Comparison of Post-operative Pachymetry After Penetrating Keratoplasty Using Prednisolone Acetate 1% Versus Loteprednol Etabonate 0.5% E. Lillian Cheng, M.D.1, Catherine Furey, M.D.1, Robert Kaplan, Ph.D.2, and Theodore M. Perl, M.D.1 1Corneal Associates of New Jersey, West Orange, NJ and 2UCLA School of Public Health, Los Angeles, CA

Financial Interests This study was conducted by Drs. Perl, Furey and Cheng at Corneal Associates of New Jersey and was supported in part by Bausch & Lomb Pharmaceuticals, Inc. Dr. Kaplan does not have any financial interests in the techniques or technologies discussed herein.

Introduction Endothelial viability is critical to ensure health and longevity of donors after penetrating keratoplasty. Central Corneal Thickness (CCT) is an indirect measure of endothelial function. Ultrasonic pachymetry is a well recognized tool for accurately measuring corneal thickness. Postoperatively, it takes a variable amount of time for the endothelial cells in the graft to reestablish function, and deturgesce the graft. Postoperative inflammation can prolong the recovery of endothelial function. Topical corticosteroids have been the mainstay of treatment of post op inflammation.

Introduction Prednisolone acetate (1%) (PA) is the “gold standard” for treatment of postoperative inflamamation after PKP. but has been associated with steroid induced IOP elevation. Loteprednol etabonate (0.5%) (LE) is known to have a lesser effect on intraocular pressure rise, and has been shown to be as effective as PA in reduction of intraocular inflammation, post-cataract extraction. The purpose of this study was to compare the anti-inflammatory effects of LE versus PA on post-operative deturgesence, and recovery of endothelial function in the graft.

Study Design We studied 115 eyes that underwent PKP or combined PKP/cataract extraction/intraocular lens implantation in one subspecialty practice. All surgeries were performed by one surgeon (TP) using the same technique, described previously. Patients were randomly assigned to use either PA (n=72) or LE (n=43) postoperatively. All patients were placed on either PA or LE every two hours for the first week post-op, and then tapered. CCTs were measured at each postoperative visit.

Patient Demographics Loteprednol Prednisolone No. Eyes 43 72 Age (range) 56.52 (16-96) 59.06 (11-93) % Female 58.1% 51.4% POAG 2.3% (1/43) 4.2% (3/72) Donor Age (range) 42.0 (13-68) 44.9 (5-67) Avg thinnest CT 540.7 535.5

Study Design Patient charts were reviewed retrospectively to determine the point at which the thinnest CCT was achieved. Differences in outcomes between LE and PA patients were evaluated using independent groups t-tests. Sub-analyses were also done for: Phakic keratoconus (KCN) patients Pseudophakic or aphakic bullous keratopathy (PBK/ABK) patients Patients who underwent triple procedures for Fuch’s corneal dystrophy (FCD) and cataracts.

Average time in weeks to thinnest central graft thickness Results Loteprednol Prednisolone ALL patients 14.6 (n=43) 10.2 (n=72) KCN - phakic 13.0 (n=17) 10.3 (n=23) FCD - triple 20.3 (n=10) 11.8 (n=12) PBK/ABK 13.6 (n=8) 9.4 (n=19) Average time in weeks to thinnest central graft thickness

Results The thinnest reading was reached significantly earlier for the PA patients (10.2 weeks) than for the LE patients, (14.6 weeks) (p < 0.001). This effect was similar for PBK/ABK patients, (13.6 weeks vs. 9.4 weeks)(p = 0.01), and even more distinct for FCD/cataract patients (20.3 weeks vs. 11.8 weeks) (p = 0.02). Differences between treatment groups were not significant for the KCN only (phakic) patients, ( 13.0 weeks vs. 10.3 weeks) (p= 0.20). Although there were more patients on PA, variances between groups were homogeneous. Differences between groups for thickness were non-significant.

Complications 11 patients (15.3%) in the PA group developed steroid-induced glaucoma, whereas none (0.0%) of the LE patients had significantly raised intraocular pressure. Graft rejection within one year of surgery developed in 3 (4.2%) of the PA patients versus 2 (4.7%) of the LE patients.

Conclusion PA is more effective than LE regarding post op graft deturgescence, and is associated with reaching the thinnest CCT earlier. The rate of rejection episodes within one year is similar between the two groups. There is a significantly greater risk of developing steroid-induced glaucoma with PA than with LE.

References Bartlett JD, et al. Intraocular pressure response to loteprednol etabonate in known steroid responders. J Ocul Pharmacol. 1993; 9(2):157-65. Ehlers N, Hjortdal J. Corneal thickness: Measurement and Implications. Exp Eye Res. 2004;78(3):543-8. Novack GD, et al. Change in intraocular pressure during long-term use of loteprednol etabonate. J Glaucoma. 1998; 7(4):266-9. Grigorian RA, et al. Comparison of loteprednol etabonate 0.5% (Lotemax) to prednisolone acetate 1% (Falcon) for inflammation treatment following cataract surgery. Poster presentation. Randleman JB and Stulting RD. Prevention and treatment of corneal graft rejection: current practice patterns (2004). Cornea. 2006; 25(3):286-90.