MedPath

Treatment of Dry Eye Using 0.03% Tacrolimus Eye Drops

Phase 4
Completed
Conditions
Sjogren Syndrome
Dry Eye Syndrome
Interventions
Registration Number
NCT01850979
Lead Sponsor
University of Sao Paulo General Hospital
Brief 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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
24
Inclusion Criteria
  • SS was diagnosed according to the SS European Criteria
  • chronic symptoms of burning, foreign body sensation, itching in both eyes
  • daily need of artificial tears
  • abnormal Schirmer (ST) I test < 5mm or rose Bengal staining (RBS) ≥ 4, or break up time (BUT) < 5 seconds.
Exclusion Criteria
  • any structural abnormalities (lid scarring, entropion, trichiasis, etc.)
  • any inflammation or active structural change in the iris or anterior chamber
  • glaucoma
  • previous eye surgery or punctual occlusion
  • use of any other topical medication other than artificial tears
  • any systemic or topical antibacterial or antiinflammatory drug treatment 90 days before study entry
  • contact lens wearer
  • the presence of any corneal infection
  • any corneal diseases (marginal ulcer, opacity, scar, bullous keratopathy, conjunctivochalasis, symblepharon or tumor)
  • pregnancy
  • change in the immunosuppressive systemic therapy 90 days before study entry

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
tacrolimusTacrolimustacrolimus 0,03% eye drops (olive oil as vehicle) every 12/12 hours for 3 months placebo as olive oil eye drops every 12/12h hours for 3 months
Olive OilOlive OilAll patients in this groups receive eye drops containing olive oil (vehicle of tacrolimus eye drops) twice a day (every 12 hours) for 90 days.
Primary Outcome Measures
NameTimeMethod
Evaluation of the quantity of lacrimal film90 days

Schirmer I test was performed using a Whatman 41 paper strip placed in the lateral lower conjunctival sac, and the measurement was recorded after 5 minutes (at least 30 minutes after BUT and staining scoring).The exam was made in the same room with control of humidity and temperature by the same examinator

Secondary Outcome Measures
NameTimeMethod
Evaluation of quality of lacrimal film90 days

The BUT(break up time) was measured 3 times and averaged, using a chronometer in the same room with control of temperature and humidity by the same examinator.

Trial Locations

Locations (1)

University of Sao Paulo General Hospital

🇧🇷

Sao Paulo, SP, Brazil

University of Sao Paulo General Hospital
🇧🇷Sao Paulo, SP, Brazil

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