Effect of Experimental Glaucoma in Primates on Oscillatory Potentials of the Slow-Sequence mfERG

Abstract

PURPOSE. To determine the effect of experimental glaucoma in macaque monkeys on oscillatory potentials (OPs) in the slowsequence multifocal electroretinogram (mfERG). METHODS. Photopic slow-sequence mfERGs were recorded from anesthetized adult macaque monkeys and normal human subjects. The stimulus consisted of 103 equal-sized hexagons within 17°of the fovea. The m-sequence was slowed, with 14 blank frames, ϳ200 ms, interleaved between flashes for monkeys and 7 blank frames, ϳ100 ms, for humans, to produce waveforms similar to the photopic full-field flash ERG. Recordings were made under control conditions (24 monkey eyes, 7 human) and after laser-induced experimental glaucoma in monkeys (n ϭ 8). A Fourier fast transform [FFT] was used to determine the frequency ranges of the major OPs. OP amplitudes were quantified by using root mean square (RMS) for two-frequency bands in five horizontal and four vertical locations. Visual field defects were assessed using behavioral static perimetry. Full-field photopic flash ERGs also were recorded. RESULTS. OPs in two distinct frequency bands were discriminated in the monkey mfERG: fast OPs, with a peak frequency of 143 Ϯ 20 Hz, and slow OPs, with a peak at 77 Ϯ 8 Hz. There were similar findings in humans and with the flash ERG in monkeys. The fast OP RMS in monkey control eyes was significantly larger in temporal than nasal retina (P Ͻ 0.01) and in superior versus inferior retina (P Ͻ 0.05) as reported previously. The slow OP RMS was largest in the foveal region. Experimental glaucoma reduced fast OP RMS in all locations studied, even when visual field defects were moderate (MD ϭ Ϫ5 to Ϫ10 dB; P Ͻ 0.05), whereas the slow OP RMS was reduced significantly primarily in the foveal region when field defects were severe (MD Ͻ Ϫ10 dB; P Ͻ 0.05). The fast OP RMS showed a moderate correlation with local visual field sensitivity and with local ganglion cell density (calculated from visual field sensitivity). For the slow OPs the correlation was much poorer. Consistent with previous studies, the photopic negative response (PhNR) amplitude was significantly reduced when the visual sensitivity was minimally affected. CONCLUSIONS. OPs in the ERG of primates fall in two frequency bands: fast OPs with a peak frequency around 143 Hz and slow OPs, with a peak frequency around 77 Hz. The fast OPs, which rely more on the integrity of retinal ganglion cells and their axons than do the slow OPs, have potential 1 The death of retinal ganglion cells in POAG is reflected by increased cupping of the optic disc, loss of nerve fiber layer and functional visual field defects. 2 Perimetry has been considered to be the gold standard in the diagnosis of glaucoma. However, a disadvantage of standard perimetry is that the first visual field defects appear only after a significant proportion (ϳ25%-40%) of ganglion cells and nerve fibers have died. 3-5 Therefore, more sensitive tests that can detect early retinal ganglion cell changes in glaucoma would be useful. One technique that objectively measures retinal function is the electroretinogram (ERG). The ERG is a useful tool for noninvasive assessment of function in normal and diseased retinas. In recent years, several studies in patients with glaucoma and in primate models of glaucoma have shown that the photopic ERG has components that are sensitive to glaucomatous optic neuropathy. These components include the negative potential at 95 ms of the transient pattern (p)ERG, known as the N95 6 -8 ; the photopic negative response (PhNR) of the photopic full-field flash ERG 9 -12 ; and the oscillatory potentials Although these components of the ERG are sensitive to glaucomatous damage, they reflect activity of the whole or large regions of the retina, and do not provide information about regional ganglion cell defects. In contrast, the results of perimetry indicate the regional nature of damage to the ganglion cells and their axons. A test that measures responses from different retinal locations might be more sensitive to early changes in the retinal ganglion cell responses that occur locally and would be lost in averaging of ERG responses over the entire retina. The multifocal ERG (mfERG) technique developed by Sutter has made it possible to obtain a topographic representation of the retinal functio