June 2015
Volume 56, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2015
Cyclosporine A using F4H5 as liquid drug carrier is effective in treating experimental dry-eye disease
Author Affiliations & Notes
  • Uta Gehlsen
    Ophthalmology, University Hospital of Cologne, Cologne, Germany
  • Tobias Braun
    Ophthalmology, University Hospital of Cologne, Cologne, Germany
  • Claus Cursiefen
    Ophthalmology, University Hospital of Cologne, Cologne, Germany
  • Philipp Steven
    Ophthalmology, University Hospital of Cologne, Cologne, Germany
  • Footnotes
    Commercial Relationships Uta Gehlsen, None; Tobias Braun, None; Claus Cursiefen, Allergan (C), Gene Signal (C), Novaliq (C); Philipp Steven, Novaliq (F)
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2015, Vol.56, 319. doi:
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    • Get Citation

      Uta Gehlsen, Tobias Braun, Claus Cursiefen, Philipp Steven; Cyclosporine A using F4H5 as liquid drug carrier is effective in treating experimental dry-eye disease. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):319.

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

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Abstract

Purpose: Dry eye disease is an inflammatory disorder that may be treated effectively with topical Cyclosporine A (CsA). As available water-based CsA is complex to formulate, a new delivery system was invented. Semifluorinated alkanes (SFAs) enable easier and preservative-free formulation of CsA. This study was designed to test the use of CsA using SFA (F4H5) as carrier for topical therapy in a mouse model of experimental dry eye disease. Since dry eye disease is known to be age-related young and senescent female mice were treated.

Methods: Experimental dry eye (EDE) was induced in 10-12 weeks old (10-12 w) and 12 months old (12 m) female C57BL/6 mice using a controlled environmental chamber (humidity 30 ± 5%, constant airflow) for 14 days and treatment with s.c. scopolamine. Topical therapy was performed 3x/day (5µl/eye) from day 11 of EDE. After 14 days mice were transferred to standard housing conditions (humidity 45-55%, no airflow). Therapy persisted until day 35. Mice were distributed in four groups: (1) 0.05% CsA/F4H5, (2) carrier only F4H5 (Novaliq, Germany) and (3) Restasis® (Allergan, USA). A control group (4) was left untreated and received no eye drops, but was kept under the same conditions as the therapy groups. Clinical readouts were undertaken weekly (amount of tear fluid; corneal epithelial staining) in combination with a final preparation of conjunctival tissue for counting goblet cell density.

Results: Senescent mice showed a significantly higher increase in epithelial staining after 14 days of EDE and a significantly stronger reduction of tear production compared to young mice. Therapeutic treatment of mice with ScA/F4H5 showed a significantly earlier and stronger increase of tear production and an earlier decrease of epithelial damage following EDE compared to untreated controls, F4H5 alone and Restasis® in both age groups. Clinically senescent mice developed a more severe EDE and efficacy of F4H5/CsA was detected later (after 3 weeks of therapy) than in younger mice (after 1 week).

Conclusions: CsA in F4H5 is highly effective in reducing corneal staining and maintaining conjunctival goblet cells in EDE. Compared to Restasis®, F4H5/CsA was shown to be equally effective, but with a faster therapeutic response in this study. Based on these results first applications in humans are on the way that may lead to a new therapeutic option in treating dry eye disease.

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