Purpose: To assess the effect of topical taprenepag isopropyl on each layer of the cornea by confocal microscopy.
Methods: Thirty-two ocular hypertensive or glaucoma patients were randomized into a 2-period, crossover study of 14 days of 0.1% taprenepag alone and in unfixed combination with 0.005% latanoprost (combination therapy). Baseline and sequential slit-lamp biomicroscopy, fluorescein staining, central ultrasonic pachymetry, and confocal microscopy were performed. Confocal images were analyzed for the density of the central superficial and basal epithelium, midstromal keratocytes, and endothelium, as well as endothelial coefficient of variation and percentage of hexagonal cells, and reflectivity of anterior stromal and midstromal layers.
Results: Corneal staining increased from baseline, reaching a peak at day 13 (69% and 63% of subjects treated with monotherapy and combination therapy, respectively), which resolved by day 35. A statistically significant increase in mean corneal thickness for both eyes and both treatments occurred on days 7 and 13 (range, 20–27 μm; P < 0.001) but recovered (≤6 μm) by day 35. No statistically significant changes were observed in the basal epithelial, midstromal, or endothelial cells. Mean ratio of average reflectivity of anterior stroma to midstroma increased on days 13 and 35 in period 1 for each treatment (range, 1.2–1.9; P < 0.001), and this increase persisted during period 2.
Conclusions: Anterior stromal reflectivity may remain increased even when biomicroscopic and confocal images of corneal layers remain normal or have recovered after topical taprenepag. This subclinical measure may be useful to detect a persistent adverse effect of a topical agent on the cornea.
*Pfizer, Inc, San Diego, CA
†Cornea Image Analysis Reading Center, Department of Ophthalmology and Visual Sciences, Case Western Reserve University and University Hospitals Eye Institute, Cleveland, OH.
Reprints: Ronald A. Schachar, Pfizer, Inc, 10646 Science Center Drive, CB10/2109, San Diego, CA 92121 (e-mail: email@example.com).
Supported by Pfizer, Inc, and P30 EY11373, Research to Prevent Blindness, and the Ohio Lions Eye Research Foundation.
Presented as abstract at the 2011 ARVO Annual Meeting, Fort Lauderdale, FL.
R. A. Schachar, S. Raber, and Min Zhang are Pfizer employees. The other authors have no commercial or conflicts of interest to disclose.
The clinicaltrials.gov identifier is NCT00934089.
Received December 21, 2011
Accepted February 24, 2012