Safety and Efficacy of Twice-Daily Pilocarpine HCl in Presbyopia: The Virgo Phase 3, Randomized, Double-Masked, Controlled Study.

PURPOSE: To evaluate the safety, efficacy, and pharmacokinetics of pilocarpine hydrochloride 1.25% (Pilo hereafter) compared with vehicle when administered bilaterally, twice daily (6 hours apart) for 14 days in participants with presbyopia. DESIGN: Phase 3, randomized (1:1), controlled, double-masked, multicenter study. METHODS: Participants (40-55 years of age) had objective and subjective evidence of presbyopia affecting daily activities with mesopic, high-contrast, binocular distance-corrected near visual acuity (DCNVA) of 20/40 to 20/100. The primary/key secondary endpoint was the proportion of participants gaining ≥3 lines in mesopic/photopic, high-contrast, binocular DCNVA on day 14 (last study visit), hour 9 (3 hours after the second dose), with no more than a 5-letter loss in mesopic/photopic corrected distance visual acuity with the same refractive correction. Key safety measures included treatment-emergent adverse events (TEAEs) and some ocular measurements. Pilocarpine plasma levels were assessed in approximately 10% of enrolled participants. RESULTS: Overall, 230 participants were randomized to Pilo twice daily (N = 114) and vehicle (N = 116). The proportion of participants achieving the primary and key secondary efficacy endpoints was statistically significantly greater with Pilo twice daily than vehicle, with between-treatment differences of 27.3% (95% CI = 17.3, 37.4) and 26.4% (95% CI = 16.8, 36.0), respectively. The most common TEAE was headache, reported in 10 participants (8.8%, Pilo group) and 4 participants (3.4%, vehicle group). Pilocarpine's accumulation index on day 14 was ≤1.11 after the second dose. CONCLUSIONS: Near-vision improvements were statistically greater with Pilo twice daily than with vehicle, without compromising distance acuity. The safety profile of Pilo twice daily was consistent with that of Pilo once daily, and systemic accumulation was minimal, supporting twice daily administration.

Quantitative assessment of aqueous flare: the effect of age and pupillary dilation.

OBJECTIVE: To assess the effect of age and pupillary dilation on aqueous flare. METHODS: In this study, 100 eyes of 100 patients ranging in ages from 23 to 84 years were examined. Anterior chamber flare was measured before and after pupillary dilation using the Kowa laser flare meter (FM-500). Predilation and postdilation flare counts were compared by paired t-test. Stepwise regression analysis was then used to determine the effect of demographic variables on pre- and postdilation flare as well as the difference between pre-and postdilation flare counts. RESULTS: The predilation and postdilation flare counts correlated with age (P < 0.0001 for both pre-and postdilation flare counts). Correlation coefficient between age and flare measurements was R2 = 0.58 predilation and 0.63 postdilation. Flare intensity significantly decreased after pupillary dilation (P < 0.001). CONCLUSIONS: Anterior chamber flare increases with age. It might be related to blood-aqueous barrier instability. Pupillary dilation significantly decreases flare counts suggesting that aqueous protein concentration is dependent on aqueous flow rates.