Benign Yellow Dot Maculopathy

Abstract

Objective To describe a novel macular phenotype that is associated with normal visual function. Design Retrospective observational case series. Participants 36 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, electrophysiological 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; Whole-exome sequencing; Haplotype sharing analysis. Results Twenty-six of 36 subjects were female. The median age at presentation was 15 years, range 5-59 years. The majority of subjects were asymptomatic and either presented following a routine eye examination (22/36 subjects), following screening due to a positive family history (13/36 subjects) or from another ophthalmologist (1/36 subjects). Of the three symptomatic subjects, 2 had reduced visual acuity. Reduced vision was attributed to diagnoses of non-organic visual loss and bilateral ametropic amblyopia with strabismus. Visual acuity was 0.18 LogMAR or better in 30/33 subjects. Color vision was normal in all subjects tested, except for the subject with non-organic visual loss. All subjects had bilateral symmetric multiple yellow dots at the macula. In the majority these were evenly distributed throughout the fovea, but in nine subjects they were concentrated in the nasal parafoveal area. The dots were hyperautofluorescent on fundus autofluorescence imaging. OCT imaging was generally normal, but in 6 subjects subtle irregularities at the inner segment ellipsoid band were seen. Electrophysiological studies identified normal macular function in 17/19 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 one family excluded linkage with the North Carolina macular dystrophy (MCDR1) locus. Conclusions A new retinal phenotype is described, which is characterised by bilateral multiple early onset yellow dots at the macula. Visual function is normal and the condition is non-progressive. In familial cases, the phenotype appears to be inherited in an autosomal dominant manner, but a causative gene is yet to be ascertained.

Benign yellow dot maculopathy

“…This is the first report of yellow dot maculopathy following the original study in which it was described. 3 The families included in that study were mostly white, and none was reported to be of North African descent, as the family we report here. This may indicate that the prevalence of this phenotype is more common, and its relatively benign nature may be responsible for its previous lack of recognition and under-reporting.…”

“…He was a young patient, with bilateral macular yellow dots compatible with those described in the original study. 3 His VA and color vision were unaffected, there was no progression over 6 years of follow up, and he had no abnormalities in OCT and electrophysiologic testing. Similar findings were discovered in his mother's eyes, but not his father, consistent with autosomal dominant inheritance.…”

“…The recent study in which it was presented included 36 patients from 23 unrelated families. 3 The macular findings of bilateral multiple yellow dots in most of these patients were discovered in routine eye examinations or because a family member has been examined. Only 3 (8.3%) of the patients were symptomatic, but had additional findings explaining their reduced VA, such as strabismus and amblyopia.…”

“…Recently, a new phenotype has been described, and termed “benign yellow dot maculopathy”. 3 This phenotype consists of bilateral macular yellow dots, which is non-progressive and without visual impairment. The reported cases were familial, and their distribution was compatible with autosomal dominant inheritance.…”

Unilateral benign yellow dot maculopathy

“…Recently, a novel macular phenotype termed ‘benign yellow dot maculopathy’ has been described by Dev Borman et al 2 To date, reports of this phenotype describe non-progressive bilateral macular yellow dots with normal visual acuity and color vision. Herein, we present the first known case of unilateral benign yellow dot maculopathy.…”