Ophthalmic Drug Delivery Enters New Era

Innovations in drug delivery are leading to a new era in medication administration for patients undergoing cataract surgery, according to Eric D Donnenfeld MD.

“We are now in a transition period, but I predict that use of topical medications as it is known today will change greatly over the next several years,” he said. “The adoption of corticosteroids and nonsteroidal anti-inflammatory drugs (NSAIDs) administered via external inserts, punctal plug systems, and intracamerally will address an important unmet need.”

The need for alternatives to topical medications relates to the issue of patient noncompliance with topical drop regimens and the adverse effects these products have on comfort, cosmesis, and the cornea. Several medications formulated in novel delivery systems with indications for controlling pain and/or inflammation after cataract surgery became available in 2023, and others are in development.

Within the corticosteroid category, two “dropless” sustained-release dexamethasone products are on the market—one is an intracanalicular hydrogel insert containing 0.4 mg dexamethasone (Dextenza, Ocular Therapeutix), and the other is an intraocular suspension containing 9% dexamethasone (Dexycu, EyePoint Pharmaceuticals) for injection into the posterior chamber behind the iris at the end of surgery.

A third dexamethasone product, OCS-01, is still under investigation, though results from a Phase 3 trial show it a promising option for allowing “less drops” surgery. OCS-01 is a preservative-free, high-concentration (15 mg/mL) dexamethasone drop formulated using nanoparticle technology that enhances corneal penetration in a vehicle with prolonged ocular surface residence time. In the Phase 3 trial, once-daily OCS-01 treatment demonstrated statistically significant superiority compared to vehicle in analyses of both the percentage of eyes with complete absence of anterior chamber cells on postoperative day 15 and the percentage with no pain on postoperative day 4.¹

A punctal plug device releasing the NSAID nepafenac over one month has also been investigated and shown in a placebo-controlled phase 2 study to be effective for reducing pain and inflammation after cataract surgery.²

“And as a surprise to me, 65% of patients in the punctal plug group and just 29% of controls had 20/20 or better BCVA at day 14,” Dr Donnenfeld reported.

Surgeons in the United States also have access to a commercially available intracameral product containing the NSAID ketorolac 0.3% and phenylephrine 1% (Omidria, Rayner), indicated for maintaining pupil size and reducing postoperative pain.

“One might postulate that the high pressure, forced infusion used in modern cataract surgery would force NSAID in the anterior chamber through the zonules into the vitreous.

In fact, early results from a trial I am conducting show a very high level of ketorolac in the vitreous in procedures performed with intracameral ketorolac/phenylephrine,” Dr Donnenfeld said.

“I believe this finding could explain results of a published study showing a reduced incidence of cystoid macular oedema in eyes undergoing surgery with intracameral phenylephrine/ ketorolac plus a topical NSAID compared with those treated with a topical NSAID and topical steroid.”³

Dr Donnenfeld spoke during the 2023 ESCRS Congress in Vienna.

Eric D Donnenfeld MD is Founding Partner, Ophthalmic Consultants of Long Island, Garden City, New York, US, and Clinical Professor of Ophthalmology, New York University Medical Center, New York, US. ericdonnenfeld@gmail.com

1. Oculis. “OCS-01, first investigational eye drop for front and back of the eye, met both primary endpoints in phase 3 OPTIMIZE trial with a once daily regimen for the treatment of inflammation and pain following cataract surgery.” August 8, 2023. https://investors.oculis.com/news-releases/news-release-details/ocs-01-first-investigational-eye-drop-front-and-back-eye-met. Accessed September 28, 2023.

2. Donnenfeld ED, Holland EJ, Solomon KD. “Safety and efficacy of nepafenac punctal plug delivery system in controlling postoperative ocular pain and inflammation after cataract surgery,” J Cataract Refract Surg., 2021 Feb 1; 47(2): 158–164.

3. Visco DM, Bedi R. “Effect of intracameral phenylephrine 1.0%-ketorolac 0.3% on postoperative cystoid macular edema, iritis, pain, and photophobia after cataract surgery,” J Cataract Refract Surg., 2020 Jun; 46(6): 867–872.