Abstract
Purpose :
To describe the photopic negative response (PhNR) following the onset of chronically elevated intra-ocular pressure (IOP) in a non-human primate (NHP) model and to correlate electroretinographic (ERG) changes with retinal layer thickness.
Methods :
Seven male cynomolgus monkeys (Macaca fascicularis, 9-11 yrs) underwent laser trabecular meshwork destruction (LTD) to elevate the IOP of one eye. IOPs were measured weekly following LTD. Full-field ERGs and flash visual evoked potentials (fVEP) were recorded at ~2-week intervals post IOP elevation. The PhNR stimulus was a 3 cd-s m-2 achromatic flash presented on a background of 80 cd m-2. Measures of PhNR included the minimum voltage 40-100 ms post flash (Pmin), Pmin relative to B-wave amplitude (Prel), and B-Pmin/B-Awave (Pw). Inter-ocular differences were evaluated by paired t-test with Bonferroni correction. Spectral domain optical coherence tomography (sdOCT) scans were obtained at baseline and 5-7 months post IOP elevation.
Results :
At baseline, no inter-ocular differences in the PhNR measures or standard A- or B-wave or fVEP measures were evident. At the first post IOP elevation measurement (60-80 d) and at each of the subsequent 11 tests across 8 months Pmin, Prel, and Pw PhNR measures were significantly reduced in the LTD eye. Inter-ocular differences in PhNR amplitude remained generally stable within an individual across 8 months. PhNR amplitude was relatively reduced in eyes with thinner retinal nerve fiber layer (RNFL). Outer nuclear (ONL) and outer plexiform layers (OPL) were increased in thickness relative to baseline in high IOP eyes and increased thickness was inversely associated with PhNR amplitude. PhNR reduction was selective: no consistent inter-ocular differences were evident for photopic A- or B-wave amplitudes or implicit times. A decrease in fVEP amplitude in the LTD eye was not consistent until 3-4 months following IOP elevation.
Conclusions :
PhNR amplitude declines dramatically within weeks after IOP elevation. The magnitude of PhNR loss then remains relatively stable within a given individual for a relatively long period. PhNR reduction was related not only to the degree of RNFL loss on sdOCT and extent of optic nerve damage histologically, but also to the thickness of outer retinal layers. This suggests that alterations in OPL and ONL can co-occur early in the course of glaucoma and may possibly be involved in loss of the PhNR.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.