Comparison of Retinal Nerve Fiber Layer Thickness (RNFLT) Measured In Vivo by Spectral Domain Optical Coherence Tomography (SDOCT) and Orbital Optic Nerve Axon Counts at an Early Stage of Experimental Glaucoma in Non-human Primates (NHPs)

Abstract

Purpose: : To compare peripapillary RNFLT measured in vivo by SDOCT with complete axon counts from the anterior retrobulbar optic nerve (ON) in early experimental glaucoma (EEG).

Methods: : Five NHPs (ages 2 to 24 yrs) had three or more weekly baseline measurements in both eyes of RNFLT by SDOCT (Spectralis, Heidelberg Engineering, GmbH). Trabecular meshwork laser treatment was performed to induce chronic intraocular pressure (IOP) elevation in one eye each. Bi-weekly measurements of RNFLT were obtained throughout the follow-up period (range 26 to 39 weeks). Animals were sacrificed within 2 months of onset of glaucomatous optic disk changes in 4 animals and 6 months later in another. Complete (100%) axon counts were obtained from each ON using an automated image analysis algorithm.¹ Parameters were compared using Wilcoxon non-parametric paired t-tests.

Results: : Average post-laser IOP in the EEG eyes ranged from 9 to 18 mmHg, peak IOP ranged from 18 to 30 mmHg and the cumulative IOP difference (between the EEG and fellow control eye) ranged from 61 to 351 mmHg-days. RNFLT at baseline was not significantly different between the EEG and control eyes (0.6% ± 1.8% difference, p = 0.62). RNFLT at the final time point was not significantly different from baseline in control eyes (-0.3% ± 1.9%, p = 1.0). In the EEG eyes, RNFLT at the final time point had declined by only 1.8% ± 6.0% relative to baseline (p = 0.62; individual changes: -3.4%, -3.9%, -4.9%, -5.6%, and +8.8%). RNFLT in the EEG eyes was only 2.1% ± 4.8% thinner than fellow control eyes at the final time point (p = 0.21). ON axon counts were reduced by 16% ± 6.0% in the EEG eyes relative to control eyes (p = 0.03, range: -11.4% to -26.3%).

Conclusions: : In early experimental NHP glaucoma, close to the onset of optic disk surface topography change, RNFLT is only minimally reduced (~2%) while complete axon counts reveal 16% axon loss. The discrepancy at this early stage could be due in part to RNFL swelling in vivo, gliosis within the RNFL and/or differences between rates of anterograde and retrograde axonal degeneration.¹Reynaud et al, ARVO 2009: 5829; ARVO 2010: 2143.

Keywords: ganglion cells • optic nerve • retinal glia