Effect of Prematurity on Foveal Development During Infancy: Increased Foveal Inner and Outer Retina Layer Thicknesses in Extremely Premature Infants.

Purpose: Foveation and inner retinal displacement are arrested in extremely premature infants through term equivalent age. We hypothesize that the effect of prematurity continues to impact the developing fovea in later stages of foveal development, well after term equivalent age. Methods: Infants enrolled in the STudy of Eye imaging in Preterm infantS (BabySTEPS1; NCT02887157) were imaged at four and nine months' corrected age. For infants with gradable imaging, foveal and parafoveal inner (IRL) and outer (ORL) retinal layer thicknesses were measured, with parafoveal/foveal thickness (P/F) ratios calculated. Univariate and multivariate regression analyses were performed to determine associations of birth and perinatal factors with foveation, and the effect of gestational age (GA) and history of macular edema on foveal thickness measurements. Results: In multivariate analysis of 99 eyes (56 infants) at four months and 70 eyes (44 infants, 34 infants overlapped with the four-months group) at nine months' corrected age, decreased P/F ratio was associated with lower GA (per week decrease) (four months: β (SE) = -0.109 (0.010, P < 0.0001; nine months: β (SE) = -0.063(0.011), P = 0.0005). Lower GA was associated with thicker foveal IRL (four months: β (SE) = 5.91 (0.76) µm, P < 0.0001; nine months: β (SE) = 3.95 (0.99) µm, P = 0.004) and ORL (four months: β (SE) = 4.86 (1.10) µm, P = 0.003; nine months: β (SE) = 4.46 (1.13) µm, P = 0.002). History of macular edema was associated with higher P/F ratios and thicker foveal ORL but not foveal IRL. Conclusions: Development of both inner and outer retina is altered in prematurity, and manifests from the time of preterm birth through infancy. During the first year of life, the most premature infants had shallower foveal pits and thicker IRL and ORL. Infants with a history of macular edema had thicker ORL.