April 2010
Volume 51, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2010
Ocular Effects of E. coli Endotoxin After Topical Administration in a Polycarbophil-Based Formulation
Author Affiliations & Notes
  • K. L. Krenzer
    Nonclinical Safety, Bausch & Lomb, Rochester, New York
  • J. F. Cooper
    Consultant, Greensboro, North Carolina
  • D. J. Hayes
    Solutions Process Development, Bausch & Lomb, Tampa, Florida
  • M. E. Richardson
    Nonclinical Safety, Bausch & Lomb, Rochester, New York
  • Footnotes
    Commercial Relationships  K.L. Krenzer, Bausch & Lomb, Inc., E; J.F. Cooper, Endotoxin Consultant, C; D.J. Hayes, Bausch & Lomb, Inc., E; M.E. Richardson, Bausch & Lomb, Inc., E.
  • Footnotes
    Support  None.
Investigative Ophthalmology & Visual Science April 2010, Vol.51, 2375. doi:
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      K. L. Krenzer, J. F. Cooper, D. J. Hayes, M. E. Richardson; Ocular Effects of E. coli Endotoxin After Topical Administration in a Polycarbophil-Based Formulation. Invest. Ophthalmol. Vis. Sci. 2010;51(13):2375.

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Abstract

Purpose: : The purpose of this study was to evaluate the effect of topical exposure to endotoxin in a polycarbophil formulation in both intact rabbits eyes and those compromised by a surgical intervention (penetrating incision or LASIK flap).

Methods: : Three corneal scenarios were assessed: (1) intact, (2) penetrating surgical incision, and (3) LASIK flap. Three adult New Zealand White rabbits were used per each test group (scenario/dose). Surgical wounds were created under general and local anesthesia by a corneal specialist. Penetrating wounds were created with a 3 mm knife. LASIK flaps were created using a 9.0 mm keratome. E. coli control standard endotoxin (CSE) was compounded daily in a polycarbophil formulation at levels of 0, 5, 50, and 500 EU/mL. Dose levels were confirmed on Days 1 and 14. Eyes were dosed QID for 14 days with the exception that on Day 1, only two doses of endotoxin were administered post-surgery in the penetrating incision and LASIK flap groups. Each dose volume was 50 µL/dose. Eyes were grossly assessed daily for inflammation using the Draize scale prior to the first dose and after the last dose. Detailed ophthalmic examinations were performed after the last daily dose on Days 2, 7 and 14. After the final dose on Day 14, the animals were euthanized and the eyes processed for microscopic examination.

Results: : In general, there were no signs of inflammation suggesting an adverse effect due to the presence of endotoxin in the polycarbophil-suspension. In the intact corneas, occasional Grade 1 injection was observed but did not correlate with dose group. In the corneal wound groups, inflammation/irritation related to the surgical procedure was observed in the first few post-operative days and generally resolved in all animals within 1 week. There were no clear dose-effects of endotoxin on the levels of inflammation observed. The only adverse reaction was the development of a corneal ulcer with Stage 2 diffuse lamellar keratitis in a LASIK vehicle control eye. There were no significant findings upon histological evaluation.

Conclusions: : The presence of endotoxin in a polycarbophil formulation up to levels of 500 EU/mL did not have a notable effect in intact eyes or in eyes that had been surgically compromised by either a penetrating incision or a LASIK flap.

Keywords: ocular irritancy/toxicity testing • drug toxicity/drug effects • cornea: basic science 
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