Alternate delivery routes offer strategies for reducing reliance on topical drugs

February 1, 2008

Use of topical drops after cataract surgery may be associated with a number of drawbacks. Alternative strategies for intraoperative drug delivery can be highly effective and more economical, as well as offer better safety, convenience, and efficacy.

Key Points

"Avoiding postoperative drops is possible by using alternate routes for medication administration and has important benefits for improving convenience and comfort and reducing treatment cost, toxicity, and compliance issues," said Dr. Gills, clinical professor of ophthalmology, University of South Florida, Tampa. "Furthermore, it allows for better dosage control and targeted delivery that results in better efficacy and faster recovery."

Dr. Gills discussed the use of intracameral, intravitreal, and subconjunctival delivery of medications for preventing endophthalmitis and cystoid macular edema (CME) and controlling postoperative pain and inflammation. He said he began using triamcinolone acetonide (Kenalog, Bristol-Myers Squibb) administered as an intracameral injection into the anterior chamber, but his technique has evolved over time. Initially, he switched to delivering the corticosteroid into the posterior chamber through the zonules but said he now prefers using a subconjunctival injection that he has found to be particularly beneficial for providing a "wow effect" to patients implanted with premium IOLs.

"Compared with intravitreal administration, subconjunctival injection of triamcinolone offers a longer duration of action and avoids causing cloudiness that can reduce visual acuity and interfere with the wow effect," Dr. Gills said.

In addition, subconjunctival triamcinolone appears safer for avoiding IOP elevations, he added. Among patients treated with an intravitreal dose of 4 mg, about 40% experienced IOP of greater than 25 mm Hg. The rate of IOP elevations was reduced to just 6% with administration of a 2 mg intravitreal dose. IOP actually can be lowered when a dose of 1.5 mg is used, however, Dr. Gills said.

Pretreatment for preventing CME also is particularly important in diabetic patients. Dr. Gills said he routinely begins topical ketorolac three times daily prior to surgery in these patients and also evaluates them with optical coherence tomography (OCT) to identify individuals who would benefit from pretreatment with intravitreal bevacizumab (Avastin, Genentech) or triamcinolone. Appropriate candidates are those with diabetic macular edema or macular degeneration and a retinal thickness of 300 µm or greater on OCT.

"In an initial patient in whom I administered a 2.5 mg dose of bevacizumab 1 week prior to surgery, I found out that by blocking the action of [vascular endothelial growth factor], it was unnecessary to use any drops after the cataract surgery to prevent CME," he said.

Discussing intracameral antibiotics, Dr. Gills said he has decades of experience with intraocular administration of antibiotics, beginning with their addition into the irrigating solution. He said he subsequently transitioned to administration of an intracameral injection at the end of the case, however, because it provides better dosage control.

His current protocol for preparing the intracameral injection results in a solution that contains 20 µg ceftazidime, 33.3 µg of vancomycin, and 99 µg dexamethasone per 0.1 ml.

"The doses in the intracameral injection represent just one-tenth of the therapeutic dose for each component and are very safe and highly effective," Dr. Gills said. "In a consecutive series that now exceeds more than 50,000 cases, we have used intraocular antibiotics effectively without a single case of endophthalmitis.

"In a study investigating the use of the addition of vancomycin to the irrigating solution during phacoemulsification, Antonio Mendivil Soto, MD, and colleagues reported a benefit for significantly reducing the rate of positive anterior chamber cultures compared with controls where no antibiotic was added to the irrigating fluid," he added.

Looking to the future, Dr. Gills said he expects biocompatible implants to play an important role as another medication delivery strategy for eliminating dependence on postoperative drops. Research to date using collagen implants shows that they can be created to release corticosteroids or nonsteroidal anti-inflammatory drugs over periods lasting from 6 weeks to 6 months, depending on the composition of the delivery system.