Corticosteroid-induced ocular hypertension in cynomolgus monkeys

Purpose: To determine whether topical ocular administration of a potent glucocorticoid is capable of generating ocular hypertension in cynomolgus monkeys. Methods: Eleven cynomolgus monkeys were trained for conscious IOP readings using only topical ocular anesthesia. After establishing baseline IOPs, 0.1% dexamethasone (DEX, 30 uL) was instilled tid in both eyes for 28 days. IOP measurements were taken by applanation tonometry at 3-4 day intervals for 42 days. After a washout period of several months, the test was repeated. Results: Five of eleven monkeys developed time-dependent, bilateral IOP increases of > 5 mm Hg. The average pressure rise in these responders was 10.6 ± 3.6 mm Hg after 28 days of DEX treatment. IOP's returned to baseline levels within two weeks of discontinuing DEX administration. In the second challenge with DEX, four of the steroid responders again developed IOP elevations of > 5 mm Hg (the fifth responder was not tested). The six non-responders remained unresponsive to DEX. Conclusions: Topical ocular administration of a potent glucocorticoid can lead to the development of reproducible ocular hypertension in monkeys. The ratio of steroid responsiveness and the ocular hypertension induction profile in this small monkey population is similar to that reported in the general human population. This may be a useful model to evaluate the effects of IOP lowering agents and to better understand the pathophysiology of corticosteroid glaucoma.