Clinical Evaluation of Rod Photoreceptor Function: Measuring Fractional Sensitivity in Normal and Diseased Retinas

Abstract

The electroretinogram (ERG) can assess photoreceptor and postreceptoral retinal function. Robson and Frishman have suggested that the prevailing model of photoreceptor contributions to the a-wave, based only on outer segment contributions, is inadequate, as it does not account for the a-wave nose, a recovery of voltage towards baseline prior to rise of the b-wave, which reflects On-bipolar cell activity. Instead, they proposed a model in which the nose is shaped by capacitive currents in the outer nuclear layer (ONL) during rod hyperpolarization. The purpose of this dissertation was to assess clinical application of the new model, focusing on a parameter of the model, fractional sensitivity (FS). Experiment 1: Dark-adapted (DA) ERG responses to brief achromatic flashes doubling in energy from 7.5 to 933 scot cd.s/m2 were recorded in healthy subjects, ages 20-29 years (n=20). The cohort’s average FS was 0.86% per R*/rod ± 0.14 and followed model template curves from 29 to 212 scot cd.s/m2. A decline in FS with increasing age for these flash energies was found for subjects, ages 11 to 72 years (-0.0055 log unit/year, n=80); Vmax did not change. FS test-retest values had a bias close to zero (-4.9% ± 15.3, n=20) and repeatability coefficient of ± 30%. Experiment 2: Rod-isolated a-waves were obtained using a paired flash paradigm in healthy subjects (n=8). Rod-isolated FS was greater than FS for mixed rod/cone responses, but mean factor of increase was just 13.2% (range=1%-29%, p=0.011). Mean rod-isolated a-wave implicit time (IT) was 3% earlier than mixed IT. Rod-isolated amplitude was 22% lower than mixed a-wave amplitude. Experiment 3: ISCEV Standard ERGs and responses to a higher energy “DA30” stimulus of 64 scot cd.s/m2, about 30 phot cd.s/m2, were elicited in subjects with 1-2 ABCA4 mutations (n=16). Subjects had at least one ISCEV light-adapted parameter outside normal limits. DA30 a-wave IT was impaired more (n=7) than DA3.0 a-wave IT (n=3) or amplitude (n=5). FS was impaired more than DA30 IT; 9 vs. 7. Conclusions: FS obtained with an achromatic flash, decreased with age and was found to be an indicator of rod dysfunction in subjects with known cone dysfunction. FS could provide a useful clinical measure.Optometry, College o