Management of Macular Hole: Pharmacological, Procedural, and Surgical Treatment-A Systematic Review

Abstract

Background: Full-thickness macular hole (FTMH) impairs central vision. Although pars plana vitrectomy (PPV) with internal limiting membrane (ILM) peeling and gas tamponade is the standard treatment, the comparative effectiveness of surgical modifications, adjunctive therapies, and selected nonsurgical approaches remains uncertain. Methods: This PRISMA 2020 systematic review was prospectively registered in PROSPERO (CRD420261391937). PubMed/MEDLINE was searched for English-language randomized controlled trials published between January 2016 and April 2026. Two reviewers independently screened studies, extracted data, and assessed risk of bias using the Cochrane RoB 2 tool. Owing to methodological heterogeneity, findings were synthesized narratively. Results: Twenty-three randomized controlled trials were included. PPV with ILM manipulation achieved high anatomical closure rates, although no intervention was consistently superior across all clinical scenarios. Inverted ILM flap, ILM repositioning, and wider or 360° ILM peeling improved closure in selected large or complex holes, whereas tissue-sparing techniques better preserved retinal architecture and retinal sensitivity. Sulfur hexafluoride (SF6) achieved higher single-surgery closure than air for small-to-medium holes, while no clear superiority was demonstrated among expansile gases. Improvements in anatomical closure did not consistently translate into superior visual outcomes. Most studies had some risk-of-bias concerns. Conclusions: Current randomized evidence supports PPV with ILM manipulation as the cornerstone of FTMH management. Surgical techniques should be individualized according to hole characteristics, balancing anatomical closure with retinal preservation. Higher quality randomized trials with standardized anatomical, functional, and safety outcome reporting are needed.