New Corticosteroid Treats Postoperative Inflammation and Pain

Durezol (difluprednate ophthalmic emulsion, 0.05%; Sirion Therapeutics, Inc., Tampa, FL) is the newest corticosteroid anti-inflammatory agent and the first to establish the classification of super steroid (data on file with Sirion Therapeutics, Inc.). Durezol is efficacious and strong because of its fluorination at the C6 and C9 positions, making it a difluorinated prednisolone derivative.¹ Rather than benzalkonium chloride, Durezol is preserved with sorbic acid, which is more comfortable for patients with sensitive eyes. This article gives an overview of how Durezol provides rapid recovery of vision after cataract surgery with premium IOLs.

CLINICAL STUDIES
Several preapproval studies were performed to evaluate Durezol's efficacy as an anti-inflammatory agent in patients with recalcitrant uveitis and as a treatment for postoperative inflammation and pain associated with routine, uncomplicated cataract surgery in low-risk patients (ie, individuals with no prior retinal pathology or previous vitreoretinal surgery) (data on file with Sirion Therapeutics, Inc.).^2-4

In one study, 1 day after unilateral ocular surgery, patients with an anterior chamber cell grade of 2 or higher were treated with Durezol b.i.d. or q.i.d. or with a placebo b.i.d. or q.i.d.² Both dosing schedules with Durezol cleared postoperative inflammation and effectively reduced pain rapidly. No anti-inflammatory medication was administered prior to cataract surgery.

No serious adverse ocular events occurred. Fewer adverse events were reported in the difluprednate-treated groups than in the placebo group. Adverse events in either arm of the study did not differ from those generally associated with the entire steroid classification of medications. The mean IOP did not change significantly during the study period and remained within the normal range in all treatment groups. A clinically significant rise in IOP (≥ 21 mm Hg or ≥ 10 mm Hg from baseline) in this study occurred in 3 patients (3%) in the difluprednate b.i.d. group (n = 111), in 3 patients (3%) in the difluprednate q.i.d. group (n = 107), and in 2 patients (1%) in the combined placebo b.i.d. and q.i.d. groups (n = 220).

In the uveitis trial, Durezol dosed q.i.d. was as relatively effective as Pred Forte 1% (Allergan, Inc., Irvine, CA) administered eight times daily. During the course of the uveitis trial, I witnessed Durezol's power, especially when treating patients in whom therapy with prednisolone acetate 1% had failed.⁴

HANDS-ON EXPERIENCE
My group had the opportunity to participate as a research site for each of Durezol's clinical trials. I found the randomized, double-masked study data compelling. Based on the study data for uveitis and postoperative inflammation, I confidently use lower doses of this agent than I did with previously available corticosteroids. Benefits include better adherence by patients to prescribed therapy as well as the avoidance of a dilution effect and medicamentosus.

Since the FDA approved Durezol, I have changed my postoperative regimen to include this agent b.i.d., an NSAID (Xibrom; Ista Pharmaceuticals, Inc., Irvine, CA) b.i.d., and a fourth-generation fluoroquinolone q.i.d. I pretreat eyes with the NSAID and antibiotic for 48 hours prior to surgery and instruct patients to continue using these medications until the bottles are empty. I recognize that many patients undergoing routine, low-risk, uncomplicated phacoemulsification heal normally after discontinuing their medications 2 weeks postoperatively. Nevertheless, my participation in studies of steroidal and nonsteroidal anti-inflammatory agents has taught me that a significant number of patients will have low-grade persistent cell and/or flare or will suffer an inflammatory rebound if their medication is withdrawn after 2 weeks. I am therefore conservative in my approach to prophylaxis.

I pretreat patients at high risk of cystoid macular edema or other manifestations of significant or prolonged inflammation with an NSAID and Durezol for 1 week preoperatively and 2 to 3 months postoperatively. These individuals have a history of diabetic retinopathy, macular edema, uveitis, a significant epiretinal membrane or macular pucker, a history of prior vitreoretinal surgery, or a systemic history of immunologic or rheumatologic disease. It is important to observe patients closely for pressure spikes when they are using a steroid for more than a couple of weeks.

CONCLUSION
Durezol has performed well in my clinical practice, and I use it for all cataract, corneal transplant, and glaucoma procedures. I also administer Durezol in the setting of iris- or angle-based glaucoma procedures for which even slight inflammation can have a significantly deleterious effect on an already compromised trabecular meshwork. I do not use this corticosteroid for LASIK or other keratorefractive procedures, since they generate minimal inflammation and the medication is typically discontinued at 1 week. The same holds true for patients undergoing a YAG laser capsulotomy.

Steven M. Silverstein, MD, is the president of Silverstein Eye Centers in Kansas City, Missouri, and he is an assistant clinical professor of ophthalmology at the University of Missouri School of Medicine and the University Health Sciences, both in Kansas City. He acknowledged no financial interest in the products and companies mentioned herein but stated that he was involved in the clinical research for Durezol. Dr. Silverstein may be reached at (816) 358-3600; silverstein@silversteineyecenters.com.

1. Bikowski J. The position not the presence of the halogen in corticosteroids influences potency and side effects. J Drugs Dermatol. 2006;5(2):125-130.
2. Korenfeld MS, Silverstein SM, Cooke D, et al, and the Difluprednate Ophthalmic Emulsion 0.05% (Durezol) Study Group. Difluprednate ophthalmic emulsion 0.05% for postoperative inflammation and pain. J Cataract Refract Surg. 2009;35(1):26-34.
3. Wittpenn RJ, Silverstein SM, Heier J, et al. A randomized, masked comparison of topical ketorolac 0.4% plus steroid versus steroid alone in low-risk cataract surgery patients. Am J Ophthalmol. 2008;146(4):483-485.
4. Abelson M, Foster S, Gupta G. Diagnosing and managing anterior uveitis. Review of Ophthalmology. 2002;9(6):1-5.