1. Biosynthetic Collagen Substitute Proves Useful to Stabilize Corneal Wounds in Combat: A Rabbit Model Karin E. Thomas, MD and Joseph F. Pasternak, MD Walter Reed National Military Medical Center The authors have no financial interests to disclose.

2. DISCLOSURES The authors have no financial interests to disclose. The opinions or assertions contained herein are the private views of the author and are not to be construed as official or as reflecting the views of the Department of the Navy or the Department of Defense. Some of the proposed solutions to trauma repair use FDA approved medications and devices off-label (i.e., fibrin & tissue glue, amniotic membrane). The Eyegenix artificial cornea is not yet FDA approved. opinior

3. PURPOSE To design a method to stabilize anterior full-thickness corneal lacerations using a cross-linked collagen substitute to stabilize eyes in combat until definitive care is available. The patch would be temporary, as a means to quickly close the eye for medical evacuation purposes.

4. METHODS Fifteen female New Zealand white rabbits (Covance, Denver, PA) with average weight of 3 kg were used. The study was approved by the USUHS IACUC in accordance with their animal use policies. Care and maintenance adhered to ARVO policy. The artificial cornea, a biosynthetic collagen device, was provided by Eyegenix TM.

5. METHODS, cont. Two phases were instituted: Phase I involved gluing the biosynthetic collagen device onto the right eye without injury. Phase II was initiated with a horizontal 5 mm incision which was closed with 3 interrupted 10- 0 nylon sutures. Then the biosynthetic collagen device was attached with glue in a novel method (see next slide). Animals were sedated in accordance with protocol.

6. Biosynthetic Collagen Device Application Device was glued onto rabbit cornea using a novel dual glue method, using 4 micro-dots n- Butyl-2 Cyanoacrylate placed peripherally with fibrin sealant in the center of the device. Tarsorraphy was performed to help keep device on the rabbit eye. The device was easily removed at the completion of the study without damage to eye.

7. RESULTS Phase I: 6 of 10 rabbits maintained the artificial cornea bandage through POD# 7. Three of the remaining rabbits held the device through POD# 2, and one rabbit held until POD#5. Phase 2: all 5 of 5 rabbits (100%) maintained the device. A learning curve existed as the experiments continued by modifying glue techniques.

8. STATISTICS There were no significant differences between right and left eyes in Phase 1 for pachymetry (P =.781) or diameter (P =.343). When comparing Phases 1 and 2, the first group had significantly higher average pachymetry (384 vs. 328, P =.004), but the groups did not differ significantly with respect to either diameter (P =.400) or weight (P =.283).

9. HISTOLOGY Phase I analysis showed that rabbits who lost the device on POD#2 had much less inflammation and corneal edema than those on POD#7. This was also noted by scoring exam of Phase 2 eyes on POD#2. All Phase II subjects maintained the device through POD#7. Histology showed mild uveitis, moderate corneal edema, and inflammation. One rabbit developed keratitis which grew Staph aureus in the lab.

10. DEVICE CLARITY The device became more opacified after post-operative day #3 but anterior chamber was still viewable in most rabbits at POD#7.

11. CONCLUSION This device may be used as an emergency bandage safely for up to 2 days, and possibly up to 5 days. Hypoxia may lead to infection if left longer than 5 days. No other emergency ocular bandage exists. Future plans are to thin the Eyegenix TM material to allow better oxygen permeability. Various designs of this material could be used to seal corneal wounds, and now the material has been improved to allow suturing.

12. MILITARY BENEFIT The potential war-time benefit is that trained providers could easily glue this bandage on the wounded eye until definitive care became available. This would prevent further intraocular contents from leaking during intubation, valsalva, and other surgical procedures that the wounded patient may endure. The device is currently under further development to be used as a keratoprosthesis for complex retina surgeries and will likely be available in the future for definitive full thickness penetrating keratoplasty.