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Michael F Marmor, Brandon Pham, Jeffrey L Goldberg; PhNR measurement independent of baseline (N-wave) for the
clinical evaluation of glaucoma. Invest. Ophthalmol. Vis. Sci. 2019;60(9):2443. doi: https://doi.org/.
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The photopic negative response (PhNR) correlates with ganglion cell function and has been used as an indicator of glaucomatous optic nerve damage. However, its clinical value has been limited because of high variability and poor repeatability, in part from baseline instability. We have explored an alternative measure, considering the response to be a distinct negative wave (N-wave) within the typical 60-80 ms time period. This can be measured independently from the baseline.
We studied 60 patients with glaucoma (in an intervention trial) who had 4 exams over an 8 month period. The PhNR was recorded with standard ISCEV stimuli (mostly with 1 Hz stimulation but some with 4 Hz), as well as 24-2 automated visual fields with mean deviation (MD). Conventional PhNR measurement was performed as well as manual measurement of identifiable N-waves. N-waves could be measured even with a shifting baseline by drawing a slope.
The N-waves showed less variability among recordings than our PhNR values, which was often affected by a degree of drift despite filters. While the PhNR was typically around 20 uV (+/- 10) in amplitude, the N-wave centered around 10 uV in patients with normal fields and fell to zero (absent) in many patients with severe field loss. Comparing response amplitudes in 3 cohorts of visual field loss (MD < 3.0, 3-15, >15.0) showed better separation using N-waves than PhNR. Graphing response amplitude vs. fields (MD) showed better correlation with N-waves than PhNR.
The exact origin and duration of the late negative ganglion cell responses remains unclear, but a defined N-wave should relate to ganglion cell function even if some components of ganglion cell responsiveness might not be measured. PhNR recording is often difficult because of electrical noise, drift and other physiological processes. Much of this type of artifact is eliminated with N-wave measurement, although there are difficulties such as defining the exact beginning and end of a waveform. We suggest that N-wave analysis might help to stabilize ganglion cell recordings for clinical applications. However, we recognize that labs vary in the stability of PhNR recordings, and that this proposal will need further evaluation and clinical study to confirm its value.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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