Reactivation of retinopathy of prematurity after anti-VEGF treatment: a review

Anti-vascular endothelial growth factor (anti-VEGF) agents have demonstrated efficacy and short-term safety in the treatment of retinopathy of prematurity (ROP), establishing them as the preferred option for zone I and zone II posterior disease. Despite their advantages, the effects of anti-VEGF agents are relatively temporary. Consequently, ROP may reactivate or recur if retinal vascularisation has not sufficiently progressed and significant areas of avascular anterior retina remain while the anti-VEGF agents are cleared from the vitreous cavity. Extreme prematurity, early onset of ROP and severe disease at baseline (aggressive ROP or zone I disease) significantly increase this risk. Reactivated ROP presents differently from initial ROP presentation and may be subtle on clinical examination; however, it can often be detected earlier with fluorescein angiography. The interval and rates of reactivation vary depending on the type and dose of anti-VEGF agents, with occurrences sometimes delayed for years after an initial quiescent period. This necessitates close follow-up after anti-VEGF monotherapy until retinal vascularisation is complete or laser treatment is administered to the persistent peripheral avascular retina. On reactivation, the condition may be managed with repeat injections or laser treatment. Repeated anti-VEGF injections pose risks, including vascular arrest, persistent avascular retina, endophthalmitis and systemic toxicity. Late-detected reactivations or cases unresponsive to initial treatments may require vitrectomy. Generally, retreatment leads to disease regression with favourable structural outcomes. Currently, longer-acting drugs and prophylactic laser treatment of the avascular anterior retina are the only supported strategies for reducing reactivation.