April 2014
Volume 55, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2014
New Oral Therapy for Diabetic Macular Edema by Fidarestat
Author Affiliations & Notes
  • Atsushi Nakajima
    Sanwa Kagaku Kenkyusho Co.,Ltd, Nagoya, Japan
  • Eiji Suzuki
    Sanwa Kagaku Kenkyusho Co.,Ltd, Nagoya, Japan
  • Noriaki Kato
    Sanwa Kagaku Kenkyusho Co.,Ltd, Nagoya, Japan
  • Takahito Jomori
    Sanwa Kagaku Kenkyusho Co.,Ltd, Nagoya, Japan
  • Yoshio Akagi
    Faculty of Medical Science, University of Fukui, Fukui, Japan
Investigative Ophthalmology & Visual Science April 2014, Vol.55, 1065. doi:
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    • Get Citation

      Atsushi Nakajima, Eiji Suzuki, Noriaki Kato, Takahito Jomori, Yoshio Akagi; New Oral Therapy for Diabetic Macular Edema by Fidarestat. Invest. Ophthalmol. Vis. Sci. 2014;55(13):1065.

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

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Abstract

Purpose: Several studies have demonstrated that vascular endothelial growth factor (VEGF) and inflammatory cytokines such as IL-6 and monocyte chemoattractant protein-1 (MCP-1) play a critical role in the development of diabetic macular edema (DME). Recently, it was reported that an aldose reductase inhibitor (ARI) suppressed VEGF and inflammatory cytokine expression. We conducted in vivo and in vitro studies and an open-label clinical study to investigate the efficacy of fidarestat, an oral ARI, on DME.

Methods: Macular edema was induced by retinal ischemia/reperfusion produced by high intraocular pressure (IOP) in monkeys with diabetes. To evaluate the efficacy of fidarestat (32 mg/kg once a day for 3 weeks), macular thickness and vitreous VEGF protein expression were measured. In the in vitro study, IL-6 and MCP-1 protein expressions were measured in lipopolysaccharide (LPS)-stimulated murine macrophages. Moreover, 21 DME patients were treated orally with fidarestat (30 mg once a day) to assess the foveal average thickness and changes in best corrected visual acuity (BCVA) from baseline to 28 weeks in an open-label study. Subgroup analysis was also performed by dividing the patients into two groups according to the foveal thickness as follows: ≥300 µm (Group1) and <300 µm (Group2).

Results: The average thickness of central macular fovea was significantly increased following elevation of the IOP in diabetic monkeys, and fidarestat significantly inhibited the increase in the average thickness. The vitreous VEGF protein was suppressed by 44% in fidarestat-treated monkeys compared as that in the control monkeys. Fidarestat significantly suppressed the increase of IL-6 and MCP-1 in LPS-stimulated macrophages. In the clinical study, foveal average thickness decreased significantly and BCVA improved significantly from baseline at 28 weeks after fidarestat treatment. Mean improvement of BCVA and decrease of foveal thickness in Group 1 were -0.05 LogMAR (p<0.05) and 32.2 µm (p<0.05) respectively.

Conclusions: Our data demonstrated that fidarestat inhibited IL-6, MCP-1 and VEGF expressions multilaterally, thereby suppressing the development of macular edema in diabetic monkeys. In addition, the clinical data indicated that macular thickness and BCVA in DME patients were improved by fidarestat treatment. These results indicate that oral fidarestat treatment may be a new therapeutic option in DME.

Keywords: 499 diabetic retinopathy • 490 cytokines/chemokines • 585 macula/fovea  
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