PROJECT SUMMARY One out of every ten infants is born preterm. Preterm birth can cause retinopathy of prematurity (ROP), a leading cause of childhood blindness. Even in the absence of ROP or neurological disability, children born preterm exhibit subtle impairments in visual acuity and visual function, though the etiology of this suboptimal vision in preterm infants remains unclear. The fovea, an indentation in the central retina, is the most critical region determining visual acuity. The fovea is surrounded by anastomosis of three layers of capillaries, forming the foveal avascular zone. It is well-established that children and adults with history of prematurity have a small or absent foveal avascular zone, retained foveal inner retinal layers, and decreased photoreceptor function, and that these abnormalities are more severe in individuals with history of treated ROP. The development of human perifoveal vasculature, however, is difficult to study due to the absence of fovea in most easily accessible animal models and the rarity of human histopathological samples during late gestation. Our multidisciplinary team with complementary expertise will work together to use advanced bedside handheld optical coherence tomography (OCT) angiography imaging to fill the gap in our knowledge of perifoveal vascular development in infants. We propose to elucidate the human perifoveal vascular development through the following specific aims: 1) optimize bedside handheld infant OCT angiography to visualize perifoveal vascular development; 2) determine if perifoveal vascular development is delayed in preterm infants compared to term infants, further delayed in ROP, and associates with poor outer retinal maturation; and 3) determine the association of macular edema and decreased perifoveal deep vascular complex formation and outer retinal maturation in preterm infants. This research will expand our knowledge of human foveal development and inform the pathophysiology of diseases of macular and retinal vascular development.