Foveal Differentiation and Inner Retinal Displacement Are Arrested in Extremely Premature Infants

Abstract

Purpose Children with a history of prematurity often have poorly developed foveae but when during development foveal differences arise. We hypothesize that the course of foveal development is altered from the time of preterm birth. Methods Eyes of 102 preterm infants undergoing retinopathy of prematurity screening examinations in the STudy of Eye imaging in Premature infantS (BabySTEPS) (NCT02887157) were serially imaged between 30 and 42 weeks postmenstrual age (PMA) using handheld optical coherence tomography systems. Total retinal thickness, inner retinal layer (IRL) thickness, and outer retinal layer (ORL) thickness were measured at the foveal center and parafovea. Foveal put depth, IRL thickness, and ORL thickness were compared between infants born at different gestational ages using mixed effects models. Results Foveal pit depth and IRL thickness were inversely related to gestational age; on average, the most premature infants had the thickest IRL and shallowest pits at all PMAs. Differences were evident by 30 weeks PMA and persisted through 42 weeks PMA. The foveal pits of the most premature infants did not progressively deepen, and the IRLs did not continue to thin with increasing chronological age. Conclusions Foveation in extremely preterm infants is arrested from the earliest observed ages and fails to progress through term equivalent age. The developmental displacement of the IRL from the foveal center into the parafovea does not occur normally after preterm birth. These observations suggest that foveal hypoplasia seen in children with history of prematurity is due to disturbances in foveal development that manifest within weeks of birth.

Characterization of Foveal Development in Treatment-Naïve Extremely Preterm Infants

“…When a foveal pit was absent, the foveal center was defined as the apex of the central bulge of the outer nuclear layer. 17 , 20 Total foveal thickness was measured from the internal limiting membrane to the inner border of the retinal pigment epithelium and Bruch's membrane complex at the foveal center (fovea), as well as the nasal and temporal foveal rim, which was defined as the thickest point in the parafoveal region (approximately 1000 µm from the foveal center). 20 The inner retinal thickness (IRT) was measured from the internal limiting membrane to the outer border of the inner nuclear layer at these same three locations (fovea, nasal, and temporal foveal rim).…”

“… 17 , 20 Total foveal thickness was measured from the internal limiting membrane to the inner border of the retinal pigment epithelium and Bruch's membrane complex at the foveal center (fovea), as well as the nasal and temporal foveal rim, which was defined as the thickest point in the parafoveal region (approximately 1000 µm from the foveal center). 20 The inner retinal thickness (IRT) was measured from the internal limiting membrane to the outer border of the inner nuclear layer at these same three locations (fovea, nasal, and temporal foveal rim). The outer retinal thickness (ORT) was measured from the inner border of the outer plexiform layer to the inner border of the retinal pigment epithelium–Bruch's membrane complex at the same three locations.…”

“…In addition, foveal rim thickness/foveal thickness (R/F) ratio was used as a parameter to describe foveal pit depth. 20 An R/F ratio closer to 1 suggests a shallower foveal pit. OCT images were also qualitatively assessed for other retinal features, including macular edema and the presence of an ellipsoid zone (EZ) in the fovea and peripheral area.…”

Association of Birth Weight With Foveolar Thickness in Adulthood: Results From a Population-Based Study

“…Furthermore, this study provides novel data analyzing retinal morphology in adults, showing that the increased rate of foveal hypoplasia grade 1 in subjects is associated with low birth weight, similar to previous reports in preterm children of an increased prevalence of foveal hypoplasia. 17 , 43 , 44 However, it is notable that the association between low birth weight and increased foveolar retinal thickness was still present in our sensitivity analysis excluding participants with foveal hypoplasia.…”

Structural, Microvascular, and Functional Findings Associated with Fovea Plana

“…Although fovea plana is primarily a developmental arrest in the formation of the optic pit with a corresponding remaining vasculature 6 , 13 , a possibility for a kind of “retrograde trans-synaptic degeneration”, which may contribute to the secondary intraretinal cystoid space changes of the fovea, is also to be considered. However, compared to primarily optic neuropathies 28 , 29 , the presence of intraretinal cystoid spaces probably represents fluid-filled empty spaces replacing non-maturated cells than true macular oedema.…”