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Paul J Gomes, Matt J Chapin, David A Hollander, Mark B Abelson; Conjunctival Inflammation Measured by Confocal Microscopy to Evaluate New Therapeutic Agents. Invest. Ophthalmol. Vis. Sci. 2019;60(9):6708.
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© ARVO (1962-2015); The Authors (2016-present)
This report describes a novel application of confocal imaging to quantify immune cell infiltration in the setting of conjunctival inflammation as an exploratory endpoint for new treatment modalities. Conjunctival inflammation was assessed using a scoring algorithm in a subset of patients participating in a trial comparing experimental and established treatments.
The assessment was performed in the context of a prospective, single-center, randomized, double-masked, vehicle and active controlled, dose ranging study to evaluate the efficacy and safety of PRT-2761, compared to vehicle, Patanol , or Patanol/Pred forte for the relief of signs and symptoms of allergic conjunctivitis. The study utilized the conjunctival allergen challenge (Ora-CAC®) model. Qualified subjects were dosed bilaterally with test agent, and after 8 hours received allergen challenge; signs and symptoms of AC, including itching and redness, were assessed post-CAC. In a subset of patients, conjunctival inflammation scores (CIS) were measured using confocal microscopy on a 0-4 scale following the last post-CAC assessment (approximately 30 minutes). Confocal scoring was conducted by trained investigators blinded to the source of the images.
There was a positive correlation between redness and CIS at the Visit 3 baseline CAC (Spearman r=0.53 [0.14, 0.78]) P=0.0095. When compared to the vehicle group, statistically significant differences in redness were observed for both doses of PRT-2761 and Patanol treatment 8 hours post treatment, at all timepoints post-CAC. In a subset of patients, the mean CIS was 3.7 (±0.76), 1.8 (0.41), 2.0 (0.82), 2.1 (1.36) for the placebo N=7, 0.5% PRT-2761 N=6, 1% PRT-2761 N=4, and Patanol N=7 groups, respectively. Compared to the placebo group, all three treatments had statistically and clinically significant reductions in CIS (P<0.05, greater than a 1 unit difference). These results indicate that PRT-2761 is an effective drug to reduce inflammation associated with AC and that CIS can be used as an additional measure of inflammation.
Measurement of inflammation correlates with conjunctival redness, validating the potential use of this novel tool measuring the clinical signs of AC. Further, assessing conjunctival inflammation with confocal microscopy is a valuable approach to evaluating ocular surface inflammation when investigating new anti-inflammatory therapeutics.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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