Visualizing spatial differences in corneal electroretinogram potentials using a three-dimensional surface spline.

Objective. The spatial distribution of activity at the retina determines the spatial distribution of electroretinogram potentials at the cornea. Here a three-dimensional surface spline method is evaluated for interpolating corneal potentials between measurement points in multi-electrode electroretinography (meERG) data sets.Approach. 25-channel meERG responses were obtained from rat eyes before and after treatment to create local lesions. A 3rd order surface spline was used to interpolate meERG values resulting in smooth color-coded maps of corneal potentials. Potential maps were normalized using standard score values. Pre- and post-treatment responses were characterized by spatial standard deviation and by difference-from-normal plots.Main results. The spatial standard deviation for eyes with local lesions were significantly higher than for healthy eyes. The 3rd order spline resulted in well-behaved corneal potential maps that maintained low error rate when up to 30% of recording channels were excluded from analysis. Post-normalization, responses could be combined within experimental groups, and individual eyes with lesions were clearly distinguished from the healthy-eye mean response. A 3rd order surface spline is an acceptable means of interpolating meERG potentials to create corneal potential maps. The spatial standard deviation is more sensitive to local dysfunction than absolute amplitudes.Significance. This work demonstrates solutions to key challenges in the recording and analysis of meERG responses: visualization, normalization, channel loss, and identification of abnormal responses. Continued development of the meERG technique is relevant to research and clinical applications, especially where local dysfunction (early progressive disease) or local therapeutic effect (subretinal injection) is of interest.

Three-Dimensional Model of Electroretinogram Field Potentials in the Rat Eye.

OBJECTIVE: The information derived from the electroretinogram (ERG), especially with regard to local areas of retinal dysfunction or therapeutic rescue, can be enhanced by an increased understanding of the relationship between local retinal current sources and local ERG potentials measured at the cornea. A critical step in this direction is the development of a robust bioelectric field model of the ERG. METHODS: A finite-element model was created to simulate ERG potentials at the cornea resulting from physiologically relevant transretinal currents. A magnetic resonance image of a rat eye was segmented to define all major ocular structures, tissues were assigned conductivity values from the literature. The model was optimized to multi-electrode ERG (meERG) data recorded in healthy rat eyes, and validated with meERG data from eyes with experimental lesions in peripheral retina. RESULTS: Following optimization, the simulated distribution of corneal potentials was in good agreement with measured values; residual error was comparable to the average difference of individual eyes from the measured mean. The model predicted the corneal potential distribution for eight eyes with experimental lesions with similar accuracy, and a measure of pre- to post-lesion changes in corneal potential distribution was well correlated with the location of the lesion. CONCLUSION: An eye model with high anatomical accuracy was successfully validated against a robust dataset. SIGNIFICANCE: This model can now be used for optimization of ERG electrode design, and to support functional mapping of the retina from meERG data via solving the inverse bioelectric source problem.

Corneal Potential Maps Measured With Multi-Electrode Electroretinography in Rat Eyes With Experimental Lesions.

Purpose: Conventional full-field flash electroretinography (ERG) yields a single response waveform that can be useful in the early detection and diagnosis of many diseases affecting the retina. It is an objective measurement that probes the entire retina. However, localized areas of dysfunction have relatively small influence on ERG amplitudes compared to normal ranges. Here we evaluate the use of corneal potential maps obtained in response to full-field flash stimuli for sensitivity to local areas of retinal damage. Methods: A contact lens electrode array was used to record 25 ERG waveforms simultaneously following saturating full-field flash stimuli (multi-electrode electroretinography, meERG) in rats. Waveforms were evaluated for a-wave and b-wave amplitudes; these values were normalized and further evaluated for spatial differences across the corneal surface. Cluster analysis and a support vector machine approach were used to classify meERG responses from healthy eyes and eyes with central (photocoagulation) or peripheral (cryocoagulation) experimental lesions. Results: A normative normalized corneal potential map was obtained from healthy eyes (n = 26). Corneal potential maps from eyes with experimental lesions (n = 13) could be classified with sensitivity and specificity of approximately 80% based solely on the normalized spatial distribution of corneal potentials, that is, with no knowledge of absolute amplitudes. Conclusions: Corneal potential maps obtained in response to full-field flash stimuli are altered in eyes with scotomas in the central and far-peripheral retina. The meERG approach yields useful spatial information following a single brief flash, analogous to body-surface potential maps used to evaluate heart and brain.