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Normal Aging, Progression With Disease, and Test-Retest Variability

David G. Birch, PhD; Donald C. Hood, PhD; Kirsten G. Locke, RN, CRA; Dennis R. Hoffman, PhD; Radoul T. Tzekov, MD, PhD

Arch Ophthalmol. 2002;120:1045-1051.

Objectives  To determine (1) reference values for cone and rod phototransduction variables derived from the a-wave of the electroretinogram, (2) their dependence on age, (3) the progression in cone and rod variables in patients with X-linked retinitis pigmentosa (XLRP), and (4) the test-retest variability in these a-wave measures compared with the variability in cone and rod b-wave measures.

Participants  One hundred control subjects aged 5 to 75 years and 24 patients with XLRP aged 5 to 38 years.

Methods  High-intensity stimuli were used to elicit electroretinograms in the dark and in the presence of a rod-saturating background. Computer averaging and computer subtraction of cone components from mixed rod-cone responses were used to derive rod-only and cone a-waves. Rod and cone phototransduction variables were derived by computer fitting physiologically based computational models to the leading edges of a-wave ensembles.

Results  Phototransduction efficiency, as indexed by the sensitivity variable (S), decreased with age for cone and rod-only responses, whereas maximum cone and rod photoresponses (Rm_P3) remained constant. In patients with XLRP tested annually for 4 years, Rm_P3 for rods and, to a lesser extent, cones declined with disease progression, whereas S remained stable. The test-retest variability in the a-wave Rm_P3 is lower than previously reported measures of the variability in b-wave peak-to-peak amplitude.

Conclusion  The leading edge of the a-wave of the electroretinogram can be related to rod and cone phototransduction variables through quantitative models. Rm_P3, rather than S, should be the outcome measure of choice when using the a-wave to follow photoreceptor function in prospective studies and treatment trials.

From the Retina Foundation of the Southwest, Dallas, Tex (Drs Birch and Hoffman and Ms Locke); the Department of Ophthalmology, The University of Texas Southwestern Medical School, Dallas (Dr Birch); Department of Psychology, Columbia University, New York, NY (Dr Hood); and Department of Ophthalmology, University of California, Davis (Dr Tzekov).

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