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Efficacy and Safety of Topical Tacrolimus Eyedrops 0.03% in the Treatment of Dry Eye Associated With Graft vs. Host Disease Empar Sanz-Marco, MD, Patricia Udaondo, MD, Mª Jesús López-Prats, MD, Amparo Vázquez MD, Manuel Díaz-Llopis, MD, PhD. Nuevo Hospital Universitario y Politécnico La Fe. Valencia. Spain. Contact email: [email protected] Results • Mean age 44,07±5,99 years (range 34-54). • Mean duration of the treatment was 3,14±3,96 months (range 1-12) • Main results • 71,42% (10/14) improved significantly • 28,57% (4/14) local intolerance • (1/14) did not complete the follow-up • No significant adverse events associated • Subjective improvement in: • Burning in 57,1% (8/14) • Hyperemia 71,4% (10/14) • No improvement in blurring vision Test 1-year run-in period of lubricant treatment After tacrolimus treatment Schirmer (mm) 6,14±2,25 7,93±2,7 Visual Acuity 0,82±0,18 0,88±0,05 TBUT (s) 3,71±0,53s 7,50±4,97s Meniscometry (μm ) 148,21 ±86,342 196,57±131,677 Frequency of artificial tear instillation (times per day) 6,29±0,65 3,43±0,46 71% 29% Significant improvement Local intolerance The study aim is to present the efficacy and safety of a new immunosuppressive eyedrops to treat patients with severe dry eye due to graft versus host disease and resistant to topical cyclosporine, an important problem in these kind of patients. I have no financial interests or relationships to disclose. Financial Disclosure To evaluate tacrolimus 0.03% eyedrops in patients with dry eye associated with graft versus host disease resistant to topical cyclosporine 0.05%. Tacrolimus and cyclosporine are calcineurin inhibitors but tacrolimus immunosuppressive potential is higher than cyclosporine(1).Topical cyclosporine eyedrops and tacrolimus ointment has been shown effective in order to treat dry eye in chronic graft versus host disease (CGVHD) (2) However some patients present local or systemic intolerance to cyclosporine and tacrolimus ointment can produce discomfort because it has been designed for skin (Protopic®, Astellas Pharma Ltd). Although the beneficial effect of topical eyedrops FK506 remains unproven in CGVHD patients, it has been proven to be effective in preventing corneal rejection (3) and severe allergic conjunctivitis (4). 10 patients improved significantly, 4 patients did not tolerate it locally. Tacrolimus improved statistically: keratitis, Schirmer test (P=0.001, Paired t- student), meniscometry (P<0.001, Paired t-student) and reduced the number of instillations of artificial tears after 3 months of treatment (P=0.01, Wilcoxon test). 14 patients who did not respond to dry eye care and presented systemic/local intolerance to cyclosporine were treated with topical tacrolimus 0.03% once per day. Patients were evaluated every 2 weeks for a minimum of 3 months. All patients provided signed informed consent. The study protocol complied with the provisions of the Declaration of Helsinki and was reviewed and approved by the Ethics Committee of the University La Fe Hospital of Valencia, Spain Visual acuity, slit-lamp appearance, Schirmer basal secretion test, fluorescein break-up time, meniscometry/tear meniscus height measurement were evaluated every 2 weeks for a minimum of 3 months. Every patient completed a dry eye questionnaire regarding symptoms of burning, tearing, and number of instillations of artificial tears daily at the beginning and at the end of the study. This prospective study suggest that dry eye associated with GVHD can be effectively treated with topical tacrolimus, especially in cyclosporine intolerant patients. These findings should be further evaluated in large-scale controlled clinical trials. Purpose Methods Conclusion 1. Schreiber SL, Crabtree GR. The mechanism of action of cyclosporine A and FK506. Immunol Today. 1992; 13: 136-42. 2. Tam PM, Young AL, Cheng LL, et al. Topical 0.03% tacrolimus ointment in the management of ocular surface inflammation in chronic GVHD. Bone Marrow Transplant. 2010; 45: 957-8. 3. Reis A, Mayweg S, Birnbaum F, et al. Long-term results of FK-506 eyedrops following corneal transplantation. Klin Monbl Augenheilkd. 2008; 225: 57-61. 4. Ohashi Y, Ebihara N, Fujishima H, et al. A randomized, placebo- controlled clinical trial of tacrolimus ophthalmic suspension 0,1% in severe allergic conjunctivitis. J Ocul Pharmacol Ther. 2010; 26: 165-74 Bibliography
