Aggressive retinopathy of prematurity: characteristics and risk factors for retreatment

Background/Aims Aggressive retinopathy of prematurity (A-ROP) is a severe subtype of ROP that can require repeated treatment yet risk factors for retreatment remain incompletely defined. This study aims to identify risk factors for anti-vascular endothelial growth factor (VEGF) re-injection in A-ROP across US-born and non-US-born infants. Methods Data from premature infants with ROP were collected across 23 sites (16 USA, 7 non-USA) from 2007 to 2021. A-ROP re-injection risk was evaluated using generalised estimating equations, adjusted for birth weight (BW), gestational age (GA) at birth, ROP zone at injection, hospital site and initial anti-VEGF agent. Results Of 1677 examined eyes, 1600 had ROP; 283 had A-ROP (mean BW 712 g, mean GA 24.8 weeks) and 1317 had non-A-ROP (mean BW 812 g, mean GA 25.9 weeks). Infants with A-ROP had lower mean BW and GA (p < 0.001). Across A-ROP cases, each 100 g increase in BW decreased re-injection risk by 26% (p=0.041). Compared with bevacizumab, ranibizumab was associated with a higher risk of re-injection in A-ROP eyes (risk ratio=4.82, p=0.009). ROP zone II was associated with a 2.48-fold higher risk of re-injection than zone I (p = 0.014), which was attenuated after correction for bilaterality. Conclusions and relevance A-ROP is associated with lower BW, lower GA at birth and more posterior ROP zone than non-A-ROP. Lower BW and initial ranibizumab treatment are related to greater risk of repeat anti-VEGF injection. There was more retreatment in zone II A-ROP eyes compared with those in zone I, which did not persist after correction for bilaterality.