Retinopathy of prematurity: Two distinct mechanisms that underlie zone 1 and zone 2 disease

PURPOSE: In its most severe form, retinopathy of prematurity (ROP) is located in posterior retina and affects the smallest, most premature infants. We hypothesize that, depending on whether vasculogenesis (de novo formation of new vessels by transformation of vascular precursor cells (VPCs)) or angiogenesis (budding from existing vessels) is perturbed, it results in significant differences in clinical presentation and therapeutic outcome observed in zone 1 vs zone 2 ROP. DESIGN: The study is a retrospective analysis of the difference in outcome between zones 1 and 2 ROP after cryotherapy and laser therapy. METHODS: A review of the clinical presentation of zones 1 and 2 ROP that correlate this with the topography of formation of human retinal vasculature through vasculogenesis and angiogenesis. RESULTS: Population data on susceptible infants, and outcome statistics of clinical trials are given. Digital images show a correlation between ROP in zone 1 with the region of the retina vascularized through vasculogenesis. CONCLUSION: Zone 1 ROP is correlated with vessel development by vasculogenesis, relative insensitivity to laser/cryotherapy and poorer anatomic and visual out, comes. This suggests that, if the vasculogenic process is perturbed, it results in a distinct clinical presentation, poorer response to therapy, and poorer visual outcome. When the current international classification was developed, knowledge of the processes of human retinal vascular development was incomplete. The work presented here provides a framework for the development of a modification to incorporate these ideas without sacrifice of the essential elements of the international classification of ROP.