Progressive loss of retinal ganglion cell function precedes structural loss by several years in glaucoma suspects

Abstract

Purpose: We determined the time lag between loss of retinal ganglion cell function and retinal nerve fiber layer (RNFL) thickness.

Methods: Glaucoma suspects were followed for at least four years. Patients underwent pattern electroretinography (PERG), optical coherence tomography (OCT) of the RNFL, and standard automated perimetry testing at 6-month intervals. Comparisons were made between changes in all testing modalities. To compare PERG and OCT measurements on a normalized scale, we calculated the dynamic range of PERG amplitude and RNFL thickness. The time lag between function and structure was defined as the difference in time-to-criterion loss between PERG amplitude and RNFL thickness.

Results: For PERG (P < 0.001) and RNFL (P = 0.030), there was a statistically significant difference between the slopes corresponding to the lowest baseline PERG amplitude stratum (≤50%) and the reference stratum (>90%). Post hoc comparisons demonstrated highly significant differences between RNFL thicknesses of eyes in the stratum with most severely affected PERG (≤50%) and the two strata with least affected PERG (>70%). Estimates suggested that the PERG amplitude takes 1.9 to 2.5 years to lose 10% of its initial amplitude, whereas the RNFL thickness takes 9.9 to 10.4 years to lose 10% of its initial thickness. Thus, the time lag between PERG amplitude and RNFL thickness to lose 10% of their initial values is on the order of 8 years.

Conclusions: In patients who are glaucoma suspects, PERG signal anticipates an equivalent loss of OCT signal by several years.

Conflict of interest statement

Disclosure: M.R. Banitt, None; L.M. Ventura, None; W.J. Feuer, None; E. Savatovsky, None; G. Luna, None; O. Shif, None; B. Bosse, None; V. Porciatti, None

Figures

Figure 1

Baseline mean RNFL thickness for four strata of baseline PERG abnormality, based on the magnitude of percentage deviation from normal. For PERG and RNFL, baseline was calculated as the average of first 3 measurements of the longitudinal series. Error bars represent the SEM. The asterisk above the bar represents the level of statistical significance (P < 0.05).

Figure 2

Pooled slopes of PERG amplitude (A) and RNFL thickness (B) for the four strata of baseline PERG abnormality. Error bars represent the SEM.

Figure 3

Dynamic ranges of PERG amplitude and RNFL thickness. Data are expressed as percent deviation from the reference stratum with highest PERG amplitude (>90% of normal). For PERG, the floor represents the mean amplitude (0.29 μV) recorded in a sample of patients with advanced glaucoma. For RNFL, the floor represents the minimum average RNFL thickness (45 μm) measured in patients with severe glaucoma using the same OCT instrument. Error bars represent the SD.