The relationship between retinal ganglion cell function and retinal nerve fiber thickness in early glaucoma

Abstract

Purpose: To compare relative reduction of retinal ganglion cell (RGC) function and retinal nerve fiber layer (RNFL) thickness in early glaucoma by means of steady-state pattern electroretinogram (PERG) and optical coherence tomography (OCT), respectively.

Methods: Eighty-four persons with suspected glaucoma due to disc abnormalities (GS: mean age 56.6 +/- 13.8 years, standard automated perimetry [SAP] mean deviation [MD] -0.58 +/- 1.34 dB) and 34 patients with early manifest glaucoma (EMG, mean age 65.9 +/- 10.7 years, SAP MD -2.7 +/- 4.5 dB) were tested with PERG and OCT. Both GS and EMG patients had small refractive errors, corrected visual acuity > or =20/25, and no systemic or retinal disease other than glaucoma.

Results: MDs from age-predicted normal values were larger for PERG amplitude (GS: -1.113 dB; EMG: -2.352 dB) compared with the PERG-matched RNFL thickness (GS: -0.217 dB; EMG: -0.725 dB). Deviations exceeding the lower 95% tolerance intervals of the normal population were more frequent for PERG amplitude (GS: 26%; EMG: 56%) than PERG-matched RNFL thickness (GS: 6%; EMG: 29%).

Conclusions: In early glaucoma, reduction in RGC electrical activity exceeds the proportion expected from lost RGC axons, suggesting that a population of viable RGCs in the central retina is dysfunctional. By combining PERG and OCT it is, in principle, possible to obtain unique information on reduced responsiveness of viable RGCs.

FIGURE 1

(A) Example of steady state PERG recorded simultaneously from both eyes of a subject with suspicion of glaucoma due to increased optic disc cupping (right eye: black, left eye: gray). Dashed tracings superimposed on the PERG waveforms represent the response component at the contrast-reversal frequency isolated by means of digital Fourier transform (DFT) analysis. (B) Example of RNFL thickness profile recorded from the right eye of a patient with suspected glaucoma. Thin gray lines: four consecutive scans. Thick black line: average of four scans. The vertical grid defines different quadrants of the scan (T, temporal; S, superior; N, nasal; I, inferior). PERG-T represents a temporal sector (60° above and 75° the horizontal meridian) recipient of the RGC axons originating from the area subtended by the PERG stimulus.

FIGURE 2

Relative size of retinal area covered by the PERG stimulus (circular pattern of horizontal bars centered on the fovea) and the RNFL scan (clock-hour circle centered on optic disc). Axons originating from ganglion cells covered by the PERG stimulus spread over a temporal sector of the RNFL scan approximately corresponding to clock-hour sectors 7, 8, 9, to 10 plus one half of 11.

FIGURE 3

A) PERG amplitude as a function of RNFL thickness of the PERG-matched temporal sector in GS and EMG patients. (B) Average PERG amplitude as a function of average RNFL thickness of the PERG-matched temporal sector in NCs (□), GS, and EMG. Averages have been adjusted to the mean age of the whole subject population. Bidirectional errors bars represent standard deviations. (C) Signed deviations in dB from age-predicted normal values of PERG amplitude and RNFL thickness of the PERG-matched temporal sector in GS and EMG patients.

FIGURE 4

Average deviations from predicted ± SEM for PERG amplitude and RNFL thickness of different regions of the optic nerve. Note that PERG deviation is larger than RNFL deviation for all regions of the optic nerve. Also note that deviations of both PERG amplitude and RNFL thickness are larger in EMG than in GS subjects.