Phenotype of bilateral EYS-associated occult macular dystrophies based on multimodal imaging

Abstract

Background: The study aimed to confirm the multimodal imaging of occult macular dystrophy (OMD) with two heterozygous mutations, including an unreported heterozygous EYS mutation.

Methods: The study utilised several diagnostic methods, including Optos wide-field imaging, Bruch's membrane opening-minimum rim width (BMO-MRW), optical coherence tomography (OCT), multifocal electroretinogram (mf-ERG), fundus fluorescein angiography (FFA), indocyanine green angiography (ICGA), and green light autofluorescence (FAF-G) imaging, and genetic testing.

Results: The mf-ERG imaging demonstrated decreased P1 amplitudes in both eyes. This was consistent with the FAF-G imaging and OCT results, confirming the bilateral discontinuity of photoreceptors in the macular region. FFA and ICGA revealed persistent macular hypoperfusion not only within the photoreceptors of the macular area but also in the choriocapillaris. Next-generation sequencing results confirmed the presence of two heterozygous mutations in the patient: RP1L1 (c.4273G>C: p. Asp1425His), a hotspot mutation for OMD, and an unreported EYS mutation (c.7382T>A: p. Leu2461Ter) commonly found in retinitis pigmentosa (RP). Analysis using AlphaFold2 further confirmed the impact of the EYS c.7382T>A: p. Leu2461Ter variant on the functional protein conformation.

Conclusion: We report an unreported heterozygous EYS mutation that could serve as a promising diagnostic marker for OMD.

Keywords: EYS; FAF-G; FFA; ICGA; Macular dystrophy; OCT.