Evaluation of the effect of topical tacrolimus 0.03% versus cyclosporine 0.05% in the treatment of dry eye secondary to Sjogren syndrome

Abstract

Purpose: To compare the effect of topical application of tacrolimus 0.03% eyedrops versus cyclosporine 0.05% in Sjogren syndrome subjects with severe dry eyes. Design: A prospective single-blinded simply randomized controlled study. Methodology: 60 Sjogren patients were randomized into Group A: 30 patients were instructed to put tacrolimus 0.03% eyedrops in one eye for 6 months and placebo eyedrops in the other eye, ( N = 30, 44.9 ± 12.58 years). Group B: 30 patients were instructed to put cyclosporine 0.05% eyedrops in one eye for 6 months and placebo eyedrops in the other eye ( N = 30, 49.4 ± 12.92 years). Main outcome measures: Patients were evaluated at day 0, 90, and 180 for Ocular Surface Disease Index Questionnaire (OSDI), frequency of use of artificial tears, average fluorescein tear break up time (TBUT), ocular surface staining scores, Schirmer I test, meibum quality, and expressibility scores. Results: Upon comparing both eyedrops, the mean value of OSDI decrease was 38.25 ± 18.29% versus 31.69 ± 18.57% ( p-value 0.09), SICCA score decrease was 2.97 ± 1.92 versus 2.27 ± 2.02 ( p-value 0.124) the decrease in artificial tear substitute use was 3.90 ± 2.22 versus 3.63 ± 1.92 ( p-value 0.616), increase in Schirmer I values were 4.10 ± 4.21 and 4.26 ± 2.00 ( p-value 0.590) in eyes treated with tacrolimus and cyclosporine respectively. Neither of them affected meibum quality or expressibility scores. Conclusion: Both tacrolimus and cyclosporine significantly improved patient symptoms, frequency of artificial tears use and ocular surface staining compared to placebo-controlled eyes. However, no significant difference regarding the efficacy of both eyedrops at the end of 6 months treatment of severe dry eyes of Sjögren syndrome patients. Trial registration: ClinicalTrials.gov. Identifier: NCT03865888.

Development and Characterization of a Tacrolimus/Hydroxypropyl-β-Cyclodextrin Eye Drop

“…Anesthetized animals (2.5% (v/v) isoflurane/oxygen) were positioned into the imaging bed, monitoring the respiration frequency. Afterward, 7.5 µL of each tacrolimus formulation, previously radiolabeled with 18 F-fluorodeoxyglucose ( 18 F-FDG), was instilled into the conjunctival sac of both eyes using a micropipette. The administered radioactivity was 0.20-0.25 MBq per eye.…”

“…Tacrolimus is a macrolide with a high molecular weight (804.02 g/mol) isolated from Streptomyces tsukubaensis, with a great immunosuppressive activity (100 times more potent than cyclosporine A) [10,11] that inhibits T cell proliferation and suppresses the release of inflammatory cytokines; it can theoretically be used to reduce inflammatory activity in uveitis patients [3]. This drug has been used in different ocular diseases including corneal graft rejection [12][13][14], vernal keratoconjunctivitis (VKC) [15][16][17], dry eye [11,18], uveitis [5,19,20], scleritis [21,22] or graft-versus-host disease [23][24][25], among others. Additionally, clinical studies have shown tacrolimus' high effectivity compared to other immunosuppressants such as cyclosporine, at lower concentrations [26].…”

Anti-Inflammatory Effect of Tacrolimus/Hydroxypropyl-β-Cyclodextrin Eye Drops in an Endotoxin-Induced Uveitis Model

“…Nowadays, TAC is commercially available in oral and intravenous formulations, used in transplanted patients, and as an ointment for the treatment of atopic dermatitis [ 47 ]. TAC eyedrops can constitute an alternative in the treatment of uveitis [ 48 , 49 ] because it has been successfully used for various immune-mediated ocular disorders such as graft rejection [ 20 ], vernal keratoconjunctivitis (VKC) [ 21 , 22 , 23 , 24 ], dry eye [ 25 ] or scleritis [ 26 , 27 ]. However, TAC eyedrops are not marketed and they must be elaborated in HPDs.…”

“…In addition, when patients do not respond to this therapy or have a contraindication for the use of corticosteroids, it is necessary to resort to ophthalmic topical immunosuppressants in order to achieve a sustained control of the inflammatory process [ 17 , 19 ]. In this context, the use of topical tacrolimus (TAC) could be an alternative which has already demonstrated safety and effectiveness in other ocular pathologies including corneal graft rejection [ 20 ], vernal keratoconjunctivitis (VKC) [ 21 , 22 , 23 , 24 ], dry eye [ 25 ] or scleritis [ 26 , 27 ] among others.…”

The Effect of Anti-Inflammatory Topical Ophthalmic Treatments on In Vitro Corneal Epithelial Cells

“…Only more recently has its efficacy been explored in clinical trials and experimental studies and found to improve the status of the ocular surface in patients with Sjögren's syndrome–related DED. 5 , 6 …”