Prevention of corticosteroid-induced intraocular pressure elevation using ISV-205

Abstract

Objective: To determine whether a topical ophthalmic diclofenac sodium formulation containing a proprietary polymeric drug delivery system (ISV-205), when dosed concomitantly with 1% prednisolone acetate, is effective in blocking the intraocular pressure (IOP) response in humans.

Design: This was a multicenter, prospective, double-masked, parallel, vehicle-controlled study. We included 136 first-degree relatives of subjects with primary open-angle glaucoma. Subjects were randomized to receive 0.06% or 0.1% ISV-205 or vehicle while concomitantly receiving 1% prednisolone for 6 weeks.

Results: During the treatment period, the mean +/- SD maximum IOP increase (7.3 +/- 6.5 mm Hg for vehicle, 4.9 +/- 4.6 mm Hg for 0.06% ISV-205, and 5.9 +/- 4.9 mm Hg for 0.1% ISV-205) was significantly less with the 0.06% formulation than with placebo (P =.02). The overall mean change in IOP was 3.6, 2.0, and 2.4 mm Hg in the vehicle, 0.06% ISV-205, and 0.1% ISV-205 groups, respectively, which was significant between the 0.06% ISV-205 and vehicle groups (P =.05). Eight (17%) of the 46 subjects receiving vehicle terminated the study because of high IOPs, compared with 1 (2%) of the 45 subjects receiving 0.06% ISV-205 and 3 (7%) of the 45 subjects receiving 0.1% ISV-205 (P =.03). The number of subjects with a clinically important corticosteroid response (> or =10-mm Hg increase) was greater in the vehicle group (12 [28%] of 43 subjects) compared with the 0.06% ISV-205 group (3 [7%] of 42 subjects) (P =.01). Adverse events were similar between treatments.

Conclusions: This study suggests that ISV-205 limits the corticosteroid-induced elevated IOP in first-degree relatives of subjects with glaucoma. Future studies are needed to confirm these results and explore the possible role of this drug in treating glaucoma.