Photoreceptor Function in Retinopathy of Prematurity

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Active retinopathy of prematurity (ROP), which is known to be a response to retinal hypoxia, occurs at the age of rapid rod outer segment development. The investigators postulate that rapidly increasing oxygen demands of the developing rods contribute to the hypoxia that instigates ROP, and, as a consequence of unmet metabolic needs, rod function is impaired. While acknowledging that the "photoreceptor hypothesis of ROP" will not be put to direct test, knowledge of the development of the photoreceptors and of ROP creates a framework for the project. Completed studies in ROP subjects at post-term ages document evidence of damaged rods. In Aim 1 of the new project, rod cell sensitivity, Srod, will be measured at pre-term ages during which ROP is typically active. This is important because demonstration of rod involvement in active ROP will warrant a new perspective on ROP management, the principle of which will be: Satisfy oxygen needs of photoreceptors. A numeric analysis of preterm retinal blood vessels will be conducted. Srod and blood vessel parameters will be analyzed for prediction of ROP outcome, the probability of high risk pre- threshold ROP, and post-term development of retinal and visual function. In healthy ROP subjects, mild acuity deficits may be the common sign of a subtle maculopathy as residua of altered neural-vascular development of fovea and foveal avascular zone. In Aim 2, central retinal function will be evaluated (including multifocal ERG in ROP infants) and tracked through early childhood. Results to date demonstrate an association of rod dysfunction and early ametropia, but more remains to be discovered about retinal mechanisms in that substantial proportion of ROP children who develop early ametropia. Accordingly, the experiments of Aim 3 will update refractive measurements and analyze retinal mechanisms in child ROP subjects who were previously studied in infancy. For each set of experiments, the analyses of the cross sectional data will evaluate the retinal and visual parameters for significant variation with ROP outcome. The longitudinal data will be evaluated for change over time and for variation with ROP outcome. The project will obtain new knowledge about the fundamental disease process, contribute to the understanding of refractive development in ROP, and provide new insights into the basis of common acuity deficits. This information may, in the future, change management of ROP in infancy and in children with a history of ROP.