Eyeworld Supplements

References 1. Drews RC, Katsev DA. Ocufen and pupillary dilation during cataract surgery. J Cataract Refract Surg. 1989;15(4):445-448. 2. Kim SJ, Flach AJ, Jampol LM. Nonsteroidal anti- inflammatory drugs in ophthalmology. Surv Ophthalmol. 2010;55:108-133. 3. O'Brien TP. Emerging guidelines for use of NSAID therapy to optimize cataract surgery patient care. Curr Med Res Opin. 2005;21:1131-1137. 4. Wittpenn JR, Silverstein S, Heier J, et al. Acular LS for Cystoid Macular Edema (ACME) Study Group. A random- ized, masked comparison of topical ketorolac 0.4% plus steroid vs. steroid alone in low-risk cataract surgery patients. Am J Ophthalmol. 2008;146:554-560. Corneal melts/toxicity: Is there still an issue? The reported complications following the use of NSAIDs in cataract surgery vary in severity, according to Dr. Kim. These cases range from things as innocuous as superficial punctate keratitis, to stromal infiltrates, immune rings, and persistent epithelial defects, to the most dreaded complication: corneal melts. Dr. Kim said this was the major issue back in 1999, when the ASCRS survey came out looking at observations of corneal melt after routine anterior segment surgery. The survey pinpointed the use of topical generic diclofenac, which was voluntarily identified and recalled by the manufacturer. There have been many similar reports with other NSAIDs, said Dr. Kim. "There is still a lot of fear among cataract surgeons when using NSAIDs during cataract surgery," he said. The deleterious effect of NSAIDs on the cornea is thought to be related to a In September 2011, pharmaceutical companies began releasing generics into the market. At the time, generic ketorolac comprised 27.9% of NSAIDs used in cataract surgery. Generic NSAIDs were first introduced with generic diclofenac. Not long after the introduction of the drug, ASCRS reported an increase in the number of corneal melts, and all NSAIDs were pulled from the market for a period of time. This, said Dr. Katsev, created a fear of using NSAIDs still felt by some surgeons today. Dr. Devgan reported a corneal melt with a generic NSAID; since then there have been several cases reported in the literature. Importantly, said Dr. Katsev, these reports show cases of corneal melt occurring with generic NSAIDs, but not with branded NSAIDs. There are additional challenges regarding these generic drugs that go beyond the clinical, said Dr. Katsev. In June 2011, the Supreme Court came out with a ruling that essentially freed generics manufacturers from the responsibilities for updating their labeling held over branded product manufacturers. Branded product manufacturers need to protect their names; with generics, they are not beholden to protecting that name. Dr. Katsev's first encounter with low quality generics was in a patient with diabetes in whom he had implanted bilateral premium IOLs. He initially started the patient on Bromday (bromfenac sodium, ISTA Pharmaceuticals). However, at the pharmacy, the patient was instead given generic ketorolac. The patient did not return until he had CME. By going back on Bromday, his vision was restored to 20/25. According to the patient, he needed to stop using the generic ketorolac due to discomfort and did not use any NSAID until his follow-up consult, by which time it was almost too late. "We as surgeons need to be vigilant about the quality of the drugs we use in our patients," said Dr. Katsev. With gener- ics, he said, the medication is supposed to be the same, but the bottle, the pH, all of these things are different and may have an effect on the quality of the drug. "There may be great generics, but there are also bad generics, and it is up to us to keep watch over these drugs to maintain a high standard for cataract surgery in our patients." group of proteases or collagenolytic enzymes called matrix metalloproteinases (MMPs). The MMP family is very large; to date, studies have identified 20 MMPs expressed in humans. These enzymes have multiple functions and are known to degrade extracellular matrix (ECM) and enhance cell-cell, cell-matrix communica- tions. Rarely detected in normal tissues, MMPs are typically expressed in tissues undergoing rapid turnover, such as during tumor breakout, normal bone and joint formation, and wound healing. In the eye, MMPs are involved in many physiologic and pathophysiologic processes, said Dr. Kim. These include disease conditions like macular degeneration and diabetic retinopathy and processes such as IOP regulation. In the cornea specifically, MMPs have been detected in corneal ulcers, keratoconus, and after PRK surgery. NSAIDs have been potentially linked to corneal melts through the upregulation of MMPs, resulting in an imbalance between ECM deposition and degradation. NSAIDs may cause excessive MMP expression, and various MMPs have been found in NSAID-related melts. Clinically, topical NSAIDs decrease normal corneal sensation 1,2 and can affect corneal epithelial healing. 3,4 To avoid complications, NSAIDs should be used properly. "I believe it is very important to follow the label dosing," said Dr. Kim. "If you look at case series that are reported in the literature, compli- cations like corneal melt usually occur when NSAIDs are not dosed properly." With improper dosing, he said, NSAIDs can cause complications within 2 hours of use. "I would also recom- mend avoiding long- term use of topical NSAIDs," he added. It is important to also examine patient characteristics, looking at risks for corneal melt. Patients with epithe- lial keratopathy or severe dry eyes, bac- terial keratitis, herpes simplex or zoster ker- atitis, ocular surface disease, concurrent topical steroids, or 2 August 2012 Anti-inflammation: Perfecting cataract surgery Since the 1999 ASCRS survey, several cases of NSAID-related corneal melt have been reported ISTA supplement_EW August 2012-DL_Layout 1 6/3/14 2:36 PM Page 3

• Cover