The Systematic Review Of Methylprednisolone Pulse Therapy And Orbital Irradiation In The Treatment Of Thyroid-associated Ophthalmopathy

ObjectiveThyroid-associated ophthalmopathy(TAO), the most frequent extrathyroidalmanifestation, is a disorder of autoimmune origin. Only a minority of patients developsevere expressions of the disease, requiring aggressive treatment. The major treatments areimmunosuppressants, orbital radiotherapy, surgery, somatostatin analogues andimmunoglobulins. Together with orbital radiotherapy and decompressive orbital surgery,methylprednisolone pulse therapy represent a mainstay and a well established treatment.However, the efficacy and tolerability of methylprednisolone pulse therapy and orbitalradiotherapy need advanced researsh. Nearly one hundred randomized clinical trials ofprostaglandin analogues in treatment of glaucoma were published. However, randomizedclinical trials usually have shown conflicting results, which hinder the drawing ofconclusions for clinical practice. Hence, systematic reviews and meta-analyses involvingrelevant all published randomized clinical trials were conducted to assess the efficacy andtolerability of methylprednisolone pulse therapy and orbital radiotherapy.Materials and MethodsThis meta-analysis was performed according to a predetermined protocol describingcomplete and detailed methods, and followed the widely accepted methodologicalrecommendations. Randomized clinical trials were identified through systematic searches.Electronic search included PubMed, EMBASE, the Cochrane Controlled Trials Register,CBM，CKNI，VIP and Wanfang with a cut-off date in May2011. The reference lists oforiginal reports and review articles retrieved through hand search were reviewed foradditional studies not yet included in the computerized databases. The patients had to bediagnosed as having untreated, moderately severe and active TAO. Interventions weremethylprednisolone pulse therapy, orbital radiotherapy or combination of them. Theoutcome measures of efficacy was improvement for oculr signs, symptoms, accessoryexamnation or subject sensation, and the outcome measures of safety were adverse eventrates. Twelve randomized clinical trials were included in the meta-analysis,7formethylprednisolone pulse therapy,5for orbital radiotherapy. Methodological quality wasevaluated using the Jadad scale or the Cochrane Handbook for Systematic Reviews list.Outcome measures were assessed on an intent-to-treat basis. For the meta-analysis, thestatistical analysis was performed by RevMan software version5.0and5.1, using the DerSimonian-Laird random effects model. Weighted mean difference was calculated forcontinuous outcomes. For dichotomous outcomes, relative risk and odds ratio wasestimated.ResultsSeven studies involving360patients were included in the meta-analysis ofmethylprednisolone pulse therapy, with the mean age being45.3years, and the sex ratiobeing1/3.14. Among these patients,79subjects were treated with methylprednisolonepulse therapy and orbital radiotherapy,100with methylprednisolone pulse therapy,78withoral prednisolone and orbital radiotherapy,88with oral prednisolone,9with placebo, and6with decompressive orbital surgery. One trial scored5, three scoret4, one scored3, onescored1, and one scored0according to the Jadad scale.The pooled relative risk(95%CI) oftotal effective rate were7.50[1.14,49.26](P=0.04) for methylprednisolone pulse therapyvs placebo,3.33[0.51,21.89](P=0.21) for methylprednisolone pulse therapy vsdecompressive orbital surgery,1.48[1.18,1.87](P=0.0007) for methylprednisolone pulsetherapy vs oral prednisolone, and1.42[1.11,1.81](P=0.005) for methylprednisolonepulse therapy combined with orbital radiotherapy vs oral prednisolone combined withorbital radiotherapy, respectively.Five studies involving289patients were included in the meta-analysis of orbitalradiotherapy, with the mean age being46.7years, and the sex ratio being1/2.94. Amongthese patients,165subjects were treated with orbital radiotherapy,50with oralprednisolone, and116with sham radiotherapy. One trial scored A quality, four scoret Bquality according to the Cochrane Handbook for Systematic Reviews list. The pooled oddsratio (95%CI) of total effective rate were0.32[0.16,0.64](P=0.001) for orbitalradiotherapy vs sham radiotherapy, and0.89[0.40,1.94](P=0.76) for orbital radiotherapyvs oral prednisolone, respectively. The weighted mean differences of proptosisimprovement was-0.30[95%CI,-0.69to0.10](P=0.14) between radiotherapy and shamradiotherapy.ConclusionsMethylprednisolone pulse therapy appears to be an effective treatment for moderatelysevere and active TAO, and seems to have increased effect when given with orbitalradiotherapy. The treatment with methylprednisolone pulse therapy and oral prednisoloneall produce relevant side-effects, and the more frequently observed were: cushingoidfeatures, hyperglycemia, gastrointestinal, sleepiness, hypertension, depression, and so on. Cushingoid feature was one of the most frequent complaints, and the incidence rate ofcushingoid feature in oral prednisolone therapy was significantly higher thanmethylprednisolone pulse therapy.Orbital radiotherapy is effective in treatment of moderately severe and active TAO,and significant difference was found when compared with sham radiotherapy. Orbitalradiotherapy is equally effective as oral glucocorticoid, there was no significant differencebetween them. And the effect of orbital radiotherapy on proptosis is insignificant.To sum up, methylprednisolone pulse therapy appears to be an effective treatment formoderately severe and active TAO, and seems to have increased effect when given withorbital radiotherapy. In addition, it had higher tolerance and better safty. Therefore,methylprednisolone pulse therapy may be a better choice as first-line moderately severeand active TAO therapy.