A model for the pathogenesis of retrolental fibroplasia based on the metabolic control of blood vessel development.

We postulate that the pathogenesis of retrolental fibroplasia (RLF) is related to the disruption of the normally coordinated ocular development and maturation in which there is an interplay between function, metabolism, and blood vessel development. The normal retina is avascular until the fourth month of gestation, at which time vascularization proceeds from the optic disk towards the peripheral retina. Until this time, the underlying choroidal circulation provides for full-thickness retinal oxygenation. We hypothesize that the centrifugal maturation of the retina, including the retinal photoreceptors (the major oxygen-consuming cell type of the adult retina), precedes this vascular outgrowth. The maturation of the photoreceptors and the concomitant increased oxygen consumption would make it impossible for the choroid to provide adequate full-thickness retinal oxygenation. The resulting progressive change in the inner retinal metabolism thus provides an orderly, controlled stimulus for the subsequent progression of retinal vascularization from the optic disk to the peripheral retina. Exposure of the premature neonate to abnormal oxygen levels would selectively retard inner retinal blood vessel development while the photoreceptors continue to mature and increase their oxygen consumption. Thus, when the infant is removed from abnormal oxygen, a neovascular proliferative stimulus will develop in direct relation to the mass of non-vascularized but metabolically active retina, initiating uncoordinated vessel growth in the inner retina.