Prostaglandin E₁ in ischemic retinal diseases: mechanisms, evidence, and clinical perspectives

Ischemic retinal diseases, including retinal vein and artery occlusions, diabetic retinopathy, and non-arteritic ischemic optic neuropathy, are major causes of vision loss worldwide and remain incompletely addressed by current therapies. Prostaglandin E1 (PGE₁) has emerged as a promising therapeutic candidate due to its unique pharmacological profile, encompassing vasodilation, anti-thrombotic and rheological effects, endothelial protection, anti-inflammatory activity, and potential neuroprotective and mitochondrial benefits. Preclinical studies demonstrate that PGE₁ improves retinal perfusion, reduces oxidative stress and edema, and promotes neuronal survival, while early clinical experiences, though limited in size, suggest favorable effects on visual outcomes and microcirculation, with an acceptable safety profile. However, evidence is limited by small sample sizes, heterogeneity, and delivery challenges. Emerging approaches, including sustained-release formulations, intravitreal delivery, and combination therapies, along with imaging biomarkers for patient selection, offer avenues to optimize clinical translation. While early clinical experiences-particularly in acutely treated central retinal artery occlusion-suggest potential benefits on retinal perfusion and visual outcomes, the current evidence remains limited by small, heterogeneous, and predominantly non-randomized studies. Consequently, PGE₁ should be regarded as an investigational or adjunctive approach, warranting further evaluation in well-designed, controlled clinical trials before any routine clinical adoption.