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1 From the Laboratory for Retina and Optic Nerve Research and the 2 Departments of Ophthalmology, 3 Physiology and Biophysics, and 4 Pharmacology, Dalhousie University, Halifax, Nova Scotia, Canada.
PURPOSE. To characterize the effect of intraocular pressure (IOP) on optic disc topography, retinal function, and axonal survival in a model of IOP-induced optic nerve damage in rat.
METHODS. Hypertonic (1.75 M) saline was injected into an episcleral vein of one eye of 49 Brown Norway rats, with the fellow untreated eye serving as the control. During the 1 to 3 months of follow-up, IOP was measured twice weekly in conscious animals with a handheld tonometer, and changes in disc topography and retinal function were monitored with scanning laser tomography and electroretinography (ERG), respectively. Peak IOP elevation in the experimental eye compared with the fellow control eye (peak 
IOP), integral of IOP elevation over time (IOP integral), and days of IOP elevation were calculated. Axon counts were obtained from electron micrographs of the sectioned optic nerves.
RESULTS. Progressive cupping was found in 9 (56.3%) of 16 eyes with peak IOP of more than 15 mm Hg and in none of 21 eyes with peak IOP less than 15 mm Hg. A strong correlation between IOP integral and progressive cupping was also found, but not with days of IOP elevation. ERG abnormalities (limited to the b-wave) were found in 11 (64.7%) of 17 eyes with peak IOP of more than 15 mm Hg and in 2 (8.7%) of 23 eyes with peak IOP of less than 15 mm Hg. Neither of the other IOP parameters was predictive of ERG damage. The proportion of surviving axons was negatively correlated to both IOP and IOP integral (P 
0.001). Progressive cupping was evident only with more than 55% axonal loss. Similarly, ERG results remained mostly within normal limits for low to moderate axonal loss, but were markedly abnormal with more than 70% axonal loss.
CONCLUSIONS. Structural and functional changes in this model are best correlated to peak IOP and not to duration of IOP elevation, suggesting the existence of an IOP-related damage threshold.
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