Abstract
Purpose :
To report on emerging and not previously noted ocular and systemic phenotypic characteristics in 7 patients (age: 28-49 yo, 4F/3M) with ARRP associated with disease-causing EYS gene mutations, all but one novel.
Methods :
Patients underwent clinical examination, semi-automated kinetic perimetry (SKP), full-field flash electroretinography (ffERG), spectral domain optical coherence tomography (SD-OCT), fundus autofluorescence (FAF), intravenous fluorescein angiography (IVFA), and broad NGS-based retinal dystrophy-specific genetic testing and, when necessary, also deletion/duplication microarrays. A detailed questionnaire and review of systems were obtained, including BMI.
Results :
With one exception, all EYS mutations were either nonsense or splice site mutations, or small deletions (all novel expect in one case). Parental or affected sibling segregation was verified in all cases. Visual acuity loss and macular involvement varied greatly, and was not age-related. In addition to the typical characteristics of RP and a rod-cone ffERG pattern, GVFs often showed altitudinal or bilateral nasal and temporal loss, in an unusual column-like vertical pattern of GVF preservation. Marked GVF constriction was seen in late stages. Papillary inflammatory features were also prominent, with marked disc staining and leakage and at the arcades on WF-IVFA, and RNFL thickening to SD-OCT. Vasculitis-like changes were also seen. Macular OCT showed in 5 of 6 subjects bilateral dense sub-foveal hyperreflective deposits (sfHRDs). In the 7th case, severe cystoid macular edema prevented reliable sfHRDs assessment. These inflammatory features were responsive to triamcinolone acetonide injections. Three of the 7 cases had BMI > 40, with clustering in Black females.
Conclusions :
Our findings expand the spectrum of known EYS disease-causing mutations and identify novel and unique phenotypic visual field loss patterns, subfoveal SD-OCT characteristics, and marked but treatable imaging inflammatory features, affecting especially the optic nerves, in patients with EYS-linked ARRP. We also found a possible gender- and perhaps race-specific association with obesity in Black female EYS patients. EYS has multiple EGF-like domains, and there is a definite association between obesity, EGF and breast cancer in women. Thus, this association may warrant further investigation.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.