Efficacy and safety of 0.1% cyclosporine A cationic emulsion in the treatment of severe dry eye disease: a multicenter randomized trial

Eur J Ophthalmol 2016; 26(4): 287 - 296


Article Subject: Cornea



Leonardi, Andrea Van Setten, Gysbert Amrane, Mourad Ismail, Dahlia Garrigue, Jean-Sebastien Figueiredo, Francisco C. Baudouin, Christophe



The SANSIKA study was conducted to assess the treatment effect of 0.1% cyclosporine A cationic emulsion (CsA CE) eye drops on signs and symptoms of patients with severe dry eye disease (DED).


This was a multicenter, randomized, double-masked, 2-parallel-arm, 6-month phase III study with a 6-month open-label treatment safety follow-up. Patients with severe DED with corneal fluorescein staining (CFS) grade 4 on the modified Oxford scale were randomized to receive once-daily CsA CE (Ikervis®) or its vehicle.


A total of 246 patients were randomized. The proportion of patients achieving ≥2 grades improvement in CFS and a 30% improvement in symptoms (Ocular Surface Disease Index [OSDI]) by month 6 was 28.6% with CsA CE vs 23.1% with vehicle (p = 0.326) (primary endpoint). Assessment of corneal damage showed greater improvement with CsA CE over vehicle in mean adjusted CFS change from baseline to month 6 (-1.764 vs -1.418, p = 0.037). There was a reduction in ocular surface inflammation assessed by human leukocyte antigen DR expression in favor of CsA CE at month 6 (p = 0.021). The mean OSDI change from baseline was -13.6 with CsA CE and -14.1 with vehicle at month 6 (p = 0.858). The main adverse event was instillation site pain (29.2% vs 8.9% in the CsA CE and vehicle groups, respectively), and it was mostly mild.


CsA CE was well-tolerated and effective in improving corneal damage and ocular surface inflammation and confirmed the positive benefit-risk ratio of this new formulation of CsA for the treatment of severe keratitis in DED.

Article History


Financial support: The SANSIKA study was sponsored by Santen SAS, Evry, France.
Conflict of interest: A. Leonardi is a consultant for Allergan, Alcon, Santen, Sifi, and Théa and was an investigator in the SANSIKA study. G. Van Setten is a consultant for Horus, Santen and Théa and was an investigator in the SANSIKA study. M. Amrane, J.S. Garrigue, and D. Ismail are employees of Santen SAS. F. Figuereido is consultant for Théa and Santen and was investigator in the SANSIKA study. C. Baudouin is a consultant for or has received a research grant from Alcon, Allergan, Santen, and Théa and was international coordinator in the SANSIKA study.

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