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The advent of drug-eluting contact lenses (DECLs) has opened up new avenues for the treatment of eye diseases. DECLs is expected to partially overcome the shortcomings of eye drops due to single-dose packaging, accurate dosing, prolonged drug elution behavior, and simplified dosing procedures. Currently, a significant proportion of the DECLs design effort has been directed towards enhancing the compatibility of contact lenses with drugs. The appropriate elution time for the drug remains unclear. Additionally, it is ambiguous for which ophthalmic diseases DECLs offers the greatest therapeutic advantage. To rationally design DECLs in practice, it is necessary to understand the acceptance of DECLs by patients and practitioners and to clarify the indications for DECLs. This review will first focus on the acceptance of DECLs by different patients and practitioners and discuss the factors that influence its acceptance. Secondly, this review presents an overview of the current effectiveness of DECLs treatments in animals and in the clinical phase, with a particular focus on the suitability of DECLs for the treatment of ophthalmic diseases. Overall, patients and practitioners expressed positive attitudes towards DECLs. However, this is related to factors such as DECLs' treatment cycle, safety, and price. In addition, DECLs has good application prospects for ocular wound healing, postoperative management, and treatment of contact lenses-related complications. Furthermore, chronic diseases such as glaucoma that necessitate long-term medication and intraocular diseases that require implants or injections represent additional potential applications for DECLs. It is hoped that this review will facilitate a deeper understanding of DECLs acceptance and indications, thereby supporting the rational design of DECLs. At the same time, this review provides a reference for the design of other drug-device combination products., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Ocular disorders remain a major global health challenge with unmet medical needs. RNA nanomedicine has shown significant therapeutic benefits and safety profiles in patients with complex eye disorders, already benefiting numerous patients with gene-related eye disorders. The effective delivery of RNA to the unique structure of the eye is challenging owing to RNA instability, off-target effects, and ocular physiological barriers. Specifically tailored RNA medication, coupled with sophisticated engineered delivery platforms, is crucial to guide and advance developments in treatments for oculopathy. Herein we review recent advances in RNA-based nanomedicine, innovative delivery strategies, and current clinical progress and present challenges in ocular disease therapy., Competing Interests: Declaration of interests W.T. declares the following competing financial interest(s): W.T. receives consults (or on scientific advisory boards) for, lectured (and received a fee), or conducts sponsored research at Harvard Medical School/Brigham and Women’s Hospital for the following entities: Novo Nordisk A/S, Henlius USA Inc. The other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Ophthalmic diseases can be presented as acute diseases like allergies, ocular infections, etc., or chronic ones that can be manifested as a result of systemic disorders, like diabetes mellitus, thyroid, rheumatic disorders, and others. Chitosan (CS) and its derivatives have been widely investigated as nanocarriers in the delivery of drugs, genes, and many biological products. The biocompatibility and biodegradability of CS made it a good candidate for ocular delivery of many ingredients, including immunomodulating agents, antibiotics, ocular hypertension medications, etc. CS-based nanosystems have been successfully reported to modulate ocular diseases by penetrating biological ocular barriers and targeting and controlling drug release. This review provides guidance to drug delivery formulators on the most recently published strategies that can enhance drug permeation to the ocular tissues in CS-based nanosystems, thus improving therapeutic effects through enhancing drug bioavailability. This review will highlight the main ocular barriers to drug delivery observed in the nano-delivery system. In addition, the CS physicochemical properties that contribute to formulation aspects are discussed. It also categorized the permeation enhancement strategies that can be optimized in CS-based nanosystems into four aspects: CS-related physicochemical properties, formulation components, fabrication conditions, and adopting a novel delivery system like implants, inserts, etc. as described in the published literature within the last ten years. Finally, challenges encountered in CS-based nanosystems and future perspectives are mentioned., Competing Interests: Declaration of competing interest The author declare that she has no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

This review article delves into the extensive use of microneedles in ocular therapy, emphasizing their efficacy in delivering drug substances to the posterior region of the eye. The conventional methods of drug delivery, while widely employed, are marred by inherent drawbacks such as neovascularization, abrasion, and infiltration. To address these limitations, the review explores various approaches to microneedle fabrication, shedding light on the diverse materials employed in the process. Furthermore, the article meticulously examines the delivered drug substances using distinct microneedle approaches and their applications in ocular therapy. By critically evaluating the drawbacks associated with conventional ophthalmic drug delivery, the review seeks to pave the way for a paradigm shift. It advocates for a novel approach centered around minimally invasive microneedles, presenting them as a promising solution to overcome the limitations of current drug delivery methods. The comprehensive discussion within this article not only offers insights into the fabrication techniques and materials used for microneedles but also provides a nuanced understanding of the applications and advantages associated with this innovative approach. As the exploration of microneedle technology continues to evolve, this review serves as a valuable resource for researchers, clinicians, and pharmaceutical professionals seeking to enhance ocular therapy by embracing the potential of minimally invasive microneedles., (Copyright © 2024 Académie Nationale de Pharmacie. Published by Elsevier Masson SAS. All rights reserved.)

Topical ophthalmic drug product development is a niche research domain as the drug formulations need to be designed to perform in the unique ocular physiological conditions. The most common array of small molecule drug formulations intended for topical ophthalmic administration include solutions, suspensions, emulsions, gels, and ointments. The formulation components such as excipients and container closure are unique to serve the needs of topical ophthalmic delivery compared to other parenteral products. The selection of appropriate formulation platform, excipients, and container closure for delivery of drugs by topical ophthalmic route is influenced by a combination of factors like physicochemical properties of the drug molecule, intended dose, pharmacological indication as well as the market trends influenced by the patient population. In this review, data from literature and packaging inserts of 118 reference listed topical ophthalmic medications marketed in the US are collected and analyzed to identify trends that would serve as a guidance for topical ophthalmic formulation development for small molecule drugs. Specifically, the topics reviewed include current landscape of the available small molecule topical ophthalmic drug products in the US, physicochemical properties of the active pharmaceutical ingredients (APIs), formulation platforms, excipients, and container closure systems., Competing Interests: Declaration of Competing Interest Anand Ubhe, Heidi Oldenkamp, Ke Wu are employees of AbbVie and may own AbbVie stock. AbbVie sponsored and funded the study; contributed to the design; participated in the collection, analysis, and interpretation of data, and in writing, reviewing, and approval of the final publication., (Copyright © 2024 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.)

Drug delivery is an important factor for the success of ocular drug treatment. However, several physical, biochemical, and flow-related barriers limit drug exposure of anterior and posterior ocular target tissues during drug treatment via topical, subconjunctival, intravitreal, or systemic routes. Mathematical models encompass various barriers so that their joint influence on pharmacokinetics (PKs) can be simulated in an integrated fashion. The models are useful in predicting PKs and even pharmacodynamics (PDs) of administered drugs thereby fostering development of new drug molecules and drug delivery systems. Furthermore, the models are potentially useful in interspecies translation and probing of disease effects on PKs. In this review article, we introduce current modeling methods (noncompartmental analyses, compartmental and physiologically based PK models, and finite element models) in ocular PKs and related drug delivery. The roles of top-down models and bottom-up simulations are discussed. Furthermore, we present some future challenges, such as modeling of intra-tissue distribution, prediction of drug responses, quantitative systems pharmacology, and possibilities of artificial intelligence.

Treatment of ocular diseases presents unique challenges and opportunities for the clinician and for the clinical pharmacologist. Ophthalmic pharmaceuticals, typically given as liquids, require consideration of solubility, physiological pH, and osmolarity, as well as sterility and stability, which in turn requires optimal pharmaceutics. Ocular tissue levels are challenging to obtain in humans, and the clinical pharmacokinetics is typically blood levels, which are primarily related to safety, rather than efficacy. The eye is a closed compartment with multiple physiological barriers with esterases and transporters, but relatively little cytochrome oxidases. Delivery routes include topical, intravitreal, and systemic. Patient dosing involves not only adherence issues common to all chronic diseases, but also performance requirements on eye drop instillation. Therapeutically, ocular diseases and their pharmacological treatments include both those analogous to systemic diseases (e.g., inflammation, infection, and neuronal degeneration) and those unique to the eye (e.g., cataract and myopia)., (© 2024, The American College of Clinical Pharmacology.)

Previously, researchers have employed Lipid nanoparticles (LNPs) to directly encapsulate medicines. In the realm of gene therapy, researchers have begun to employ lipid nanoparticles to encapsulate nucleic acids such as messenger RNA, small interfering RNA, and plasmid DNA, which are known as nucleic acid lipid nanoparticles. Recent breakthroughs in LNP-based medicine have provided significant prospects for the treatment of ocular disorders, such as corneal, choroidal, and retinal diseases. The use of LNP as a delivery mechanism for medicines and therapeutic genes can increase their effectiveness while avoiding undesired immune reactions. However, LNP-based medicines may pose ocular concerns. In this review, we discuss the general framework of LNP. Additionally, we review adjustable approaches and evaluate their possible risks. In addition, we examine newly described ocular illnesses in which LNP was utilized as a delivery mechanism. Finally, we provide perspectives for solving these potential issues., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Masson SAS.)

Extracellular vesicles (EVs) are nanoscale membrane vesicles of various sizes that can be secreted by most cells. EVs contain a diverse array of cargo, including RNAs, lipids, proteins, and other molecules with functions of intercellular communication, immune modulation, and regulation of physiological and pathological processes. The biofluids in the eye, including tears, aqueous humor, and vitreous humor, are important sources for EV-based diagnosis of ocular disease. Because the molecular cargos may reflect the biology of their parental cells, EVs in these biofluids, as well as in the blood, have been recognized as promising candidates as biomarkers for early diagnosis of ocular disease. Moreover, EVs have also been used as therapeutics and targeted drug delivery nanocarriers in many ocular disorders because of their low immunogenicity and superior biocompatibility in nature. In this review, we provide an overview of the recent advances in the field of EV-based studies on the diagnosis and therapeutics of ocular disease. We summarized the origins of EVs applied in ocular disease, assessed different methods for EV isolation from ocular biofluid samples, highlighted bioengineering strategies of EVs as drug delivery systems, introduced the latest applications in the diagnosis and treatment of ocular disease, and presented their potential in the current clinical trials. Finally, we briefly discussed the challenges of EV-based studies in ocular disease and some issues of concern for better focusing on clinical translational studies of EVs in the future.

Significance: This is one of the first reports to summarize the enrollment metrics for ophthalmology trials completed in the United States (US)., Purpose: This study aimed to describe US ophthalmology clinical trial enrollment metrics to facilitate planning and budgeting of US Food and Drug Administration-regulated ophthalmological drugs trials., Methods: A GlobalData PLC search was conducted on or before February 27, 2024, to evaluate the clinical trial landscape for completed ophthalmology clinical trials conducted in the US. The primary search contained only the term "ophthalmology," which was restricted to trials that were completed and were conducted within the US. Trials were classified as multicenter when trials included three sites or more, and when the enrollment search resulted in ≥30 multicenter trials for an individual indication, enrollment data were further broken down by Food and Drug Administration trial phase., Result: The search yielded 2229 trials, which analyzed 980 different drugs produced by 854 different sponsors. The most common indications evaluated in US trials were macular degeneration, glaucoma, macular edema, allergies, and keratoconjunctivitis. Multicenter trials by indication had an overall median enrollment period range of 4.8 to 35.1 months; number of subjects enrollment, range of 36 to 518 subjects; number of sites utilized, range of 4 to 74 sites; and enrollment rate, range of 0.11 to 4.04 subjects/sites per month. There were 17 indications with ≥30 multicenter trials, which allowed for enrollment metric calculation by trial phase., Conclusions: This study provides sponsors with an understanding of the number of subjects and sites needed to complete a trial while also setting realistic enrollment timelines. Although this work represents the US market, more work is needed to better understand other countries given that country-specific guidelines and subject beliefs may impact enrollment metrics., Competing Interests: Conflict of Interest Disclosure: Andrew D. Pucker has served as consultants to Alcon, Bausch + Lomb, HanAll Biopharma, Essilor, and Euclid Systems over the past year; none of these activities are directly related to the content of this report. Nicole Derthick and Lanita Scott have no conflicts of interest to disclose. All authors were employees of Lexitas Pharma Services during the conduct of this project. Lexitas Pharma Services has an interest in projecting accurate enrollment timelines, although the presented work is unbiased given that Lexitas Pharma Services only benefits from accurate clinical trials data., (Copyright © 2024 American Academy of Optometry.)

As spaceflight becomes increasingly accessible and expansive to humanity, it is becoming ever more essential to consider the treatment of various eye diseases in these challenging environments. This paper delves into the increasing fascination with interplanetary travel and its implications for health management in varying environments. It specifically discusses the pharmacological management of ocular diseases, focusing on two key delivery methods: topical eye drops and intravitreal injections. The paper explores how microgravity impacts the administration of these treatments, a vital aspect in understanding drug delivery in space. An extensive analysis is presented on the pharmacokinetics of eye medications, examining the interaction between pharmaceuticals and ocular tissues in zero gravity. The goal of the paper is to bridge the understanding of fluid dynamics, microgravity and the human physiological systems to pave the way for innovative solutions faced by individuals in microgravity., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Committee on Space Research (COSPAR). Published by Elsevier B.V. All rights reserved.)

The forkhead box protein O3 (FOXO3a) belongs to the subgroup O of the forkhead transcription factor family and plays an important role in regulating the aging process by participating in the regulation of various life processes, including cell cycle arrest, apoptosis, autophagy, oxidative stress, and DNA repair. The eye is an organ that is affected by aging earlier. However, the functional role and potential clinical applications of FOXO3a in age-related eye diseases have not received widespread attention and lacked comprehensive and clear clarification. In this review, we demonstrated the relationship between FOXO3a and visual system health, summarized the functional roles of FOXO3a in various eye diseases, and potential ocular-related therapies and drugs targeting FOXO3a in visual system diseases through a review and summary of relevant literature. This review indicates that FOXO3a is an important factor in maintaining the normal function of various tissues in the eye, and is closely related to the occurrence and development of ophthalmic-related diseases. Based on its vital role in the normal function of the visual system, FOXO3a has potential clinical application value in related ophthalmic diseases. At present, multiple molecules and drugs targeting FOXO3a have been reported to have the potential for the treatment of related ophthalmic diseases, but further clinical trials are needed. In conclusion, this review can facilitate us to grasp the role of FOXO3a in the visual system and provide new views and bases for the treatment strategy research of age-related eye diseases., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Funduscopic diseases, including diabetic retinopathy (DR) and age-related macular degeneration (AMD), significantly impact global visual health, leading to impaired vision and irreversible blindness. Delivering drugs to the posterior segment of the eye remains a challenge due to the presence of multiple physiological and anatomical barriers. Conventional drug delivery methods often prove ineffective and may cause side effects. Nanomaterials, characterized by their small size, large surface area, tunable properties, and biocompatibility, enhance the permeability, stability, and targeting of drugs. Ocular nanomaterials encompass a wide range, including lipid nanomaterials, polymer nanomaterials, metal nanomaterials, carbon nanomaterials, quantum dot nanomaterials, and so on. These innovative materials, often combined with hydrogels and exosomes, are engineered to address multiple mechanisms, including macrophage polarization, reactive oxygen species (ROS) scavenging, and anti-vascular endothelial growth factor (VEGF). Compared to conventional modalities, nanomedicines achieve regulated and sustained delivery, reduced administration frequency, prolonged drug action, and minimized side effects. This study delves into the obstacles encountered in drug delivery to the posterior segment and highlights the progress facilitated by nanomedicine. Prospectively, these findings pave the way for next-generation ocular drug delivery systems and deeper clinical research, aiming to refine treatments, alleviate the burden on patients, and ultimately improve visual health globally., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Calamine and its related medicines came into China as articles of tribute from other countries in ancient times. It was not recorded in the books of Chinese materia medica before the Song Dynasty but was widely used in ophthalmology, dermatology and traumatology and was, recorded specifically in the Ming and Qing Dynasty. This paper systematically examines the evolution of calamine herb in the archives of traditional Chinese medicine in terms of ophthalmic eternal treatment prescriptions. It was found that a total of 320 ophthalmic treatment formulas or prescriptions involved calamine, mainly finding its expression in 67 books on herbal medicines, formula and prescriptions, clinical syndrome comprehension and ophthalmic monographs. It was also found that calamine, as an important ophthalmic external medicine, had a wide range of clinical applications, covering internal and external obstructive eye diseases. Its flexibility, diverse compatibility and use in various processing are of great value and significance for in-depth exploration of its current application, its further use in ophthalmic treatment formulas or prescriptions and the redevelopment of classic formulas and prescriptions as well.

Several blinding diseases affecting the retina and optic nerve are exacerbated by or caused by dysregulated inflammation and oxidative stress. These diseases include uveitis, age related macular degeneration, diabetic retinopathy and glaucoma. Consequently, despite their divergent symptoms, treatments that reduce oxidative stress and suppress inflammation may be therapeutic. The production of inflammatory cytokines and their activities are regulated by a class of proteins termed Suppressors of Cytokine Signaling (SOCS). SOCS1 and SOCS3 are known to dampen signaling via pathways employing Janus kinases and signal transducer and activator of transcription proteins (JAK/STAT), Toll-like Receptors (TLR), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), mitogen activated kinase (MAPK) and NLR family pyrin domain containing 3 (NLRP3). We have developed cell-penetrating peptides from the kinase inhibitory region of the SOCS1 and SOCS3 (denoted as R9-SOCS1-KIR and R9-SOCS3-KIR) and tested them in retinal pigment epithelium (RPE) cells and in macrophage cell lines. SOCS-KIR peptides exhibited anti-inflammatory, anti-oxidant and anti-angiogenic properties. In cell culture, both Th1 and Th17 cells were suppressed together with the inhibition of other inflammatory markers. We also observed a decrease in oxidants and a simultaneous rise in neuroprotective and anti-oxidant effectors. In addition, treatment prevented the loss of gap junction proteins and the ensuing drop in transepithelial electrical resistance in RPE cells. When tested in mouse models by eye drop instillation, they showed protection against autoimmune uveitis, as a prophylactic as well as a therapeutic. Mice with endotoxin-induced uveitis were protected by eye drop administration as well. R9-SOCS3-KIR was particularly effective against the pathways acting through STAT3, e.g. IL-6 and VEGF-A mediated responses that lead to macular degeneration. Eye drop administration of R9-SOCS3-KIR stimulated production of antioxidant effectors and reduced clinical symptoms in mouse model of oxidative stress that replicates the RPE injury occurring in AMD. Because these peptides suppress multiple pathogenic stimuli and because they can be delivered topically to the cornea, they are attractive candidates for therapeutics for uveitis, macular degeneration, diabetic retinopathy and glaucoma., Competing Interests: CA and HJ are listed as inventors in a patent held by the University of Florida for the technology involving R9-SOCS3-KIR peptide. The remaining author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Ahmed, Johnson and Lewin.)

Ocular inflammation-associated diseases are leading causes of global visual impairment, with limited treatment options. Adiponectin, a hormone primarily secreted by adipose tissue, binds to its receptors, which are widely distributed throughout the body, exerting powerful physiological regulatory effects. The protective role of adiponectin in various inflammatory diseases has gained increasing attention in recent years. Previous studies have confirmed the presence of adiponectin and its receptors in the eyes. Furthermore, adiponectin and its analogs have shown potential as novel drugs for the treatment of inflammatory eye diseases. This article summarizes the evidence for the interplay between adiponectin and inflammatory eye diseases and provides new perspectives on the diagnostic and therapeutic possibilities of adiponectin., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Traditional medicines are commonly used worldwide, especially in Africa-however, there is limited information on the prevalence and types of traditional eye medicine utilization in Ethiopia. The goal of this study was to determine the prevalence, the type and nature of traditional eye medicine use and practices related to self-medication for ophthalmic diseases in a rural Ethiopian population., Methods: A cross-sectional study was conducted in six randomly selected primary health centers in rural Gurage Zone, Southern Ethiopia. Health-seeking behavior, use of self-medication, and traditional eye medicine were assessed in the population using a semi-structured questionnaire. Descriptive statistics and multivariable logistic regression analysis were computed to determine associated factors for using self-medication and traditional eye medicine., Result: Of the 814 participants interviewed, 487 (59.8%) reported using traditional eye medicine, mainly for combinations of symptoms of ocular redness, irritation, and eye discharge (95.5%). Besides, 604 (74.2%) participants reported self-treatment with tetracycline 1% eye ointment. Older age, females, low income, no formal education, and lack of access to media were risks for utilizing traditional eye medicine., Conclusion: The use of traditional eye medicine and self-treatment are common in this population. Regulatory legislation, public awareness, and making eye care are vital activities required to monitor such practices., (© 2024. The Author(s).)

Background: Recombinant intracameral tissue plasminogen activator (rTPA) administration can aid clearance of fibrin from the anterior chamber., Materials and Methods: In this retrospective multicentre case series, the effect of intracameral rTPA administration to treat fibrin in the anterior chamber resulting from trauma or inflammatory ocular disease was evaluated. Clinical data from 30 treatments in 29 horses were obtained from medical records from 2003 to 2022. Association between time from onset of clinical signs and time for rTPA treatment to effect was studied with regression analysis., Results: Twenty-seven horses (93.1%) had no previous history of ophthalmic disease; one had an iridic cyst, and another had equine recurrent uveitis. The majority of cases were related to trauma (79.3%). Median time from the onset of clinical signs to treatment was 12 h (IQR = 4-48 h). rTPA (72% 20 µg; 24% 25 µg; 3.3% 40 µg) was administered once in all but one eye, which was treated twice. Resolution of fibrin was seen in 96.9% (29/30) of treatments. Fibrin accumulation recurred in one case but resolved 14 days after the second treatment. Complications were seen in four treatments (13.3%): moderate pain for 24 h, intracameral debris and mild intracameral haemorrhage in a horse that received 40 µg of tissue plasminogen activator. Recurrence of fibrin accumulation was absent in 96.7% of cases. Median time to effect was 20 min (IQR = 10-45 min). Time for rTPA treatment to effect was not associated with time from fibrin formation (R 2  = 0.09; p = 0.11)., Conclusion: Intracameral rTPA treatment can be considered at 20-25 µg in 0.1 mL solution to aid resolution of fibrin accumulation., (© 2024 The Authors. Veterinary Medicine and Science published by John Wiley & Sons Ltd.)

The development of intravitreally injected biologic medicines (biologics) acting against vascular endothelial growth factor (VEGF) substantially improved the clinical outcomes of patients with common VEGF-driven retinal diseases. The relatively high cost of branded agents, however, represents a financial burden for most healthcare systems and patients, likely resulting in impaired access to treatment and poorer clinical outcomes for some patients. Biosimilar medicines (biosimilars) are clinically equivalent, potentially economic alternatives to reference products. Biosimilars approved by leading health authorities have been demonstrated to be similar to the reference product in a comprehensive comparability exercise, generating the totality of evidence necessary to support analytical, pre-clinical, and clinical biosimilarity. Anti-VEGF biosimilars have been entering the field of ophthalmology in the US since 2022. We review regulatory and scientific concepts of biosimilars, the biosimilar development landscape in ophthalmology, with a specific focus on anti-VEGF biosimilars, and discuss opportunities and challenges facing the uptake of biosimilars., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr Neil M Bressler reported receiving grants from Samsung Bioepis to Johns Hopkins University and receiving grants from Bayer, Biogen, Boehringer Ingelheim, F. Hoffman-LaRoche, Genentech, and Regeneron and having a patent to System and Method for Automated Detection of Age-Related Macular Degeneration and Other Retinal Abnormalities issued. Dr Peter Kaiser reported being a consultant for Allergan, Allgenesis, Bayer, Bausch and Lomb, Biogen Idec, Boehringer Ingelheim, Carl Zeiss Meditec, Coherus, Genentech/Roche, Innovent, Kanghong, Kodiak, Novartis, Ocular Therapeutix, Regeneron, RegenxBio, and Samsung Bioepis. Dr Kyu Hyung Park reported receiving lecture fee and being a consultant for Bayer, Novartis, Roche and Samsung Bioepis. Dr Se Joon Woo reported being a consultant for Samsung Bioepis, Janssen, Novartis, Curacle, Novelty Nobility, Sometech, Rznomics; being an equity owner of Retimark and Panolos Bioscience; receiving grants from Samsung Bioepis, Novelty Nobility, Pharmabcine, Novartis, Alteogen, Geneuintech, and Curacle; and receiving lecture fees from Novartis, Bayer, Allergan, Abbvie, Retimark, and Alcon outside the submitted work. Dr Min Sagong reported being a consultant for and receiving grant support from Samsung Bioepis, Novartis, Bayer, Roche, Allergan/Abbvie, Celltrion, Alteogen, Alcon and Curacle, and receiving lecture fee from Novartis, Bayer, Roche, and Allergan/Abbvie. Dr Mario Bradvica obtained honoraria for presentations by Novartis and Abbvie. He is part of the advisory board of Novartis and obtained grants for clinical trials from Iveric Bio (former Optotech), Novartis, Roche, Ophthea, and Samsung Bioepis. Mercy Yeeun Kim and Seungkee Kim are reported being employees of Samsung Bioepis. Dr SriniVas R Sadda reported receiving honoria as a consultant for 4DMT, Abbvie/Allergan, Alexion, Amgen, Apelis, Astellas, Bayer, Biogen, Boerhinger Ingelheim, Catalyst, Centervue, Roche/Genentech, Gyroscope, Heidelberg, IvericBio, Jannsen, Merck, Nanoscope, Novartis, Optos, Oxurion, Osyterpoint, Eyepoint, Pfizer, Regeneron, Samsung Bioepis, and Vertex Pharmaceuticals. He has also received honoraria for talks given at symposia sponsored by Roche, Novartis, Apellis, Heidelberg, Optos, and Nidek. He has received research funding from Carl Zeiss Meditec and he has received research instruments from Optos, Nidek, Centervue, Topcon, Heidelberg, and Carl Zeiss Meditec. Dr Diana Do and Dr Quan Dong Nguyen declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Ocular disorders, encompassing both common ailments like dry eye syndrome and more severe situations for instance age-related macular degeneration, present significant challenges to effective treatment due to the intricate architecture and physiological barriers of the eye. Polysaccharides are emerging as potential solutions for drug delivery to the eyes due to their compatibility with living organisms, natural biodegradability, and adhesive properties. In this review, we explore not only the recent advancements in polysaccharide-based technologies and their transformative potential in treating ocular illnesses, offering renewed optimism for both patients and professionals but also anatomy of the eye and the significant obstacles hindering drug transportation, followed by an investigation into various drug administration methods and their ability to overcome ocular-specific challenges. Our focus lies on biological adhesive polymers, including chitosan, hyaluronic acid, cellulose, cyclodextrin, and poloxamer, known for their adhesive characteristics enhancing drug retention on ocular surfaces and increasing bioavailability. A detailed analysis of material designs used in ophthalmic formulations, such as gels, lenses, eye drops, nanofibers, microneedles, microspheres, and nanoparticles, their advantages and limitations, the potential of formulations in improving therapeutic outcomes for various eye conditions. Moreover, we underscore the discovery of novel polysaccharides and their potential uses in ocular drug delivery., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Ocular drug delivery is constrained by anatomical and physiological barriers, necessitating innovative solutions for effective therapy. Natural polymers like hyaluronic acid, chitosan, and gelatin, alongside synthetic counterparts such as PLGA and PEG, have gained prominence for their biocompatibility and controlled release profiles. Recent strides in polymer conjugation strategies have enabled targeted delivery through ligand integration, facilitating tissue specificity and cellular uptake. This versatility accommodates combined drug delivery, addressing diverse anterior (e.g., glaucoma, dry eye) and posterior segment (e.g., macular degeneration, diabetic retinopathy) afflictions. The review encompasses an in-depth exploration of each natural and synthetic polymer, detailing their individual advantages and disadvantages for ocular drug delivery. By transcending ocular barriers and refining therapeutic precision, these innovations promise to reshape the management of anterior and posterior segment eye diseases., (© 2024 Wiley Periodicals LLC.)

Melatonin, a versatile hormone produced by the pineal gland, has garnered considerable scientific interest due to its diverse functions. In the eye, melatonin regulates a variety of key processes like inhibiting angiogenesis by reducing vascular endothelial growth factor levels and protecting the blood-retinal barrier (BRB) integrity by enhancing tight junction proteins and pericyte coverage. Melatonin also maintains cell health by modulating autophagy via the Sirt1/mTOR pathways, reduces inflammation, promotes antioxidant enzyme activity, and regulates intraocular pressure fluctuations. Additionally, melatonin protects retinal ganglion cells by modulating aging and inflammatory pathways. Understanding melatonin's multifaceted functions in ocular health could expand the knowledge of ocular pathogenesis, and shed new light on therapeutic approaches in ocular diseases. In this review, we summarize the current evidence of ocular functions and therapeutic potential of melatonin and describe its roles in angiogenesis, BRB integrity maintenance, and modulation of various eye diseases, which leads to a conclusion that melatonin holds promising treatment potential for a wide range of ocular health conditions., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Medicated eye drops may have dual therapeutic and diagnostic uses that form part of the ophthalmic assessment paradigm. In this review article, commonly administered and prescribed eye drops were analyzed for their use as a diagnostic tool. It examines the common categories of eye drops-antimicrobial agents, topical anesthetics, mydriatics, and ocular anti-hypertensives, with respect to their therapeutic and diagnostic applications. Knowledge of the pharmacological effects of eye drops is an important aspect in performing clinical duties. Diagnostic tests by utilization of eye drops are safe, efficient, noninvasive, and informative to the eye care professional.

Posterior eye disorders, such as age-related macular degeneration, diabetic retinopathy, and glaucoma, have a significant impact on human quality of life and are the primary cause of age-related retinal diseases among adults. There is a pressing need for innovative topical approaches to treat posterior eye disorders, as current methods often rely on invasive procedures with inherent risks. Limited success was attained in the realm of topical ophthalmic delivery through non-invasive means. Additionally, there exists a dearth of literature that delves into the potential of this approach for drug delivery and theranostic purposes, or that offers comprehensive design strategies for nanocarrier developers to surmount the significant physiological ocular barriers. This review offers a thorough and up-to-date state-of-the-art overview of 40 studies on therapeutic loaded nanocarriers and theranostic devices that, to the best of our knowledge, represent all successful works that reached posterior eye segments through a topical non-invasive administration. Most importantly, based on the successful literature studies, this review provides a comprehensive summary of the potential design strategies that can be implemented during nanocarrier development to overcome each ocular barrier., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Intravitreal injections of angiogenesis inhibitors have proved efficacious in the majority of patients with ocular angiogenesis. However, one-fourth of all treated patients fail to derive benefits from intravitreal injections. tRNA-derived small RNA (tsRNA) emerges as a crucial class of non-coding RNA molecules, orchestrating key roles in the progression of human diseases by modulating multiple targets. Through our prior sequencing analyses and bioinformatics predictions, tRNA-Cys-5-0007 has shown as a potential regulator of ocular angiogenesis. This study endeavors to elucidate the precise role of tRNA-Cys-5-0007 in the context of ocular angiogenesis., Methods: Quantitative reverse transcription PCR (qRT-PCR) assays were employed to detect tRNA-Cys-5-0007expression. EdU assays, sprouting assays, transwell assays, and Matrigel assays were conducted to elucidate the involvement of tRNA-Cys-5-0007 in endothelial angiogenic effects. STZ-induced diabetic model, OIR model, and laser-induced CNV model were utilized to replicate the pivotal features of ocular vascular diseases and evaluate the influence of tRNA-Cys-5-0007 on ocular angiogenesis and inflammatory responses. Bioinformatics analysis, luciferase activity assays, RNA pull-down assays, and in vitro studies were employed to elucidate the anti-angiogenic mechanism of tRNA-Cys-5-0007. Exosomal formulation was employed to enhance the synergistic anti-angiogenic and anti-inflammatory efficacy of tRNA-Cys-5-0007., Results: tRNA-Cys-5-0007 expression was down-regulated under angiogenic conditions. Conversely, tRNA-Cys-5-0007 overexpression exhibited anti-angiogenic effects in retinal endothelial cells, as evidenced by reduced proliferation, sprouting, migration, and tube formation abilities. In diabetic, laser-induced CNV, and OIR models, tRNA-Cys-5-0007 overexpression led to decreased ocular vessel leakage, inhibited angiogenesis, and reduced ocular inflammation. Mechanistically, these effects were attributed to the targeting of vascular endothelial growth factor A (VEGFA) and TGF-β1 by tRNA-Cys-5-0007. The utilization of an exosomal formulation further potentiated the synergistic anti-angiogenic and anti-inflammatory efficacy of tRNA-Cys-5-0007., Conclusions: Concurrent targeting of tRNA-Cys-5-0007 for anti-angiogenic and anti-inflammatory therapy holds promise for enhancing the effectiveness of current anti-angiogenic therapy., (© 2024. The Author(s).)

This review article provides a comprehensive overview of the advancements in using nanosuspensions for controlled drug delivery in ophthalmology. It highlights the significance of ophthalmic drug delivery due to the prevalence of eye diseases and delves into various aspects of this field. The article explores molecular mechanisms, drugs used, and physiological factors affecting drug absorption. It also addresses challenges in treating both anterior and posterior eye segments and investigates the role of mucus in obstructing micro- and nanosuspensions. Nanosuspensions are presented as a promising approach to enhance drug solubility and absorption, covering formulation, stability, properties, and functionalization. The review discusses the pros and cons of using nanosuspensions for ocular drug delivery and covers their structure, preparation, characterization, and applications. Several graphical representations illustrate their role in treating various eye conditions. Specific drug categories like anti-inflammatory drugs, antihistamines, glucocorticoids, and more are discussed in detail, with relevant studies. The article also addresses current challenges and future directions, emphasizing the need for improved nanosuspension stability and exploring potential technologies. Nanosuspensions have shown substantial potential in advancing ophthalmic drug delivery by enhancing solubility and absorption. This article is a valuable resource for researchers, clinicians, and pharmaceutical professionals in this field, offering insights into recent developments, challenges, and future prospects in nanosuspension use for ocular drug delivery., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Ocular delivery is the most challenging aspect in the field of pharmaceutical research. The major hurdle for the controlled delivery of drugs to the eye includes the physiological static barriers such as the complex layers of the cornea, sclera and retina which restrict the drug from permeating into the anterior and posterior segments of the eye. Recent years have witnessed inventions in the field of conventional and nanocarrier drug delivery which have shown considerable enhancement in delivering small to large molecules across the eye. The dynamic challenges associated with conventional systems include limited drug contact time and inadequate ocular bioavailability resulting from solution drainage, tear turnover, and dilution or lacrimation. To this end, various bioactive-based nanosized carriers including liposomes, ethosomes, niosomes, dendrimer, nanogel, nanofibers, contact lenses, nanoprobes, selenium nanobells, nanosponge, polymeric micelles, silver nanoparticles, and gold nanoparticles among others have been developed to circumvent the limitations associated with the conventional dosage forms. These nanocarriers have been shown to achieve enhanced drug permeation or retention and prolong drug release in the ocular tissue due to their better tissue adherence. The surface charge and the size of nanocarriers (10-1000 nm) are the important key factors to overcome ocular barriers. Various nanocarriers have been shown to deliver active therapeutic molecules including timolol maleate, ampicillin, natamycin, voriconazole, cyclosporine A, dexamethasone, moxifloxacin, and fluconazole among others for the treatment of anterior and posterior eye diseases. Taken together, in a nutshell, this extensive review provides a comprehensive perspective on the numerous facets of ocular drug delivery with a special focus on bioactive nanocarrier-based approaches, including the difficulties and constraints involved in the fabrication of nanocarriers. This also provides the detailed invention, applications, biodistribution and safety-toxicity of nanocarriers-based therapeutcis for the ophthalmic delivery., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Botulinum toxin (BoNT) has been known for over 50 years. It has conquered many areas of medicine and has become indispensable in contemporary medicine. Now, BoNT is used to treat at least 26 conditions in six medical specialties. Although the use of BoNT began in strabology, it became the gold standard for many ophthalmologic pathologies. The present review of the literature focuses on the use of BoNT in ophthalmology and treatment of the following conditions: blepharospasm, facial hemispasm, facial palsy, spastic entropion, strabismus, endocrine orbitopathy, convergence spasm, and facial trauma. We conclude that nearly half a century of experience in utilizing BoNT in ophthalmology ensured a satisfactory level of effectiveness and safety for patients with many pathologies. Areas of future research include the application of BoNT in new selected indications, the development of the route of application without injections, and the development of long-acting BoNT forms for patients who require repeated long-term treatment., (Copyright © 2024 Copyright: © 2024 Indian Journal of Ophthalmology.)

Posterior ocular disease, a disease that accounts for 55% of all ocular diseases, can contribute to permanent vision loss if left without treatment. Due to the special structure of the eye, various obstacles make it difficult for drugs to reach lesions in the posterior ocular segment. Therefore, the development of highly permeable targeted drugs and delivery systems is particularly important. Exosomes are a class of extracellular vesicles at 30-150 nm, which are secreted by various cells, tissues, and body fluids. They carry various signaling molecules, thus endowing them with certain physiological functions. In this review, we describe the ocular barriers and the biogenesis, isolation, and engineering of exosomes, as exosomes not only have pharmacological effects but also are good nanocarriers with targeted properties. Moreover, their biocompatibility and immunogenicity are better than synthetic nanocarriers. Most importantly, they may have the ability to pass through the blood-eye barrier. Thus, they may be developed as both targeted nano-drugs and nano-delivery vehicles for the treatment of posterior ocular diseases. We focus on the current status and potential application of exosomes as targeted nano-drugs and nano-delivery vehicles in posterior ocular diseases., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Injectable hydrogels based on biopolymers, fabricated utilizing diverse chemical and physical methodologies, exhibit exceptional physical, chemical, and biological properties. They have multifaceted applications encompassing wound healing, tissue regeneration, and across diverse scientific realms. This review critically evaluates their largely uncharted potential in ophthalmology, elucidating their diverse applications across an array of ocular diseases. These conditions include glaucoma, cataracts, corneal disorders (spanning from age-related degeneration to trauma, infections, and underlying chronic illnesses), retina-associated ailments (such as diabetic retinopathy, retinitis pigmentosa, and age-related macular degeneration (AMD)), eyelid abnormalities, and uveal melanoma (UM). This study provides a thorough analysis of applications of injectable hydrogels based on biopolymers across these ocular disorders. Injectable hydrogels based on biopolymers can be customized to have specific physical, chemical, and biological properties that make them suitable as drug delivery vehicles, tissue scaffolds, and sealants in the eye. For example, they can be engineered to have optimum viscosity to be injected intravitreally and sustain drug release to treat retinal diseases. Their porous structure and biocompatibility promote cellular infiltration to regenerate diseased corneal tissue. By accentuating their indispensable role in ocular disease treatment, this review strives to present innovative and targeted approaches in this domain, thereby advancing ocular therapeutics., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

MEK inhibitors (MEKi) represent innovative and promising treatments for managing manifestations of neurofibromatosis type 1 (NF1). To mitigate potential ophthalmic side effects, such as MEKi-associated retinopathy (MEKAR), patients undergoing MEKi therapy routinely receive ophthalmology evaluations. Our study aims to assess the necessity of this regular screening within a predominantly pediatric NF1 population by examining the occurrence of ocular adverse events (OAE). A retrospective study evaluated 45 NF1 patients receiving MEKi. Inclusion criteria included baseline and follow-up examinations following the initiation of MEKi therapy. At each assessment, a comprehensive eye evaluation was performed, comprising a dilated fundus examination, ocular coherence tomography of the macula and nerve fiber layer, and Humphrey visual field testing. Twenty-six patients, with an average age of 13 years (range 2-23 years) and an average follow-up duration of 413 days were included in the analysis. Three different MEKi were used: selumetinib (77%), trametinib (23%), and mirdametinib (4%). None of the patients experienced retinopathy at any point during the study. Some patients had pre-existing optic neuropathies (27%), but no instances of nerve changes occurred after commencing MEKi therapy. Four patients (15%) exhibited symptoms of dry eye, all of which were effectively managed with topical lubrication.

The aims of this survey were to determine how veterinary ophthalmologists worldwide use compounded ophthalmic drugs to treat ocular diseases, define their attitudes regarding compounding pharmacies, and identify commonly dispensed veterinary ophthalmic formulations as well as the diseases for which those preparations are most often prescribed. Respondents voluntar i ly and anonymously completed a questionnaire that was sent to a total of 1014 veterinary ophthalmologists at universities, specialty colleges, and ophthalmology associations in 24 countries. One hundred thirty (12.83%) veterinary ophthalmologists replied. Of those, 87 (66.92%) had worked in  veterinary ophthalmology for more than 10 years. Ten to 30% of their total prescriptions were compounded ophthalmic drugs, the most common of which were tacrolimus and cyclosporine for the treatment of keratoconjunctivitis sicca. Reported advantages of treatment with a compound included the accessibility of preparations that were not commercially available and the ability to customize formulations; reported disadvantages included brief shelf life, delivery time, and cost., (Copyright© by International Journal of Pharmaceutical Compounding, Inc.)

The eye is one of the most complex organs in the human body, with a unique anatomy and physiology, being divided into anterior and posterior segments. Ocular diseases can occur in both segments, but different diseases affect different segments. Glaucoma and cataracts affect the anterior segment, while macular degeneration and diabetic retinopathy occur in the posterior segment. The easiest approach to treat ocular diseases, especially in the anterior segment, is through the administration of topical eye drops, but this route presents many constraints, namely precorneal dynamic and static ocular barriers. On the other hand, the delivery of drugs to the posterior segment of the eye is far more challenging and is mainly performed by the intravitreal route. However, it can lead to severe complications such as retinal detachment, endophthalmitis, increased intraocular pressure and haemorrhage. The design of new drug delivery systems for the anterior segment is very challenging, but targeting the posterior one is even more difficult and little progress has been made. In this review we will discuss various strategies including the incorporation of additives in the formulations, such as viscosity, permeability, and solubility enhancers, namely based on Deep eutectic systems (DES). Natural deep eutectic systems (NADES) have emerged to solve several problems encountered in pharmaceutical industry, regarding the pharmacokinetic and pharmacodynamic properties of drugs. NADES can contribute to the design of advanced technologies for ocular therapeutics, including hydrogels and nanomaterials. Here in, we revise some applications of (NA)DES in the development of new drug delivery systems that can be translated into the ophthalmology field., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Encapsulated cell technology (ECT) is a targeted delivery method that uses the genetically engineered cells in semipermeable polymer capsules to deliver cytokines. Thus far, ECT has been extensively utilized in pharmacologic research, and shows enormous potentials in the treatment of posterior segment diseases. Due to the biological barriers within the eyeball, it is difficult to attain effective therapeutic concentration in the posterior segment through topical administration of drug molecules. Encouragingly, therapeutic cytokines provided by ECT can cross these biological barriers and achieve sustained release at the desired location. The encapsulation system uses permeable materials that allow growth factors and cytokines to diffuse efficiently into retinal tissue. Moreover, the ECT based treatment can be terminated timely when we need to retrieve the implant, which makes the therapy reversible and provides a safer alternative for intraocular gene therapy. Meanwhile, we also place special emphasis on optimizing encapsulation materials and enhancing preservation techniques to achieve the stable release of growth factors and cytokines in the eyeball. This technology holds great promise for the treatment of patients with dry AMD, RP, glaucoma and MacTel. These findings would enrich our understandings of ECT and promote its future applications in treatment of degenerative retinopathy. This review comprises articles evaluating the exactness of artificial intelligence-based formulas published from 2000 to March 2024. The papers were identified by a literature search of various databases (PubMed/MEDLINE, Google Scholar, Cochrane Library and Web of Science)., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Plants are an incredible source of metabolites showing a wide range of biological activities. Among these, there are the alkaloids, which have been exploited for medical purposes since ancient times. Nowadays, many plant-derived alkaloids are the main components of drugs used as therapy for different human diseases. This review deals with providing an overview of the alkaloids used to treat eye diseases, describing the historical outline, the plants from which they are extracted, and the clinical and molecular data supporting their therapeutic activity. Among the different alkaloids that have found application in medicine so far, atropine and pilocarpine are the most characterized ones. Conversely, caffeine and berberine have been proposed for the treatment of different eye disorders, but further studies are still necessary to fully understand their clinical value. Lastly, the alkaloid used for managing hypertension, reserpine, has been recently identified as a potential drug for ameliorating retinal disorders. Other important aspects discussed in this review are different solutions for alkaloid production. Given that the industrial production of many of the plant-derived alkaloids still relies on extraction from plants, and the chemical synthesis can be highly expensive and poorly efficient, alternative methods need to be found. Biotechnologies offer a multitude of possibilities to overcome these issues, spanning from genetic engineering to synthetic biology for microorganisms and bioreactors for plant cell cultures. However, further efforts are needed to completely satisfy the pharmaceutical demand., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

In drug discovery, selecting targeted molecules is crucial as the target could directly affect drug efficacy and the treatment outcomes. As a member of the CCN family, CTGF (also known as CCN2) is an essential regulator in the progression of various diseases, including fibrosis, cancer, neurological disorders, and eye diseases. Understanding the regulatory mechanisms of CTGF in different diseases may contribute to the discovery of novel drug candidates. Summarizing the CTGF-targeting and -inhibitory drugs is also beneficial for the analysis of the efficacy, applications, and limitations of these drugs in different disease models. Therefore, we reviewed the CTGF structure, the regulatory mechanisms in various diseases, and drug development in order to provide more references for future drug discovery.

Since the theory of free radical-induced aging was proposed in 1956, it has been constantly proven that reactive oxygen species (ROS) produced by oxidative stress play a vital role in the occurrence and progression of eye diseases. However, the inherent limitations of traditional drug therapy hindered the development of ophthalmic disease treatment. In recent years, great achievements have been made in the research of nanomedicine, which promotes the rapid development of safe theranostics in ophthalmology. In this review, we focus on the applications of antioxidant nanomedicine in the treatment of ophthalmology. The eye diseases were mainly classified into two categories: ocular surface diseases and posterior eye diseases. In each part, we first introduced the pathology of specific diseases about oxidative stress, and then presented the representative application examples of nano-antioxidants in eye disease therapy. Meanwhile, the nanocarriers that were used, the mechanism of function, and the therapeutic effect were also presented. Finally, we summarized the latest research progress and limitations of antioxidant nanomedicine for eye disease treatment and put forward the prospects of future development.

Melatonin's cytoprotective properties may have therapeutic implications in treating ocular diseases like glaucoma and age-related macular degeneration. Literature data suggest that melatonin could potentially protect ocular tissues by decreasing the production of free radicals and pro-inflammatory mediators. This study aims to summarize the screened articles on melatonin's clinical, pharmacological, and formulation evaluation in treating ocular disorders. The identification of relevant studies on the topic in focus was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA 2020) guidelines. The studies were searched in the following databases and web search engines: Pubmed, Scopus, Science Direct, Web of Science, Reaxys, Google Scholar, Google Patents, Espacenet, and Patentscope. The search time interval was 2013-2023, with the following keywords: melatonin AND ocular OR ophthalmic AND formulation OR insert AND disease. Our key conclusion was that using melatonin-loaded nano-delivery systems enabled the improved permeation of the molecule into intraocular tissues and assured controlled release profiles. Although preclinical studies have demonstrated the efficacy of developed formulations, a considerable gap has been observed in the clinical translation of the results. To overcome this failure, revising the preclinical experimental phase might be useful by selecting endpoints close to clinical ones.

Different degrees of visual impairment lead to a decrease in patient wellbeing, which has an adverse effect on many facets of social and professional life. Eye disorders can affect several parts of the eye, most notably the retina and the cornea, and the impacted areas might share a common form of cellular damage or dysfunction (such as inflammation, oxidative stress and neuronal degeneration). Considering that marine organisms inhabit a broad variety of marine habitats, they display a great degree of chemical diversity. As a result, molecules with a marine origin are receiving more and more attention in the hopes of developing novel therapeutic approaches. For instance, fucoxanthin has been demonstrated to be effective in protecting the retina against photo-induced damage, while largazole, astaxanthin and spirulina have all shown antioxidant, anti-inflammatory and antiapoptotic activities that can be useful for the management of several ocular diseases, such as age-related macular degeneration and ocular surface disorders. The aim of this review is to analyze the scientific literature relating to the therapeutic effects on the eye of the main natural marine products, focusing on their mechanism of action and potential clinical uses for the management of ocular diseases., Competing Interests: The authors declare no conflicts of interest.