Effect of Oxygen on Developing Retinal Vessels with Particular Reference to the Problem of Retrolental Fibroplasia

Abstract

THE evidence for regarding an abnormal overgrowth of the developing retinal vessels as the pathological basis of retrolental fibroplasia has been reviewed and discussed in an earlier paper in this issue (Ashton, 1954a).This fundamental dysplasia considered alone appeared to indicate thatthe disease was probably no more than a violent" activation of the normal process of retinal vascularization, so that the narrow confines of the nerve fibre layer could no longer contain the exuberant vaso-formative tissue, which consequently burst through the limiting membrane to invade the vitreous and so initiated a train of events terminating in total retinal detachment and the formation of a retrolental fibrous membrane.The stimulus which normally attracts the vessels into the retina is itself unknown, but it has been assumed, in general terms, to be a response to the oxygen demands of the inner layers of the retina, which the choroidal circulation is no longer able to satisfy as the eye develops.If retrolental fibroplasia began simply as an overgrowth of normal vaso-formative tissue, it seemed possible that it might occur in response to a stimulus identical in nature with the normal but excessive in degree, a variation which thus appeared to be related to a disparity between oxygen supply and demand.On such a basis, however, it was difficult if not impossible to reconcile the apparently conflicting theories that retrolental fibroplasia was due to anoxia (Ingalls, 1948; Szewczyk, 1951, 1952; Ingalls and others, 1952; Rubinstein, 1952), or to the toxic effects of high oxygen (K.Campbell, 1951; Ryan, 1952; Goldman and Tobler, 1952; Patz and others, 1952; Von Winning, 1952), or to a relative anoxia following high oxygen administration (Crosse and Evans, 1952; Jefferson, 1952), or that oxygen was not causative or might be only one of the factors concerned (Houlton, 1951; Bembridge and others, 1952; Zacharias, 1952; Silverman and others, 1952).In an attempt to clarify the aetiological problem, it was therefore decided to carry out an experimental investigation of the influence of varying concentrations of oxygen upon the developing retinal vasculature in the kitten, which, as will be seen, is closely comparable to that in man, and a preliminary report on our findings has already been published (Ashton and others, 1953; Ashton, 1954b).The normal development of the retinal circulation was thoroughly studied in man, the rat, and the cat by Michaelson (1948a, b), and the mode of devel- opment was found to be similar in each case.In the human embryo the 397