Retinopathy of prematurity: inflammation, choroidal degeneration, and novel promising therapeutic strategies

Abstract

Retinopathy of prematurity (ROP) is an important cause of childhood blindness globally, and the incidence is rising. The disease is characterized by initial arrested retinal vascularization followed by neovascularization and ensuing retinal detachment causing permanent visual loss. Although neovascularization can be effectively treated via retinal laser ablation, it is unknown which children are at risk of entering this vision-threatening phase of the disease. Laser ablation may itself induce visual field deficits, and there is therefore a need to identify targets for novel and less destructive treatments of ROP. Inflammation is considered a key contributor to the pathogenesis of ROP. A large proportion of preterm infants with ROP will have residual visual loss linked to loss of photoreceptor (PR) and the integrity of the retinal pigment epithelium (RPE) in the macular region. Recent studies using animal models of ROP suggest that choroidal degeneration may be associated with a loss of integrity of the outer retina, a phenomenon so far largely undescribed in ROP pathogenesis. In this review, we highlight inflammatory and neuron-derived factors related to ROP progression, as well, potential targets for new treatment strategies. We also introduce choroidal degeneration as a significant cause of residual visual loss following ROP. We propose that ROP should no longer be considered an inner retinal vasculopathy only, but also a disease of choroidal degeneration affecting both retinal pigment epithelium and photoreceptor integrity.

Keywords: Choroidal degeneration; Inflammation; Neuron-derived factors; Retinopathy of prematurity.

Fig. 1

Summary of the current inflammatory and neuronal-derived factors involved in the pathogenesis of ROP. At birth, premature infants are deficient in factors essential for healthy blood vessel development. When premature infants are exposed to excess supplemental oxygen, the latter contributes to retinal and choroidal vascular obliteration due to oxidant stress, suppression of oxygen-regulated pro-angiogenic factors, and an excessive production of pro-inflammatory factors. Because of the vascular dropout, a compensatory, albeit aberrant and destructive, neovascularization occurs, driven by hypoxia-induced angiogenic factors. Some of the current therapeutic interventions rely on invasive procedures, such as laser photocoagulation, whereby affected areas of the retina are cauterized. Other treatments, including anti-VEGF therapy, as well as IGF-1 and omega-3, are currently being more thoroughly evaluated. In addition, the development of anti-inflammatory drugs as well as, future regenerative therapeutic interventions involving stem cells are also being explored and considered for the treatment of ROP