A 71-year-old female was referred for neovascular age-related marcular degeneration. She noticed recent vision loss in her right eye and was fairly asymptomatic in her left eye. Vision was counting fingers OD and 20/80 OS.

Optos color RGB imaging shows somewhat turbid, yellowish foveal fluid OD and a vitelliform lesion OS (Figures 1 and 2). Triton swept-source OCT shows hyperreflective subretinal vitelliform material (yellow arrows) and hyperreflectivity from a subretinal pigment clump (red arrows). Subretinal fluid and a complex pattern of loculated pockets of intraretinal fluid are noted OD. On Optos fundus autofluorescence (FAF), the lesion shows central hypo-FAF and peripheral hyper-FAF OD, and marked hyper-FAF OS (Figure 3). Anti-VEGF therapy was started for macular neovascularization (MNV) in her right eye.

Best disease is associated with a mutation in the BEST1 gene, which encodes for the bestrophin-1 protein. Bestrophin-1, a calcium-activated chloride channel, is primarily found in the basolateral plasma membrane of the RPE. In Best disease, these chloride channels are altered in such a way that it disrupts outer segment phagocytosis by the RPE. The toxic compounds of outer segments start to accumulate between the RPE and photoreceptors, leading to formation of vitelliform lesions. Since these lesions are comprised of photoreceptor outer segments, they always exhibit hyperautofluorescence.1,2,3

BEST1 mutations cause a variety of phenotypes, including adult-onset foveomacular vitelliform dystrophy (our patient), best vitelliform macular dystrophy, autosomal recessive bestrophinopathy, and autosomal dominant vitreoretinochoroidopathy. Although our patient had a Best phenotype, genetic testing revealed uncertain significant heterozygous variants SAG, SLC7A14 and VCAN.4

In our experience, MNV is rarely associated with Best lesions, although MNV has been found in 18% of eyes in their retrospective Asian population.5

References

  1. Freund KB, Laud K, Lima LH, Spaide RF, Zweifel S, Yannuzzi LA. Acquired Vitelliform Lesions: correlation of clinical findings and multiple imaging analyses. Retina. 2011 Jan;31(1):13-25. doi: 10.1097/IAE.0b013e3181ea48ba. PMID: 21102371.
  2. Chowers I, Tiosano L, Audo I, Grunin M, Boon CJ. Adult-onset foveomacular vitelliform dystrophy: A fresh perspective. Prog Retin Eye Res. 2015 Jul;47:64-85. doi: 10.1016/j.preteyeres.2015.02.001. Epub 2015 Feb 11. PMID: 25681578.
  3. Spaide R. Autofluorescence from the outer retina and subretinal space: hypothesis and review. Retina. 2008 Jan;28(1):5-35. doi: 10.1097/IAE.0b013e318158eca4. PMID: 18185134.
  4. Shah M, Broadgate S, Shanks M, Clouston P, Yu J, MacLaren RE, Németh AH, Halford S, Downes SM. Association of Clinical and Genetic Heterogeneity With BEST1 Sequence Variations. JAMA Ophthalmol. 2020 May 1;138(5):544-551. doi: 10.1001/jamaophthalmol.2020.0666. PMID: 32239196; PMCID: PMC7118667.
  5. Miyagi M, Takeuchi J, Koyanagi Y, Mizobuchi K, Hayashi T, Ito Y, Terasaki H, Nishiguchi KM, Ueno S. Clinical findings in eyes with BEST1-related retinopathy complicated by choroidal neovascularization. Graefes Arch Clin Exp Ophthalmol. 2022 Apr;260(4):1125-1137. doi: 10.1007/s00417-021-05447-y. Epub 2021 Oct 18. PMID: 34661736.