Medical hypothesis discovery and innovation in ophthalmology

Efficacy and safety of pilocarpine as a secretagogue versus artificial tears in the management of dry eye disease

2026-04-26T06:16:06+0330

Association of the TGF-beta1 polymorphism with primary open-angle glaucoma: a case-control study

2026-04-26T06:17:51+0330

Background: 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.

Methods: 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).

Results: We included 105 individuals diagnosed with POAG and 105 healthy controls, with comparable mean age and sex distribution between the two groups (both P > 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 P > 0.05). Analysis under various inheritance models (codominant, dominant, recessive, overdominant) showed no significant associations either (P > 0.05).

Conclusions: 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.

Management of myopia: a mini-review

2026-04-26T06:18:23+0330

Background: 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.

Methods: 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 < 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.

Results: 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.

Conclusions: 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 more diverse populations, validated treatment cessation strategies, and independent safety and performance standards for light-based devices.

Systemic and ocular complications related to intravitreal administration of anti-VEGF agents

2026-04-26T06:19:15+0330

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Topical pyridostigmine for ocular myasthenia gravis: a translational hypothesis

2026-04-26T06:20:40+0330

Designing and conducting systematic reviews and meta-analyses in ophthalmology

2026-04-26T06:20:12+0330

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.