Tackling postop IOP head-on with sustained-release option

One dose of dexamethasone intraocular suspension 9% (DEXYCU, EyePoint Pharmaceuticals) affects the IOP the same way that short-term prednisolone acetate does in patients who have undergone cataract surgery based on the results of two phase III studies.

“Decreasing the postoperative drop burden and increasing compliance can be accomplished with Dexycu, the only FDA-approved intraocular steroid that has the same IOP safely profile as the time-tested topical prednisolone acetate suspension,” according to Cynthia Matossian, MD, who is in private practice in Mercer County, NJ, and Bucks County, PA.

The drug is contained in a delivery device made of acetyltriethyl citrate. This sustained-release product has received FDA approval to treat inflammation postoperatively. After the suspension is injected into the aqueous, under the iris, a 2-mm spherical bolus forms that bio-erodes over time, releasing higher levels of drug initially with a gradual taper over 30 days, she explained.

The phase 3 studies

A total of 575 patients undergoing cataract surgery were included in the two studies. The first study was a prospective, randomly selected, double-masked, multicenter trial in which the 394 patients were randomly assigned to either 5 μL of a 517-μg dexamethasone intraocular suspension (marketed dose) (n = 156) or 5 μL of placebo (vehicle) (n = 80). (The 394 patients were randomly selected; however, the active and placebo arms only add up to 236 patients, because this study focused on the 342-ucg marketed dose received by 158 patients and does not include the 342-mcg dose arm.)

The primary outcome measure was the clearing of the anterior chamber cells from the eyes on postoperative day eight; the secondary outcome measures were anterior chamber flare and the clearing of the anterior chamber cells plus anterior chamber flare in the study eye. In the second phase III study, 181 patients were randomly assigned to receive one injection of dexamethasone intraocular suspension 9% (n = 126) or prednisolone acetate 1% drops instilled four times daily (n = 55). The safety outcomes included the incidence and severity of the treatment-emergent adverse events.

The study was not powered to detect differences in efficacy, but the clearing of the anterior chamber cells and the anterior chamber flare were graded, Dr. Matossian explained.

The results of the first study showed that on postoperative day eight, 60% of the patients treated with one dose of dexamethasone intraocular suspension 9% had no cells in the anterior chamber compared with 20% of those randomized to placebo, a difference that reached significance (P < 0.001). The IOP outcomes and the effect of dexamethasone intraocular suspension 9% on IOP compared with placebo (vehicle injection) or topical prednisolone acetate 1% were analyzed in both phase III studies.

The effect of the drug on the IOP is important because in a normal population, 4% to 6% of patients can be steroid responders, which, if not detected or treated, may lead to irreversible optic nerve damage and visual field loss. The increases generally occur after 3 to 6 weeks of topical corticosteroid use and almost never before five days of use. Patients with a familial history of glaucoma, diabetes, high myopia, and young age under 10 years are at an increased risk.

Dr. Matossian explained that IOP levels of the study eye were categorized as below 25 mm Hg, 25 to 29 mm Hg, 30 to 34 mmHg, and 35 mm Hg or higher. The distribution of the patients across the IOP categories and the proportion of patients with IOP increases of 10 mmHg or higher compared with baseline were summarized by treatment group and time point.

The investigations also looked at the numbers of patients who needed IOP-lowering drugs.

The results

Both phase III studies showed that the percentages of patients in each IOP category were similar between the treatment and controls at each time point. In the prednisolone-controlled study, the proportions of patients with IOP increases of 10 mm Hg or higher were comparable in the dexamethasone intra-ocular suspension and topical prednisolone groups on postoperative day 1, 23.9% versus 18.2%, respectively; on postoperative day 8, 4.0% versus 0.0%, respectively; and on postoperative day 30, 0.0% versus 0.0%, respectively.

Twelve patients randomly selected to dexamethasone intra-ocular suspension and two randomly selected to topical prednisolone required IOP-lowering medications, which successfully lowered the IOP by the time of the next measurement.

In the placebo-controlled study, the IOP increases requiring medication also resolved in all cases (13 with the dexamethasone intraocular suspension and 5 with placebo) by postoperative day 15. Dr. Matossian summarized the salient points of the study.

“In both phase III studies, the proportions of patients in each IOP category were similar in the treatment and control groups at each time point,” she concluded. “The percentages of patients with IOP increases that were 10 mm Hg or higher were similar in the dexamethasone intra-ocular suspension and topical prednisolone groups at each time point. The IOP elevations that needed treatment with IOP-lowering medication resolved by the time of the next measurement. The effect on the IOP of one dose of dexamethasone intraocular suspension 9% is comparable to short-term topical prednisolone acetate after cataract surgery.”

Disclosures:

Cynthia Matossian, MD
E: cmatossian@matossianeye.com
Dr. Matossian has no relevant financial interests to disclose