Efficacy of tacrolimus eyedrops topical application for herpes simplex disciform stromal keratitis and its influence on tear

Abstract

Background Herpes simplex virus (HSV) disciform stromal keratitis is a T cell-mediated delayed-type hypersensitivity of corneal stroma.The treatment of HSV disciform stromal keratitis is the combination of glucocorticoid and antiviral drug before.However, the therapy is limited for intolerantble patients to glucocorticoid.In addition, the adverse reactions following usage of glucocorticoid can not be ignored.FK506 solution is proved to has the immunosuppressive and antiinflammatory acttions with less side effects than glucocorticoid drug.But the study on the application of FK506 solution in treatment of HSV disciform stromal keratitis is lack. Objective This prospective clinical trail was to evaluate the efficacy of topical tacrolimus for HSV disciform stromal keratitis and its safety. Methods A prospective study was performed on 18 consecutive cases (18 eyes) who were diagnosed as active HSV disciform stromal keratitis from June 2011 to June 2012 in Zhongshan Ophthalmic Center under the approval of the Ethic Committee of Zhongshan Ophthalmic Center and informed consent of the patients, including 3 patients with refractory to prior steroid eyedrops.All patients received a combination topical tacrolimus eyedrops 4 times per day with topical and systemic anti-viral therapy for mean (56.0±7.9)days.Corneal thickness by slit lamp biomicroscope, visual acuity, intraocular pressure, corneal fluorescein staining, SchirmerⅠtest (SⅠt) and tear break-up time (BUT) were performed on the patients before and 1 month, 2 months after treatment and at the drug withdrawal to assess the treating efficacy of FK506, and the adverse reactions of eyes were recorded. Results Corneal edema was alleviated in (8.3±2.5)days after treatment in all the patients and returned to normality in (25.3±11.5) days.Corneal edema of 2 eyes with refractory to previous steroid eyedrops showed a slower recovery procedure than that of the others.Corneal fluorescence staining scores were 4(6, 2), 1(2, 1), 1(1, 0) and 0(1, 0) before and 1 month, 2 months and at drug withdrawal, respectively, with a significant difference among the four time points (H=39.90, P<0.001), and the scores were significantly lower after treatment than before (all at P<0.01).The SⅠt values were (6.78±1.90), (7.39±3.53), (8.06±2.92) and (8.11±3.05)mm/5 min, respectively in the 4 time points, without statistically significant difference among various time points (F=0.94, P=0.43).The BUT values were (0.39±0.50), (1.11±0.90), (2.00±1.08) and (3.39±0.92)seconds, respectively, showing a significant difference among the 4 time points (F=34.54, P<0.01) and had the increased values after treatment of FK506.Recurrence was seen in 2 eyes in 2 months and 5 months after cessation of tacrolimus.However, the eyes were healed after a second round regimen.No elevation of intraocular pressure and secondary infection were found in the patients during the treatment and follow-up period. Conclusions The combination therapy of tacrolimus with antiviral drug is effective and safe for HSV disciform stromal keratitis by alleviating corneal edema and promoting the rehabilitation of tear film. Key words: Tacrolimus/administration & dosage; Immunosuppressive agents/administration & dosage; Keratitis, herpetic/therapy; Drug administration schedul; Treatment outcome