Varun Kumar

Background:  Retinopathy of prematurity (ROP) is best defined as the excessive growth of vasculature in the retina and its associated deleterious consequences (Brown & Nwanyanwu, 2023). ROP is strongly associated with prematurity, low birth weight, and early exposure to a high oxygen environment (Brown & Nwanyanwu, 2023). In the US, nearly 15M premature infants had some level of ROP and 30,000 had significant longstanding visual impairment (Brown & Nwanyanwu, 2023).

Methods:  Preliminary Google searches and careful vetting of sources was performed to obtain an understanding of ROP. Literature searches were performed primarily utilizing PubMed with keyword searches including “retinopathy of prematurity,” “retinopathy of prematurity drug,” and “retinopathy of prematurity randomized controlled trial” (RCT). Once an understanding of the landscape of ROP drug therapy was obtained and it was clear that the field is primarily exploring anti-VEGF therapies, searches including the term “VEGF” were performed. Finally, searches regarding ROP drug therapy were limited to the last five years.

Results:  There are several RCTs on new pharmacologic regimens for ROP, particularly in the realm of VEGF inhibitors. Here, four key clinical trials and their results are highlighted. First, the RAINBOW trial evaluated ranibizumab intravitreal injection versus laser photocoagulation therapy (LPT). The trial showed ranibizumab was noninferior to LPT and that long-term (5-year) visual outcomes showed a lower incidence of severe myopia (Marlow et al., 2024). Next, the FIREFLEYE trial evaluated aflibercept versus LPT. Unfortunately, aflibercept was unable to conclusively exhibit noninferiority (Stahl et al., 2022). Third, the BEAT-ROP trial evaluated bevacizumab versus LPT. Bevacizumab showed superior outcomes for Zone I Stage 3+ ROP and noninferiority for all other stages/zones of ROP examined (Mintz et al., 2011). Although this trial was performed back in 2011, its results are important for a thorough understanding of the following clinical trial. A trial comparing bevacizumab and ranibizumab showed bevacizumab associated strongly with a dose-dependent reduction in the need for retreatment (Patel et al., 2023). Finally, it is worth noting that a variety of “benign” drugs such as antihypertensives and antioxidants, to name a few, are currently being explored for potential utility in ROP treatment (Xie et al., 2023).

Conclusions:  ROP has been a primarily surgical disease, a possibly problematic endeavor for a fragile premature neonate. However, with the burst of new clinical trials exploring anti-VEGF therapies and positive results, ROP may become a disease that only requires medical therapy, thus reducing neonatal morbidity and mortality.

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