EyeWorld is the official news magazine of the American Society of Cataract & Refractive Surgery.
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June 2012 Tracking MMP-9 to forestall dry eye after LASIK www.AcrySofReSTOR.com by Maxine Lipner Senior EyeWorld Contributing Editor CAUTION: Federal (USA) law restricts this device to the sale by or on the order of a physician. INDICATIONS: The AcrySof® IQ ReSTOR® Posterior Chamber Intraocular Lens (IOL) is intended for primary implantation for the visual correction of aphakia second- ary to removal of a cataractous lens in adult patients with and without presby- opia, who desire near, intermediate and distance vision with increased spectacle independence. The lens is intended to be placed in the capsular bag. WARNING/PRECAUTION: Careful pre- operative evaluation and sound clinical judgment should be used by the surgeon to decide the risk/benefit ratio before implanting a lens in a patient with any of the conditions described in the Direc- tions for Use labeling. Physicians should target emmetropia, and ensure that IOL centration is achieved. Care should be taken to remove viscoelastic from the eye at the close of surgery. Some patients may experience visual disturbances and/or discomfort due to multifocality, especially under dim light conditions. Clinical studies with the Ac- rySof® ReSTOR® Dry eye marker may help improve outcomes I lens indicated that pos- terior capsule opacification (PCO), when present, developed earlier into clinically significant PCO. Prior to surgery, physi- cians should provide prospective pa- tients with a copy of the Patient Informa- tion Brochure available from Alcon for this product informing them of possible risks and benefits associated with the AcrySof® IQ ReSTOR® IOLs. Studies have shown that color vision dis- crimination is not adversely affected in individuals with the AcrySof® Natural IOL and normal color vision. The effect on vi- sion of the AcrySof® Natural IOL in sub- jects with hereditary color vision defects and acquired color vision defects sec- ondary to ocular disease (e.g., glaucoma, diabetic retinopathy, chronic uveitis, and other retinal or optic nerve diseases) has not been studied. Do not resterilize; do not store over 45° C; use only sterile ir- rigating solutions such as BSS® PLUS® or BSS Sterile Intraocular Irrigating Solu- tions. ATTENTION: Reference the Directions for Use labeling for a complete listing of in- dications, warnings and precautions. n the first 3 months after re- fractive surgery as many as 60% of patients can suffer from transient dry eye, according to Robert P. Sambursky, M.D., Manatee Sarasota Eye Clinic, Bradenton, Fla. Anything that could indicate patients who might be par- ticularly vulnerable here would be welcomed. Findings from a study published in Current Opinions in Oph- thalmology show that an increase in activity of the enzyme matrix metal- loproteinase-9 (MMP-9) is the type of marker for which practitioners have been looking. For some time scientists have been scouting for a marker that could indicate patients who might be particularly vulnerable to dry eye after refractive surgery. "The idea was to find a biomarker that would reflect ocular surface disease and in particular be relevant for dry eyes," Dr. Sambursky said. "MMP-9 has the most literature support for being a good biomarker in that capacity—in the normal population it's not ele- vated, but it certainly elevates in the presence of dry eye." Valuable dry eye marker Terrence P. O'Brien, M.D., chair and professor of ophthalmology, Bascom Palmer Eye Institute, Uni- versity of Miami Miller School of Medicine, sees having a dry eye marker to screen for those who don't yet have clinically noticeable dry eye but who may be tipped over by refractive surgery as invaluable. This was something that pushed investigators to take a closer look at MMP-9. "There is a small subset for whom LASIK surgery puts them over the edge, and they are among the most vocal and discontented [pa- tients]," Dr. O'Brien said. "Our idea was, if we have a marker where we could screen people in advance and also follow them post-operatively, we'd be able to better prepare people prior to performing the LASIK sur- gery and then also treat them more aggressively in the post-operative period to try and rescue the eye so that it doesn't succumb to the chal- lenge." It seemed that MMP-9 would make a natural choice. "MMP-9 has been shown to be a non-specific in- flammatory marker that is consis- tently elevated in the tears of people with dry eyes," Dr. O'Brien said. "That was one of the reasons why we felt that this could be a useful tool for the LASIK surgeon." Screening potential Investigators did a literature review of LASIK and dry eye papers. "The idea was to demonstrate first that identifying dry eye patients had a value perioperatively," Dr. Sambursky said. "We found a lot of articles to support the idea that the patients physicians knew had dry eyes before LASIK seemed to do worse after." Investigators also looked to see if there was a good correlation between MMP-9 and dry eye. "We identified it as a good bio- marker," Dr. Sambursky said. In ad- dition, they looked to see whether LASIK outcomes benefit from identi- fying those at risk and intervening. Dr. Sambursky stressed they were able to find good evi- dence of this. Findings showed that LASIK can change tear film dynamics. "We found that the reduction in tear function after LASIK can induce an increase in the osmolarity of the tear film, and that can consequently raise the concentration of pro- inflammatory cytokines including MMP-9 in the tear film," Dr. O'Brien said. "This can result in not only dry eye—it can lead to other complica- tions such as poor attachment of the corneal flap and corneal bed or possibly increase flap slippage with epithelial ingrowth and other com- plications." The upshot of flagging those with dry eye prior to LASIK would be fewer of these problems. "We felt that recognizing this in ad- vance and treating it could reduce complications after LASIK through proper diagnosis and management of dysfunctional tear syndromes," Dr. O'Brien said. All of this points to MMP-9's potential for screening prior to LASIK. "I think that the key finding here is that in a quick, easy test of the ocular surface perioperatively, we can identify patients who have dry eyes," Dr. Sambursky said. "Here we have an objective way to identify these patients and can then initiate a treatment algorithm that includes more aggressive perioperative treat- ments, either with artificial tears or potentially with anti-inflammatory agents that will lead to better out- comes." While currently the only way to test for MMP-9 in the U.S. is to send the tears out to a specialized lab, Dr. Sambursky hopes that may soon change. He pointed to an interna- tionally available test dubbed InflammaDry (Rapid Pathogen Screening, Sarasota, Fla.) that can detect the presence of MMP-9 in tears and offer a level. "A large clini- cal trial (on InflammaDry) was per- formed and the data submitted to the FDA," he said. "It is currently under review, and there is optimism that some time in the near future it will be available in the U.S." Going forward Dr. O'Brien hopes that other potential markers will also be identified. "I would hope that this is the first of many approaches that looks for factors that are consistently present in dis- ease states that would affect the ocu- lar surface. By developing rapid assays that can give us a semi-quan- tifiable or a quantifiable level of these markers, we can then be more sophisticated in our pre-operative, intraoperative, and post-operative approach to improve outcomes," Dr. O'Brien said. EW Editors' note: Dr. O'Brien is a non- salaried consultant for Alcon (Fort Worth, Texas), Allergan (Irvine, Calif.), Bausch + Lomb (Rochester, N.Y.), ISTA Pharmaceuticals (Irvine, Calif.), and Santen (Osaka, Japan). Dr. Sambursky is chief medical officer for Rapid Pathogen Screening. Contact information O'Brien: 561-515-1544, tobrien@med.miami.edu Sambursky: 941-748-1818, sambursky@rpsdetectors.com © 2011 Novartis 8/11 RES11067JAD