Asymmetric Peripheral Retinal Vascular Extension in Anti-Vascular Endothelial Growth Factor-Treated Type 1 Retinopathy of Prematurity: Disparity Between Nasal and Temporal Hemispheres.

Abstract

Anti-vascular endothelial growth factor (anti-VEGF) therapy is an important treatment for type 1 retinopathy of prematurity (T1ROP). We previously found that regulation of VEGF signaling increased developmental vascularization into the temporal peripheral retina while reducing intravitreal neovascularization in T1ROP. To address our hypothesis that extension of retinal vascularization by early treatment with anti-VEGF could reduce T1ROP, we determined the effects of anti-VEGF therapy on retinal vascular extension in both retinal hemispheres. Retrospective, masked, nonrandomized, matched, comparative case series. Over 3 years, 34 of 382 screened infants developed bilateral T1ROP. Consent was obtained from parents of 21 infants for infants receiving bevacizumab 0.25 mg OU. Seven treated eyes (7 infants) had suitable imaging and were included in the treatment group. Seven untreated eyes (7 infants) without T1ROP were randomly selected after matching for birthweight and postmenstrual age from the 382 screened infants and assigned to the control group. Infants had gradable 100° field-of-view fundus photographs of both retinal hemispheres at 2 time points: baseline before treatment, if administered, and follow-up, 12 to 35 days later. No eyes with vascularization to the ora at baseline or follow-up were included. Retinal vascular extent was measured in pixels from the optic disc margin to the temporal or nasal vascular borders and divided by the optic disc diameter in pixels to create disc diameter units (DD). Measurements were confirmed by a second masked analyst. The Mann-Whitney U test and Wilcoxon signed-rank test were used for statistical analysis. Temporal and nasal vascular extension in DD. Relative to control eyes, treated eyes had greater nasal (1.27 ± 0.59 vs 0.55 ± 0.44 DD; P = .038) and temporal (1.69 ± 1.16 vs 0.62 ± 0.49 DD; P = .04) extensions. There was greater disparity in vascular extension between nasal and temporal hemispheres in the treated group than in the control group (0.98 ± 0.64 vs 0.10 ± 0.10 DD; P = .005). Nasal extension was greater than temporal extension in 3 of 7 treated vs 1 of 7 control eyes. Treated eyes had significantly greater vascular extension in both hemispheres than control eyes, with greater nasal-temporal asymmetry. Although limited by sample size, our findings raise the question of uneven anti-VEGF diffusion in the infant vitreous. Further studies testing injection site, needle length, anti-VEGF agent, and molecular size differences and further follow-up periods are indicated.