Causes of retinopathy of prematurity: an epidemiologic perspective

This chapter presents a strategy for integration of the current thinking about the causes of ROP. Application of these concepts assumes that results of any etiologic study are derived from valid methods. Discussion of principles of validity in epidemiologic studies is beyond the scope of this paper. However, reference was made to two sources of invalidity in studies of the causes of ROP: 1) the empirical or operational definition and measurement of the conceptual cause, and 2) confounding by degree of immaturity of retinal vasculatures, particularly with regard to interpretation of duration of ventilatory support as a cause of ROP. The distinction was made between an agent that initiates or promotes disease mechanism and a cause. Failure to appreciate this distinction has contributed to the confusion about the role of oxygen in the pathogenesis of retinopathy. Apart from settings of oxygen mismanagement, oxygen per se is part of the mechanism for development of disease. Certainly there are other biochemical requirements in addition to oxygen that set the stage for full-blown disease. Factors that are associated with the disruption of normal development of retinal vasculature and are susceptible to manipulation (either by reduction or elimination) during the prenatal and postnatal period may be more useful component causes to investigate.