Assessing rod function in cone dystrophy patients with ABCA4 mutations using rod fractional sensitivity estimates based on ERG a-wave rise time

Abstract

Purpose : About 30% of patients with cone dystrophy begin to develop rod dysfunction within 10 years of diagnosis¹. Detecting early changes in rod function is a challenge. Rod fractional sensitivity (RFS), defined as the proportion of the maximum rod response produced by a weak stimulus of unit strength (eg 1 scot Td s), was recently suggested as a simple measure of rod sensitivity that can be estimated from the ERG a-wave response to a strong stimulus². Subtraction of cone responses from mixed rod-cone (DA30) ERGs results in slightly increased FS, suggesting reduced RFS in cone dystrophies would not be due to cone dysfunction. This study measured RFS in subjects with ABCA4 mutations and varying cone dysfunction to assess RFS as an adjunct to ISCEV standard ERG testing for rod dysfunction.

Methods : Full-field ISCEV standard DA, light adapted (LA) and additional bright flash (DA30 cd.s.m^-2) ERGs were recorded in 14 subjects (17-69 yrs) with 1 or 2 variants in ABCA4. ERGs were recorded with DTL (UH, N=7) using Diagnosys Epsion xenon flash and with bipolar Burian-Allen electrodes (NEI, N=7) using LKC SunBurst LED flash, both with DA30 flashes of 1ms or less. ERG parameters were compared to normal databases for electrode type. Estimates of RFS were calculated from the 10-90% rise time of the DA30 a-wave².

Results : Across all 14 subjects with varying DA b-wave amplitudes, 8 had RFS below age matched 95% confidence limits. All subjects showed cone dysfunction: 11 had delayed LA3 b-wave implicit time (IT) and 8 had delayed 30Hz flicker responses; 9 had decreased LA3 flash or flicker amplitudes or both. For DA3, all subjects had normal a-wave IT, but delayed b-wave IT; 5 had decreased a-wave and 4, decreased b-wave amplitudes.

Conclusions : For the 14 cone dystrophy patients, delayed b-wave IT was the most common finding in DA ERG. However, reduced RFS was the most common finding specific to rod photoreceptor function. Standard ERGs did not consistently identify subjects with reduced RFS. Future structure function analysis would determine whether subjects with reduced RFS have altered outer retinal integrity compared to those with normal RFS.
References:
1. Langwinska-Wosko E et al. Doc Ophthalmol 2015;130:103 -109.
2. Robson JG, Frishman LJ. Prog Retin Eye Res 2014;39:1-22.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.