PMC4539287_01
Pedigree of the family and segregation of the MMACHC mutations with the disease phenotype. The open circle and squares represent the unaffected female and male family members, respectively; the closed circle represents the affected female patient.
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A 28-year-old Hispanic female (Figure 1) presented in 2006 with decreased central vision and mild photoaversion of approximately two years duration. The patient reported no family history of a retinal dystrophy, and examination of both parents and a brother (Figure 1) showed essentially normal maculae; only a few fine drusen near the fovea were observed in the examinations of both parents.   
Goldmann visual fields of the left (A) and right (B) eyes from the initial visit in 2006, showing ring scotomas consistent with the bull's eye-appearing macular lesions. Shaded areas indicate the target was not seen in that area. Fundus photos from 2006 (C, right eye and D, left eye) and 2013 (E and F) show some extension of RPE atrophy, apparent at the peripheral boundaries, as well as in the foveal region, in both eyes over 7 years. Near-infrared autofluorescence (G and H) from the 2013 follow-up visit shows hyper-autofluorescence at the fovea, surrounded by hypo-autofluorescence (bull's eye), further surrounded by a ring of hyper-autofluorescence.
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Goldmann visual field testing demonstrated a pericentral ring scotoma in each eye (Figure 2A and B). Funduscopy showed bilateral bull's eye-appearing macular lesions (Figure 2C and D) with no visible fundus flecks, vessel attenuation, optic nerve pallor or peripheral pigmentary changes. Fundus photos (Figure 2E and F), and near-infrared autofluorescence (Figure 2G and H) demonstrated bull's eye macular dystrophy with relative preservation of the retinal pigment epithelium (RPE) at the foveolar region.
Spectral domain optical coherence tomography line scans (right eye top and left eye bottom, corresponding to the location of the horizontal lines on the near-infrared autofluorescence images in Figures 2G and H, respectively) show intact RPE at the foveola in the presence of marked foveal thinning, surrounded by atrophy of the outer retinal layers and retinal pigment epithelium, with relatively more normal retinal structure at the margins of the line scans in both eyes.
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Spectral-domain optical coherence tomography also showed preservation of the RPE at the fovea in the presence of marked foveal thinning (Figure 3).
Full-field electroretinogram (Espion E3, Diagnosys LLC, Littleton, MA) of the patient's right eye at age 35 during a follow-up visit. Boxes represent ranges of 13 visually-normal subjects. The cone isolated amplitudes and implicit times (top), and the rod isolated single flash response (bottom left) are within the normal range. The combined rod and cone single flash response (bottom right) is mildly reduced and delayed compared to normal.
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A repeat full field ERG (Figure 4) of the right eye at that visit still showed amplitudes and implicit times that were within normal limits under both scotopic rod isolated and photopic cone isolated test conditions, whereas the scotopic rod and cone combined response b-wave was mildly reduced and delayed compared to normal.