Characterization of the Relationship between the Rate of IOP Change and Glaucomatous Damage in Non-human Primates with Ocular Hypertension

Abstract

Abstract: : Purpose: To investigate the relationship between the rate of change in intraocular pressure and the progression of damage in experimental glaucoma, before and after surgical lowering of IOP. Methods: Ocular hypertension was induced in one eye by laser trabeculoplasty in 16 cynomologous monkeys. Fellow eyes served as unaffected controls. When a stable, elevated IOP was obtained in lasered eyes, trabeculectomy surgery, with and without antiproliferative agents, was performed. Animals were followed for 260 days after surgery before sacrifice by perfusion fixation. IOP measurements and optic disc photographs were taken throughout the course of the experiment. Evidence of glaucomatous damage was confirmed by histologic evaluation of the retina (ganglion cell number and nerve fiber layer thickness) and optic nerve of each eye. Results: The cumulative IOP days (cIOP) for each eye was determined and the relative exposure of IOP-related stress for each experimental eye was calculated as the difference between the two eyes of each monkey (ΔcIOP). These data were then grouped into 4 intervals, with the first interval being the period before surgery and intervals 2-4 being ~86 days each after surgery. The rate of change in ΔcIOP was calculated for each interval. Damage to each eye over the course of the experiment was also evaluated by monitoring the change in Cup:Disc ratio (C:D) for the experimental eye. C:D changes predominantly occurred only after the ΔcIOP rate reached a threshold of 10 mmHg days/day. 3/16 monkeys sustained maximal damage before surgery and could not be analyzed further. 6/16 monkeys failed to reach the damage threshold prior to surgery and exhibited no damage during the course of the experiment. 1/16 monkeys showed complete resistance to damage even at high ΔcIOP rates. 6/16 monkeys exhibited partial damage during the presurgery interval, which correlated with suprathreshold levels of ΔcIOP. Further damage was arrested in these animals when surgery reduced the ΔcIOP rate to subthreshold levels. Conclusions: In a short duration study of experimental glaucoma, an increase in the C:D ratio is likely to occur when a threshold of IOP stress is reached. Lowering IOP to subthreshold levels by surgical intervention halts further progression of damage.

Keywords: ganglion cells • apoptosis/cell death • animal model