Reversibility of dry eye deceleration after topical cyclosporine 0.05% withdrawal

J Ocul Pharmacol Ther. 2011 Dec;27(6):603-9. doi: 10.1089/jop.2011.0073. Epub 2011 Oct 14.


Purpose: To assess the reversibility of clinical benefits of cyclosporine 0.05% (Restasis(®); Allergan, Inc., Irvine, CA) therapy and the therapeutic gain after its delayed use by switching treatment modalities in patients with dry eyes who completed a 1-year course of therapy with artificial tears (Refresh Endura(®); Allergan, Inc., Irvine, CA) or cyclosporine 0.05%.

Methods: This was a single-center, prospective, investigator-masked, longitudinal extension trial. Patients who had been treated with cyclosporine 0.05% in the first year of study were randomized in a 2:1 ratio to either cyclosporine 0.05% (Cs-Cs; n=20) or artificial tears (Cs-At; n=8), and those who had been originally randomized to artificial tears were switched to cyclosporine 0.05% (At-Cs; n=20) in the second year of study. Patients received study drugs twice daily for 12 months. Disease severity was assessed according to the International Task Force consensus guideline at months 0 and 12. Signs and symptoms were evaluated at baseline (month 0) and months 4, 8, and 12.

Results: At baseline, most patients with Cs-Cs and Cs-At (>90%) had level 2 disease severity, whereas almost half of the patients with At-Cs had level 3 disease severity. At month 12, a significantly higher percentage of patients with Cs-Cs and At-Cs than patients with Cs-At had the same or lower disease severity (P<0.001); whereas half of patients with Cs-At, compared with patients with no Cs-Cs and At-Cs, had disease progression at month 12. Throughout the study, dry eye signs and symptoms continuously improved in patients with Cs-Cs and At-Cs, whereas they constantly worsened in patients with Cs-At. At month 12, patients with Cs-Cs and At-Cs had significantly greater mean percentage improvement from baseline than did patients with Cs-At in Schirmer test scores, tear breakup time, Oxford staining scores, Ocular Surface Disease Index scores, and conjunctival goblet cell density (P<0.001). Overall, sign and symptom scores of patients with At-Cs did not improve as much as they did for patients with Cs-Cs.

Conclusions: Cyclosporine 0.05% withdrawal led to disease progression, thus indicating the necessity for maintenance therapy. Earlier treatment with cyclosporine 0.05% may result in improved outcomes.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Count
  • Cyclosporine / administration & dosage
  • Cyclosporine / adverse effects
  • Cyclosporine / therapeutic use*
  • Disease Progression
  • Drug Administration Schedule
  • Dry Eye Syndromes / drug therapy*
  • Dry Eye Syndromes / pathology
  • Female
  • Goblet Cells / pathology
  • Humans
  • Immunosuppressive Agents / administration & dosage
  • Immunosuppressive Agents / adverse effects
  • Immunosuppressive Agents / therapeutic use*
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Ophthalmic Solutions / administration & dosage
  • Ophthalmic Solutions / adverse effects
  • Ophthalmic Solutions / therapeutic use
  • Prospective Studies
  • Severity of Illness Index
  • Single-Blind Method
  • Substance Withdrawal Syndrome*


  • Immunosuppressive Agents
  • Ophthalmic Solutions
  • Cyclosporine