Expanding the phenotype of genetically associated electronegative ERG retinopathies: Comparing the full field ERG b:a ratio

Abstract

Purpose : X-linked retinoschisis (RS1) and complete and incomplete congenital stationary night blindness (cCSNB, iCSNB) are inherited retinal dystrophies with a classically electronegative electroretinogram (ERG) defined as b:a ratio ≤1.0. Significant heterogeneity in ERG findings has been shown in these conditions, likely reflecting genotypic and thus mutation-target variation. Comparing these phenotypes through b:a ratio gives insights into genotype-phenotype correlations, questions current ERG diagnostic criteria and aids in localising pathology.

Methods : We conducted a retrospective analysis of ERG and genetic results in patients with a clinical diagnosis of iCSNB, cCSNB and RS1 at Save Sight Institute Sydney, Australia. Dark adapted (DA) 3.0 and DA 12.0 traces as per ISCEV standards were analysed and b:a ratios calculated. Mean b:a ratios were compared using 2-tailed unpaired student t-tests. An association between electropositive ERG and genetic diagnosis was assessed using chi-squared tests at b:a >1.0 and b:a >1.50 thresholds.

Results : 25 iCSNB, 13 cCSNB and 16 RS1 patients were included - 8 iCSNB, 2 cCSNB and 11 RS1 patients had genetic confirmation. Mean b:a ratios were equivalent for DA 3.0 and DA 12.0 ERGs. Genetically proven iCSNB cases had lower mean b:a compared to the overall iCSNB cohort (0.62 vs 0.80, p = 0.0008), while there was no difference for cCSNB or RS1. In genetically proven patients, mean b:a ratios in cCSNB (0.52) was significantly lower than iCSNB (0.62, p=0.042) and RS1 (1.04, p<0.0001), and iCSNB was significantly lower than RS1 (p<0.0001). The proportion of patients with b:a >1.0 was iCSNB 1/8, cCSNB 0/2 and RS1 7/11, while 0/8 iCSNB, 0/2 cCSNB and 2/11 RS1 patients had b:a >1.50. An electropositive ERG was significantly more likely to be associated with RS1 than iCSNB (p=0.026) at b:a >1.0 threshold.

Conclusions : These findings highlight the expanded variability in b:a ratios. A diagnosis of a classical electronegative inner retinal dystrophy should include ratios up to at least 1.5. RS1 patients were frequently found to be electropositive whilst a b:a ratio of > 1.50 did not encompass any CSNB cases. No cCSNB case had a ratio >1.0. The variation in ERG b:a ratio between the groups further assists in guiding genetic testing and their interpretation.

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