Because optometrists are closely involved with the pre- and postoperative surgical care of our cataract patients, it often falls to us to manage the inflammation and pain that commonly occur postoperatively, and steroids have long been the mainstay. Loteprednol etabonate (LE) 0.5% suspension (Lotemax, Bausch+ Lomb) has been extensively studied and, for over a decade, has been a recommended treatment for our postoperative patients due to its lesser propensity to raise intraocular pressure as compared to other corticosteroids like dexamethasone or prednisolone acetate.1,2
In 2011, the FDA approved a preservative-free ointment form of LE after multi-center studies concluded that the formulation was safe and effective for the control of postop inflammation and pain.3 On October 1, 2012, a gel formulation of loteprednol etabonate 0.5% was FDA approved. It will be available as a 10ml bottle. The launch date is yet to be determined.
The gel is supposed to provide increased viscosity on the eye for better retention, which in turn would improve patient compliance by eliminating the need to shake the bottle prior to instillation. Also, the loteprednol gel contains glycerin, propylene glycol and a 0.003% concentration of benzalkonium chloride (BAK), compared to the 0.01% concentration of BAK in the suspension form, which should provide greater patient comfort.4
The Safety Trials
The safety and efficacy of loteprednol etabonate 0.5% gel was assessed in a multi-center, double-masked, parallel group, vehicle-controlled study at 20 American and two German sites.5 A total of 407 patients were enrolled: 206 in the loteprednol etabonate 0.5% gel group and 201 in the vehicle group (which contained the exact concentration, amount and formulation of all the inactive ingredients and preservative, but without any loteprednol etabonate).
Eligible candidates were over the age of 18, not pregnant and with a potential visual acuity of 20/200 O.U. or better. Only patients with an anterior chamber reaction of Grade 2 or better on the first postoperative day were included. Subjects that were excluded were those who had the potential need for postoperative NSAIDs, systemic or ocular steroids, concurrent ocular therapy with immunosuppressants during the 18 days following surgery or within 30 days prior to the surgery, a history of generalized systemic disease or with severe ocular conditions, monocular patients, uncontrolled glaucoma or treatment for glaucoma in the fellow eye or a known sensitivity to the study drug or any of its components.
The study period was four weeks and required seven visits.Cataract surgery by phacoemulsification with posterior chamber intraocular lens implantation was performed on the second visit. All patients received either the loteprednol etabonate gel or placebo (one to two drops used four times a day for 14 days).The patients were seen on postoperative days one, three, eight, 15 and 18. Compliance was assessed via a patient diary and by weighing the drug bottle.
Efficacy was determined by the complete resolution of anterior chamber inflammation and no pain on postoperative day eight. The secondary efficacy endpoints were complete resolution of anterior chamber cells and flare (individual and combined) at each visit, and the difference in change from baseline at each follow-up. Safety was determined by the incidence of adverse events, change in intraocular pressure, visual acuity, slit lamp and fundus findings.
The study results:6
• 31.1% of gel patients, compared to 13.9% of the vehicle group, showed complete resolution of anterior chamber inflammation.
• The gel patients had a statistically significantly greater rate (75.7%) of Grade 0 pain vs. the vehicle group (45.8%)
• Mean intraocular pressure, via applanation, was similar between the two groups. One patient in the gel group experienced a significant increase in pressure that was not considered drug related because of a similar increase in the untreated fellow eye. One patient in the vehicle group had a 6mm Hg increase in pressure at day 15 that was potentially drug related.
• Fewer adverse events occurred in the gel group (16%) vs. the vehicle group (28.9%).
• Only 30.1% of the gel-treated patients required rescue medication (NSAIDs and/or corticosteroids) compared to 61.2% of the vehicle group
Lotemax gel appears to be safe, effective and well tolerated. Also, remember that loteprednol etabonate in alternate formulations (suspension and ointment) have been well studied, and deemed safe and effective in reducing postoperative pain and inflammation. Greater contact time and improved patient compliance would allow the possibility of greater efficacy than previous formulations of LE.
For practitioners, the ability to deliver a suspension drop formulation that requires no shaking, contains a lower concentration of preservative and has a pH level that is more compatible with human tears is certainly a nice addition to our patient care toolkit.
1. Stewart R, Horwitz B, Howes J, et al. Double-masked, placebo-controlled evaluation of loteprednol etabonate 0.5% for post-operative inflammation. Loteprednol Etabonate Post-Operative Inflammation Study Group. J Cataract Refract Surg.1998 Nov;24(11):1480-9.
2. Bartlett JD, Horwitz B, Laibovitz R, Howes JF. Intraocular pressure response to loteprednol etabonate in known steroid responders. J Ocul Pharmacol. 1993 Summer;9(2);157-65.
3. Comstock TL, Paterno MR, Singh A, et al. Safety and efficacy of loteprednol etabonate ophthalmic ointment 0.5% for the treatment of inflammation and pain following cataract surgery. Clin Ophthalmol. 2011 Feb;5:177-86.
4. Coffey MJ, Davio SR. Viscoelastic and sedimentation characterization of loteprednol etabonate ophthalmic gel 0.5%. Poster presented at the annual Association for Research in Vision and Ophthalmology meeting, May 6-9, 2012; Ft. Lauderdale, Fla.
5. Fong R, Leitritz M, Siou-Mermet R, Erb T. Loteprednol etabonate gel 0.5% for postoperative pain and inflammation after cataract surgery: results of a multicenter trial. Clin Ophthalmol. 2012;6:1113-24.