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Lisa Walker, Rebecca Rice, Wendy Martin, Keven Williams, Chris Steele, Suzette Craig, Sally Buck; Validation of the Rabbit Intracameral Inflammatory Assay as a Lot Release Test for Ophthalmic Viscosurgical Devices. Invest. Ophthalmol. Vis. Sci. 2016;57(12):933.
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© ARVO (1962-2015); The Authors (2016-present)
Due to the biologically derived nature of Ophthalmic Viscosurgical Devices (OVDs), a reliable and reproducible assay is essential to detect potential inflammatory contaminants. These preclinical studies validate a rabbit intracameral inflammatory assay for OVDs to predict their inflammatory potential as discussed in FDA Guidance document Endotoxin Testing Recommendations for Single-Use Intraocular Ophthalmic Device issued August 17, 2015.
Forty-five male rabbits were randomized into 3 replicate studies containing 3 groups of 5 animals each. Each rabbit received a single 100µl intracameral injection into the right eye of Balanced Salt Solution (BSS), a control OVD lot or an OVD lot spiked with ~ 1 EU/ml of endotoxin. A different lot of OVD was utilized for each replicate. Rabbits were examined for the following pivotal inflammatory criteria via slit lamp at approximately 8 and 24 hours post-injection: conjunctival congestion, anterior chamber white blood cells (WBCs), aqueous flare, aqueous fibrin, and iritis. Flare and WBCs were graded according to the SUN scale while remaining criteria were graded utilizing the Hackett-McDonald Ocular Scoring System. Pilot studies were conducted to determine optimal observation times, procedure-related background inflammation, and threshold inflammatory criteria for each parameter in this model.
Based on pilot study data, the following criteria were set for each of the pivotal parameters: Anterior Chamber WBCs, x ≤ 1.5; Aqueous flare, x ≤ 1.5; Iritis, x ≤ 1.0; Fibrin, x ≤ 1.0; Conjunctival Congestion, x ≤ 2.0, where x indicates the mean score of 5 eyes. Exceeding the criteria for one or more of the parameters at 8 or 24 hours resulted in lot failure. Furthermore, if any individual animal’s WBC score was 4 at 8 or 24 hours, or if any 2 individual animal’s WBC score was ≥ 3 at 8 or 24 hours, the lot would fail regardless of the mean score. During the pivotal evaluation, three replicate studies demonstrated that three individual lots of OVD spiked with ~ 1.0 EU/ml endotoxin exceeded at least one of the acceptance criteria for the assay while BSS and three individual lots of control OVD met all of the acceptance criteria.
Based on the criteria set in the pilot studies, the pivotal studies were successfully completed, validating the Rabbit Intracameral Release Assay using endotoxin as a positive control.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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