title: Surgical lowering of elevated intraocular pressure in monkeys prevents progression of glaucomatous disease.
abstract: Recent reports from large clinical trials have clearly demonstrated that lowering intraocular pressure (IOP) in persons with ocular hypertension has a beneficial effect on reducing the progression of glaucomatous disease. Few studies of this effect have been conducted in controlled laboratory settings, however, none have been conducted using non-human primates, the model of experimental glaucoma considered most similar to the human disease. Using data collected retrospectively from a trabeculectomy study using 16 cynomolgous monkeys with experimental ocular hypertension, we evaluated both the threshold of elevated IOP required to cause clinically observable damage to the optic nerve head and also if lowering IOP below this threshold prevents further damage. An index of the level of elevated IOP experienced by experimental eyes (the Pressure Insult) was calculated as the slope of the difference in cumulative IOP between experimental and control eyes during four intervals of time over the course of the experiment, while damage to the optic nerve head was evaluated by measuring the Cup:Disc ratio for each eye from stereoscopic photographs taken at the end of each interval. An increase in the Cup:Disc ratio was significantly associated with both the maximum IOP obtained in the experimental eye during each interval (r=0.573, P<0.001) and the Pressure Insult (r=0.496, P<0.001). Pressure Insult values less than 11 mm Hg Days/Day were not associated with glaucomatous damage in monkey eyes, whereas values greater than 11 showed a significant correlation with increasing Cup:Disc ratios (P<0.001). Trabeculectomy to reduce the Pressure Insult below 11 was correlated with an attenuation of the rate of progression of the Cup:Disc ratio in eyes that had exhibited damage before surgery. These results contribute further to our understanding of this model of experimental glaucoma by demonstrating a threshold at which IOP needs to be elevated to stimulate damage, while also providing corroborating evidence that lowering IOP in ocular hypertensive monkeys can attenuate the progression of glaucomatous disease.
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Wisconsin, Madison, WI 53706, USA. nickells@wisc.edu
authors.forename: Robert W
authors.initials: RW
authors.lastname: Nickells
authors.forename: Cassandra L
authors.initials: CL
authors.lastname: Schlamp
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Paul L
authors.initials: PL
authors.lastname: Kaufman
authors.forename: Gregg
authors.initials: G
authors.lastname: Heatley
authors.forename: John C
authors.initials: JC
authors.lastname: Peterson
authors.forename: Barbara
authors.initials: B
authors.lastname: Faha
authors.forename: James N
authors.initials: JN
authors.lastname: Ver Hoeve
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D018450:Disease Progression; D015316:Genetic Therapy / Q000379:methods; D005901:Glaucoma / Q000503:physiopathology / Q000517:prevention & control* / Q000601:surgery; D007429:Intraocular Pressure / Q000502:physiology*; D008252:Macaca fascicularis; D009798:Ocular Hypertension / Q000503:physiopathology / Q000601:surgery*; D009898:Optic Disk / Q000473:pathology; D012189:Retrospective Studies; D014130:Trabeculectomy / Q000379:methods; D014945:Wound Healing / Q000502:physiology