New drug aims to treat intraoperative miosis, reduce pain

A recently approved intracameral phenylephrine and ketorolac 1%/0.3% product is expected to produce better surgical outcomes following cataract surgery or IOL replacement by preventing miosis and reducing intraoperative pain.

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By Nancy Groves; Reviewed by Eric D. Donnenfeld, MD

New York-Intracameral phenylephrine and ketorolac injection 1%/0.3% (Omidria, Omeros Corp.)-approved by the FDA for its combined properties of maintaining pupil dilation and reducing pain-is expected to provide multiple advantages to both surgeons and patients during cataract surgery or IOL replacement.

“The goal is to maintain intraoperative mydriasis, to reduce inflammation at the time of surgery, and to reduce the pain associated with surgery,” said Eric D. Donnenfeld, MD, who helped in the clinical trials for the product. Dr. Donnenfeld is a founding partner of Ophthalmic Consultants of Long Island and Connecticut and clinical professor ophthalmology, New York University Medical Center, New York.

Phenylephrine, acting as a mydriatic agent, contracts the radial muscle of the iris, while ketorolac inhibits both cyclooxygenase enzymes, providing a reduction in pain through a decrease in the production of prostaglandins.

“This product is in the perfect place at the perfect time, in that surgeons are looking for both better surgical outcomes and ways to make the procedure more comfortable for patients,” Dr. Donnenfeld said. “We know that a well-dilated pupil improves operative results, reduces complications, and reduces total surgical and phacoemulsification time, so patients end up having more rapid return of visual acuity.”

In addition, the availability of the new agent removes a step that previously was being performed in the operating room, that of compounding a medication that would prevent intraoperative miosis. According to Dr. Donnenfeld, this off-label activity places the patient and the surgeon at risk of formulation errors.

“In the current legal environment, my concerns are that using a compounded medication puts surgical centers and surgeons at risk when something of equal or better efficacy is available in an FDA-approved form,” he explained.

Surgeons have routinely used intraoperative dilating agents, but the new product adds ketorolac for the first time as an intraoperative nonsteroidal.

“In the FDA trials, not only was dilation extraordinarily achieved but pain was also significantly reduced,” Dr. Donnenfeld said.

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He added that the new product also bridges a difference in perception between surgeons and patients. While ophthalmologists consider visual acuity the most important determinant of surgical success, to patients, comfort during and after surgery is often as important as the clinical outcome.

Dr. Donnenfeld predicted that when the new formulation becomes routinely used during cataract surgery and lens replacement, the reduction in pain will mean that fewer patients will be dissatisfied with the comfort of their procedure despite having attained excellent visual acuity.

The product may also have another benefit. It is known that prostaglandins cause intraocular miosis, and that nonsteroidals inhibit their production. Placing a nonsteroidal in the irrigating solution may reduce inflammation postoperatively as well as intraoperatively, Dr. Donnenfeld said, although this was not studied in the FDA trials.

“I view inflammation as a surgical iceberg, with the tip of the iceberg being pupillary miosis,” he said. “If the pupil constricts, it also means that prostaglandins are being released into the eye and into the pain receptors, and it may increase the risk of cystoid macular edema. By reducing intraoperative surgically induced prostaglandin production, I think we can improve our surgical outcomes.”

Pass-through Status: The Centers for Medicare and Medicaid Services (CMS) has issued transitional pass-through payment status for Omidria. This reimbursement decision was based on CMS conclusion that Omidria substantially improves clinical outcomes compared with currently available treatments. Beginning Jan. 1, 2015, ASCs and other outpatient facilities can use a unique HCPCS billing code, C9447, to bill CMS for a separate payment for Omidria, outside the bundled APC payment. Transitional pass-through status typically remains in place for 2 to 3 years.

Leading up to FDA approval, the agent was evaluated in two phase III randomized, multicenter, double-masked, placebo-controlled clinical trials in 808 adult subjects undergoing cataract surgery or IOL replacement. In the group treated with the test product, mydriasis was maintained, while subjects treated with placebo experienced significant progressive constriction.

Pupil diameter was measured throughout the procedures. The results showed that following cortical cleanup, 23% of placebo-treated subjects and 4% of those treated with the combination product had a pupil diameter of less than 6 mm (p < 0.0001).

To assess the secondary outcome, pain during the early postoperative period was evaluated with self-administered visual analog scales with a range of 0 to 100 mm. The results showed that pain 10 to 12 hours postoperatively was statistically significantly less in patients treated with the combination agent than in those treated with placebo.

Ocular adverse reactions such as eye irritation, posterior capsular opacification, increased IOP, and anterior chamber inflammation were similar between the two study groups.

“This is a welcome addition to the surgical armamentarium for refractive cataract surgery,” Dr. Donnenfeld said. “It has everything we’re looking for as surgeons. It improves outcomes, it reduces stress to the surgeon by maintaining pupillary dilation, it is compliant with operating room regulations of not using compound medications, and it makes the patient experience more comfortable while providing better visual outcomes.”

Eric D. Donnenfeld, MD

E:ericdonnenfeld@gmail.com

Dr. Donnenfeld is a consultant for Omeros Corp.