Phase IIb, III data show anti-inflammatory/mydriatic agent reduces miosis
An investigational combination drug could facilitate the ease of performing surgical procedures and help reduce the incidence of intraoperative miosis.
By Lynda Charters; Reviewed by J. Steven Whitaker, MD, JD
Seattle-An investigational combination drug (OMS302, Omeros Corp.) seems to facilitate the ease of performing surgical procedures and helps reduce the incidence of intraoperative miosis.
The preservative-free and bisulfite-free drug contains the active agents phenylephrine hydrochloride and ketorolac tromethamine. Added to the balanced salt solution routinely used as irrigation, the combination drug is administered intracamerally during the surgical procedure, bathing the targeted the receptors and enzymes within the anterior chamber and establishing and maintaining steady-state concentrations.
J. Steven Whitaker, MD, JD, highlighted the results of phase IIb and phase III randomized, double-masked, vehicle-controlled, multicenter studies to determine the effect of the anti-inflammatory/mydriatic agent on the incidence of intraoperative miosis during IOL replacement surgery in the setting of standard preoperative mydriatic drops.
The goals with use of the drug are to maintain mydriasis intraoperatively, prevent intraoperative miosis, and reduce postoperative pain in patients undergoing IOL replacement surgery, explained Dr. Whitaker, vice president, clinical development and chief medical officer, Omeros. The drug, which is added to standard irrigation solution used during IOL replacement surgery, provides a consistently low concentration of both components intraoperatively.
In this study, miosis was defined as a pupil diameter of ≤6 mm or pupil constriction of at least ≥2.5 mm from baseline. A masked central reader measured the pupil diameters every minute using a validated program (ImageJ) available from the National Institutes of Health.
A pupil diameter of ≤6 mm is associated with increased complications, such as posterior capsule tears, retained lens fragments, and vitreous loss, Dr. Whitaker noted.
In the phase IIb study of patients undergoing cataract surgery, the combination drug (49 patients) was compared with phenylephrine hydrochloride alone (49 patients), ketorolac alone (52 patients), and the vehicle (53 patients). The incidence rates of a pupil diameter of 6 mm or less, respectively, were 22%, 35%, and 46% compared with 6% in patients treated with the combination drug. All comparisons reached significance (p = 0.04, p = 0.0005, and p < 0.0001, respectively).
The reduction in pupil diameter was ≥2.5 mm in 11 patients treated with ketorolac alone (p = 0.02), one patient treated with phenylephrine alone (no significant difference), and 12 patients who received the vehicle (p = 0.008) compared with the combination drug (two patients).
In the phase III study of patients undergoing IOL replacement surgery, 180 patients received placebo and 184 patients received the combination drug. Significantly fewer patients had an intraoperative pupil diameter of ≤6 mm when the combination drug was used. Ten percent of patients treated with the combination drug compared with 46% of those who received placebo had a pupil diameter of ≤6 mm at any point during surgery. The respective percentages were 4% and 23% at the end of cortical clean-up. The differences were significant (p < 0.001) for both comparisons.
Fifty patients who received placebo compared with six patients who received the combination drug had a change in pupil diameter of ≥2.5 mm compared with baseline (p < 0.0001), Dr. Whitaker noted.
Dr. Whitaker commented that during these studies, fewer patients treated with the combination drug had intraoperative miosis as measured by a pupil diameter of ≤6 mm or pupil constriction of ≥2.5 mm compared with placebo, ketorolac, or phenylephrine alone. These findings are consistent with the pharmacologic actions of ketorolac, which inhibits prostaglandin release, and phenylephrine, which is an alpha-adrenergic agonist, he noted.
“The combination of the two drugs achieved [results superior] to those achieved with either drug alone,” Dr. Whitaker concluded. “[This anti-inflammatory/mydriatic agent] could ease surgical procedures and reduce the incidence of complications.”
J. Steven Whitaker, MD, JD
Dr. Whitaker is an employee of Omeros Corp, which provided financial support for this study. This article was adapted from Dr. Whitaker’s presentation during the annual meeting of the American Society of Cataract and Refractive Surgery.