REDUCING INFLAMMATION

  Greater use of topical non-steroidal anti-inflammatory drugs (NSAIDs), as well as sustained release and injected corticosteroids, may reduce inflammation following anterior segment surgery more than do the topical steroids now most commonly used, presenters told the Journal of Cataract & Refractive Surgery Symposium at the XXXIII Congress of the ESCRS in Barcelona, Spain. While nearly twice as many European surgeons reported using topical steroids than NSAIDs after cataract surgery in 2014, published studies show that NSAIDs are more effective in preventing post-op flare, said Rudy MMA Nuijts MD, PhD, of the University Eye Clinic Maastricht, The Netherlands. Topical NSAIDs alone or combined with topical steroids also better prevent cystoid macular oedema (CME) than do steroids alone, and NSAIDs may generate better visual acuity (VA) outcomes among diabetic patients, he added. Studies also show that intracameral and sustained release corticosteroids may reduce inflammation-related complications including CME, iritis, flare cells and corneal oedema better than conventional topical steroids after many types of anterior segment surgery, said Eric D Donnenfeld MD, of New York University, USA. Intracameral steroid injections may be particularly useful after complex procedures such as corneal transplants, and phacoemulsification with vitrectomy, he noted. Emerging delivery methods and better understanding of the pathophysiology of inflammation may make it possible to avoid sight-threatening inflammatory complications altogether, Dr Donnenfeld said. “Our goal should be to eliminate inflammation rather than to treat it. This can be done with aggressive corticosteroid therapy pre-op and intracamerally to not only suppress inflammation but prevent it from occurring at all.” NSAIDS UNDERUSED? In 2014, 87 per cent of 490 surgeons surveyed by the European Observatory of Cataract Surgery reported prescribing corticosteroid drops after surgery to combat inflammation, while only 38 per cent prescribed NSAIDs, Dr Nuijts said. Yet several studies have shown that NSAIDs are more effective. For example, a multicentre double-masked randomised controlled trial found that adding nepafenac 0.1 per cent two days before surgery and added to dexamethasone 0.1 per cent for three weeks after surgery reduced anterior chamber (AC) flare cells, as measured by laser photometry one day after surgery compared with dexamethasone alone (Zaczek. J Cataract Refract Surg 2014; 40:1498). A systematic review and meta-analysis found NSAIDs more effective than steroids in reducing post-op flare at one week, and preventing CME at one month after surgery (Kessel. Ophthalmology. 2014 Oct;121(10):1915). Another meta-analysis found adding NSAIDs to topical corticosteroids reduced the odds of developing CME, and improved corrected distance visual acuity at three months more in diabetic patients than steroids alone. However, the quality of the evidence is low to moderate, and better studies are needed, Dr Nuijts pointed out. To develop better evidence-based recommendations for preventing CME after cataract surgery, the ESCRS is currently sponsoring the PREMED study. It compares topical bromfenac alone with topical dexamethasone alone, and with a combination of the two in 823 non-diabetic patients. The topical NSAID and corticosteroid combination is also being tested alone, and combined with either a 40mg subconjunctival injection of triamcinolone acetonide, a 1.25mg intravitreal injection of bevacizumab, or both injected agents in 185 diabetic patients. Early PREMED data suggest that one of the four diabetic treatments does a much better job of preventing central macular subfield swelling, but which one and whether it is significant is uncertain as the data are still masked, Dr Nuijts said. One question the study may help answer is whether NSAIDs plus steroids are more effective than NSAIDs alone. IMPROVED DELIVERY Injecting anti-inflammatory drugs has several advantages over topical drops, Dr Donnenfeld said. Intraocular delivery of corticosteroids places medication at the site of inflammation and should have higher efficacy. Intraoperative delivery also avoids non-compliance, potentially reducing dosing error risk associated with eye drops in the largely elderly cataract population. In one study, a single intracameral injection of triamcinolone acetonide cleared transplanted corneas that remained cloudy after maximum topical steroid treatment (Maris et al, Cornea 2008). Injecting Triesence (Alcon), 0.1ml of preservative-free triamcinolone, into the AC also reduced post-op inflammation in cataract surgeries with vitrectomy (Bar-Sela. J Cat Refractiv Surg 2014). “It improves outcomes quite dramatically, with many patients coming in the next day with 20/20 VA,” Dr Donnenfeld said. A range of anti-inflammatory drugs including extended release inserts are already approved for treating retinal disease, and Dr Donnenfeld expects they will soon be routine for cataract and corneal surgery as well. “We are already placing steroids in the posterior segment, why shouldn’t we place them in the anterior segment as well?” Extended release eye drops, subconjunctival delivery, punctal plugs and other external devices that will keep drug levels more stable with less bother for patients are also in the pipeline, Dr Donnenfeld said. “I predict that over the next five years topical drugs will change greatly and will cease to exist as we know them today,” he added. Rudy MMA Nuijts: rudy.nuijts@mumc.nl Eric Donnenfeld: ericdonnenfeld@gmail.com