IOLs as drug delivery devices: the future for antibiotic provision?

Antibiotic-soaked IOLs could present a viable alternative to topical antibiotics for surgeons wanting to provide a sustained release of antibiotic in cataract patients, according to Randall Olson, MD, Presidential Professor and Chair of the Department of Ophthalmology and Visual Sciences at the John A. Moran Eye Centre, Salt Lake City, Utah, USA.

Bacterial resistance to certain antibiotics has forced cataract surgeons to consider alternative antibiotic agents and methods of administration to prevent postoperative infection in their cataract patients. With this in mind, Dr Olson discussed several studies that supported the use of IOLs pre-soaked in fourth-generation fluoroquinolone antibiotics during a clinical research symposium on ocular drug delivery systems.

Referring to a study conducted by Mather and co-workers from the University of Pittsburgh, USA, Dr Olson drew the audience's attention to the top-line results, which indicated the high resistance of bacterial endophthalmitis isolates to the third-generation fluoroquinolones ciprofloxacin, ofloxacin and levofloxacin. There was, however, little, if any, resistance to the fourth-generation agents gatifloxacin and moxifloxacin.

A study published in the American Journal of Ophthalmology in 2006, however, gave cause for further concern when Deramo and colleagues found a rapid resistance developing amongst bacterial endophthalmitis isolates to fourth-generation fluoroquinolones, when administered in the concentrations required for topical antibiosis.

In light of these studies as well as the results of the ESCRS endophthalmitis study, presented at last year's ESCRS congress, in which intraocular cefuroxime faired much better than topical antibiotics, Dr Olson set about discovering whether there was a better, less invasive, approach to providing high concentration antibiotic protection in cataract patients.

Last year, a team led by Dr Guy Kleinmann investigated the use of IOLs as antibiotic delivery vehicles for cataract surgery patients. He developed a study protocol to examine the possibility of using the hydrophilic C-flex IOL (Rayner) as a drug delivery system for commercially available gatifloxacin and moxifloxacin. His results suggested that C-flex is capable of serving as an excellent and safe drug delivery system for fourth-generation fluoroquinolones and the concentrations achieved in his studies exceeded those of all topical drop protocol studies. Gatifloxacin did, however, prove to be more efficacious than moxifloxacin, even at a lower starting concentration.

With this in mind, Dr Olson chose to compare antibiotic-soaked IOLs versus intracameral antibiotics. He suggested that both forms of antibiotic could be combined to provide an early spike in antibiotic concentration (from intracameral administration), and with a half-life of four hours, the IOL-delivered antibiotic could provide a prolonged antibiotic effect, thus reducing the frequency of postoperative antibiotic administration.

Dr Olson called for further investigations into the benefits of a variety of IOL materials, different antibiotics and varying antibiotic concentrations in the hope that an IOL can be developed that releases an adequate dose of antibiotic over a prolonged period of time.

"In the future, it may be that pre-soaked IOLs become a suitable alternative to intracameral antibiotics or, they may even be used as adjunct antibiotic therapy in cataract surgery - emerging resistance may actually warrant such an approach," concluded Dr Olson.