Benign yellow-dot maculopathy: case report and review of the literature

Abstract

The differential diagnosis for yellow macular dots is extensive and includes toxic, genetic, degenerative, and idiopathic etiologies. In many cases, these conditions are progressive, result in decreased central visual acuity, and can be associated with systemic findings. A thorough history, examination, and multimodal visualization techniques, including optical coherence tomography (OCT), fluorescein angiography (FA), and fundus autofluorescence (FAF), are often used to diagnose these conditions.1Kovach JL Isildak H Sarraf D. Crystalline retinopathy: unifying pathogenic pathways of disease.Surv Ophthalmol. 2019; 64: 1-29Abstract Full Text Full Text PDF PubMed Scopus (20) Google Scholar Benign yellow-dot maculopathy, however, is a recently characterized asymptomatic, typically bilateral macular phenotype.2Borman AD Rachitskaya A Suzani M et al.Benign yellow dot maculopathy: a new macular phenotype.Ophthalmology. 2017; 124: 1004-1013Abstract Full Text Full Text PDF PubMed Scopus (8) Google Scholar To our knowledge, only 45 cases from 28 families in 5 reports that have been described in the literature. Thus far there is no definite etiology of this condition, but it appears to have a sporadic or autosomal-dominant inheritance pattern without an identified causative gene.2Borman AD Rachitskaya A Suzani M et al.Benign yellow dot maculopathy: a new macular phenotype.Ophthalmology. 2017; 124: 1004-1013Abstract Full Text Full Text PDF PubMed Scopus (8) Google Scholar, 3Mishra AV Pollmann AS Choudhry N Demmings E Gupta RR. Unilateral benign yellow dot maculopathy.Am J Ophthalmol Case Rep. 2021; 22101068PubMed Google Scholar, 4Moisseiev E. Benign yellow dot maculopathy.Am J Ophthalmol Case Rep. 2018; 10: 13-15Crossref PubMed Scopus (3) Google Scholar, 5Murro V Mucciolo DP Giorgio D et al.Multimodal imaging of benign yellow dot maculopathy.Ophthalmic Genet. 2019; 40: 135-140Crossref PubMed Scopus (1) Google Scholar, 6Ninet L David T Gascon P. Multimodal imaging for benign yellow dot maculopathy.Ophthalmol Retina. 2022; 6: 307Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar Herein we describe another case of benign yellow-dot maculopathy in a young Hispanic male who remained stable through 2-year follow-up and review the literature surrounding this rare entity. A 17-year-old Hispanic male was referred to the retina clinic for evaluation of a possible macular dystrophy. He had no visual complaints, and his past ocular history was significant for mild myopia in both eyes. His past medical history was significant for depression treated with aripiprazole. He also had a history of a suicide attempt 3 years earlier after ingesting approximately 75 Aspirin tablets and 5 aripiprazole tablets. He had no history of intravenous drug use. His family history was nonrevealing for any inherited ocular disorders. His best-corrected visual acuity (BCVA) was 20/20 in both eyes with normal intraocular pressures and no relative afferent pupillary defect. Visual fields, ocular motility, and anterior-segment examination were unremarkable. His funduscopic examination revealed multiple perifoveal fine, discrete yellow spots bilaterally (Fig. 1A, B). The retinal periphery was unremarkable. OCT was normal bilaterally (Fig. 1E, F). Because the patient was asymptomatic, he was observed with no electroretinography (ERG) or FA. On examination 2 years later, the patient's BCVA remained 20/20. He remained asymptomatic, and his fundus examination (Fig. 1C, D) and OCT images (Fig. 1G, H) remained stable. FAF demonstrated hyper-autofluorescent foci corresponding to the yellow lesions seen on clinical examination (Fig. 1I, J). No further work-up, including genetic testing, was pursued. The differential diagnosis for yellow dots within the macula includes drug toxicities (e.g., canthaxanthin), inherited diseases (e.g., oxalosis, Bietti crystalline dystrophy), degenerative (e.g., drupelets or medium-sized drusen seen in age-related macular degeneration), and idiopathic conditions.1Kovach JL Isildak H Sarraf D. Crystalline retinopathy: unifying pathogenic pathways of disease.Surv Ophthalmol. 2019; 64: 1-29Abstract Full Text Full Text PDF PubMed Scopus (20) Google Scholar7Drenser K Sarraf D Jain A Small KW. Crystalline retinopathies.Surv Ophthalmol. 2006; 51: 535-549Abstract Full Text Full Text PDF PubMed Scopus (37) Google Scholar8Ferris 3rd, FL Wilkinson CP Bird A et al.Clinical classification of age-related macular degeneration.Ophthalmology. 2013; 120: 844-851Abstract Full Text Full Text PDF PubMed Scopus (899) Google Scholar Degenerative changes such as drupelets would be unlikely given the symmetrical foveal location, the age of the patient, and the normal OCT images and hyper-autofluorescence seen on FAF.8Ferris 3rd, FL Wilkinson CP Bird A et al.Clinical classification of age-related macular degeneration.Ophthalmology. 2013; 120: 844-851Abstract Full Text Full Text PDF PubMed Scopus (899) Google Scholar9Ly A Nivison-Smith L Assaad N Kalloniatis M. Fundus autofluorescence in age-related macular degeneration.Optom Vis Sci. 2017; 94: 246-259Crossref PubMed Scopus (31) Google Scholar Because the patient did not have a known family history of retinal disease, a toxic etiology was initially considered given the recent Aspirin and aripiprazole overdose, but neither have been reported to cause crystalline retinopathy.10Faure C Audo I Zeitz C Letessier JB Robert MP. Aripiprazole-induced chorioretinopathy: multimodal imaging and electrophysiological features.Doc Ophthalmol. 2015; 131: 35-41Crossref PubMed Scopus (11) Google Scholar11Zhu W Wu Y Xu D et al.Aspirin use and risk of age-related macular degeneration: a meta-analysis.PLoS ONE. 2013; 8: e58821Crossref PubMed Scopus (30) Google Scholar However, after 2 years of follow-up, these findings were seen to be more characteristic of a recently described phenotype—benign yellow-dot maculopathy. Borman et al.2Borman AD Rachitskaya A Suzani M et al.Benign yellow dot maculopathy: a new macular phenotype.Ophthalmology. 2017; 124: 1004-1013Abstract Full Text Full Text PDF PubMed Scopus (8) Google Scholar described a series of 36 patients from 23 unique families in the initial report of benign yellow-dot maculopathy in 2017. In their report, 33 of 36 patients were asymptomatic, with the other 3 patients experiencing visual symptoms that were not attributable to these macular findings. Funduscopic findings included bilateral discrete yellow dots at the level of the retinal pigment epithelium (RPE). Additionally, these dots tended to be evenly distributed around the fovea or in the nasal parafoveal region. There were no other retinal findings.2Borman AD Rachitskaya A Suzani M et al.Benign yellow dot maculopathy: a new macular phenotype.Ophthalmology. 2017; 124: 1004-1013Abstract Full Text Full Text PDF PubMed Scopus (8) Google Scholar Since this report, 9 additional cases have been described with similar presentations,4Moisseiev E. Benign yellow dot maculopathy.Am J Ophthalmol Case Rep. 2018; 10: 13-15Crossref PubMed Scopus (3) Google Scholar, 5Murro V Mucciolo DP Giorgio D et al.Multimodal imaging of benign yellow dot maculopathy.Ophthalmic Genet. 2019; 40: 135-140Crossref PubMed Scopus (1) Google Scholar, 6Ninet L David T Gascon P. Multimodal imaging for benign yellow dot maculopathy.Ophthalmol Retina. 2022; 6: 307Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar with Mishra et al. describing the first case of unilateral benign yellow-dot maculopathy.3Mishra AV Pollmann AS Choudhry N Demmings E Gupta RR. Unilateral benign yellow dot maculopathy.Am J Ophthalmol Case Rep. 2021; 22101068PubMed Google Scholar Our patient shared similar characteristics with those described in the literature, such as bilateral nonprogressive maculopathy, no visual impairments, and multiple yellow dots evenly distributed in the perifoveal macula. In the 45 cases described in the literature, the median age of the patients was 16 years (range, 5–69 years), which is like our patient's age on initial presentation. This phenotype favoured females (67%) versus males (33%). BCVA was excellent overall in these patients, with 64% of eyes having 20/20 vision (Table 1). Ophthalmic imaging findings are essential when evaluating these rare macular phenotypes. In the cases described in the literature, OCT of the macula was performed in 58% and was normal in 58% and showed ellipsoid zone irregularity in 23% and RPE irregularity in 19%. FA was only obtained in 13% of patients and revealed early hyperfluorescence of the dots (50%), normal FA (33%), and mild unilateral RPE irregularities with window defect (17%). FAF was obtained in 64% of patients, and all showed hyper-autofluorescence of the dots. ERG was obtained in 49% of patients, and all were normal except from 1 patient who was mildly abnormal. Pattern ERG was abnormal in 2 of these patients. Our patient's unremarkable OCT findings and hyper-autofluorescent dots on FAF were similar to those of the other patients described in the literature. It is likely that these hyper-autofluorescent dots on FAF are due to photoreceptor and RPE dysfunction that has been previously reported. Because of the size and non-progressive nature of these dots, the focal changes in the photoreceptors and RPE are unlikely to be visually significant and undetectable on many of our imaging modalities, which explains the unremarkable imaging findings reported in the literature. Demographically, our patient is a Hispanic male, and this has not yet been described in the literature.2Borman AD Rachitskaya A Suzani M et al.Benign yellow dot maculopathy: a new macular phenotype.Ophthalmology. 2017; 124: 1004-1013Abstract Full Text Full Text PDF PubMed Scopus (8) Google Scholar, 3Mishra AV Pollmann AS Choudhry N Demmings E Gupta RR. Unilateral benign yellow dot maculopathy.Am J Ophthalmol Case Rep. 2021; 22101068PubMed Google Scholar, 4Moisseiev E. Benign yellow dot maculopathy.Am J Ophthalmol Case Rep. 2018; 10: 13-15Crossref PubMed Scopus (3) Google Scholar, 5Murro V Mucciolo DP Giorgio D et al.Multimodal imaging of benign yellow dot maculopathy.Ophthalmic Genet. 2019; 40: 135-140Crossref PubMed Scopus (1) Google Scholar, 6Ninet L David T Gascon P. Multimodal imaging for benign yellow dot maculopathy.Ophthalmol Retina. 2022; 6: 307Abstract Full Text Full Text PDF PubMed Scopus (0) Google ScholarTable 1Summary of demographic data of patients presenting with benign yellow-dot maculopathy in the literatureCase numberAuthor(s)AgeFamilySexBCVA OD (LogMAR)BCVA OS (logMAR)1Borman et al.2Borman AD Rachitskaya A Suzani M et al.Benign yellow dot maculopathy: a new macular phenotype.Ophthalmology. 2017; 124: 1004-1013Abstract Full Text Full Text PDF PubMed Scopus (8) Google Scholar51F002Borman et al.2Borman AD Rachitskaya A Suzani M et al.Benign yellow dot maculopathy: a new macular phenotype.Ophthalmology. 2017; 124: 1004-1013Abstract Full Text Full Text PDF PubMed Scopus (8) Google Scholar281F0–0.083Borman et al.2Borman AD Rachitskaya A Suzani M et al.Benign yellow dot maculopathy: a new macular phenotype.Ophthalmology. 2017; 124: 1004-1013Abstract Full Text Full Text PDF PubMed Scopus (8) Google Scholar501F–0.08–0.084Borman et al.2Borman AD Rachitskaya A Suzani M et al.Benign yellow dot maculopathy: a new macular phenotype.Ophthalmology. 2017; 124: 1004-1013Abstract Full Text Full Text PDF PubMed Scopus (8) Google Scholar142M–0.0805Borman et al.2Borman AD Rachitskaya A Suzani M et al.Benign yellow dot maculopathy: a new macular phenotype.Ophthalmology. 2017; 124: 1004-1013Abstract Full Text Full Text PDF PubMed Scopus (8) Google Scholar432F0.180.186Borman et al.2Borman AD Rachitskaya A Suzani M et al.Benign yellow dot maculopathy: a new macular phenotype.Ophthalmology. 2017; 124: 1004-1013Abstract Full Text Full Text PDF PubMed Scopus (8) Google Scholar453F–0.08–0.087Borman et al.2Borman AD Rachitskaya A Suzani M et al.Benign yellow dot maculopathy: a new macular phenotype.Ophthalmology. 2017; 124: 1004-1013Abstract Full Text Full Text PDF PubMed Scopus (8) Google Scholar63M–0.08–0.088Borman et al.2Borman AD Rachitskaya A Suzani M et al.Benign yellow dot maculopathy: a new macular phenotype.Ophthalmology. 2017; 124: 1004-1013Abstract Full Text Full Text PDF PubMed Scopus (8) Google Scholar154F0.780.789Borman et al.2Borman AD Rachitskaya A Suzani M et al.Benign yellow dot maculopathy: a new macular phenotype.Ophthalmology. 2017; 124: 1004-1013Abstract Full Text Full Text PDF PubMed Scopus (8) Google Scholar184F0010Borman et al.2Borman AD Rachitskaya A Suzani M et al.Benign yellow dot maculopathy: a new macular phenotype.Ophthalmology. 2017; 124: 1004-1013Abstract Full Text Full Text PDF PubMed Scopus (8) Google Scholar454F0.180.1811Borman et al.2Borman AD Rachitskaya A Suzani M et al.Benign yellow dot maculopathy: a new macular phenotype.Ophthalmology. 2017; 124: 1004-1013Abstract Full Text Full Text PDF PubMed Scopus (8) Google Scholar104M–0.08–0.0812Borman et al.2Borman AD Rachitskaya A Suzani M et al.Benign yellow dot maculopathy: a new macular phenotype.Ophthalmology. 2017; 124: 1004-1013Abstract Full Text Full Text PDF PubMed Scopus (8) Google Scholar225F–0.08–0.0813Borman et al.2Borman AD Rachitskaya A Suzani M et al.Benign yellow dot maculopathy: a new macular phenotype.Ophthalmology. 2017; 124: 1004-1013Abstract Full Text Full Text PDF PubMed Scopus (8) Google Scholar—5F0014Borman et al.2Borman AD Rachitskaya A Suzani M et al.Benign yellow dot maculopathy: a new macular phenotype.Ophthalmology. 2017; 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124: 1004-1013Abstract Full Text Full Text PDF PubMed Scopus (8) Google Scholar78F0020Borman et al.2Borman AD Rachitskaya A Suzani M et al.Benign yellow dot maculopathy: a new macular phenotype.Ophthalmology. 2017; 124: 1004-1013Abstract Full Text Full Text PDF PubMed Scopus (8) Google Scholar458F0021Borman et al.2Borman AD Rachitskaya A Suzani M et al.Benign yellow dot maculopathy: a new macular phenotype.Ophthalmology. 2017; 124: 1004-1013Abstract Full Text Full Text PDF PubMed Scopus (8) Google Scholar138M0022Borman et al.2Borman AD Rachitskaya A Suzani M et al.Benign yellow dot maculopathy: a new macular phenotype.Ophthalmology. 2017; 124: 1004-1013Abstract Full Text Full Text PDF PubMed Scopus (8) Google Scholar89F0023Borman et al.2Borman AD Rachitskaya A Suzani M et al.Benign yellow dot maculopathy: a new macular phenotype.Ophthalmology. 2017; 124: 1004-1013Abstract Full Text Full Text PDF PubMed Scopus (8) Google Scholar610M0.70.824Borman et al.2Borman AD Rachitskaya A Suzani M et al.Benign yellow dot maculopathy: a new macular phenotype.Ophthalmology. 2017; 124: 1004-1013Abstract Full Text Full Text PDF PubMed Scopus (8) Google Scholar1011F0025Borman et al.2Borman AD Rachitskaya A Suzani M et al.Benign yellow dot maculopathy: a new macular phenotype.Ophthalmology. 2017; 124: 1004-1013Abstract Full Text Full Text PDF PubMed Scopus (8) Google Scholar512F0026Borman et al.2Borman AD Rachitskaya A Suzani M et al.Benign yellow dot maculopathy: a new macular phenotype.Ophthalmology. 2017; 124: 1004-1013Abstract Full Text Full Text PDF PubMed Scopus (8) Google Scholar1013F0027Borman et al.2Borman AD Rachitskaya A Suzani M et al.Benign yellow dot maculopathy: a new macular phenotype.Ophthalmology. 2017; 124: 1004-1013Abstract Full Text Full Text PDF PubMed Scopus (8) Google Scholar1214F0.4028Borman et al.2Borman AD Rachitskaya A Suzani M et al.Benign yellow dot maculopathy: a new macular phenotype.Ophthalmology. 2017; 124: 1004-1013Abstract Full Text Full Text PDF PubMed Scopus (8) Google Scholar1415M0.080.1429Borman et al.2Borman AD Rachitskaya A Suzani M et al.Benign yellow dot maculopathy: a new macular phenotype.Ophthalmology. 2017; 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124: 1004-1013Abstract Full Text Full Text PDF PubMed Scopus (8) Google Scholar821F0035Borman et al.2Borman AD Rachitskaya A Suzani M et al.Benign yellow dot maculopathy: a new macular phenotype.Ophthalmology. 2017; 124: 1004-1013Abstract Full Text Full Text PDF PubMed Scopus (8) Google Scholar1622F0036Borman et al.2Borman AD Rachitskaya A Suzani M et al.Benign yellow dot maculopathy: a new macular phenotype.Ophthalmology. 2017; 124: 1004-1013Abstract Full Text Full Text PDF PubMed Scopus (8) Google Scholar5.523F0037Murro et al.5Murro V Mucciolo DP Giorgio D et al.Multimodal imaging of benign yellow dot maculopathy.Ophthalmic Genet. 2019; 40: 135-140Crossref PubMed Scopus (1) Google Scholar4324M0038Murro et al.5Murro V Mucciolo DP Giorgio D et al.Multimodal imaging of benign yellow dot maculopathy.Ophthalmic Genet. 2019; 40: 135-140Crossref PubMed Scopus (1) Google Scholar3424M0039Murro et al.5Murro V Mucciolo DP Giorgio D et al.Multimodal imaging of benign yellow dot maculopathy.Ophthalmic Genet. 2019; 40: 135-140Crossref PubMed Scopus (1) Google Scholar6924F0040Murro et al.5Murro V Mucciolo DP Giorgio D et al.Multimodal imaging of benign yellow dot maculopathy.Ophthalmic Genet. 2019; 40: 135-140Crossref PubMed Scopus (1) Google Scholar5525M0041Murro et al.5Murro V Mucciolo DP Giorgio D et al.Multimodal imaging of benign yellow dot maculopathy.Ophthalmic Genet. 2019; 40: 135-140Crossref PubMed Scopus (1) Google Scholar5325F0042Mishra et al.5Murro V Mucciolo DP Giorgio D et al.Multimodal imaging of benign yellow dot maculopathy.Ophthalmic Genet. 2019; 40: 135-140Crossref PubMed Scopus (1) Google Scholar,*Unilateral presentation only in the right eye.2526M0043Moisseiev4Moisseiev E. Benign yellow dot maculopathy.Am J Ophthalmol Case Rep. 2018; 10: 13-15Crossref PubMed Scopus (3) Google Scholar2427M0.1044Moisseiev4Moisseiev E. Benign yellow dot maculopathy.Am J Ophthalmol Case Rep. 2018; 10: 13-15Crossref PubMed Scopus (3) Google Scholar—27F0045Ninet et al.6Ninet L David T Gascon P. Multimodal imaging for benign yellow dot maculopathy.Ophthalmol Retina. 2022; 6: 307Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar3828F0046This study1729M00BCVA, best-corrected visual acuity Unilateral presentation only in the right eye. Open table in a new tab BCVA, best-corrected visual acuity Limitations of this report include the single case, the lack of ophthalmic examinations prior to the Aspirin overdose, and the lack of the examinations of family members. Because this phenotype is typically asymptomatic, it is possible that our patient's family members have similar findings that have previously gone undiagnosed, especially without routine examination. Genetic testing was not performed, which may have helped elucidate a specific causative gene locus. In conclusion, there is a paucity of literature on benign yellow-dot maculopathy. Including our case, only 46 total cases have been described in the literature to date. It is possible that this entity is underreported in the literature because patients may not present for routine examination given that they are typically asymptomatic. Because no known etiology has been described thus far, we recommend examining family members of patients presenting with this phenotype, obtaining a thorough history of the patient and his or her family, and considering genetic testing. While this condition has not been shown to significantly affect visual acuity, we believe that it is important to increase awareness of this phenotype, allowing ophthalmologists to keep this in the differential diagnosis when evaluating patients with similar presentations and to prevent misdiagnosis. The authors have no proprietary or commercial interest in any materials discussed in this correspondence.