1. Topical Interleukin-1 receptor antagonist therapy and corneal healing after photorefractive keratectomy in New Zealand White rabbits Brett Davies, Capt, USAF, MC; Vasudha Panday, Maj, USAF, MC; Charles Reilly, Lt Col, USAF, MC ; Matthew Caldwell, Maj, USAF, MC Wilford Hall Air Force Medical Center San Antonio, TX The authors have no financial interest to disclose Topical IL-1ra provided by TheraKine, Inc. The conclusions do not necessarily reflect the views of the USAF or the DOD ASCRS 2010, Boston, MA

2. Purpose This is a randomized, blinded study designed to compare topical Interleukin-1 antagonist (IL-1ra) against standard steroid treatment following photorefractive keratectomy (PRK). Vs

3. Steroids Glaucoma Cataracts Secondary infection Delayed wound healing

4. Interleukin-1

5. Methods 48 eyes 18 (OD) IL-1ra Vigamox 6OD 2.5mg 6 OD 1.25 mg 6 OD 0.75mg 6 (OD) Flurometh 0.1%, Vigamox 24 OS Vigamox, Systane

6. Outcome Measures Time to re-epithelization Weekly slit lamp exam for haze Pentacam evaluation prior to and at weeks 1,2,3, and 7 Histologic exam at week 7

7. Results No difference in epithelial healing time Time to re-epithelization:

8. Results- Slit lamp exam p=0.392 p<0.005 p=0.536 Subjective Haze

9. Results- Pentacam Haze p<0.0001

10. Results-Histology Steroids2.5mg1.25mg0.25mg Central Foam Layer p = 0.725 Thickest Foam Layer p = 0.997

11. Conclusions AgainstFor Epithelial healing HistopathologyPentacamSide effects?Subjective Further studies needed to determine side effects of IL-1ra as well as response in human cornea IL-1ra does not increase epithelial healing time No difference in foam layer between treatment groups Steroids significantly better than other groups on subjective haze analysis at weeks 4 and 5 IL1-ra reduced objective haze (Pentacam) similar to steroids at 1 month post op Lower doses of IL1-ra reduced objective haze more than higher dose

12. References Dinarello CA, Wolff SM. The role of interleukin-1 in disease. N Engl J Med 1993; 328: 106 Le J, Vilcek J. Tumor necrosis factor and interleukin 1: cytokines with multiple overlapping biological activities. Lab Invest 1987; 56: 234. Kijlstra A. The role of cytokines in ocular inflammation. Br J Ophthalmol 1994; 78: 885 Girard MT, Matsubara M, Fini ME. Transforming growth factor-beta and interleukin-1 modulate metalloproteinase expression by corneal stromal cells. Invest Ophthalmol Vis Sci 1991; 32: 2441. Yamada, J, Dana MR, Sotozono C, Kinoshita S. Local suppression of IL-1 by receptor antagonist in the rat model of corneal alkali injury. Experimental Eye Research2003; 76(2): 161-7. Biswas PS, Banerjee K, Zheng M, Rouse BT. Counteracting corneal immunoinflammatory lesion with interleukin- 1 receptor antagonist protein. J Leukoc Biol. 2004; 76(4): 868-75 Netto MV. Wilson SE. Corneal wound healing relevance to wavefront guided laser treatments. [Review] [58 refs] Ophthalmology Clinics of North America 2004; 17(2): 225-31 Kaji Y. Yamashita H. Oshika T. Corneal wound healing after excimer laser keratectomy. [Review] [28 refs] Seminars in Ophthalmology 2003; 18(1): 11-6 Alio JL. Perez-Santonja JJ. Tervo T. Tabbara KF. Vesaluoma M. Smith RJ. Maddox B. Maloney RK. Postoperative inflammation, microbial complications, and wound healing following laser in situ keratomileusis. [Review] [82 refs] Journal of Refractive Surgery 2000; 16(5): 523-38 Wachtlin J. Langenbeck K. Schrunder S. Zhang EP. Hoffmann F. Immunohistology of corneal wound healing after photorefractive keratectomy and laser in situ keratomileusis. Journal of Refractive Surgery 1999; 15(4): 451-8 Kato T. Nakayasu K. Hosoda Y. Watanabe Y. Kanai A. Corneal wound healing following laser in situ keratomileusis (LASIK): a histopathological study in rabbits. British Journal of Ophthalmology 1999; 83(11): 1302-5 Gan, L., Hamberg-Nystrom, H, Fagerholm, P, Van Setten, G. Cellular proliferation and leukocyte infiltration in the rabbit cornea after photorefractive keratectomy. Acta Ophthalmologica Scandinavica. 79(5):488-492, October 2001