A literature review of macular holes in age-related macular degeneration: insights into the pathogenesis, prognosis and surgical outcomes

Summary

This review, published in the Graefes Archive for Clinical and Experimental Ophthalmology, looks at macular holes in people who also have age-related macular degeneration. It says the link between the two conditions is still not fully clear, but both pulling forces in the eye and degenerative changes may help explain why macular holes develop. The review also notes that anti-VEGF injections for wet AMD have been linked to macular hole formation in some cases.

The paper says that surgery with vitrectomy and peeling the internal limiting membrane is still the main treatment for restoring vision, but that each case needs careful individual assessment. It also says there is no proof yet that stem cell treatment helps in this setting, and that more research is needed because the current evidence is limited and sometimes conflicting.

Keywords: age-related macular degeneration, macular hole, full-thickness macular hole, lamellar macular hole, anti-VEGF, vitrectomy, prognosis, surgery.

Abstract

The pathogenesis of macular holes in eyes with background of age-related macular degeneration (AMD) and the potential causative relationship between these entities remains unclear. In this narrative review, we aim to explore the intricate relationship between the formation of macular holes, both full-thickness and lamellar, and neovascular / non-subtype of AMD. A literature search was performed using the National Center for Biotechnology Information (NCBI) PubMed database, and studies published up to March 2025 were included. We summarize the current evidence on AMD-associated macular holes, and provide insights into the underlying pathophysiological mechanisms, prevalence, prognosis and surgical outcomes. Research to date suggests that macular holes can uncommonly develop in eyes with coexistent AMD, with a contributing role of tractional and degenerative component in their development and progression. Intravitreal anti vascular endothelial growth factor injections for neovascular AMD have been implicated in macular hole formation. Surgical intervention with vitrectomy and internal limiting membrane peel remains the optimal proven method for restoring vision in macular holes, however comprehensive evaluation and individualized management approaches may optimize anatomical and functional outcomes in this patient population. Recent findings underscore that there is no evidence yet of a benefit to using stem cell therapy in macular holes with coexistent AMD. This review sheds light on the postulated pathogenesis of AMD-associated macular holes, discusses practical aspects of prognostic prediction and examines appropriate management options. Current evidence needed to guide clinical practice is both limited and often contradictory, and further studies are warranted to elucidate these findings.

Keywords: Age related macular degeneration; Full thickness macular hole; Intravitreal anti-VEGF; Lamellar macular hole; Vitrectomy.