Abstract
Purpose :
Preterm birth leads to down regulation of VEGF (phase 1 ROP) resulting in a delayed rate of retinal vascularization relative to neuronal maturation. Because of this disconnect, the infant will have varying degrees of avascular but metabolically active retina, providing a hypoxic stimulus for neovascularization (Phase 2). This study aims to provide normative data for morphology & rate of human retinal vascularization under “physiological hypoxia” (PH) & to explore application of fluorescein angiography (FA) as a tool in the determination of 'DV' as a prognostic indicator of progression to severe ROP.
Methods :
A developmental series of CD34 stained human retinal wholemounts were analysed to determine the area covered by superficial & deep vascular plexi & total retinal area from 14-40 Weeks Gestation (WG). Specimens at 18, 21, 25, 31 & 40 WG were montaged for high-resolution visualization of entire superficial plexus & evaluated for lobular topography, branching pattern, vascular density & morphology of peripheral vascular arcades relevant to ridge formation. FAs were performed on a separate cohort of preterm infants 31-40WG to diagnose or measure DV.
Results :
We provide normative data for morphology & area of superficial & deep vascular plexus under “PH”. Under PH at 18, 21, 25, 31 & full-term, the superficial plexus covered 53, 76, 74, 88 & 99.97% of the total retinal area. DV is characterized by a pallid fundus with reduction in vascular perfusion. The maturation of vasculature is presented in context of astrocyte & neuronal maturation from published work. The age of first appearance of ROP at 31WG, is coincident with significant increase in energy demands of rod photoreceptors where 88% of retina is vascularized. In contrast, ROP infants’ peripheral retina at 31WG is typically avascular indicative of uncoupling of normal neurovascular relationships & diagnosis of DV. Angiographic features including leakage, shunts & hyperfluorescent lesions at junction btw vascular & avascular zone are predictive of development of severe ROP.
Conclusions :
This study provides normative data to assist clinicians managing ROP infants in determining whether the extent of retinal vascularization is delayed relative to in utero development. Our findings lead us to suggest that 'extent of DV' could be a prognostic indicator of susceptibility to severe ROP.
This is a 2020 ARVO Annual Meeting abstract.