Three-dimensional assessment of vascular changes secondary to neovascularization in retinopathy of prematurity

Abstract

Purpose : Neovascularization during retinopathy of prematurity (ROP) is hypothesized to be caused by increase in oxygen concentration with subsequent vasodilation and vascular budding. While microscopic study of the stepwise processes has been extensive in animal models, such data are lacking from infants. Our goal is to study physiologic and abnormal retinal vascular development in three-dimensions (3-D) in human infants using non-contact optical coherence tomography (OCT) imaging to better understand mechanisms of neovascularization in ROP.

Methods : Under an IRB approved protocol, using 840 nm wavelength SDOCT system (Envisu, Bioptigen Inc.), we captured volumes of the macula and the vascular-avascular (V-AV) junction in preterm infants at the time of ROP examinations (between 31-41 weeks postmenstrual age).3D volume maps and en face images of SDOCT images were constructed to enhance visualization for analysis of retinal vascular patterns.

Results : Fourteen eyes from 8 preterm infants with ROP, with and without areas of neovascularization, were analyzed. On 3D-rendered volumes we found multiple morphologically different patterns of retinal microvasculature. We observed 3 stages of development of neovascularization.1) retina is composed of a bland inner surface without focal elevation of vasculature. 2) vascular budding occurs both at the macula and posterior to V-AV junction. These vascular buds appear isolated or grouped along vessels (Fig 1) or tangentially along V-AV junction. 3) webs of neovascular tissue connect and elevate from retinal surface (Fig 2). Intravitreal traction is often observed with neovascular tissue.Elevated neovascular tissue is sometimes associated with inner retinal split, a schisis-like change anterior to V-AV junction.

Conclusions : We demonstrate for the first time, ability to document vascular budding and stages of neovascularization in preterm infants with ROP; not readily visible on clinical examination. Different patterns of buds could indicate possible difference in underlying mechanisms of neovascularization. Further studies are needed to demonstrate vascular flow within these structures and their clinical relevance in ROP.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

 

Fig 1: Zone 1 Stage 3 infant (24 weeks GA) at 32 weeks PMA demonstrating isolated buds (red arrow) along the course of a vessel.

 

Fig 2: Zone 2 Stage 3 infant (25 weeks GA) at 35 weeks PMA with elevated neovascularization (yellow arrow)