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Hyperoxia leads to suppression of oxygen-regulated angiogenic growth factors, particularly erythropoietin39,40 and vascular endothelial growth factor (VEGF),41 which in turn causes both cessation of retinal vessel growth and loss of some existing retinal vessels42 (a process that has been partly reversed in mice with the replacement of VEGF and erythropoietin).39-42 Some investigators43 speculate that in more mature infants, exposure to high oxygen concentrations causes loss of existing vessels not seen with controlled oxygen delivery, which mainly causes cessation of vessel growth.
In severe disease, phase 2 begins when the increasingly metabolically active yet poorly vascularised retina (caused by suppression of vessel growth in phase 1) becomes hypoxic.
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