral vectors offer distinct comparative advantages, including large cargo capacity for diverse CRISPR tools and transient expression to minimize off-target effects, but must overcome the eye’s formidable static and dynamic barriers, specifically the corneal epithelium, vitreous humor, and the inner limiting membrane. In this review, we present an anatomically guided framework for non-viral CRISPR/Cas9 delivery, mapping engineering strategies to specific ocular tissue targets. We first delineate the mechanisms of key physiological barriers, including the corneal stroma, aqueous humor circulation, and the vitreous–retina interface. Subsequently, we critically evaluate the latest advancements in non-viral platforms, such as pH-responsive lipid nanoparticles and engineered virus-like particles. The core focus of this review is on site-specific breakthrough strategies: from utilizing mucoadhesive polymers to counteract tear clearance in the cornea to exploiting specialized administration routes, such as suprachoroidal space and subretinal injection, to bypass retinal barriers, and deep-penetrating intravitreal carriers for targeting the photoreceptor-RPE complex. By integrating material science with precise administration routes, this review highlights feasible translational pathways for next-generation, carrier-free, or biomimetic ocular gene editing therapies. Full article

Sebaceous glands (SGs) and their specialized subtype, Meibomian glands (MGs), play essential roles in skin and ocular surface homeostasis by producing lipids that maintain barrier integrity and stabilize the tear film. Dysregulation of SG and MG biology contributes to a spectrum of disorders, ranging from benign hyperplasia to sebaceous carcinoma and age-related MG dysfunction. Accumulating evidence highlights the importance of epigenetic regulation, including histone modifications, DNA methylation, and non-coding RNAs (ncRNAs), in controlling SG and MG development, homeostasis, and disease susceptibility. Notably, histone modifiers and ncRNAs modulate acinar differentiation, lipid synthesis, and progenitor cell function. Despite these advances, many epigenetic mechanisms, such as histone lactylation, sumoylation, and phosphorylation, remain underexplored, and several common SG/MG disorders, including chalazion and seborrhea, lack mechanistic studies at the epigenetic level. This review synthesizes current knowledge on SG and MG biology, emphasizing epigenetic regulation, and highlights critical gaps to guide future research aimed at improving the understanding and treatment of SG- and MG-related disorders. Full article

Environmental exposures are increasingly recognized as important drivers of ocular surface inflammation, yet their combined contribution to the onset, exacerbation, and clinical burden of allergic conjunctivitis (AC) has not been comprehensively synthesized. This systematic review evaluated the evidence linking air pollutants, aeroallergens, and indoor or occupational exposures with allergic conjunctivitis. The review was conducted according to PRISMA 2020 and AMSTAR-2 guidelines and registered in PROSPERO (CRD420251162399). PubMed, Web of Science, and Scopus were searched from inception to 18 September 2025. Two independent reviewers screened studies, extracted data, and assessed methodological quality using the MINORS tool. Owing to substantial heterogeneity, findings were synthesized narratively. Twenty-nine studies were included, encompassing more than three million outpatient visits. Consistent associations were observed between particulate matter, nitrogen oxides, sulfur dioxide, carbon monoxide, and ozone with increased AC incidence and symptom severity, with variations by age, sex, and season. Pollen and air pollutants frequently acted synergistically. Indoor exposures were associated with increased risk in children, while occupational settings demonstrated exposure–response relationships. Experimental studies identified mechanisms involving epithelial barrier disruption, NF-κB activation, and thymic stromal lymphopoietin signaling. Overall, environmental exposures substantially contribute to allergic conjunctivitis and may inform improved prevention and personalized clinical management. Full article