Characterization of the Retinal Phenotype in PYGM-related McArdle Disease

Abstract

Purpose : To characterize the range of retinal phenotypes associated with McArdle disease

Methods : This observational study was approved by the Sickkids Hospital research ethics board and included 21 subjects (including a sib-ship) with molecularly confirmed McArdle disease. Metabolic specialists referred nineteen subjects who had no known retinal involvement. The clinical assessment included: best corrected visual acuity (BCVA) measurement, fundus examination, multimodal retinal imaging [fundus photography and autofluorescence (FAF) imaging, and spectral-domain optical coherence tomography (SD-OCT)], and electrophysiology testing [full-field electroretinogram (ffERG), pattern electroretinogram (PERG), and electrooculogram (EOG)].

Results : Eleven men and 10 women participated in the study (age range 28 – 80 years). Eleven had abnormal retinal findings, 7 men and 4 women. The mean age of affected and unaffected subjects was 52.9 years and 47.7 years, respectively. Photophobia was the commonest symptom observed in 5 affected subjects. The BCVA ranged from 20/16 to 20/200 and 20/16 to 20/32 in the affected and unaffected subjects, respectively. Three patterns of retinal involvement were noted: a) both macular and extramacular pigmentary changes (7/11), b) extramacular retinal changes alone (3/11) and c) macular changes alone (1/11). Macular changes commonly included pattern-type dystrophy of the retinal pigment epithelium (RPE) with grayish-yellow dots, while extramacular changes included a reticular pigmentary pattern. Extensive scalloped chorioretinal atrophy was seen in the sib-ship, who presented with macular dystrophy. A pattern of hyper-autofluorescence at the macula was the commonest FAF abnormality (5/11). The SD-OCT commonly demonstrated localized ellipsoid zone disruption corresponding to the RPE changes and hyper-reflective RPE deposits. Twenty subjects underwent electrophysiology testing; all had normal EOG and all except 2 had normal ERG. Seven had an abnormal PERG consistent with central macular dysfunction. Seventeen subjects had the common p.R50X pathogenic variant in one or both alleles, but no significant correlation was observed between the genotype and the presence or absence of retinopathy.

Conclusions : This study has characterized in detail the retinal phenotype in McArdle disease. Our results indicate a high occurrence of retinopathy, and hence, it is important to conduct periodic eye exam in these patients.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.