July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
Positive Diabetic Retinopathy Outcomes with Emixustat in a Pilot Study
Author Affiliations & Notes
  • Chirag Jhaveri
    Retinal Consultants of Austin, Austin, Texas, United States
    Clinical Assistant Professor, Dell Medical School, University of Texas, Austin, Texas, United States
  • John M Koester
    Acucela, Seattle, Washington, United States
  • Jeffrey Gregory
    Acucela, Seattle, Washington, United States
  • Ryo Kubota
    Acucela, Seattle, Washington, United States
  • Footnotes
    Commercial Relationships   Chirag Jhaveri, Acucela (F); John Koester, Acucela (E), Acucela (I); Jeffrey Gregory, Acucela (E), Acucela (I); Ryo Kubota, Acucela (E), Acucela (I), Acucela (P)
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 1729. doi:
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      Chirag Jhaveri, John M Koester, Jeffrey Gregory, Ryo Kubota; Positive Diabetic Retinopathy Outcomes with Emixustat in a Pilot Study. Invest. Ophthalmol. Vis. Sci. 2019;60(9):1729.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Emixustat, an oral visual cycle modulator, inhibits the enzyme RPE65, resulting in decreased 11-cis-retinal and increased free opsin. Increased free opsin, which activates phototransduction, prevents complete dark adaptation and decreases the energy- and oxygen-intensive dark current. Lowering retinal oxygen consumption may be a useful strategy to treat hypoxia-driven conditions such as proliferative diabetic retinopathy (PDR). A pilot study was conducted to evaluate emixustat in the treatment of PDR.

Methods : 23 subjects with PDR with and without diabetic macular edema (DME) were randomized to 84 days of once-daily oral treatment with emixustat (dose-titration up to 40 mg) or placebo. The primary objective was to assess changes in levels of 7 aqueous humor cytokines (VEGF, IL-6, IL-8, IP-10, TGFβ-1, MCP-1, and IL-1β) associated with DR severity. Secondary objectives included assessing changes in central subfield thickness (CST), area of retinal neovascularization, extent of vitreous and preretinal hemorrhages, and visual acuity. Statistical significance was pre-specified at P≤0.10.

Results : There were no significant differences in change from baseline aqueous humor cytokine levels between treatment groups. However, subjects treated with emixustat experienced a numerically superior reduction in VEGF levels compared to placebo. Among the pre-specified secondary endpoints, a positive trend was seen in CST in subjects with DME (difference in means of 67.2 microns favoring emixustat, P=0.151). A post hoc analysis showed a significant difference favoring emixustat for CST in subjects with or without DME (difference in means of 48.1 microns favoring emixustat, p=0.0764). Additionally, the emixustat group experienced a significant reduction in total macular volume (TMV) compared to placebo (difference in means of 0.361 mm3 favoring emixustat, p=0.0263).

Conclusions : Treatment with emixustat resulted in a statistically significant reduction in CST and TMV in PDR subjects with or without DME at baseline. Further studies are planned to investigate the effects of emixustat in DR.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

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