Validation of Tonometers and Evaluation of Aqueous Humor Flow in the Nonhuman Primate

Date

2019-05

Journal Title

Journal ISSN

Volume Title

Publisher

Abstract

PURPOSE: Intraocular pressure (IOP) is a major risk factor for glaucoma, and the only therapeutic intervention for clinical care. While glaucoma has an elusive cause, much about disease pathophysiology has been established using animal models of ocular hypertension. There is a gap in the literature on validation of IOP measuring tools and aqueous dynamics in experimental models. The main emphasis of this thesis is on; 1) validating non-invasive clinical measures of IOP, and 2) determining the role of homeostasis for maintaining IOP in healthy Non-Human Primate eyes.

METHODS: For these experiments, each eye was cannulated with a 27G butterfly needle, which was attached to a pressure transducer and syringe pump system. In the first experiment, 17 eyes, 11 normal and 6 with experimental intervention, of 12 rhesus macaque monkeys were used. IOP was adjusted between 10 and 60 mmHg in 5 mmHg steps, and tonometry measures obtained using the Tono-Pen and TonoVet systems at pressures 10-50 mmHg. For the second experiment, 5 healthy monkeys were used. To assess response to transient, but sustained elevated pressure, the fluid needed to maintain a pressure of 25 mmHg and 40 mmHg was established for a duration of 2hrs.

RESULTS: Experiment 1: TonoVet measures overestimated IOP at all pressure settings (mean difference of 3.17 mmHg, 95% CI 12.53 to −4.74 normal, 3.90 mmHg, 95% CI 12.90 to −6.53 experimental glaucoma). In contrast, Tono-Pen measures overestimated IOP at lower IOPs and underestimated at higher IOP (slope = −0.26 normal, −0.21 experimental glaucoma). Experiment 2: The total inflow, rate of inflow, and variability was greater at 40 mmHg (total fluid median=2.49 mL, range = 0.80- 5.8mL), (rate of fluid inflow median=13.2µl/min, range 4.26 – 42.88 µl/min) compared to 25 mmHg (total fluid median=1.5mL, range = 0.44- 1.85mL), (rate of increase of fluid inflow median=5.4 µl/min, range 1.8 – 9.6 µl/min).

CONCLUSIONS: In the rhesus macaque, the Tono-Pen and TonoVet generally reflect IOP, but for accurate measures, both instruments require individualized calibration. Outflow of the healthy NHP eye responds rapidly to changes in IOP, but with significant inter-individual variability. These findings are important for future work in understanding the impact of IOP and topical medications in experimental models.

Description

Keywords

Tonometry, Non-human primates, Aqueous Humor

Citation

Portions of this document appear in: McAllister, Faith, Ronald Harwerth, and Nimesh Patel. "Assessing the True Intraocular Pressure in the Non-human Primate." Optometry and vision science: official publication of the American Academy of Optometry 95, no. 2 (2018): 113-119.