Pathophysiology, screening and treatment of ROP: A multi-disciplinary perspective


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Abstract

The population of infants at risk for retinopathy of prematurity (ROP) varies by world region; in countries with well developed neonatal intensive care services, the highest risk infants are those born at less than 28 weeks gestational age (GA) and less than 1 kg at birth, while, in regions where many aspects of neonatal intensive and ophthalmological care are not routinely available, more mature infants up to 2000 g at birth and 37 weeks GA are also at risk for severe ROP. Treatment options for both groups of patients include standard retinal laser photocoagulation or, more recently, intravitreal anti-VEGF drugs. In addition to detection and treatment of ROP, this review highlights new opportunities created by telemedicine, where screening and diagnosis of ROP in remote locations can be undertaken by non-ophthalmologists using digital fundus cameras. The ophthalmological care of the ROP infant is undertaken in the wider context of neonatal care and general wellbeing of the infant. Because of this context, this review takes a multi-disciplinary perspective with contributions from retinal vascular biologists, pediatric ophthalmologists, an epidemiologist and a neonatologist. This review highlights the latest insights regarding cellular and molecular mechanisms in the formation of the retinal vasculature in the human infant, pathogenesis of ROP, detection and treatment of severe ROP, the risks and benefits of anti-VEGF therapy, the identification of new therapies over the horizon, and the optimal neonatal care regimen for best ROP outcomes, and the benefits and pitfalls of telemedicine in the remote screening and diagnosis of ROP, all of which have the potential to improve ROP outcomes.HighlightsThis review takes a multi-disciplinary perspective on ROP, bringing together contributions from retinal vascular biologists, pediatric ophthalmologists, epidemiologists and neonatologists.With two distinct populations of infants with ROP in the developed and developing world, different approaches to the disease must be undertaken.This review details the current understanding of the cellular and molecular mechanisms of human retinal vascular formation, detailing the mechanisms underlying the pathogenesis of the two phases of acute ROP.We highlight the risks and benefits of anti-VEGF therapy in ROP. The potential harm from systemic exposure to anti-VEGF agents needs further study, given that VEGF has key roles in the development of many organs and also acts as a neuronal survival factor during embryonic development.We recommend with the exception of certain key circumstances, use of anti-VEGF agents as a therapeutic intervention in ROP still needs to be approached with caution because of; 1) the risk of late recurrence of retinopathy due to incomplete peripheral retinal vascularization; 2) possible long term systemic side effects; and 3) the uncertainty about the correct dosage.We identify new therapies over the horizon, and the optimal neonatal care regimen for best ROP outcomes, and the benefits and pitfalls of telemedicine in the remote screening and diagnosis of ROP, all of which have the potential to improve ROP outcomes.

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