Maad Rayan Publishing Company Biomedical Research Bulletin 2980-9924 3 4 2025 12 29 Montelukast in Ophthalmology: Molecular Mechanisms, Current Evidence, and Future Therapeutic Perspectives 226 240 10.34172/biomedrb.9105 EN Safieh Amiraslanzadeh https://orcid.org/0009-0002-5930-4685 Hamid Mahmoudpour https://orcid.org/0000-0001-9216-9441 Mojtaba Ziaee https://orcid.org/0000-0002-9725-3033 REVIEW 10.34172/biomedrb.9105 2025 07 11 2025 12 15 Leukotrienes have traditionally been viewed as key mediators of allergic inflammation, but growing evidence indicates their involvement in immune responses, oxidative stress (OS), vascular dysfunction, and neuroinflammation, highlighting their therapeutic potential. Among available agents, montelukast, a selective cysteinyl leukotriene receptor 1 (CysLT₁) antagonist, represents a promising candidate for drug repurposing in ophthalmology. Therefore, this review summarizes current knowledge of leukotriene biology in ocular tissues and critically evaluates the experimental and clinical evidence supporting montelukast across diverse ophthalmic diseases. According to preclinical studies, montelukast suppresses inflammatory signaling, reduces OS, attenuates leukocyte recruitment and microglial activation, and preserves vascular barrier integrity and retinal neuronal homeostasis. Moreover, clinical observations are most convincing in allergic conjunctivitis, while encouraging experimental data have been reported for dry eye disease, diabetic retinopathy, retinal ischemic injury, glaucoma, and uveitis. Contrarily, evidence for age-related macular degeneration remains preliminary and largely mechanistic. Despite these encouraging findings, clinical translation into remains limited by uncertain ocular pharmacokinetics following systemic administration, the absence of formulations optimized for posterior-segment delivery, and insufficient validated biomarkers and a lack of adequately powered randomized clinical trials. Overall, current evidence supports leukotriene signaling as a convergent inflammatory pathway across multiple ocular diseases, identifying montelukast as an important proof-of-concept for leukotriene-directed therapy. Future advances in ocular drug delivery, biomarker-guided patient selection, and well-designed clinical studies will determine whether the modulation of this pathway can evolve into a disease-modifying therapeutic strategy in ophthalmology.