Electroretinography as a biomarker to monitor Stargardt disease

Abstract

Purpose : To determine which electroretinographic (ERG) responses best correspond with disease progression in Stargardt disease (STGD1).

Methods : 42 patients with STGD1 (ABCA4 retinopathy) were included. Group 1 harboured two null mutations (8 patients, 3 male), while group 2 had other genotypes (34 patients, 10 male). Age at the time of exam, age at onset and decimal Snellen visual acuity were collected from the medical records. Full-field ERG and pattern ERG (24°X30° checkerboard) were recorded according to ISCEV standards. S-cone ERG was also recorded, according to the ISCEV approved extended protocol. The amplitudes of the following responses were analysed cross-sectionally with age: PERG P50, dark-adapted (DA) 0.01 ERG b wave, 3.0 ERG a wave and oscillatory potentials; light-adapted (LA) 30 Hz flicker ERG and 3.0 ERG b wave; and S-cone ERG. The right patients' eyes were taken for the analysis. Correlation between ERG responses and age at the exam was compared using simple linear regression. Mann-Whitney U Test was used for comparing age at the exam, age at onset, visual acuity and ERG amplitudes between the two groups.

Results : The median age of onset was significantly earlier in group 1 (8 vs 18 years; p<0.01); however, disease duration was similar between the two groups (12.5 and 12.0 yrs; p>0.05). Group 1 had also significantly worse visual acuity (0.02 vs 0.16; p<0.01) and significantly lower all ERG responses (p<0.01). Group 1 had no detectable macular function measured with PERG P50, whereas it was detectable in 79% of patients in group 2. Simple linear regression analysis revealed that in group 1, age had a significant effect on DA 0.01 ERG b wave (β=−0.8, R²=0.6, p<0.01) and DA 3.0 ERG a wave (β=−0.9, R²=0.7, p<0.01). In contrast, other ERG parameters did not show age dependency. In group 2, age was significantly associated with S-cone ERG amplitude (β=−0.7, R²=0.5, p<0.01).

Conclusions : For double null patients, the best ERG biomarkers for follow-up were DA 0.01 and 3.0 ERG responses, representing retina rod system response. For other genotypes expected to confer residual ABCA4 function, the best ERG biomarker for follow-up was S-cone ERG. Different ERG responses may be best suited to monitor disease progression in different Stargardt genotypes. However, additional studies on larger datasets with precisely grouped genotypes would be needed.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.