Evaluation of Normal Human Foveal Development Using Optical Coherence Tomography and Histologic Examination

Figure 1. Foveal layer assignment in the human retina. A, Shown is an optical coherence tomography image of a 28-year-old retina (JC_0002). B, A 17-month-old retina (WW_0585) is compared with histologic images at parafoveal (1) and foveal (2) locations. A1 and B1 show the assignment of outer retinal layer bands 0 through 4, illustrated with gray lines connecting the optical coherence tomography image, longitudinal reflectivity profile, and histologic image for the parafoveal area. Band assignments in the foveal region are shown in A2 and B2.

Figure 2. Spectrum of the foveal pit morphologic structure observed with optical coherence tomography. Shown are foveal images from all examinations meeting the inclusion criteria. Images are single frames extracted from a macular volume. Considerable variability exists at the stage of 32 weeks' to 33 weeks' postmenstrual age (PMA). By age 17 months, the retina appears adultlike. Another notable feature is that some individuals have a diplike structure located temporal to the macula (DC_0604 at 33 weeks' PMA, DC_0576 at 34 weeks' PMA, and DC_0688 at 37 weeks' PMA). We refer to this structure as a “temporal divot.”

Figure 3. Comparison of foveal development and layer assignment in a macaque at fetal day (Fd) 131 (A) and in a human of 32 weeks' postmenstrual age (DC_0368) (B). Gray lines 1 through 3 represent perifoveal, parafoveal, and foveal locations, respectively. Insets C1 through C3 at the bottom are comparisons of histologic and optical coherence tomography images, with layer assignment for perifoveal (C1), parafoveal (C2), and foveal (C3) locations. At the perifoveal location, bands 0, 1/2, and 3/4 are present, whereas only bands 0 and 3/4 are present at the parafoveal and foveal locations.

Figure 4. Comparison of foveal development and layer assignment. A, Histologic section from a human donor of 35 weeks' postmenstrual age (PMA). B, Infant of 35 weeks' PMA (DC_0688) imaged with optical coherence tomography (B). Gray lines 1 through 3 represent perifoveal, parafoveal, and foveal locations, respectively. Insets C1 through C3 at the bottom are comparisons of histologic and optical coherence tomography images, with layer assignment for perifoveal (C1), parafoveal (C2), and foveal (C3) locations. At the perifoveal location, bands 0, 1/2, and 3/4 are present, whereas only bands 0 and 3/4 are present at the parafoveal and foveal locations. The retina at 35 weeks' PMA shows moderate edema in the central fovea, which causes buckling of the retina (between C2 and C3) and blisterlike distortion of the innermost layer.

Figure 5. Comparison of foveal development and layer assignment in a histologic section from a human donor of 41 weeks' postmenstrual age (PMA) (A) and in an infant of 38 weeks' PMA (DC_0576) (B). Gray lines 1 through 3 represent perifoveal, parafoveal, and foveal locations, respectively. Insets C1 through C3 at the bottom are comparisons of histologic and optical coherence tomography images, with layer assignment for perifoveal (C1), parafoveal (C2), and foveal (C3) locations. At the perifoveal location, bands 0, 1, 2, and 3/4 are present, whereas only bands 0, 1/2, and 3/4 are present at the parafoveal location and bands 0 and 3/4 at the foveal location.

Figure 6. Time course of photoreceptor maturation at foveal (top row), parafoveal (middle row), and perifoveal (bottom row) locations. Images are labeled with band assignments as seen on optical coherence tomography. The retina at 35 weeks' postmenstrual age (PMA) shows moderate edema in the central fovea, which causes buckling of the retina and blisterlike distortion of the innermost layer; however, these tissue artifacts do not interfere with layer identification. Arrows indicate the presence of a distinct band (not layer thickness). Band 0 corresponds to the outer plexiform layer; band 1, the external limiting membrane; band 2, the inner segment ellipsoid; band 3, the retinal pigment epithelium × photoreceptor interdigitations; and band 4, the retinal pigment epithelium. Fd 131 indicates fetal day 131 in a macaque.