Long-term peripheral retinal vascular behavior in retinopathy of prematurity patients treated with ranibizumab intravitreal injection as monotherapy using fluorescein angiography

Abstract

Background: Few challenges are faced with the introduction of anti-VEGF agents as a modality of treatment for retinopathy of prematurity. The clinical behavior and time course of regression post injection differ compared to post laser ablation. This study aims to evaluate the long-term peripheral retinal vascularization outcome of Ranibizumab intravitreal injections monotherapy in the treatment of retinopathy of prematurity.

Method: Hospital-based quasi-experimental study. Include ROP patients who received intravitreal ranibizumab (IVR), as primary treatment for type 1 ROP. Patients were examined under general anaesthesia to ensure documentation of all junctions of vascular and avascular zones. Images were taken by RetCam III, Phoenix ICON and fluorescein angiography was performed to describe vascular behaviors.

Results: The mean gestational age was 24.67 weeks and the mean postmenstrual age at the time of intravitreal ranibizumab treatment was 36.3 weeks. Fluorescein angiography was performed at 155-288 weeks; most eyes showed two disk diameters of avascular peripheral retina. Only eyes with original aggressive ROP who required a second injection (six eyes) showed extensive peripheral avascular retina reaching zone I (13.64%). Neovascularization was evident in five eyes (11.36%), all with an original aggressive ROP and received multiple injections.

Conclusions: Ranibizumab treated babies with incomplete retinal vascularization require close and long-term follow-up visits to assess post injection vascular behavior. Peripheral retinal avascular zone of more than two-disc diameters was present in most of the patients evidenced by fluorescein angiography. Babies with initial diagnosis of aggressive ROP are more likely to have persistent peripheral neovascularization.

Keywords: Anti- VEGF; Fluorescein Angiography; Peripheral retinal vascularization; Ranibizumab; Reactivation of ROP; Regression of ROP; RetCam; Retinopathy of Prematurity.

Fig. 1

Montage of the fluorescein angiography images showing features of the junction between vascular and avascular retina in ROP patients treated with IVR: A Finger-like branching of vessels (arrowhead). B Circumferential vascular shunt at the junction (arrowhead). C Vascular leakage from terminal vessels at the junction area between vascular and avascular retina (dotted circle). D Blunted vascular terminal where the vessels ended abruptly in a stunted or blunted fashion, instead of the normal tapered endings (dotted line). E Popcorn vascular ending (arrowhead). F Finger-like anastomosis, where two adjacent terminal vessels anastomose at an apical point (arrowhead). G Areas of neovascularization at the junction between vascular and avascular retina (arrowhead)

Fig. 2

Montage of the fluorescein angiography images showing features of posterior pole in ROP patients treated with IVR: A Persistent vascular tortuosity. B Focal dilatation of capillaries (arrowhead). C Vascular shunt crossing the horizontal raphe (arrowhead)

Fig. 3

Montage of the fluorescein angiography images showing changes in choroid and capillary bed in ROP patients treated with IVR: A Extensive peripheral avascular area, with diffuse RPE atrophy. B Linear choroidal filling pattern with hypofluorescent areas. C Lacy or feathery retinal capillary bed (area inside dotted line)

Fig. 4

Fluorescein angiography image demonstrating changes in fovea and macula in ROP patients treated with IVR: vessels encroaching onto the fovea