Eyeworld CME Supplements

EW JUL 2013 - Supported by Bausch + Lomb

This is a supplement to EyeWorld Magazine that doctors can take a test after reading and receive CME credits for.

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"The optimized pH represents an advanced formulation designed to facilitate penetration into the eye," said Dr. Kim, adding that it will be available as 1.6 mL and 3 mL in a 7.5-mL bottle. Nepafenac, on the other hand, is now available in a higher concentration of 0.3%, Ilevro. Originally available at a concentration of 0.1% (Nevanac), the new formulation is also approved for once-a-day dosing 1 day preop, on the day of surgery, and 2 weeks postoperatively, and will be available as 1.7 mL in a 4-mL bottle. In terms of corticosteroids, Durezol (difluprednate emulsion 0.05%) is not new, having been launched in 2008. However, said Dr. Kim, "The launch of difluprednate represented a new class of corticosteroid medication that we had not seen in quite a few years. It is indicated for the treatment of inflammation and pain associated with ocular surgery and anterior uveitis with QID dosing." More recently approved for the same indications is Lotemax gel (loteprednol ophthalmic gel 0.5%), which uses a unique and innovative mucoadhesive technology to ensure adherence to the ocular surface and enhance penetration into the eye. Impact of inflammation on the posterior segment and the role of anti-inflammatory therapy "As a retinal surgeon dealing with patients who have posterior segment disease, many times I'm the person that's bringing a gun to a knife fight," said Keith A. Warren, MD, professor of ophthalmology, University of Kansas, and founder, Warren Retina Associates, Overland Park, Kan. "For these patients, you really don't want any inflammation so it becomes very important to try to stem that." Dr. Warren offered a retina specialist's perspective on the effects of inflammation during refractive cataract surgery, highlighting its impact on the posterior segment and the role of anti-inflammatory therapy. Dr. Warren believes that patients undergoing refractive cataract surgery "have little or no tolerance" for any intraocular inflammation. Advanced technology IOLs, such as multifocal IOLs in particular, don't work if inflammation is present. "Basically, [patients] want to get their money's worth," he said. "Inflammatory control in refractive cataract surgery patients is tantamount to any successful outcome." Common pathophysiology Many retinal diseases share a common inflammatory pathophysiology. In particular, surgeons performing refractive cataract surgery should remember that pseudophakic cystoid macular edema (CME) occurs by similar mechanisms. During surgery, inflammation is caused by the release of cytokines and other signals meant to induce protection against insults to the body. In the uveal tract, inflammation thus occurs by a number of mecha- Figure 1. Risk factors for CME nisms, but is ultimately characterized by a breakdown in the blood–retina barrier. This in turn leads to leakage of proteinaceous fluid, leading to swelling in the retina and in the ocular media. This inflammation, with its resulting prostaglandin-mediated breach of the blood–retina barrier, puts any patient undergoing refractive cataract surgery at high risk for CME. CME is a late onset complication, usually occurring 4-6 weeks after surgery. Studies have shown that increased retinal thickening occurs in a staggering 12% of cases following uncomplicated cataract surgery,1 appearing 4-6 weeks after surgery.2 A full evaluation of each patient should be conducted prior to surgery. This includes identifying risk factors in the clinical history by examining factors such as duration of systemic disease, length of surgery, complications that may have occurred during surgery, and co-morbidities such as diabetes, as well as conducting a thorough preop exam to look for any signs of pre-existing retinopathy (Figure 1). Dr. Warren also recommended performing optical coherence tomography (OCT) during preop evaluation. The precise measurement of the retinal thickness provided by OCT allows surgeons to evaluate risk, helps them educate patients regarding their preand postop outcomes, and provides an objective way to monitor response to therapy. Steroids, NSAIDs, anti-VEGF When approaching the patient at risk, corticosteroids are the drug of choice for treating inflammatory diseases including CME and should be used at maximum strength preand postop to control inflammation. They are the best agents because their mechanism of action is very broad and non-specific: They regulate VEGF production and expression as well as inhibit the release of cytokines and other inflammatory mediators; in short, they influence multiple pathways in the inflammatory cascade. Prednisolone acetate 1% has been the "standard of care" in the U.S.,3 having been used as a comparator in clinical trials for more than 20 years, but newer formulations such as difluprednate and loteprednol gel are certainly worth considering. For instance, being a prodrug allows difluprednate to rapidly penetrate the corneal epithelium and maintain a consistent concentration of a high level of drug in the target tissue. The drug is formulated as an emulsion to further improve dose uniformity—without requiring shaking—compared with prednisolone suspension. Meanwhile, the mucoadhesive technology used in loteprednol gel facilitates better adherence to the ocular surface, thus also allowing for better penetration of the drug and higher concentrations in the target tissue. In addition to corticosteroids, NSAIDs can be used as indicated for postoperative pain and inflammation. It should be noted that while none are indicated for CME, studies have shown that newer NSAIDs have some efficacy in both prophylaxis and treatment of the condition.4,5 NSAIDs have a narrower, more specific mechanism of action. They are believed to work by cyclooxygenase (COX) enzyme inhibition, thereby reducing prostaglandin production. Of the two COX isoforms, COX-2 is induced by trauma—i.e., surgery— and so is the primary target for inhibition with NSAIDs. Newer NSAIDs may address more COX-2-mediated prostaglandin synthesis. The use of NSAIDs has other benefits, including the induction of a larger pupil for a longer duration of time, as well as reductions in both postoperative pain and photophobia.5,6

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