Medical Hypothesis, Discovery, and Innovation in Ophthalmology最新文献

{"title":"Topical pyridostigmine for ocular myasthenia gravis: a translational hypothesis.","authors":"Edsel B Ing, Kate Lim, Neal M Davies, Raimar Lobenberg, Md Harunur Rashid, Tyson S Le, Jacob Rullo","doi":"10.51329/mehdiophthal1540","DOIUrl":"https://doi.org/10.51329/mehdiophthal1540","url":null,"abstract":"<p><strong>Background: </strong>Myasthenia gravis (MG) is an autoimmune disorder of the neuromuscular junction predominantly mediated by antibodies that target the acetylcholine receptors in the skeletal muscles. Ocular involvement of the levator palpebrae superioris and extraocular muscles is common, resulting in ptosis and diplopia. Oral pyridostigmine, an acetylcholinesterase, is typically the first-line therapy, but its administration is frequently limited by systemic cholinergic adverse effects and inconsistent relief of ocular symptoms.</p><p><strong>Hypothesis: </strong>We hypothesize that pyridostigmine can be reformulated as a topical ocular/periocular formulation to directly enhance the neuromuscular transmission of the levator palpebrae superioris and extraocular muscles, thereby improving ptosis and strabismus while minimizing systemic side effects. The levator palpebrae superioris and extraocular muscles underlie the conjunctiva. Pyridostigmine bromide is a small, hydrophilic quaternary ammonium compound with topical application properties that favor conjunctival permeability while limiting transcorneal penetration. Its formulation pH closely approximates that of conjunctival tissue. Clinical precedent from alpha-adrenergic eye drops (e.g., apraclonidine) that elevate the eyelid via Müller's muscle support the plausibility of a topical approach. Although limited residence time on the ocular surface is a potential barrier, advances in delivery systems, including hydrogels, nanoparticles, and ionic liquids, may enhance retention and conjunctival penetration. Periocular transdermal delivery may further exploit the thin periocular skin to achieve localized vascular access. Based on the pharmacological mechanism of acetylcholinesterase inhibition, we propose that <i>ex vivo</i> animal model ocular permeability and tissue integrity be examined to determine the feasibility of topical pyridostigmine formulation providing effective localized neuromuscular transmission enhancement in patients with ocular MG.</p><p><strong>Conclusions: </strong>If preliminary <i>ex vivo</i> animal model observations find that topical pyridostigmine formulations are stable with appropriate conjunctival penetration and preserved epithelial integrity, it would support progression to <i>in vivo</i> animal studies and translational modelling. The feasibility of topical or periocular pyridostigmine as a localized treatment strategy for ocular MG deserves further investigation. If validated, this approach could shift management toward targeted, better-tolerated topical therapies with reduced systemic risk.</p>","PeriodicalId":36524,"journal":{"name":"Medical Hypothesis, Discovery, and Innovation in Ophthalmology","volume":"15 1","pages":"69-77"},"PeriodicalIF":0.0,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13135656/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147843903","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of the TGF-beta1 polymorphism with primary open-angle glaucoma: a case-control study.","authors":"Akbar Derakhshan, Mohammad Javad Zia, Jalil Tavakkol Afshari, Amin Reza Nikpoor, Saeed Shokoohi Rad, Ramin Daneshvar, Seyed Hossein Ghavami Shahri, Javad Firozi, Rashin Ganjali, Elham Bakhtiari, Javad Sadeghi","doi":"10.51329/mehdiophthal1537","DOIUrl":"https://doi.org/10.51329/mehdiophthal1537","url":null,"abstract":"<p><strong>Background: </strong>Primary open-angle glaucoma (POAG) is characterized by increased resistance to aqueous humor outflow. Transforming growth factor beta-1 (TGF-beta1) contributes to this resistance by promoting synthesis and remodeling of the extracellular matrix in the trabecular meshwork, thereby reducing outflow facility. This study aimed to investigate the association between the TGF-beta1 gene polymorphism at position -800 G>A (rs1800468) and POAG in patients from Khorasan Razavi Province, Iran.</p><p><strong>Methods: </strong>In this case-control study, patients with POAG referred to Khatam-al-Anbia Hospital were enrolled as the case group, and age-matched healthy individuals served as controls. Demographic and clinical data of participants were recorded, collecting 5 mL of whole blood from each individual. DNA was extracted, genotyping the TGF-beta1 -800 G>A polymorphism using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).</p><p><strong>Results: </strong>We included 105 individuals diagnosed with POAG and 105 healthy controls, with comparable mean age and sex distribution between the two groups (both <i>P</i> > 0.05). In the case group, genotype frequencies were 88.6% GG (n = 93), 10.5% GA (n = 11), and 1.0% AA (n = 1), in the control group 79.0% GG (n = 83), 19.1% GA (n = 20), and 1.9% AA (n = 2). Allele frequencies were 94.0% G (n = 197) and 6.0% A (n = 13) in cases, compared to 88.6% G (n = 186) and 11.4% A (n = 24) in controls. No significant association was observed between genotype frequencies and POAG or between alleles and POAG (both <i>P</i> > 0.05). Analysis under various inheritance models (codominant, dominant, recessive, overdominant) showed no significant associations either (<i>P</i> > 0.05).</p><p><strong>Conclusions: </strong>The TGF-beta1 -800 G>A polymorphism does not appear to play a significant role in POAG development in this population. Inheritance of the mutant A allele is not a risk factor for POAG in northeastern Iran.</p>","PeriodicalId":36524,"journal":{"name":"Medical Hypothesis, Discovery, and Innovation in Ophthalmology","volume":"15 1","pages":"10-18"},"PeriodicalIF":0.0,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13135657/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147844009","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Designing and conducting systematic reviews and meta-analyses in ophthalmology.","authors":"Abbasali Keshtkar, Mohammadreza Ghasemi","doi":"10.51329/mehdiophthal1541","DOIUrl":"https://doi.org/10.51329/mehdiophthal1541","url":null,"abstract":"<p><strong>Background: </strong>Systematic reviews and meta-analyses represent the highest level of evidence in clinical research, yet their methodological quality in ophthalmology remains inconsistent despite a substantial increase in publication volume. The complexity of existing methodological guidance, such as comprehensive handbooks, may limit their practical use by clinicians and researchers. This study aims to provide a structured, field-specific guide to improve the design and execution of systematic reviews in ophthalmology.</p><p><strong>Methods: </strong>This methodological review synthesizes established international standards and guidelines for systematic reviews, including protocol development, search strategy design, and study selection processes. Key methodological components were critically appraised and adapted to the context of ophthalmic research. The review focuses on the planning and execution phases prior to quantitative synthesis, outlining a stepwise framework encompassing question formulation, preliminary searching, protocol development and registration, database searching, screening, selection, and Risk of Bias (RoB) assessment.</p><p><strong>Results: </strong>A comprehensive, step-by-step framework for conducting systematic reviews in ophthalmology is presented, structured into four phases and eleven key steps. The review highlights essential methodological considerations, including the formulation of focused research questions using structured frameworks (e.g., PICO and alternatives), the importance of preliminary searches, and the necessity of prospective protocol registration. It emphasizes transparent and reproducible search strategies using multiple databases and gray literature sources, as well as rigorous dual-reviewer screening and selection processes. Additionally, the appropriate application of RoB assessment tools based on study design is detailed. The findings underscore common methodological limitations in ophthalmology reviews, particularly low rates of protocol registration and adherence to reporting standards.</p><p><strong>Conclusions: </strong>This review provides a practical and structured guide to enhance the methodological quality of systematic reviews in ophthalmology. By translating established methodological standards into a field-specific framework, it aims to improve transparency, reproducibility, and overall research quality. Adoption of these recommendations may address existing gaps in methodological rigor and support the generation of high-quality evidence in ophthalmic research.</p>","PeriodicalId":36524,"journal":{"name":"Medical Hypothesis, Discovery, and Innovation in Ophthalmology","volume":"15 1","pages":"78-89"},"PeriodicalIF":0.0,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13135661/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147844016","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Management of myopia: a mini-review.","authors":"Andrzej Grzybowski, Carla Lanca","doi":"10.51329/mehdiophthal1538","DOIUrl":"https://doi.org/10.51329/mehdiophthal1538","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Myopia is becoming more common in many populations worldwide, particularly in East Asia. It is primarily driven by axial elongation, a structural change associated with increased risks of myopic maculopathy, retinal detachment, glaucoma, and cataracts. The expanding range of myopia‑control options can make treatment selection and management decisions more challenging in routine pediatric care. This narrative review synthesizes contemporary evidence and guidance for delaying myopia onset and slowing progression in children.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;A targeted, non-systematic search was conducted in PubMed/MEDLINE, Embase, and the Cochrane Library for English-language records published between January 2015 and July 2025, supplemented by the inclusion of seminal pre‑2015 trials. Eligible records included randomized or comparative clinical studies, systematic reviews/meta-analyses, and professional consensus/guideline statements in participants &lt; 18 years reporting spherical equivalent refraction and/or axial length (AL). Non-comparative studies were included to provide additional information on safety, including adverse events. Findings were synthesized and presented using a narrative approach.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;The evidence reviewed indicated that increased outdoor time consistently reduced incident myopia and modestly slowed progression, supporting the adoption of low-cost prevention strategies. Associations between near work and digital exposure and myopia were less consistent, though moderation in these activities remains advisable. Optical interventions showed consistent efficacy compared to single‑vision correction, with strong evidence for defocus incorporated multiple segments (DIMS) lens with highly aspherical lenslet technology spectacles, and dual‑focus/high‑add soft contact lenses. Safety was generally favorable, although contact lens wear requires infection-risk mitigation. Orthokeratology was effective in slowing AL but requires specialist fitting and structured follow-up, and may be followed by rebound after cessation. Atropine showed a concentration‑dependent effect; 0.01% atropine produced inconsistent AL benefit in several non‑Asian trials, but longer-term European data suggest a cumulative advantage with continued 0.01% treatment versus placebo. Repeated low‑level red‑light therapy reduced axial elongation in early trials but was limited by protocol heterogeneity, rebound, and uncertainty regarding long-term safety. Combination regimens (notably orthokeratology plus low‑dose atropine and DIMS plus atropine) may provide additional slowing of AL, particularly in children with faster progression.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;Evidence supports a risk‑stratified pathway integrating outdoor time with effective optical and/or pharmacological therapy. Future research should prioritize head‑to‑head comparative trials with standardized AL endpoints, longer follow-up, inclusion of m","PeriodicalId":36524,"journal":{"name":"Medical Hypothesis, Discovery, and Innovation in Ophthalmology","volume":"15 1","pages":"19-39"},"PeriodicalIF":0.0,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13135658/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147844046","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Systemic and ocular complications related to intravitreal administration of anti-VEGF agents.","authors":"Seher Koksaldi, Mustafa Kayabasi, Omer Karti, Ali Osman Saatci","doi":"10.51329/mehdiophthal1539","DOIUrl":"https://doi.org/10.51329/mehdiophthal1539","url":null,"abstract":"<p><strong>Background: </strong>Intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections are the backbone of the treatment of neovascular retinal disorders and among the most frequently performed procedures in ophthalmic practice. This narrative review aims to summarize the current evidence on systemic and ocular adverse events associated with intravitreal anti-VEGF therapy and to reiterate their clinical implications in daily practice.</p><p><strong>Methods: </strong>A structured PubMed/MEDLINE database search was conducted to identify relevant manuscripts published between 1 January 2004 and 31 March 2026. Search strategies included combinations of keywords and controlled vocabulary related to intravitreal anti-VEGF therapy and associated adverse events. Evidence from randomized trials, observational research, meta-analyses, experimental models, and case reports or series were included to provide a broad perspective.</p><p><strong>Results: </strong>Systemic adverse events associated with intravitreal anti-VEGF therapy appear to be uncommon; however, potential cardiovascular events, blood pressure alterations, and renal effects have been reported, particularly in patients with preexisting vascular risk factors. Ocular complications represent the most frequently discussed as safety concerns. Sterile intraocular inflammation is among the most clinically relevant events and may range from mild self-limited reactions to severe inflammatory blinding conditions such as occlusive retinal vasculitis. Distinguishing sterile inflammation from infectious endophthalmitis is critical, as clinical management and prognosis differ substantially. Elevation of intraocular pressure is another frequently observed complication and may present either as a transient spike occurring immediately after the injection or as sustained ocular hypertension following repeated treatments. Additional ocular complications reported in the literature include rhegmatogenous retinal detachment, retinal tears, retinal vascular occlusions, cataract formation, and retinal pigment epithelium tears.</p><p><strong>Conclusions: </strong>Although intravitreal anti-VEGF therapy is generally safe, a wide variety of ocular and systemic adverse events has been described. Timely recognition and individualized monitoring strategies are key to excel in treatment safety and achieve better visual outcomes.</p>","PeriodicalId":36524,"journal":{"name":"Medical Hypothesis, Discovery, and Innovation in Ophthalmology","volume":"15 1","pages":"40-68"},"PeriodicalIF":0.0,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13135659/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147843884","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and safety of pilocarpine as a secretagogue versus artificial tears in the management of dry eye disease.","authors":"Ehab Mohamed Elsayed Saad, Hazem Elbadry Mohammed Mohammed, Ehab Tharwat, Ahmed Abdelmohsen Ali Ayoub, Omar Hassan Salama Selim, Sayed Mostafa Elsayed Abdelhafeez, Nehad Mohammed Yusef, Taha Ahmed Farouk Soltan, Ahmed Abdelfattah Abdelhamid Elfar, Mahmoud Abdelhalim Ali Ali","doi":"10.51329/mehdiophthal1536","DOIUrl":"https://doi.org/10.51329/mehdiophthal1536","url":null,"abstract":"<p><strong>Background: </strong>Dry eye disease (DED) is a common multifactorial ocular surface disorder that substantially impairs quality of life and remains among the leading reasons for ophthalmic consultations worldwide. We aimed to compare the efficacy and safety of oral pilocarpine versus artificial tears (AT) in the treatment of DED.</p><p><strong>Methods: </strong>This randomized clinical trial study enrolled patients with DED, randomly allocated to a pilocarpine group receiving 5 mg pilocarpine hydrochloride tablets four times daily (20 mg/day) or an AT group receiving 0.2% sodium hyaluronate eye drops four times daily, for eight weeks. Primary outcomes were changes in Dry Eye Quality of Life Score (DEQS), tear film breakup time (TBUT), and Schirmer's test after treatment. Secondary outcomes were incidence of adverse events like brow ache, sweating, nausea, headache, diarrhea, and allergic conjunctivitis (AC).</p><p><strong>Results: </strong>Enrolment comprised 120 patients, randomly assigned to the Pilocarpine group (n = 60) or the AT group (n = 60), with comparable mean age and sex distribution between groups (both <i>P</i> > 0.05). Both groups demonstrated significant post-treatment improvements in DEQS, TBUT, and Schirmer's test as opposed to baseline (all <i>P</i> < 0.001). The AT group showed a significantly diminished mean (standard deviation [SD]) DEQS (12.1 [2.7] vs. 21.9 [8.4]; <i>P</i> < 0.001) and longer mean (SD) TBUT (11.8 [1.4] s vs. 9.8 [1.8] s; <i>P</i> < 0.05) than the pilocarpine group, while Schirmer's test results were comparable (<i>P</i> > 0.05). Adverse events were significantly more frequent in the pilocarpine group, with sweating (n = 38, 63%), brow ache (n = 17, 28%), and nausea (n = 15, 25%) occurring exclusively in pilocarpine-treated patients (all <i>P</i> < 0.05); conversely, AC was reported only in the AT group (n = 8, 13%) but did not differ significantly between groups (<i>P</i> > 0.05).</p><p><strong>Conclusions: </strong>Both pilocarpine and AT produced significant improvements in DED symptoms and objective clinical parameters. However, AT demonstrated superior efficacy in enhancing tear film stability and reducing symptom scores, with a better safety profile. Pilocarpine may still have a role in severe or refractory cases requiring enhanced tear secretion but should be prescribed cautiously due to its systemic cholinergic adverse events.</p>","PeriodicalId":36524,"journal":{"name":"Medical Hypothesis, Discovery, and Innovation in Ophthalmology","volume":"15 1","pages":"1-9"},"PeriodicalIF":0.0,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13135660/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147843985","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sutureless-dehydrated amniotic membrane (Omnigen®) mounted on contact lens (OmniLenz®) in the treatment of small corneal perforations secondary to exposure keratitis in ICU patients.","authors":"Nancy M Lotfy, Mubarak Alrasheedi, Rola Y Khachaba, Hamad Alshatti, Yousef Taleb Ali","doi":"10.51329/mehdiophthal1532","DOIUrl":"https://doi.org/10.51329/mehdiophthal1532","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Exposure keratopathy is a common ocular complication in patients admitted to the intensive care unit (ICU) and may progress from superficial epithelial breakdown to corneal perforation, a vision-threatening emergency requiring timely management. Conventional treatments often necessitate urgent surgery, which is challenging in critically ill individuals who are unsuitable for surgical intervention. OmniLenz®, a customized bandage contact lens pre-lined with vacuum-dried Omnigen® amniotic membrane, offers a practical, non-surgical, bedside alternative for managing small corneal perforations. This study evaluates its clinical outcomes in ICU patients with a small corneal perforation secondary to exposure keratitis.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;This prospective interventional case series included ICU patients with &lt;1 mm corneal perforations secondary to exposure keratitis, recruited over a two-year interval. All patients underwent corneal scraping with culture and sensitivity testing, followed by targeted antimicrobial therapy. A dehydrated amniotic membrane (Omnigen®) was applied beneath a customized bandage contact lens (OmniLenz®) at the bedside under sterile conditions. Patients were examined daily using a portable slit-lamp and followed for one month. The primary outcome was perforation closure, defined by a negative Seidel test and anterior chamber reformation. Secondary outcomes included improvement in epithelial integrity, corneal infiltration, and ciliary injection.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Five ICU patients, aged 18 to 70 years, with &lt; 1 mm corneal perforations secondary to exposure keratitis were included. All eyes demonstrated rapid tectonic recovery following Omnigen®/OmniLenz® device application. Anterior chamber reformation and a negative Seidel test were achieved by day 7 in four patients and by day 10 in one patient. Complete perforation closure occurred in all cases. Marked improvement in keratitis was observed, with full epithelial defect healing and resolution of corneal infiltrates in every patient, followed by stable grade-3 stromal scarring. No neovascularization, device-related adverse events, or treatment complications occurred during the one-month follow-up.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;Omnigen®/OmniLenz® device provides a safe, effective, and non-invasive bedside treatment for small corneal perforations secondary to exposure keratitis in critically ill ICU patients. Its use enabled consistent tectonic restoration, rapid perforation closure, and resolution of infection-associated corneal pathology without procedure-related complications. This approach offers a practical alternative to urgent surgical intervention in patients unsuitable for operative care and may serve as a valuable addition to corneal perforation management protocols. Further studies with larger cohorts are needed to evaluate its safety and efficacy in larger perforations and to determine long-term outcomes, i","PeriodicalId":36524,"journal":{"name":"Medical Hypothesis, Discovery, and Innovation in Ophthalmology","volume":"14 4","pages":"194-203"},"PeriodicalIF":0.0,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12840571/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146094075","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluating the predictive value of optical coherence tomography angiography metrics and central corneal thickness among glaucoma suspect patients: a comparative cross-sectional study.","authors":"Fathy Mohamed Abo Elftouh Elsalhy, Sarah Abbas Alshamarti, Saif Abbas Alshamarti, Abdelrahman Ahmed Ali Khattab, Mahmoud Mohammed Ahmed Ali Khalil, Mahmoud Fawzy Zaky Morsy, Ahmad Mohammad Salah Eldeen Abdul Hay, Ezzat Nabil Abbas Ibrahim, Ahmed Mohammed Madinah Alkady, Mahmoud Ahmed Shafeek, Bassem Ismail Khalil Gomaa, Mohamed Sayed Taha Abouzeid","doi":"10.51329/mehdiophthal1531","DOIUrl":"https://doi.org/10.51329/mehdiophthal1531","url":null,"abstract":"<p><strong>Background: </strong>Glaucoma suspects (GS) exhibit risk factors such as elevated intraocular pressure (IOP), suspicious optic disc or retinal nerve fiber layer (RNFL) findings, or a positive family history, yet their risk of progression varies widely. Optical coherence tomography angiography (OCTA) and central corneal thickness (CCT) have emerged as important markers for detecting early structural and microvascular changes in GS patients. We aimed to estimate the predictive value of OCTA-derived metrics and CCT, and to assess their correlations in GS individuals.</p><p><strong>Methods: </strong>This comparative cross-sectional study included eyes from GS patients and eyes from age- and sex-matched healthy individuals as a comparison group. All participants underwent a detailed medical history and comprehensive ophthalmologic examination. Investigations included visual field perimetry; optical coherence tomography (OCT) to assess structural optic nerve head parameters, RNFL thickness, and ganglion cell layer (GCL) thickness; OCTA to measure papillary vascular density (PVD) and radial peripapillary capillary density (RPC); and non-contact specular microscopy to determine CCT.</p><p><strong>Results: </strong>The GS group had a mean age of 36.9 years, with 52.4% male (n = 11). GS eyes showed significantly larger CDR values, reduced rim area, thinner RNFL and GCL, and lower CCT compared with healthy eyes (all <i>P</i> < 0.05). Mean RPC, quadrant-specific RPC values, and mean PVD were significantly reduced in GS individuals (all <i>P</i> < 0.05). CCT showed significant correlations with all vascular metrics and structural parameters (all <i>P</i> < 0.05), except disc area (<i>P</i> > 0.05). In univariate logistic regression all variables were associated with GS status. After multivariate adjustment, only CCT ≤ 506 µm remained an independent predictor. Receiver operating characteristic curve analysis showed good diagnostic performance for CCT (area under the curve [AUC] = 0.757) and mean RPC (AUC = 0.820) in identifying GS eyes.</p><p><strong>Conclusions: </strong>Patients with GS revealed significantly lower structural parameters and vascular metrics compared with the healthy group, and only thin CCT remained an independent predictor of GS status. Both CCT and mean RPC demonstrated good diagnostic performance for identifying GS eyes.</p>","PeriodicalId":36524,"journal":{"name":"Medical Hypothesis, Discovery, and Innovation in Ophthalmology","volume":"14 4","pages":"183-193"},"PeriodicalIF":0.0,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12840569/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146093924","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Crosslinking of tarsal collagen as a hypothetical therapy for dry eye disease.","authors":"Alexandra I Manta, Shuko Suzuki, Traian V Chirila","doi":"10.51329/mehdiophthal1535","DOIUrl":"https://doi.org/10.51329/mehdiophthal1535","url":null,"abstract":"<p><strong>Background: </strong>Dry eye disease (DED) is one of the most prevalent and distressing ocular conditions worldwide; it primarily results from alterations in the natural tear film that covers the ocular surface and is often due to enhanced evaporation of its aqueous component. This process is frequently associated with dysfunction of the meibomian glands (MGs), which are embedded within the tarsal plate of our eyelids and secrete the meibum, an oily mixture of proteins and lipids. Meibum forms the outermost layer of the tear film, playing a critical role in controlling water evaporation and stabilizing the tear film by lowering surface tension. Meibomian gland dysfunction (MGD) may result from structural abnormalities in the MGs, such as tortuosity, which impair normal delivery of meibum. Increased laxity of the eyelid is also associated with development of MGD and DED, likely due to insufficient mechanical support for the glands, and causing morphological changes.</p><p><strong>Hypothesis: </strong>We designed and initiated the development of a noninvasive method to strengthen and stiffen the tarsal collagen containing the embedded MGs. By reducing tissue laxity, our aim is to halt further morphological deterioration of the glands and promote uniform and smooth delivery of meibum to the ocular surface. Our previous studies showed that both mechanical tensile strength and rigidity (Young's modulus) of tarsal collagen in animal and human eyelids were significantly enhanced by exposure to ultraviolet-A (UV-A) radiation with a wavelength of 365 nm in the presence of riboflavin as a photosensitizer.</p><p><strong>Conclusions: </strong>We propose that performing this procedure at the initial manifestations of MGD and DED may prevent disease progression by restoring and preserving the normal morphology of the glands through reduced laxity, thereby ensuring proper secretion of the meibum into the tear film. The underlying principles and safety of the procedure were discussed in detail, and further pre-clinical evaluation steps were proposed and justified. Based on the proposed concept and the results of previous ex-vivo studies, in-vivo animal experiments and human clinical trials are currently in preparation.</p>","PeriodicalId":36524,"journal":{"name":"Medical Hypothesis, Discovery, and Innovation in Ophthalmology","volume":"14 4","pages":"233-250"},"PeriodicalIF":0.0,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12840572/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146093853","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of reactive oxygen species and oxidative stress in the pathomechanism of glaucoma.","authors":"Nicholas T H Chan, Ushasree Pattamatta, Andrew White","doi":"10.51329/mehdiophthal1533","DOIUrl":"https://doi.org/10.51329/mehdiophthal1533","url":null,"abstract":"<p><strong>Background: </strong>Glaucoma is a major cause of vision impairment and blindness, characterized by damage to retinal ganglion cells (RGC) at the optic nerve head (ONH). The pathomechanism underlying glaucoma is heterogeneous and theories explaining the pathomechanism can be categorized as mechanical, vascular, or immunological. This mini-review explores the involvement of reactive oxygen species (ROS) and oxidative stress in these established mechanisms of glaucoma.</p><p><strong>Methods: </strong>A review of literature was conducted using PubMed/MEDLINE, with the query including the following keywords: \"antioxidants\", \"glaucoma\", \"glaucoma pathomechanism\", \"immunological\", \"intraocular pressure\", \"mechanical\", \"reactive oxygen species\", \"ocular hypertension\", \"oxidative stress\", and \"vascular\". The date filter was set from January 2010 to September 2025. Papers that were relevant to ROS or oxidative stress in the glaucoma pathomechanism were thoroughly reviewed. Their reference lists were also reviewed for relevant papers of any date.</p><p><strong>Results: </strong>Following a comprehensive literature search, 67 journal articles were selected for review. They revealed the role of ROS and oxidative stress in the mechanical, vascular, and immunological pathomechanism theories of glaucoma. In the mechanical theory, oxidative stress mediates RGC apoptosis and trabecular meshwork damage. In vascular processes, retinal ischemia causes oxidative stress and vice versa, thus causing RGC death and ONH damage. With the immunological theory, ROS is implicated in glial cell and inflammasome activity that causes RGC injury. Key players in the generation of oxidative stress include NADP oxidase 2, dynamin-related protein 1, mitofusin 2, nuclear factor (erythroid-derived 2)‑like 2, and nitric oxide. Conversely, various antioxidant factors are also implicated in glaucoma, yet in oxidative stress conditions their effects are outweighed by those of ROS.</p><p><strong>Conclusions: </strong>ROS and oxidative stress are important mediators in the glaucoma pathomechanism. They contribute to and unify the existing theories of mechanical, vascular, and immunological injury in glaucoma. Investigating specific oxidative stress players in the pathomechanism may reveal new therapeutic targets in the treatment of glaucoma.</p>","PeriodicalId":36524,"journal":{"name":"Medical Hypothesis, Discovery, and Innovation in Ophthalmology","volume":"14 4","pages":"204-215"},"PeriodicalIF":0.0,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12840570/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146094111","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}