Fluorescein Angiography in Retinopathy of Prematurity: Comparison of Infants Treated with Bevacizumab to Those with Spontaneous Regression

Abstract

Objective: Medium- and long-term sequelae of intravitreal bevacizumab (IVB) for type 1 retinopathy of prematurity (ROP) are uncertain. Our aim was to describe the fluorescein angiography (FA) findings in patients who received IVB as primary treatment for type 1 ROP and compare them to findings in patients with ROP that spontaneously regressed.

Design: Retrospective cohort.

Participants: Twenty-eight patients with a history of ROP who underwent fluorescein angiography between December 1, 2013, and July 31, 2018. Patients were divided into 2 groups based on whether they had received IVB or had ROP that spontaneously regressed.

Methods: We reviewed the angiograms in the 2 groups for neovascularization (NV) and other abnormal vascular patterns in both the periphery and the posterior pole.

Main outcome measures: Fluorescein angiography findings, including NV, peripheral, and macular vascular abnormalities.

Results: Forty eyes of 20 infants were included in the IVB group and 16 eyes of 8 infants in the untreated group. Median gestational age at birth was similar in the 2 groups (24.5 and 24.7 weeks, respectively; P = 0.44), as was the median birth weight (648.5 and 560.0 g, respectively; P = 0.26). Median postmenstrual age at the time of FA was 65.1 and 83.9 weeks, respectively (P = 0.0002). Review of angiograms demonstrated NV in 30.0% and 37.5% in the IVB and untreated cohorts, respectively (P = 0.75). Abnormal vascular patterns in the periphery were similar in both groups (100.0%), whereas posterior pole findings of vessels encroaching onto the fovea were more prevalent in the IVB cohort (65.0% vs. 25.0%; P = 0.009).

Conclusions: Fluorescein angiography after bevacizumab for ROP reveals abnormal vascular patterns in all eyes and NV in approximately one-third. Similar abnormal vascular patterns on FA are seen at a similar prevalence after spontaneous regression of ROP. These findings suggest that the abnormal vascular patterns identified by FA in patients with ROP result from the disease process itself rather than as a result of exposure to anti-vascular endothelial growth factor medications.

Figure 1-

Fluorescein angiogram showing leakage (arrows) from vessels at the vascular-avascular junction in a patient from the anti-VEGF cohort (left) and untreated cohort (right)

Figure 2-

Fluorescein angiogram demonstrating recurrent neovascularization (arrows) in a patient with retinopathy of prematurity following intravitreal bevacizumab (left) Fluorescein angiogram showing neovascularization (arrow) in a 9-year-old from the untreated cohort presenting with spontaneous vitreous hemorrhage (right)

Figure 3-

Fluorescein angiogram demonstrating anomalous non-dichotomous branching and blunted vessel terminals in a patient from the anti-VEGF cohort (left) and untreated cohort (right)

Figure 4-

Fluorescein angiogram demonstrating an unusual double- blunted vascular pattern seen only in the anti-VEGF cohort

Figure 5-

Fluorescein angiogram demonstrating abnormal lacy or feathery capillary bed (seen best in the boxed area) in a patient from the anti-VEGF cohort (left) and untreated cohort (right)

Figure 6-

Fluorescein angiogram demonstrating vessel shunt (arrow) in a patient from the anti-VEGF cohort (left) and shunt vessel along vascular-avascular junction (arrow) in a patient from the untreated cohort (right)

Figure 7-

Fluorescein angiogram demonstrating vessels encroaching onto the fovea in a patient from the anti-VEGF cohort (left) and the untreated cohort (right)

Figure 8-

Fluorescein angiogram demonstrating vessels crossing the fovea in a patient from the anti-VEGF cohort (left) and from the untreated cohort (right)