Early Optic Neuropathy in a Spontaneous Feline Model of Congenital Glaucoma

Abstract

Purpose: To determine whether structural changes in the optic nerve (ON) precede irreversible loss of visual function in early stage feline inherited primary congenital glaucoma (PCG).

Methods: ON head (ONH) cube and raster scans were acquired by spectral domain optical coherence tomography (OCT) and cortical visual evoked potentials (VEPs) and full-field ERGs (ffERG) were recorded in 16 2mo kittens (7 normal, 9 PCG) derived from a colony that represents the ortholog of human PCG (GLC3D) due to LTBP2 mutation. Testing was carried out in 2 sessions 7-14 days apart. VEP responses were recorded from sub-dermal needle electrodes overlying the occipital cortices and ffERG responses were recorded using corneal contact lens electrodes. Ganzfeld stimuli were 4.1 Hz white flashes (2.7 cd-sm2 on a white 30 cd m2 background) presented monocularly for VEP, and ffERG responses were recorded to light intensities from 0.068 to 10.8 cd m2 presented binocularly. Following the last testing session, optic nerves were processed for light microscopic assessment of damage and axons quantified using a semi-automated targeted sampling method. Specific ONH parameters evaluated included peri-papillary thickness of the retinal nerve fiber layer, cup depth, posterior laminar displacement, width of neural canal opening and pre-laminar tissue thickness. For VEP analysis, RMS amplitude of the early wavelets (0-35 ms) and peak amplitude of the late positive component (“P2”) that characterize the feline VEP were calculated. For ffERG analysis, a-wave and b-wave amplitudes calculated and plotted vs intensity. For each parameter, values were averaged for both eyes and over both testing sessions as appropriate and then compared between groups by unpaired student t-test, with p<0.05 considered significant.

Results: In 2mo PCG kittens, IOP was significantly higher than normal and posterior displacement of the LC was observed on OCT. The amplitudes of P2 and the early wavelets were variable between animals, but were consistent between testing sessions. Amplitudes of P2 and early wavelet RMS were lower than normal in all but one PCG kitten but the difference between groups was not significant. Mean axon count in PCG was significantly lower than normal but no histologic evidence of axonal damage was evident.

Conclusions: Kittens with PCG show symmetric IOP elevation and posterior displacement of the LC but minimal or no loss of ON axons at 2 months of age.

Keywords: 508 electrophysiology: non-clinical • 629 optic nerve • 551 imaging/image analysis: non-clinical