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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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Topical Interleukin-1 receptor antagonist therapy and corneal healing after photorefractive keratectomy in New Zealand White rabbits Brett Davies, Capt,

Dec 21, 2015

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Page 1: Topical Interleukin-1 receptor antagonist therapy and corneal healing after photorefractive keratectomy in New Zealand White rabbits Brett Davies, Capt,

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, TX

The 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: Topical Interleukin-1 receptor antagonist therapy and corneal healing after photorefractive keratectomy in New Zealand White rabbits Brett Davies, Capt,

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: Topical Interleukin-1 receptor antagonist therapy and corneal healing after photorefractive keratectomy in New Zealand White rabbits Brett Davies, Capt,

SteroidsGlaucomaCataractsSecondary infectionDelayed wound healing

Page 4: Topical Interleukin-1 receptor antagonist therapy and corneal healing after photorefractive keratectomy in New Zealand White rabbits Brett Davies, Capt,

Interleukin-1

Page 5: Topical Interleukin-1 receptor antagonist therapy and corneal healing after photorefractive keratectomy in New Zealand White rabbits Brett Davies, Capt,

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: Topical Interleukin-1 receptor antagonist therapy and corneal healing after photorefractive keratectomy in New Zealand White rabbits Brett Davies, Capt,

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: Topical Interleukin-1 receptor antagonist therapy and corneal healing after photorefractive keratectomy in New Zealand White rabbits Brett Davies, Capt,

Results

No difference in epithelial healing time

Time to re-epithelization:

Page 8: Topical Interleukin-1 receptor antagonist therapy and corneal healing after photorefractive keratectomy in New Zealand White rabbits Brett Davies, Capt,

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

Su

bje

ctiv

e H

aze

Page 9: Topical Interleukin-1 receptor antagonist therapy and corneal healing after photorefractive keratectomy in New Zealand White rabbits Brett Davies, Capt,

Results- Pentacam Haze

Week 1 Week 2 Week 3 Week 740

50

60

70

80

90

100

0.25mg1.25mg2.5mg

Den

sit

y

p<0.0001

Page 10: Topical Interleukin-1 receptor antagonist therapy and corneal healing after photorefractive keratectomy in New Zealand White rabbits Brett Davies, Capt,

Results-HistologySteroids 2.5mg 1.25mg 0.25mg

Central Foam Layer

p = 0.725

Thickest Foam Layer

p = 0.997

Page 11: Topical Interleukin-1 receptor antagonist therapy and corneal healing after photorefractive keratectomy in New Zealand White rabbits Brett Davies, Capt,

Conclusions

Against For

Epithelial healing

Histopathology

Pentacam

Side 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 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: Topical Interleukin-1 receptor antagonist therapy and corneal healing after photorefractive keratectomy in New Zealand White rabbits Brett Davies, Capt,

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