Treatment of Dry Eye Using 0.03% Tacrolimus Eye Drops
Condition: Sjogren Syndrome; Dry Eye Syndrome
MeSH terms: Sjogren's Syndrome; Dry Eye Syndromes; Keratoconjunctivitis Sicca; Syndrome
Study type: Interventional
Phase: Phase 4

Summary: 
      Aqueous deficiency dry eye is mainly caused by Sjogren syndrome (SS), an autoimmune, chronic,
      inflammatory and systemic disease which affects most commonly the lacrimal and salivary
      glands.The ocular treatment is focused in increasing lubrification and decreasing
      inflammation with topical autologous serum, topical immunosuppressive agents and
      corticotherapy. Use of topical immunosuppressants has increased in recent years because the
      topical corticotherapy leads to ocular complications. The most used immunosuppressant is
      cyclosporine. Tacrolimus , another immunosuppressant, has been used in treatment of immune
      and inflammatory ocular diseases.This study describes a prospective controlled double-blinded
      randomized study of the clinical outcome of SS dry eyes patients treated with 0.03%
      tacrolimus eye drops. As secondary purposes, outcome of dry eye symptoms and any ocular
      symptoms of the eye drops were also questioned to the patients.
    

Detailed description: 
      Aqueous deficiency dry eye is mainly caused by Sjogren syndrome (SS), an autoimmune, chronic,
      inflammatory and systemic disease which affects most commonly the lacrimal and salivary
      glands. The hyperreactivity of B lymphocytes causes lymphoplasmacytic infiltration, which
      induces production of antibodies against antigens of the acinar epithelium and ducts of the
      lacrimal exocrine gland . The ocular treatment is focused in increasing lubrification and
      decreasing inflammation with topical autologous serum, topical immunosuppressive agents and
      corticotherapy. Use of topical immunosuppressants has increased in recent years because the
      topical corticotherapy leads to ocular complications.

      Among topical immunosuppressants the most used ones are tacrolimus, also known as FK506 and
      cyclosporine A (CsA). Their mechanism of action is similar, but FK 506 is described to be 10
      to 100 times more potent than CsA. Tacrolimus is a macrolide with immunomodulatory action and
      becomes biologically active only when it binds to immunophilin and acts by inhibiting
      calcineurin, limiting transduction of the signal that carries information from the cell
      membrane to the nucleus, with the aim of stimulating interleukin (IL) - 2 synthesis, and
      inhibiting T and B lymphocyte activation . Generally, tacrolimus suppresses the immune
      response by inhibiting the release of other inflammatory cytokines (eg, IL-3, IL-4, IL-5,
      IL-8, interferon- ϒ, and tumor necrosis factor - α) .

      The systemic and topical use of tacrolimus is already well established in ophthalmologic
      treatments of immune-mediated diseases , uveitis, graft-versus-host disease , corneal
      transplants and ocular pemphigoid . In veterinary medicine, topical tacrolimus aqueous
      suspension is well established to treat dry eye in dogs . In humans, tacrolimus eye drops
      were reported to be effective in treating severe allergic conjunctivitis . In a previous
      report, our group has showed the clinical outcomes of a case series of eight patients with
      dry eye using 0.03% tacrolimus eye drops 5 based on evidence in treating animals with KCS.

      This study describes a prospective controlled double-blinded randomized study of the clinical
      outcome of SS dry eyes patients treated with 0.03% tacrolimus eye drops. As secondary
      purposes, outcome of dry eye symptoms and any ocular symptoms of the eye drops were also
      questioned to the patients.
    

Intervention name(s): Tacrolimus; Olive Oil
Intervention type(s): Drug; Drug
Intervention description(s): tacrolimus 0,03% eyedrops (olive oil vehicle) every 12 hours for 3 months placebo : olive oil eyedrops every 12 hours for 3 months; All patients in this groups receive eye drops containing olive oil (vehicle of tacrolimus eye drops) twice a day (every 12 hours) for 90 days.
Other intervention name(s): FK 506; placebo
Intervention MeSH terms: Tacrolimus
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: CYCLOSPORINE/TACROLIMUS [VA Drug Interaction]