March 2009

 

CATARACT/ IOL

 

Drug delivery alternatives


by Matt Young EyeWorld Contributing Editor

   
Hydrophilic acrylic IOLs have occasionally been known to discolor or opacify—as this one did—but new research suggests these lenses may be good modalities for delivering antibiotic prophylaxis to the eye Source: Scott X. Stevens, M.D.

As surgeons continue to debate the merits of intracameral antibiotics for cataract surgery to prevent endophthalmitis, new research poses an alternative—yet in some ways similar—method of drug delivery. In the October 2008 issue of Current Eye Research, researchers looked at whether an intraocular lens itself could serve as a vehicle to deliver much-needed prophylaxis. The scientists used a Meridian hydrophilic acrylic lens (Bausch & Lomb Surgical, San Dimas, Calif.) to deliver gatifloxacin for experiments in vivo. It was pitted against intracameral delivery of the same drug. “Preventive effects against endophthalmitis were similar between antibiotic-treated IOL implantation and intracameral antibiotic administration,” reported Shinichiro Kobayakawa, M.D., Ph.D., The First Department of Ophthalmology, School of Medicine, Toho University, Tokyo, and colleagues. Although that was the researchers’ conclusion, there were distinct differences between the two methods. The gatifloxacin concentration in rabbit aqueous humor, for instance, was much higher after intracameral injection 4 hours post-op, but was similar to an IOL-administered concentration by the next day.

More similarities and differences

In the in vivo portion of the experiment, an isolated strain of Enterococcus faecalis was used to induce endophthalmitis. “Visual outcome after endophthalmitis involving Enterococcus faecalis in particular is generally poor, and only 6.9% of cases achieve a final best correctable visual acuity equal to or better than 20/50 when the infection involves this organism,” Dr. Kobayakawa reported. “Moreover, in cases of early-onset post-cataract endophthalmitis in Japan, the most frequently cultured organisms were coagulase-negative staphylococcal isolates (28 strains), E. faecalis (21 strains), and S. aureus (18 strains) between 1983 and 2002.”

Twelve Meridian IOLs with antibiotics were used, and concentrations in the aqueous humor and effects against bacterial proliferation were analyzed. According to Medscape.com, “Like other fluoroquinolones, gatifloxacin has only modest and highly variable activity against enterococci.” Clearly, higher concentrations of the drug would be desirable as prophylaxis. It was therefore important that researchers compare a 0.5% gatifloxacin injection group in rabbits with the same concentration of the drug used in the IOL delivery method. Fifty-one rabbits were used in total. Here’s what they found in the IOL group: • The gatifloxacin concentration in the aqueous humor was highest at 4 hours post-op, the first time point measured.

• The decrease was very rapid on the first day. • It decreased over a three-day period (5.3 μg/ml at 4 hours and 0.05 μg/ml on the third day).

• In the intracameral group, • Gatifloxacin concentration also was highest at 4 hours, and decreased rapidly by 8 hours post-op.

• The concentrations in the injection group were higher at 4 hours and 8 hours.

“However, they had become comparable by the next day (0.25 μg/ml in the IOL group and 0.28 μg/ml in the injection group),” the researchers reported.

“The bacterial populations in eyes were significantly smaller in the IOL and injection groups than in the control group through 72 hr postoperatively,” the researchers noted. The researchers also performed analysis in vitro, which suggested IOL-delivered antibiotic concentrations in very experimental circumstances are greater than in more real-world ones. “With the Meridian IOL soaked in 0.5% GFLX for 24 [hours], antibiotic concentrations in the aqueous humor decreased to 0.25 μg/ml on the first day (24 [hours] postoperatively) in vivo, while it took 3 days in vitro for it to decline to a similar concentration,” Dr. Kobayakawa reported. “It is difficult to describe precise pharmacologic kinetics in the anterior chamber, especially in the case of surgical eyes.”

By day one post-op, both prophylaxis methods had this in common: They became ineffective. “Interestingly, one day after the surgery, the antibiotic concentrations in both groups were below the MIC 90 value for the strain used,” Dr. Kobayakawa noted. Dr. Kobayakawa suggested that intracameral delivery of antibiotics could be hazardous, and therefore alternative methods such as IOL antibiotic administration could prove helpful. Some research has found “that even a short period of exposure of ocular tissues to intracameral 1% lidocaine can induce histological changes that may result in functional defects,” Dr. Kobayakawa reported. “Intracameral antibiotic injection may cause damage to corneal endothelium cells depending on the concentration or the type of drug.”

Bjorn Johansson, M.D., Linkoping University Hospital, Sweden, however, noted that intracameral antibiotics—specifically, intracameral cefuroxime—is tried and true. “Basically my bottom line is that we have proved from various sources now that [intracameral] cefuroxime works, not only in Sweden but in England, Australia, and in other countries with other bacterial spectrums,” Dr. Johansson said. Antibiotic IOL implantation is an interesting new development, he added. “If the IOL can be used as a vehicle, then we certainly know the antibiotic is there,” Dr. Johansson said. The development will have to be evaluated against the best proven strategy, and in Dr. Johansson’s book, that’s intracameral administration of antibiotics. Evaluating new modalities to prevent endophthalmitis will be challenging considering the high volume of cataract surgery analysis required to study endophthalmitis prevention, Dr. Johansson noted.

Editors’ note: Dr. Kobayakawa and colleagues have no financial interests related to this study. Dr. Johansson has no financial interests related to his comments.

Contact information

Kobayakawa: covanet@aol.com
Johansson: bjorn.johansson@lio.se

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