Medical hypothesis discovery and innovation in ophthalmology

Background: The cornea and ocular surface serve as a vital barrier and the eye’s primary refractive medium, requiring precise coordination to maintain transparency, structural integrity, and immune protection. Constantly exposed to environmental stressors, this interface relies on the stability of the tear film, epithelial architecture, mucin layers, and limbal stem cells to preserve function. Disruption in any component can impair vision and increase vulnerability to disease. Advances in imaging and molecular diagnostics have deepened our understanding of these structures, offering new avenues for early detection and personalized treatment strategies. A comprehensive review is needed to integrate recent findings and assess their clinical relevance.
Methods: A targeted literature search was conducted using PubMed/MEDLINE and Google Scholar to identify English-language publications from 1 January 2000 to 30 May 2025. Keywords included “anatomy,” “histology,” “cornea,” “ocular surface,” “epithelium,” “Bowman’s layer,” “stroma,” “Descemet’s membrane,” “endothelium,” “conjunctiva,” “lacrimal functional unit,” and “eyelids.” Studies were selected irrespective of design, and reference lists of included articles were manually screened for additional relevant sources.
Results: Eighty-six publications were reviewed. Findings highlight that the cornea and ocular surface constitute an integrated anatomical and physiological continuum essential for optical clarity, visual acuity, and ocular health. This dynamic unit comprises the cornea, conjunctiva, tear film (mucin, aqueous, and lipid layers), meibomian glands, goblet cells, and the limbal stem cell niche. Collectively, these elements provide lubrication, immune defense, epithelial homeostasis, and structural integrity. Disruption in any component—such as in dry eye disease, limbal stem cell deficiency, or meibomian gland dysfunction—can precipitate epithelial breakdown, neovascularization, or stromal scarring, ultimately compromising vision. Recognizing this interdependence has reframed ocular surface disease as a multifactorial condition rather than an isolated disorder. A comprehensive understanding of the structural and immunological dynamics of this system is therefore critical for refining surgical strategies and developing targeted therapies.
Conclusions: The cornea and ocular surface components function synergistically to maintain a transparent, stable refractive surface essential for vision. Their coordinated roles in protection, lubrication, immune defense, and tissue repair reveal the importance of anatomical understanding for developing targeted therapies and improving clinical outcomes. A comprehensive understanding of this anatomy is essential for clinicians and researchers aiming to develop more precise therapeutic strategies and surgical techniques to enhance patient outcomes and preserve visual function. Future research should focus on advancing regenerative strategies and personalized treatments to address complex ocular surface disorders more effectively.

Background: Scleral lenses (SLs) and prosthetic replacement of the ocular surface environment (PROSE) are the same device, designed to enhance the optical quality of irregular surfaces or ectatic corneas. They also improve the corneal surface epithelium and the ocular surface microenvironment for patients with severe ocular surface diseases, including dry eye. This review aims to provide a comprehensive overview of the indications for SL/PROSE, as well as an exhaustive analysis of the corresponding complications, their possible remedies, and future challenges in this rapidly evolving field of ophthalmology.
Methods: We conducted a review of the English language literature on the indications and complications of SL/PROSE devices using the following website search engines: National Library of Medicine’s PubMed, Google Scholar, EMBASE, Web of Science, and Scopus for articles in English published from inception up to July 2025. The following scientific reports were considered for analysis: systematic reviews and meta-analyses, randomized controlled trials, cohort studies, case-control series, case reports, editorials, and short communications.
Results: Research and development in SL/PROSE have made significant strides, broadening its applications, improving structural materials and designs, and adapting it to benefit a diverse range of patients facing numerous pathologies. These include keratoconus, post-refractive surgery ectasia, corneal transplantation, severe dry eye, and chronic cicatrizing ocular surface disorders, among many others. For patients suffering from these emerging pathologies, apart from medical therapy and surgical procedures there are limited treatment options. Currently, SL/PROSE offer a less invasive potential solution for many of these challenging conditions, raising hope and motivation within the field of corneal and ocular surface disease. However, they are not without potential complications, which differ significantly from those associated with soft contact lenses and rigid gas-permeable contact lenses. The most frequently reported SL/PROSE complications relate to improper lens adaptation and patients’ handling.
Conclusions: While much of the existing literature has focused on the benefits and applications of SL/PROSE devices, the potential complications associated with their use have received less attention and aren’t as widely explored.

Background: Retinal diseases, including neovascular age-related macular degeneration, diabetic retinopathy, and retinal vein occlusion, are leading causes of vision loss worldwide. The introduction of anti-vascular endothelial growth factor (anti-VEGF) therapies has dramatically changed the management of these conditions, offering targeted treatment that can preserve and even improve vision. We aimed to provide a comprehensive review of the development, clinical applications, and emerging indications of anti-VEGF therapies in ophthalmology, including biosimilar agents.
Methods: A comprehensive literature search was conducted in PubMed/MEDLINE for English-language articles published up to 31 July 2025. Additional sources were identified through manual screening of reference lists. Included studies spanned various designs: clinical trials, meta-analyses, observational studies, and preclinical research. Keywords used in the search strategy included terms such as “anti-VEGF therapy”, “biosimilar pharmaceuticals”, “intravitreal and intrastromal anti-VEGF injections”, “retinal diseases” including “macular degeneration” and “retinal neovascularization”, “ranibizumab”, and “bevacizumab”, as well as relevant MeSH terms where applicable.
Results: Anti-VEGF agents have transformed the management of retinal diseases such as neovascular age-related macular degeneration, diabetic macular edema, proliferative diabetic retinopathy, retinal vein occlusion, and retinopathy of prematurity. Newer agents such as brolucizumab and faricimab offer prolonged durability and enhanced anatomic outcomes, while biosimilars provide cost-effective alternatives. Anti-VEGF therapy has also shown promise in off-label or emerging indications such as neovascular glaucoma, corneal neovascularization, and other retinal or choroidal disorders including secondary macular edema and/or macular neovascularization associated with various forms of uveitis, diffuse choroidal hemangioma in Sturge-Weber Syndrome, hereditary retinal disorders such as fundus flavimaculatus, Coats-Like retinitis pigmentosa, Peripherin-2-associated retinopathy, immune checkpoint inhibitor use, radiation retinopathy, retinitis pigmentosa, Bietti crystalline dystrophy, autosomal recessive bestrophinopathy, melanocytoma-associated macular neovascular membrane, Best disease, Wyburn-Mason syndrome, choroidal osteoma, peripheral exudative hemorrhagic chorioretinopathy, traumatic choroidal rupture, torpedo maculopathy, optic disc melanocytoma, type 2 proliferative macular telangiectasia, and Coats disease. High-dose formulations and innovative delivery systems are under active investigation to reduce the treatment burden and extend dosing intervals.
Conclusions: Anti-VEGF therapies have revolutionized the field of ophthalmology, providing sight-saving treatment for a range of retinal diseases that were once considered untreatable or inevitably blinding. Today, anti-VEGF drugs are the go-to option for managing neovascular retinal disorders, thanks to their proven efficacy, favorable safety profile, and transformative impact on modern eye care.

Background: Reactive oxygen species and oxidative stress are increasingly recognized as central drivers in the development of major ocular diseases, including cataracts, age-related macular degeneration, glaucoma, and diabetic retinopathy. The eye’s unique environment—continuous light exposure, high oxygen tension, and abundant photosensitizers—renders it particularly vulnerable to ROS-mediated damage. This narrative review aims to synthesize current evidence on the molecular mechanisms of oxidative stress in ocular disease and highlight emerging therapeutic approaches.
Methods: Targeted searches of PubMed, Scopus, and Google Scholar for literature published between 2000 and June 2025 were conducted. Keywords included “oxidative stress”, “reactive oxygen species”, “ocular disease”, “cataract”, “age-related macular degeneration”, “glaucoma”, and “diabetic retinopathy”. Only English-language, peer-reviewed articles were considered. Relevant primary studies, clinical trials, reviews, and experimental reports were selectively incorporated, with an emphasis on recent publications and high-impact contributions to the field.
Results: Evidence consistently demonstrates that ROS induce lipid peroxidation, protein oxidation, DNA damage, mitochondrial dysfunction, and disruption of redox-sensitive cellular signaling pathways across ocular tissues. In cataracts, oxidation of crystalline proteins and glutathione depletion are primary drivers of lens opacification. In age-related macular degeneration, mitochondrial dysfunction and lipofuscin accumulation promote retinal pigment epithelium degeneration and neovascularization. Glaucoma involves both trabecular meshwork oxidative injury, contributing to elevated intraocular pressure, and mitochondrial-driven retinal ganglion cell apoptosis. In diabetic retinopathy, hyperglycemia-induced ROS overload activates pathogenic pathways, leading to microvascular damage and neuronal dysfunction. Clinical and experimental studies support antioxidant therapies as adjunctive strategies, with the strongest evidence for Age-Related Eye Disease Study-based formulations in age-related macular degeneration and promising results for agents such as Coenzyme Q10 in glaucoma and sulforaphane in diabetic retinopathy. For cataracts, supplementation trials have yielded mixed outcomes and surgery remains the definitive treatment.
Conclusions: Oxidative stress represents a unifying mechanism in the pathogenesis of vision-threatening ocular diseases. Antioxidant-based interventions show potential, particularly when integrated with existing treatment regimens, but their translation into routine practice remains limited by heterogeneous trial results and the absence of robust biomarkers for patient selection. Future research should focus on precision antioxidant therapy, leveraging stage-specific interventions, novel delivery systems, and pathway-targeted compounds, to transform ocular care from reactive management toward prevention.

Background: Acanthamoeba keratitis represents a devastating corneal infection caused by free-living protozoan organisms. This condition has evolved from an extraordinarily rare disease to a significant public health concern, with increasing global incidence. The infection predominantly affects contact lens wearers and poses substantial diagnostic and therapeutic challenges. This narrative review aims to provide analysis of current knowledge regarding Acanthamoeba keratitis, including epidemiology, pathogenesis, diagnostic approaches, treatment strategies, and prevention methods, to guide clinicians in optimal patient management.
Methods: This review was conducted through a literature search of PubMed-indexed journals from January 2000 to August 2025, incorporating current information on pathophysiology, clinical features, diagnosis, therapy, and outcomes of Acanthamoeba keratitis. Keywords included “Acanthamoeba keratitis”, “contact lens-related keratitis”, “Acanthamoeba diagnosis”, and “Acanthamoeba treatment”. English-language publications including original articles, reviews, case reports, and clinical studies were included based on relevance to current diagnostic and therapeutic practices, with an emphasis on recent advances in the field.
Results: Contact lens wearers comprised the vast majority of cases, with soft contact lens users representing the predominant affected population. Peak occurrence involves young adults aged 20–40 years, with water-based transmission through contaminated domestic supplies representing a significant risk pathway. Clinical manifestations commonly include epithelial abnormalities, stromal infiltration, and ring infiltrates in advanced cases. Traditional culture methods evidence limited sensitivity (33–67%), while advanced diagnostic approaches include polymerase chain reaction (PCR) and in vivo confocal microscopy (IVCM) achieving superior accuracy (sensitivity 77–100%, specificity 84–100%). First-line therapy employs biguanides and diamidines with prolonged administration. Advanced treatment options include oral miltefosine for refractory cases, azole antifungals, and surgical interventions ranging from epithelial debridement to corneal transplantation. Early diagnostic recognition represents the strongest predictor of visual recovery, with diagnostic delays associated with poor prognosis.
Conclusions: Acanthamoeba keratitis management requires high clinical suspicion, rapid diagnosis using advanced techniques such as IVCM and PCR, and prolonged antimicrobial therapy. Early diagnosis remains the most important predictor of visual recovery. Prevention through proper contact lens hygiene and water exposure avoidance is paramount. Future research priorities include development of novel antimicrobial agents and enhanced prevention strategies.

Background: A-pattern esotropia is defined as an increase of more than 10 prism diopters (PD) divergence in down-gaze than in up-gaze. The long-term outcomes of bilateral superior oblique tendon suture extension (SOSE), a hardware-free technique, were evaluated in pediatric A-pattern esotropia with bilateral superior oblique overaction (bi-SOOA), addressing complications associated with traditional silicone spacers and tenotomy.
Methods: In this retrospective cohort study, all participants with A-pattern esotropia and bi-SOOA underwent bilateral SOSE using nonabsorbable polypropylene sutures combined with medial rectus recession. Preoperative and postoperative assessments included prism cover testing in nine gazes, fundus photography for objective torsion quantification, and grading of superior oblique overaction (SOOA).
Results: This study included 64 eyes from 32 children with a mean (SD) age of 7.0 (3.1) years and a mean (SD) postoperative follow-up of 35.2 (15.6) months (range: 8–55). The mean (SD) A-pattern esodeviation collapsed from 23.4 (7.7) PD preoperatively to 2.4 (2.3) PD postoperatively (P < 0.001), representing an 88.3% reduction. The mean (SD) horizontal esodeviation improved from 37.5 (10.9) PD to 1.7 (1.8) PD in primary gaze (P < 0.001). The mean (SD) objective fundus torsion decreased from 10.9 (2.5) degrees to 1.1 (1.4) degrees (P < 0.001), with no cases of torsional diplopia or vertical deviation. SOOA grades normalized from 2.8 (0.7) to 0.2 (0.4) (P < 0.001). No suture-related complications were observed, and alignment stability was maintained through to the final follow-up visit.
Conclusions: In pediatric A-pattern esodeviation surgery, SOSE provided biomechanical precision, anatomical preservation, and elimination of hardware-related risks. Its effectiveness in collapsing A-pattern esotropia, normalizing torsion, and achieving durable outcomes establishes it as a first-line surgical intervention for bi-SOOA. This study addresses a significant gap in pediatric ophthalmology, offering extended follow-up data and highlighting the value of minimally invasive, growth-compatible techniques in protecting visual development. Larger randomized trials with extended follow-up are needed to confirm the efficacy and safety of this procedure for A-pattern esotropia.