title: Topical isopropyl unoprostone for retinitis pigmentosa: microperimetric results of the phase 2 clinical study.
abstract: The purpose of this study was to determine whether topical 0.15% isopropyl unoprostone (IU), a BK-channel activator, could improve or maintain the central retinal sensitivity in patients with middle- to late-stage retinitis pigmentosa (RP). IU was approved for glaucoma and ocular hypertension in 1994. The drug re-profiling strategy is one of the effective ways to develop safe drugs for patients with RP.
  
  
  
  A randomized, double-blind, and placebo-controlled phase II safety/efficacy trial was conducted. One hundred and nine patients with middle- to late-stage RP having a visual acuity of ≥0.5 were studied at six ophthalmological centers in Japan. The treatments of IU/day were divided into three groups: placebo group; two-drop group; and four-drop group for 24 weeks. The primary outcome measure was changes in the retinal sensitivity from baseline in the central 2° determined by MP-1 microperimetry (MP-1, Nidek, Japan). The secondary outcomes were changes in best-correct visual acuity, contrast sensitivity, retinal sensitivity of the central 10° by MP-1, mean deviation (MD) by a Humphrey field analyzer (HFA; Carl Zeiss Meditec, Dublin, CA, USA) 10-2, and the Visual Functioning Questionnaire 25 (VFQ-25) questionnaire scores.
  
  
  
  There was a tendency for a dose-dependent responsiveness in retinal sensitivity in the central 2°, MD, and total VFQ-25 score after 24 weeks of IU instillation by a simple linear regression analysis. A stratified analysis showed a significant dose-dependent responsiveness of the 2° central retinal sensitivity in more advanced patients (P = 0.028). The number of patients having a ≥4 dB decrease in the primary outcome measure was significantly fewer in the four-drop group than in the placebo group (P = 0.02). No adverse reactions were observed.
  
  
  
  A higher dose of IU can delay progression of the central retinal sensitivity decrease through an improvement of retinal sensitivity.
authors.affiliation: Department of Ophthalmology and Visual Science, Chiba University Graduate School of Medicine, Chiba, Japan, shuyama@faculty.chiba-u.jp.
authors.forename: Shuichi
authors.initials: S
authors.lastname: Yamamoto
authors.forename: Takeshi
authors.initials: T
authors.lastname: Sugawara
authors.forename: Akira
authors.initials: A
authors.lastname: Murakami
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Nakazawa
authors.forename: Nobuhisa
authors.initials: N
authors.lastname: Nao-I
authors.forename: Shigeki
authors.initials: S
authors.lastname: Machida
authors.forename: Yuko
authors.initials: Y
authors.lastname: Wada
authors.forename: Yukihiko
authors.initials: Y
authors.lastname: Mashima
authors.forename: Yozo
authors.initials: Y
authors.lastname: Myake