Abstract
Purpose :
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.
Methods :
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.
Results :
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.
Conclusions :
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.