Bifocal retinal degeneration observed on ultra-widefield autofluorescence in some cases of CRX-associated retinopathy

Abstract

Purpose : Variants in CRX can be associated with dominantly inherited retinal degeneration with considerable phenotypic variability. Many patients have central retinal degeneration; in some patients, we have observed an additional focus of degeneration in the nasal retina. In this study we sought to quantify the prevalence of such a pattern.

Methods : We retrospectively reviewed clinical information and imaging of patients with disease associated with heterozygous pathogenic variants in CRX at two centres. Those patients with available ultra-widefield (SLO) pseudocolor and autofluorescence imaging (Optos plc, Dunfermline, UK) were included. Those with the specific bifocal degeneration pattern (additional focus in nasal retina) in both eyes were identified.

Results : 37 patients with CRX-associated retinal dystrophy and ultra-widefield fundus images were identified. Of these, three patients (males aged 30, 45 and 75) displayed a pattern consisting of a central retinal degeneration (involving the macula or posterior pole) and an additional area of discrete abnormality in the nasal periphery (with altered autofluorescence characteristics), which was non-contiguous with the macular degeneration, and which affected a similar area in both eyes. The CRX variants in these patients comprised a missense change (c.121C>T, p.(Arg41Trp)) and two frameshifting variants (c.605deIG, p.(Cys202SerfsTer17) and c.615delC, p.(Ser206ProfsTer13)). International-standard pattern and full-field electroretinography were consistent with severe macular dysfunction in all three patients, with additional mild generalised retinal dysfunction in the two older patients.

Conclusions : Bifocal retinal lesions have been described in progressive bifocal chorioretinal atrophy, a rare early onset chorioretinal dystrophy associated with a noncoding variant upstream of PDRM13. Our findings show that some patients (8% in our study) with CRX-related disease show bifocal areas of retinal degeneration, with a different appearance. Identifying such a pattern can help direct genetic investigations towards variants in CRX as such a distinctive appearance is not so frequently seen in other inherited retinal diseases. Identifying CRX-associated disease can be important due to the need for counselling families in view of the frequent dominant inheritance and phenotypic variability.

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