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Delayed closure after PRK with topical besifloxacin I t seemed to be a natural— use of the recently modified fluoroquinolone topical besi- floxacin (Besivance, Bausch + Lomb, Rochester, N.Y.) follow- ing PRK to keep infections at bay, according to Jonathan H. Talamo, MD, associate clinical professor of ophthalmology, Harvard University, B oston. Because of its chlorinated structure, besifloxacin 0.6% could not be used systemically, unlike the other fluoroquinolones. This made it appealing from the point of view of resistance, he explained. Still, what was not expected was the effect that Besivance would have on epithelial closure after the PRK procedure. In the August 2013 issue of Cornea, Dr. Talamo reported that nearly all of those treated with besifloxacin underneath a bandage contact lens following PRK exhibited significant problems with corneal epithelial healing, pain, and delayed visual recovery. Use of topical antibiotics after refractive procedures such as PRK is nearly ubiquitous in this country, Dr. Talamo said, adding that this is off-label. While other topical fluoro- quinolones would certainly do, with methicillin-resistant Staphylococcus aureus (MRSA) in the mix, Dr. Talamo felt that there were advan- tages to trying Besivance for PRK patients. "The thinking was we have a drug that's not going to breed systemic resistance, it's got a good MRSA spectrum, and it's not going to be used in the livestock popula- tion like ciprofloxacin, so it's likely to have good staying power and it ought to be a great topical drug," Dr. Talamo said. "Like some other more recent preparations, it was made with a sustained-release vehicle to prolong the contact between the drug and the ocular surface." The idea was that you could get higher drug levels and decrease dose frequency, hopefully improving convenience and compliance. Besivance also appeared well tol- erated topically. "There were studies looking at Besivance for conjunctivi- tis and also in the literature in ani- mals. Bausch + Lomb sponsored some studies looking at it in the presence of corneal epithelial defects to see if it would be safe," Dr. Talamo said. "The idea [was] could you treat a corneal ulcer with this preparation? The answer seemed to be yes." Accordingly, he decided to begin using Besivance in conjunc- tion with PRK. "We would prophy- lax the patient about three days p rior and then use some on the eye at the time of surgery," he said. His practice for two decades had been to place a bandage contact lens imme- diately after PRK. "I would often put antibiotic on the underside of the contact lens and then put the con- tact lens on the eye and off [the pa- tient] went," Dr. Talamo said. Patient difficulties There was a day in the summer of 2010 when Dr. Talamo recalls using Besivance in a large number of PRK patients. "Because it was white and viscous my assistant was handing it to me and I was putting it on the contact," he said. Still getting used to applying the medication, some of the eyes got Besivance under the contacts and some on top and some got an older fluoroquinolone instead. Dr. Talamo was surprised to find that nearly all of the patients who received the Besivance had issues four days after surgery, coming in with complaints of pain and photo- phobia. "All but one of the seven eyes that got Besivance under the contact lens had significant healing problems, discomfort, and devel- oped haze, and one actually lost best corrected visual acuity," he said. "That patient had a tremendously protracted and difficult healing course that included persistent ep- ithelial defects, super infection, and prolonged discomfort and dryness." He quickly realized that some- thing was amiss. "I began to smell that something had gone wrong, and we looked back at those surgical days and compared every single vari- able we could find," Dr. Talamo said. "The only reason we could come up with why those patients were having difficulty was the Besivance." Similar experiences Dr. Talamo found that his experi- ence was bolstered by that of other refractive practitioners who also noticed healing abnormalities after Besivance use in conjunction with PRK. He had personal communica- tion with two physicians in 2012 who experienced similar difficulties. One of the two, Lance S. Ferguson, MD, wrote a letter on this to the editor in Review of Ophthalmology in April 2012, Dr. Talamo noted. It is not the Besivance itself, Dr. Talamo theorizes, but the vehicle that it is contained in that was caus- ing the problems here. He pointed out that there's no theoretical reason to believe that the chlorinated fluoroquinolone compound, the besifloxacin, has any reason to be more toxic than any other fluoro- quinolone. "My theory is that it's the BAK in the vehicle," Dr. Talamo said. It is possible that the problem stems from the fact that the vehicle is holding the preservatives in place and prolonging contact with the tis- sues. Dr. Talamo cited a paper by William Trattler, MD, et al., published in the July 2007 issue of Cornea showing that when the drug nepafenac (Nevanac, Alcon, Fort Worth, Texas) was placed on the stromal bed underneath a contact lens, there was a significant increase in the incidence of corneal haze, pain, burning, and delayed epithe- lial closure. "It was the same symp- tom profile as our patients," Dr. Talamo noted. Both Besivance and nepafenac are designed for pro- longed contact with the eye, he observed, adding that these two have some sort of carboxyl-contain- ing polymer that swells in water when exposed to a lower PH envi- ronment. "It's a high molecular weight substance to block dissolving and carriage of the drug away from the surface of the cornea," he said. Dr. Talamo noted that in February 2013, the ASCRS Refractive Surgery and Cornea Committees is- sued an advisory statement stressing EW REFRACTIVE SURGERY February 2011 81 by Maxine Lipner EyeWorld Senior Contributing Writer Epithelial experience One patient who received Besivance under the contact lens developed inferior corneal haze after healing of persistent epithelial defect and lost BCVA. OCT of corneal scarring after prolonged post-PRK healing from Besivance Source (all): Jonathan H. Talamo, MD March 2014 continued on page 82 76-87 Refractive_EW March 2014-DL_Layout 1 3/6/14 3:17 PM Page 81