Clinical findings are summarized in Table 1. The heterozygous mother (III-1) had visual acuity of 20/32 in the right eye resulting from a nuclear sclerotic cataract and 20/20 in the left eye; in V-1, visual acuity was 20/16 in each eye; visual fields and color vision were normal in each eye of both obligate heterozygous study participants. Family members with RD developed glare and photosensitivity during childhood; nyctalopia in adolescence; decreased contrast sensitivity, peripheral vision, and color vision loss in the third decade of life; and visual acuity loss in the fourth decade. The youngest affected member, IV—4, retained visual acuity of 20/40 in the right eye at age 32 years, although visual acuity in the left eye was reduced to 20/100. Color vision was abnormal in all affected members and showed diffuse color defects. Figure 2A, D, G, and J show the fundus appearance for the heterozygous mother, III-1, and 3 affected family members (IV—1, IV—3, and IV—4). Affected members showed a bull's eye pattern of retinal pigment epithelial (RPE) atrophy in the macula and circular patches of RPE atrophy anterior to the arcades, with retinal vascular attenuation and bone spicule pigmentation. In addition, IV—1 had glaucoma with an enlarged cup-disc ratio in each eye and mildly elevated intraocular pressure (21-24 mm Hg) beginning at age 40 years. Visual fields (Figure 2B, E, H, and K) were normal in III-1 but showed peripheral islands of vision temporally and inferiorly with central vision loss in IV—1 and severe constriction with small central islands in IV—3 and IV—4. The SD-OCT images (Figure 2C, F, I, and L) were obtained with horizontal scans through the anatomic fovea in each eye, with the exception of IV—1; a vertical scan was obtained as close as possible to the anatomic fovea. In all affected family members, SD-OCT (Figure 2F, I, and L) showed thinning and loss of the outer nuclear, IS, and OS layers. However, the outer retinal layers were relatively preserved in the area surrounding the anatomic fovea in IV—3 and IV—4. In addition, SD-OCT images showed hyperreflective lesions within the attenuated outer nuclear layer in regions where the IS ellipsoid portion20 or IS-OS junction was not observed in IV—4 (Figure 2L and Figure 3F, black arrows) and external to the external limiting membrane and IS ellipsoid or IS-OS junction in IV—3 and IV—4 (Figures 2F and L and 3F, red arrows). The clinically normal heterozygous mother, III-1, showed subtle disruptions in reflectivity of the OS-RPE junction (Figures 2C and 3D, red arrows) in a region that corresponded to mild RPE depigmentation on the color fundus photograph (Figures 2A and 3A, red arrows). The other heterozygous family member who underwent SD-OCT imaging was V-1; results of the scans were normal, without hyperreflective abnormalities (data not shown). Electroretinographic responses were within 2 SDs of the normal mean in the heterozygous carrier, III-1. In the homozygous individuals, both rod-mediated and cone-mediated responses were severely reduced below levels that can be reliably measured (Figure 4 and Table 2).