Retinopathy of prematurity: a new look at an old disease.

The neovascular changes of the retinopathy of prematurity can occur in premature infants in three settings: (1) when high levels of supplemental oxygen are administered, neovascularization usually commences shortly after cessation of oxygen therapy; (2) when supplemental oxygen is given for long periods of time, neovascularization can develop while the infant is still receiving oxygen; and (3) neovascularization can occur without exposure to any supplemental oxygen. We propose a model which can explain the occurrence of the retinopathy of prematurity in all these settings. Our model demonstrates that whenever the retinopathy of prematurity occurs, arterial oxygen levels are inappropriately high in relation to the stage of retinal vessel development, even in premature neonates not given supplemental oxygen. The inhibitory effect of these elevated oxygen tensions upon carbon dioxide removal is indicated as a possible cause of neovascularization by leading to tissue acidosis and vasodilatation.