Search Results (155)

Background: Pathological angiogenesis and stromal fibrosis after ocular chemical injury are primary drivers of corneal opacification and permanent vision loss. Topical administration of anti-VEGFA antibody is hampered by rapid tear clearance and poor penetration across the corneal epithelial barrier, resulting in insufficient intraocular drug accumulation and suboptimal therapeutic efficacy. Although intraocular injection elevates local drug concentration, this invasive procedure carries risks of complications and is not suitable for long-term repeated treatment. This study constructed red cabbage-derived exosome-like nanovesicles (Rabexo) to load an anti-VEGFA antibody, formulated into PVA/HA hydrogel, aiming to develop a topical sustained-release ocular delivery system for alleviating corneal angiogenic and fibrotic lesions. Methods: Rabexo was isolated and physicochemically characterized. Anti-VEGFA antibody was encapsulated into Rabexo via electroporation to prepare aV-Rabexo, which was further incorporated into commercial PVA/HA hydrogel. Cellular uptake, anti-angiogenic functions were verified in vitro, and therapeutic efficacy was evaluated in a mouse corneal alkali burn model via ophthalmic topical administration. Results: The prepared Rabexo showed uniform size and favorable colloidal stability with 40.3% antibody encapsulation efficiency. aV-Rabexo exhibited stronger in vitro anti-migration, anti-proliferation and anti-tube formation effects than free antibody. In vivo, aV-Rabexo-Gel substantially suppressed corneal neovascular area and length, restored stromal collagen arrangement, and downregulated CD31, VEGFA and α-SMA expression at day 14 post-injury, with statistically significant differences compared with the free antibody gel. Conclusions: This plant-derived nanocarrier hydrogel system realizes synergistic therapeutic effects via nanocarrier delivery, antibody neutralization and prolonged ocular retention. With advantages of easy production and low immunogenicity, it provides a promising non-surgical strategy for treating ocular surface pathological angiogenesis and fibrosis. Full article

Vision impairment affects approximately 2.2 billion people worldwide, with glaucoma, age-related macular degeneration, fungal keratitis, and diabetic retinopathy among the leading causes of preventable blindness. Effective pharmacotherapy remains severely constrained by the eye’s multilayered barrier architecture. Tear film, the corneal epithelium, the blood–aqueous barrier, and the blood–retinal barrier collectively restrict conventional topical drug bioavailability to less than 5% of the administered dose. Liposomal drug delivery systems have emerged as a clinically translatable platform capable of overcoming these barriers through targeted surface modification. This review provides a brief introduction to ocular barriers to drug delivery and transport and critically examines numerous surface-modification strategies applied to liposomal carriers to enhance corneal permeation and ocular bioavailability of drugs. It highlights the advantages and disadvantages of each modification strategy, as well as the convergent mechanism of liposomal surface modification in overcoming ocular barriers, and provides a comparative analysis of different surface-modification strategies of liposomes in terms of safety, efficacy and corneal retention. Additionally, it describes challenges associated with liposomal ophthalmic formulations in industrial scaling up. The review also sheds light on some FDA-approved liposomal ophthalmic products, active clinical trials on liposomal formulations, and relevant patents, demonstrating the potential benefits of liposomal drug delivery in the treatment of ocular disorders. Full article

Kaempferol is a natural flavonol compound widely present in various single-herb remedies and compound formulations used for the treatment of ocular diseases. Despite its inherent pharmaceutical limitations, accumulating evidence indicates that kaempferol exerts broad protective effects against diverse ocular disorders through multiple biological pathways, highlighting its potential as a multi-target therapeutic candidate in ophthalmology. However, current evidence regarding kaempferol-based ophthalmic applications remains fragmented across different ocular diseases and mechanistic investigations, and a comprehensive evaluation of its therapeutic potential, translational challenges, and existing limitations is still lacking. This review systematically summarizes the research progress on kaempferol in the treatment of eye diseases, encompassing its source distribution, structural characteristics, ocular delivery strategies, disease spectrum coverage, molecular mechanisms, and safety profile. By critically evaluating currently available evidence, this review further identifies unresolved issues and translational barriers that hinder the clinical application of kaempferol in ophthalmology. Regarding delivery strategies, carriers such as gelatin nanoparticles, porous bovine serum albumin membranes, platelet-derived extracellular vesicles, and polyvinylpyrrolidone-based nanocomposites have preliminarily improved ocular surface retention and corneal permeability of kaempferol in models of corneal neovascularization and alkali burns. In terms of therapeutic indications, kaempferol has demonstrated protective effects in diverse experimental models, including age-related macular degeneration (AMD), diabetic retinopathy, diabetic cataract, dry eye disease, fungal keratitis, corneal transplant rejection, acute glaucoma, and retinoblastoma. At the mechanistic level, kaempferol exerts comprehensive pharmacological actions—anti-inflammatory, antioxidant, metabolic regulation, anti-angiogenic, and immunomodulatory—by modulating multiple signaling pathways, including MAPK, NF-κB, STAT1/IRF7, Nrf2/HO-1, VEGF/PI3K/Src/Akt/ERK, aldose reductase, estrogen-related receptor alpha (ERRα), and the NOD-like receptor family pyrin domain-containing protein 3 (NLRP3) inflammasome. Available safety assessments suggest that kaempferol exhibits a generally favorable safety profile across ocular, cellular, systemic, and genetic evaluations. Despite these advances, the clinical translation of kaempferol in ophthalmology remains limited by insufficient clinical and pharmacokinetic evidence, underdeveloped targeted delivery strategies, and a lack of integrated understanding of its molecular basis in ocular protection. By systematically integrating evidence from ocular disease models, molecular mechanisms, delivery strategies, and safety evaluations, this review bridges fragmented knowledge regarding kaempferol-based ophthalmic applications and provides an integrated framework for understanding its therapeutic potential and translational prospects. Overall, this review highlights kaempferol as a promising multi-target therapeutic candidate for ocular diseases and provides insights into its future translational development. Full article

Background/Objectives: Dry eye disease (DED) is a multifactorial disorder characterized by tear film instability, inflammation, and ocular surface damage, which significantly impairs visual function and quality of life. Conventional ophthalmic formulations, such as eye drops, have low bioavailability owing to rapid elimination, necessitating frequent administration. In this study, we developed an eyelid-applied drug delivery system (DDS) based on troxipide (TRO) nanoparticle formulation (TRO-NP@EG) to achieve sustained ocular surface delivery. Methods: TRO nanosuspensions were prepared by wet bead milling and incorporated into a Carbopol-based gel. Particle size, dispersion stability, and uniformity were evaluated, and in vitro drug release studies was compared with that of TRO-MP@EG. In vivo drug transfer into tear fluid was assessed in rabbits following eyelid application, and therapeutic efficacy was evaluated in an N-acetylcysteine-induced dry eye model. Results: TRO nanosuspensions had a mean particle size of approximately 118 nm. TRO-NP@EG exhibited superior dispersion stability and uniformity and achieved 2.5-fold higher drug release than TRO-MP@EG, while the nanoparticles remained in solid form. In vivo studies in rabbits, TRO-NP@EG significantly enhanced drug transfer into tear fluid, primarily via the meibum pathway. Furthermore, TRO-NP@EG significantly improved mucin levels, tear secretion, and tear film stability compared with TRO-MP@EG in an N-acetylcysteine-induced dry eye model. Conclusions: These findings suggest that eyelid application of nanoparticle-based formulations enables efficient and sustained drug delivery to the ocular surface via the meibomian glands. Therefore, TRO-NP@EG represents a promising therapeutic strategy for DED, providing enhanced efficacy and a novel route of administration for ophthalmic DDSs. Full article

Eye drops remain the principal topical treatment for ocular infections, yet rapid precorneal clearance, variable dose delivery and limited tissue penetration can restrict local drug availability and necessitate frequent administration. Conjunctival inserts have long been investigated as a means of extending ocular residence and thin film inserts offer a more adaptable solid dosage form that may provide a defined drug-containing unit, prolonged local exposure and hydration-dependent dissolution or transformation within the conjunctival sac. Clinical translation remains limited by substantial variability in formulation design, manufacturing control and performance testing. This review critically evaluates the manufacture and characterisation of ocular anti-infective thin film inserts, with the aim of identifying the principal factors that determine reproducibility, interpretability and progression beyond formulation feasibility. Film architecture, polymer selection and drug-loading strategy are considered in relation to the physicochemical characteristics of the active pharmaceutical ingredient and the intended behaviour of the finished insert. Solvent casting remains the most extensively investigated manufacturing approach, while extrusion, electrospinning and additive manufacturing broaden the available processing options. Across these methods, incomplete specification of material and process variables frequently restricts comparison and reproducibility. Testing procedures are similarly heterogeneous and often assess individual attributes without establishing how the finished insert performs under conditions relevant to conjunctival administration. Particular limitations concern dosage-unit uniformity, hydration and matrix transformation, drug-release models and the interpretation of antimicrobial activity. Progression towards clinically relevant products will require indication-led development in which manufacturing control, pharmaceutical quality, ocular compatibility and biorelevant performance evaluation are considered as connected elements. This approach may provide a stronger basis for determining whether the potential advantages of ocular anti-infective thin film inserts can be translated into reproducible and clinically useful dosage forms. Full article

Background: Cyclosporin A (CyA) is widely investigated for ophthalmic drug-delivery systems, including hydrogel contact lenses, where reliable quantification is essential for evaluating drug loading, release, and formulation performance. However, the analytical UV response of CyA may depend on the physicochemical characteristics of the surrounding buffered environment, potentially affecting quantitative measurements. Objectives: This study aimed to determine whether changes in the buffered aqueous environment influence the UV spectral response of CyA and whether such variability may introduce systematic bias into UV-based quantitative analysis. Methods: UV spectra of CyA were recorded in citrate-phosphate buffered media over the pH range 3.28–9.10, including several near-neutral conditions relevant to ophthalmic formulations and artificial lacrimal media. Spectral changes were evaluated using univariate statistical analysis, principal component analysis (PCA), and Gaussian deconvolution. Results: CyA exhibited a progressive hypsochromic shift of the apparent absorption maximum from approximately 234 nm to 210–214 nm, accompanied by pronounced changes in absorbance intensity and the overall absorption profile. Comprehensive statistical analyses demonstrated systematic spectral differences across the investigated buffered media. PCA performed on 42 spectra (31 wavelength variables) explained 84.20% of the total variance within the first two principal components, while Gaussian deconvolution indicated progressive redistribution of overlapping spectral contributions. The observed spectral behavior is consistent with changes in the molecular environment and redistribution of conformational populations; however, the UV–Vis data alone do not provide direct structural evidence for these processes. The resulting wavelength-dependent spectral variability produced substantial apparent analytical bias, demonstrating that fixed-wavelength UV measurements may lead to systematic quantification errors when calibration standards and analytical samples differ in their buffered environment. Conclusions: These findings demonstrate that the analytical UV response of cyclosporin A is environment-dependent and highlight the importance of matrix-matched calibration and validation under the intended analytical conditions when UV spectroscopy is used for quantitative determination of CyA in aqueous drug-delivery systems. Full article

Nanomedicine-based liposomal delivery systems are gaining increasing attention as advanced therapeutic platforms for managing ocular infections associated with antimicrobial resistance (AMR) and biofilm formation. The primary objective of this review is to critically evaluate the potential of liposomal drug delivery systems for improving the treatment of antimicrobial-resistant and biofilm-associated ocular infections by integrating current knowledge on antimicrobial resistance mechanisms, biofilm-targeted therapeutic strategies, and advances in liposomal formulations, while also identifying the major limitations, translational challenges, and knowledge gaps in this rapidly evolving field. Traditional ocular antimicrobial treatments are frequently limited by poor drug penetration, short precorneal residence time, low bioavailability, systemic side effects, and inadequate activity against resistant microorganisms and biofilm-embedded pathogens. This review provides a comprehensive overview of different liposomal systems, including conventional, cationic, polyethylene glycol (PEG)-modified, deformable, and stimulus-responsive liposomes, and discusses their advantages in ophthalmic drug delivery, such as enhanced corneal permeation, prolonged drug retention, controlled release, improved biocompatibility, and reduced ocular toxicity. The review further examines the mechanisms through which liposomes help overcome AMR, including improved epithelial transport, membrane disruption, intracellular drug delivery, efflux pump evasion, and enhanced antimicrobial efficacy. In addition, liposomal approaches targeting ocular biofilms are explored, focusing on improved biofilm penetration and the delivery of anti-biofilm agents such as antibiotics, enzymes, quorum-sensing inhibitors, and antimicrobial peptides. Current evidence from in vitro and in vivo ocular infection models is summarized together with disease-specific applications in keratitis, endophthalmitis, and contact lens-related infections. The article also compares liposomes with other ocular nanocarriers and addresses important considerations related to safety, stability, sterilization, large-scale production, and regulatory translation. In addition to highlighting recent advances, this review critically discusses the current limitations of liposomal formulations, the major barriers to clinical translation, and the key knowledge gaps that should be addressed to facilitate the future development and successful clinical application of these systems. Finally, emerging directions including ligand-targeted and stimulus-responsive liposomes, AI-driven formulation development, personalized nanotherapy, and gene therapy combinations are discussed as promising future strategies for combating resistant ocular infections. Full article

Wet age-related macular degeneration (wAMD) is characterized by choroidal neovascularization (CNV) and remains a major cause of severe vision loss in older adults. Intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy is the current standard of care for wAMD. However, repeated injections are associated with poor adherence, procedure-related complications, and a substantial cumulative treatment burden. Topical nanocarrier-based systems have therefore attracted increasing attention as needle-free approaches for improving posterior segment drug exposure. Complementing broader reviews of ocular nanomedicine, this review specifically examines topical nanocarrier-mediated posterior segment delivery for wAMD, with a focus on three representative platforms: liposomes, polymeric nanoparticles, and polymeric micelles. These systems are engineered through the optimization of particle size, surface properties, drug-loading strategies, and functional modifications to improve payload stability, ocular surface residence, tissue penetration, and lesion-relevant delivery. By integrating formulation design, ocular barrier transport, ocular posterior segment bioavailability, and translational feasibility in the context of wAMD, this review provides a disease-focused and application-oriented perspective that complements existing broader reviews of ocular nanocarriers and ophthalmic nanomedicine. We summarize current evidence from preclinical and translational studies and discuss major barriers limiting clinical application, including insufficient posterior segment drug exposure, dose–safety trade-offs, pharmacokinetic instability, limited targeting efficiency, and challenges in delivering macromolecular biologics, such as anti-VEGF antibodies and fusion proteins. At present, topical nanocarrier-based strategies remain investigational, but they hold potential for development as therapeutic approaches for wAMD. Key priorities for future development include quantitative posterior segment pharmacokinetic/pharmacodynamic evaluation, long-term safety assessment, payload-specific carrier design, scalable manufacturing, and clinically relevant efficacy endpoints. This review provides a focused framework for the rational design and translational assessment of nanocarrier-based topical strategies for wAMD management. Full article

Background: Conventional ophthalmic eye drops have low bioavailability (<5%) and poor patient adherence, driving the development of sustained-release ophthalmic drug delivery systems. The lacrimal drainage system represents a unique anatomical site for minimally invasive depot formulations. Objective: To summarize and critically appraise punctal and intracanalicular drug delivery systems, occlusive devices, and in situ-forming hydrogels with respect to composition, release mechanisms, clinical efficacy, safety, and critical quality attributes (CQAs). Methods: A narrative literature review was conducted using PubMed, Scopus, Web of Science, Google Scholar, ClinicalTrials.gov, and patent/regulatory sources, including FDA materials and Google Patents, covering 2001–2026. Anatomical features, materials, active pharmaceutical ingredients, release profiles, and adverse events were analyzed. Results: Seventy-one sources were included. Occlusive plugs without an active pharmaceutical ingredient demonstrate premature expulsion in up to 57.4% of cases and bacterial colonization in 44%. Drug delivery systems provide release from 7 days (PEGDA hydrogels) to 3 months (Eximore, Ocular Therapeutix™). DEXTENZA^® (dexamethasone) is FDA-approved for postoperative inflammation, whereas pivotal trials of travoprost (OTX-TP) and latanoprost systems (L-PPDS, EXP-LP) did not demonstrate superiority over placebo or eye drops. In situ systems eliminate size-fitting requirements but face challenges related to gelation control and biodegradation. Conclusions: We propose the following candidate CQAs: retention (>80% over 4 weeks), swelling degree (30–60%), controlled burst release (<40% within 24 h), and mechanical compatibility. The proposed QTPP matrices for punctal, intracanalicular, and in situ systems may guide the development of ophthalmic drug delivery platforms. Full article

Background/Objectives: Despite available treatment options, glaucoma continues to be a leading cause of irreversible blindness. Current medications have multiple limitations, including rapid drainage, ocular irritation, requirement for multiple daily dosings, and systemic side effects. The current study was designed to engineer and characterize a pregabalin-containing enhanced delivery formulation (PRG-EDF) to directly address these inadequacies. Methods: PRG-EDF eye drops were prepared using ingredients that are either U.S. Food and Drug Administration (FDA)-approved for ophthalmic use or have established safety profiles. The formulation was characterized using multiple evaluations, including pH, zetasizer analyses, viscosity, in vitro drug release, transcorneal permeability, determination of dose concentration and volume, systemic exposure, and potential for tachyphylaxis. Efficacy was evaluated using both Dutch belted rabbits and baboons. Results: PRG-EDF provides extended release for up to 24 h. Ex vivo data reveal that PRG-EDF does not alter the inherent high PRG corneal permeability. An intraocular pressure (IOP) study using DB rabbits demonstrates that 40 µL of PRG-EDF, 0.6%, is the optimum dose of our formulation. Comparison of the efficacy of PRG-EDF with commercial products demonstrated its superiority in overall IOP-lowering efficacy. An extended in vivo assessment demonstrated that the potency of PRG-EDF reached maximum IOP-lowering amplitude after 4 weeks of daily dosing. Moreover, an in vivo bioadhesion assay demonstrated that EDF remained on the ocular surface for up to 24 h. Impressively, PRG-EDF is as effective in baboons as in rabbits. Conclusions: We have successfully engineered a highly promising once-daily glaucoma medication with superior efficacy, as illustrated by higher IOP-lowering ability and prolonged duration of action. Full article

Non-invasive drug delivery for ocular diseases remains a significant challenge in ophthalmology, as conventional eye drops offer less than 5% bioavailability due to pre-corneal barriers and the corneal epithelium. This review explores the intranasal (IN) route as a promising strategy for targeting both the anterior and posterior segments of the eye. The IN route leverages several distinct pathways: the nasolacrimal reflex for remote physiological stimulation; the “neural bridge” through the cribriform plate, allowing direct perineural and vascular transport via the olfactory and trigeminal nerves to bypass the blood–retinal barrier; and systemic absorption that avoids hepatic first-pass metabolism. Pre-clinical evidence indicates that IN administration of agents such as erythropoietin, nerve growth factor, and insulin achieves superior retinal concentrations compared to topical or systemic dosing, offering neuroprotection in models of retinal degeneration and glaucoma. Clinically, varenicline nasal spray is already FDA-approved for dry eye disease, while intranasal steroids demonstrate a favorable ocular safety profile without significantly increasing intraocular pressure. Although limited by mucociliary clearance and small delivery volumes, the IN route offers a painless, non-invasive alternative to intraocular injections, potentially enhancing patient compliance. Future advancements in mucoadhesive nanocarriers are essential to optimize drug residence time and realize the full potential of nose-to-eye delivery in chronic ophthalmic care. Full article

Background/Objectives: Corneal epithelial defects and ulcers remain a significant clinical challenge, often leading to vision impairment and requiring prolonged treatment. In this context, topical insulin has recently gained attention in ophthalmic research. However, conventional eye drops suffer from short residence time and poor bioavailability. To overcome these limitations, the present study evaluates, for the first time in vitro, multiple commercially available soft contact lenses as sustained insulin delivery platforms, analyzing how protein loading influences the essential physicochemical and optical properties of these materials. Methods: The physicochemical properties of eight different commercially available soft contact lens materials, including light transmittance, wettability, and central thickness, were examined before and after insulin loading via a soaking method. Loading efficiency and in vitro release profiles were assessed over time. Corneal cytotoxicity and permeability were evaluated using a human epithelial cell-based model (HCE-2). Results: Among the eight commercial materials screened, Nesofilcon A, Stenfilcon A, and Delefilcon A were selected due to their superior physicochemical performance after insulin loading. At initial concentrations of 1750 and 875 μg/mL, drug loading efficiency reached maximum values of up to 69.3% and 63.1%, with cumulative release values reaching up to 32.4% and 55.1% after 24 h, respectively. Permeability studies confirmed effective insulin diffusion across the HCE-2 cell layer, while cell viability assays indicated no significant cytotoxicity at the lower loading concentration. Conclusions: Insulin-loaded commercial soft contact lenses represent a promising drug–device combination product for the management of persistent epithelial defects and refractory corneal ulcers. These in vitro findings suggest that this approach may enhance drug performance by prolonging residence time and improving corneal bioavailability, while maintaining essential lens properties. However, further in vivo and clinical studies are required to confirm these potential benefits and establish therapeutic efficacy for the management of persistent epithelial defects. Full article

Glaucoma is a collection of disorders that result in permanent vision loss and is characterized by a gradual decline in retinal ganglion cells. While it may not always be high, intraocular pressure (IOP) is the sole risk factor that can be modified according to extensive clinical research. Glaucoma remains the leading cause of irreversible blindness, yet early treatment lowering intraocular pressure is effective in slowing the rate of visual deterioration. Issues like poor absorption, low bioavailability, and short drug resistance time have thus made the management of glaucoma challenging when using conventional ophthalmic drugs. Thus, extensive research has been conducted to explore specific nanodrug delivery systems from various nanocarriers such as nanoparticles, micelles, liposomes and nanofibers, with a focus on systems that have achieved drug release for more than 12 h. These carriers have demonstrated substantial improvements in a lot of the evaluated aspects: enhancing ocular barrier-crossing capabilities, improving bioavailability, prolonging drug release, targeting active tissues of interest, and reducing IOP. This review covers recent developments in nanocarrier ocular delivery systems regarding the management of glaucoma. In this study, the advantages and disadvantages of each system were evaluated and their potential for advancing translation from research to clinic were assessed. 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

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