Abstract
Purpose :
To evaluate the pressure and time dependent changes in retina and optic nerve of ocular hypertensive African green monkeys (Chlorocebus sabaeus) to guide interpretation of interventional studies evaluating neuroprotective glaucoma therapies.
Methods :
Monkeys (n=15) underwent laser scarification of the trabecular meshwork to obstruct aqueous outflow applying circumferential laser spots of 50-100 mm, pulse duration 0.5 or 1 second, and power 0.3- 0.75 Watts by four mirror gonioscope. All animals underwent weekly slit lamp exam, color fundus imaging, and optical coherence tomography (OCT) with determination of retinal ganglion cell (RGC), retinal nerve fiber layer (RNFL), and Bruch’s membrane opening minimum rim width (BMO-MRW) measures. A subset of eyes received timolol at week 2, with repeat OCT 4-6 hours post-treatment. Hematoxylin and eosin (H&E) histopathology was performed at the end of the study.
Results :
Eyes exhibited variable IOP elevation and durations of elevation, reflecting varied applied energy and inter-animal differences in response to laser induction. Eyes with durable IOP elevation > 30 mmHg exhibited a decrease in RGC or RNFL thickness, whereas eyes with transient IOP elevation persisting less then 2 weeks did not. Likewise, eyes with durable IOP elevation > 30 mmHg exhibited a progressive decrease in BMO-MRW. Of the OCT endpoint measures BMO-MRW was most closely correlated to IOP elevation, and changes from baseline in optic nerve head (ONH) cupping was the least correlated, which was corroborated by histology. Measures of BMO-MRW following transient timolol alleviation of IOP elevation resulted in partial recovery of BMO-MRW, suggesting that some component of thinning is related to hydrostatic pressure 2 weeks post elevation.
Conclusions :
The nonhuman primate trabecular laser model of hyperphysiological IOP recapitulates important aspects of human glaucoma such as RNFL and BMO-MRW thinning, ONH cupping, and responsiveness to timolol suppression of aqueous production. We have defined that BMO-MRW is the most pressure correlated of evaluated glaucomatous changes, the rate of BMO-MRW change at given pressures, and methods for evaluating retinal and ONH atrophy versus tissue compressive effects, establishing a valuable test system for therapeutic evaluation.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.