Spatial differences in corneal electroretinogram potentials measured in rat with a contact lens electrode array

PURPOSE: It has been known for several decades that the magnitude of the corneal electroretinogram (ERG) varies with position on the eye surface, especially in the presence of focal or asymmetric stimuli or retinal lesions. However, this phenomenon has not been well-characterized using simultaneous measurements at multiple locations on the cornea. This work provides the first characterization of spatial differences in the ERG across the rat cornea. METHODS: A contact lens electrode array was employed to record ERG potentials at 25 corneal locations simultaneously following brief full-field flash stimuli in normally sighted Long-Evans rats. These multi-electrode electroretinogram (meERG) responses were analyzed for spatial differences in a-wave and b-wave amplitudes and implicit times. RESULTS: Spatially distinct ERG potentials could be recorded reliably. Comparing relative amplitudes across the corneal locations suggested a slight non-uniform distribution when using full-field, near-saturating stimuli. Amplitudes of a- and b-waves were approximately 3 % lower in the inferior quadrant than in the superior quadrant of the cornea. CONCLUSIONS: The present results comprise the start of the first normative meERG database for rat eyes and provide a basis for comparison of results from eyes with functional deficit. Robust measures of spatial differences in corneal potentials will also support optimization and validation of computational source models of the ERG. To fully utilize the information contained in the meERG data, a detailed understanding of the roles of the many determinants of local corneal potentials will eventually be required

Three-Dimensional Finite Element Models of Corneal Electroretinogram Potentials in Rat

Multi-electrode electroretinography (meERG) measures biopotential signals at multiple locations simultaneously on the cornea following a visual stimulus. The recorded signals have the same waveform components of conventional ERG signals. Ultimately, the goal of meERG is to produce maps of electrophysiological retinal function. To predict local retinal function using meERG, a quantitative model relating retinal sources to corneal potentials is needed. Here, a three-dimensional, anatomically-accurate model of the rat eye was created, optimized and validated to recently available meERG measurements for normally-sighted and rats with experimental retinal lesions. The model predicted the spatial distributions of corneal ERG potentials in normal rat eyes with reasonable agreement, but did not reflect a slight asymmetry in measured potentials. Models incorporating hypotheses to explain the slight asymmetry were constructed, and based on quantitative agreement and an assessment of likelihood, it was determined that a slightly misaligned recording lens was the best explanation. Assessment of confidence in each tissue conductivity value derived from the literature led to optimization of the ciliary body conductivity. The optimized model yielded simulation results that agreed with measured values to within the measurement error (i.e. model error was less than the variability between meERG measured animals). The model was validated by predicting corneal potential profiles in rats with experimental peripheral retina lesions. Measured and simulated corneal potentials decreased in locations closest to the retinal lesion. Error measures between simulated and predicted profiles for experimental lesion rats were no greater than error of normally-sighted rats. The ability to predict the location of a retinal lesion from the corneal potential profile (inverse problem) was evaluated by iteratively solving the forward problem for a standard set of lesion models, and minimizing error between measured and simulated corneal potentials. There was a trade-off between classification sensitivity and specificity for detection of presence of lesion, and techniques described elsewhere for detecting presence of lesion were more robust. However, this method accurately predicted lesion location in seven out of eight experimental lesioned rats, suggesting its utility for producing maps of retinal function. This work demonstrates proof-of-concept for detecting local dysfunction in the peripheral retina from corneal potential maps, an area of the retina that is difficult to evaluate using other techniques yet is highly relevant to prevalent, potentially blinding eye diseases