Benign Yellow Dot Maculopathy: A New Macular Phenotype

Abstract

Purpose: To describe a novel macular phenotype that is associated with normal visual function.

Design: Retrospective, observational case series.

Participants: Thirty-six affected individuals from 23 unrelated families.

Methods: This was a retrospective study of patients who had a characteristic macular phenotype. Subjects underwent a full ocular examination, electrophysiologic studies, spectral-domain optical coherence tomography (OCT), and fundus autofluorescence imaging. Genomic analyses were performed using haplotype sharing analysis and whole-exome sequencing.

Main outcome measures: Visual acuity, retinal features, electroretinography, and whole-exome sequencing.

Results: Twenty-six of 36 subjects were female. The median age of subjects at presentation was 15 years (range, 5-59 years). The majority of subjects were asymptomatic and presented after a routine eye examination (22/36 subjects) or after screening because of a positive family history (13/36 subjects) or by another ophthalmologist (1/36 subjects). Of the 3 symptomatic subjects, 2 had reduced visual acuity secondary to nonorganic visual loss and bilateral ametropic amblyopia with strabismus. Visual acuity was 0.18 logarithm of the minimum angle of resolution (logMAR) or better in 30 of 33 subjects. Color vision was normal in all subjects tested, except for the subject with nonorganic visual loss. All subjects had bilateral symmetric multiple yellow dots at the macula. In the majority of subjects, these were evenly distributed throughout the fovea, but in 9 subjects they were concentrated in the nasal parafoveal area. The dots were hyperautofluorescent on fundus autofluorescence imaging. The OCT imaging was generally normal, but in 6 subjects subtle irregularities at the inner segment ellipsoid band were seen. Electrophysiologic studies identified normal macular function in 17 of 19 subjects and normal full-field retinal function in all subjects. Whole-exome analysis across 3 unrelated families found no pathogenic variants in known macular dystrophy genes. Haplotype sharing analysis in 1 family excluded linkage with the North Carolina macular dystrophy (MCDR1) locus.

Conclusions: A new retinal phenotype is described, which is characterized by bilateral multiple early-onset yellow dots at the macula. Visual function is normal, and the condition is nonprogressive. In familial cases, the phenotype seems to be inherited in an autosomal dominant manner, but a causative gene is yet to be ascertained.

Figure 1

Pedigrees of Familes 4, 8 and 22 that underwent molecular analysis. Family 4 had 5 affected individuals in two successive generations; Family 8 had 2 affected individuals in two successive generations; Family 22 had only one affected individual. Black circles / squares denote affected individuals

Figure 2

Fundus images of Benign Yellow Dot Maculopathy Subjects. A – Familial benign yellow dot maculopathy, Subject 11; B – Sporadic benign yellow dot maculopathy, fine, discrete, dots, Subject 24; C – Sporadic benign yellow dot maculopathy, concentrated in the nasal parafoveal region, Subject 26; D – Sporadic benign yellow dot maculopathy, confluent, Subject 28; E - Sporadic benign yellow dot maculopathy, Subject 34; F – Familial benign yellow dot maculopathy, Subject 19

Figure 3

Fundus autofluorescence of Benign Yellow Dot Maculopathy Subjects. The yellow dots show hyperautofluorescence on fundus autofluorescence imaging. A –Subject 11; B –Subject 24; C –Subject 26; D – Subject 28; E – Subject 34; F – Subject 19

Figure 4

OCT images of Benign Yellow Dot Maculopathy Subjects. A – Normal OCT, Subject 24; B – Slight irregularity of the inner segment ellipsoid band, indicated by the arrow, Subject 26; C – Slight irregularity of the RPE layer, indicated by the arrow, Subject 11. Arrows correspond to the location of the dots as identified from the infrared reflectance images obtained during fundus autofluorescence image acquisition