title: Subclinical increased anterior stromal reflectivity with topical taprenepag isopropyl.
abstract: OBJECTIVE
  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.
authors.affiliation: Pfizer, Inc, San Diego, CA 92121, USA. ronald.schachar@pfizer.com
authors.forename: Ronald A
authors.initials: RA
authors.lastname: Schachar
authors.forename: Susan
authors.initials: S
authors.lastname: Raber
authors.forename: Kristina V
authors.initials: KV
authors.lastname: Thomas
authors.forename: Beth Ann M
authors.initials: BA
authors.lastname: Benetz
authors.forename: Loretta B
authors.initials: LB
authors.lastname: Szczotka-Flynn
authors.forename: Min
authors.initials: M
authors.lastname: Zhang
authors.forename: Scott J
authors.initials: SJ
authors.lastname: Howell
authors.forename: Jonathan H
authors.initials: JH
authors.lastname: Lass
mesh_terms: D000085:Acetates / Q000009:adverse effects* / Q000627:therapeutic use; D000287:Administration, Topical; D000368:Aged; D000369:Aged, 80 and over; D002452:Cell Count; D003316:Corneal Diseases / Q000139:chemically induced* / Q000175:diagnosis; D060527:Corneal Keratocytes / Q000187:drug effects / Q000473:pathology; D063171:Corneal Pachymetry; D003319:Corneal Stroma / Q000187:drug effects* / Q000473:pathology; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004728:Endothelium, Corneal / Q000187:drug effects; D019573:Epithelium, Corneal / Q000187:drug effects; D005902:Glaucoma, Open-Angle / Q000175:diagnosis / Q000188:drug therapy*; D006801:Humans; D000077338:Latanoprost; D018613:Microscopy, Confocal; D008875:Middle Aged; D009798:Ocular Hypertension / Q000175:diagnosis / Q000188:drug therapy; D009883:Ophthalmic Solutions; D011461:Prostaglandins F, Synthetic / Q000627:therapeutic use; D058307:Receptors, Prostaglandin E, EP2 Subtype / Q000819:agonists*; D012029:Refraction, Ocular / Q000502:physiology; D013449:Sulfonamides / Q000009:adverse effects* / Q000627:therapeutic use; D014792:Visual Acuity / Q000502:physiology
chemical_list: D000085:Acetates; D009883:Ophthalmic Solutions; C568861:PF 04217329; D011461:Prostaglandins F, Synthetic; D058307:Receptors, Prostaglandin E, EP2 Subtype; D013449:Sulfonamides; D000077338:Latanoprost