the authors have no financial interest to disclose topical il-1ra provided by therakine , inc

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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 ASCRS 2010, Boston, MA

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ASCRS 2010, Boston, MA. 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 - PowerPoint PPT Presentation

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Page 1: The authors have no financial interest to disclose Topical IL-1ra provided by  TheraKine , Inc

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, MCWilford Hall Air Force Medical Center

San Antonio, TXThe authors have no financial interest to discloseTopical IL-1ra provided by TheraKine, Inc.The conclusions do not necessarily reflect the views of the USAF or the DOD

ASCRS 2010, Boston, MA

Page 2: The authors have no financial interest to disclose Topical IL-1ra provided by  TheraKine , Inc

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

Page 3: The authors have no financial interest to disclose Topical IL-1ra provided by  TheraKine , Inc

SteroidsGlaucomaCataractsSecondary infectionDelayed wound healing

Page 4: The authors have no financial interest to disclose Topical IL-1ra provided by  TheraKine , Inc

Interleukin-1

Page 5: The authors have no financial interest to disclose Topical IL-1ra provided by  TheraKine , Inc

Methods

48 eyes

18 (OD)IL-1ra

Vigamox

6OD 2.5mg

6 OD1.25 mg

6 OD0.75mg

6 (OD)Flurometh

0.1%, Vigamox

24 OS Vigamox, Systane

Page 6: The authors have no financial interest to disclose Topical IL-1ra provided by  TheraKine , Inc

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

Page 7: The authors have no financial interest to disclose Topical IL-1ra provided by  TheraKine , Inc

Results

No difference in epithelial healing time

Time to re-epithelization:

Page 8: The authors have no financial interest to disclose Topical IL-1ra provided by  TheraKine , Inc

Results- Slit lamp exam

Week 3 Week 4 Week 5 Week 60

0.5

1

1.5

2

2.5

3

3.5

SteroidIL-1raControl

p=0.392

p<0.005 p<0.005

p=0.536

Subj

ectiv

e H

aze

Page 9: The authors have no financial interest to disclose Topical IL-1ra provided by  TheraKine , Inc

Results- Pentacam Haze

Week 1 Week 2 Week 3 Week 740

50

60

70

80

90

100

0.25mg1.25mg2.5mg

Den

sity

p<0.0001

Page 10: The authors have no financial interest to disclose Topical IL-1ra provided by  TheraKine , Inc

Results-HistologySteroids 2.5mg 1.25mg 0.25mg

Central Foam Layer

p = 0.725

Thickest Foam Layer

p = 0.997

Page 11: The authors have no financial interest to disclose Topical IL-1ra provided by  TheraKine , Inc

Conclusions

Against For

Further studies needed to determine side effects of IL-1ra as well as response in human cornea

IL-1ra does not increase epithelial healing timeNo difference in foam layer between treatment groupsSteroids significantly better than other groups on subjective haze analysis at weeks 4 and 5IL1-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

Page 12: The authors have no financial interest to disclose Topical IL-1ra provided by  TheraKine , Inc

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