Methotrexate is an antimetabolite which has been used to control uveitis from 1960s and its usage in the field of ophthalmology is increasing more and more [8-12]. Reviewing literatures, a lot of ophthalmologists used MTX at various dose ranging from 5 to 40mg per week [8, 13-15]. However, studies which revealed effectiveness of MTX at very low dose of 5mg/week are few.
In this study, 27 patients with chronic noninfectious uveitis were treated with oral MTX at dose of 5mg/week. For the first time, 2 patients were given 7.5mg/week as initial dose of therapy for the first 4 weeks. At first follow-up, these patients strongly complained of adverse effects such as nausea, dizziness and headache. So we adjusted dosage to 5mg/week in order to reduce side effects. Although MTX was given at very low dose, these patients showed satisfactory results both in controlling of uveitis and steroid-sparing effects. Since then, we were very interested in efficacy of MTX at low dose of 5mg/week and investigated it in 27 case series of patients.
In this study, inflammation was controlled in 92.6% of patients at dose of 5mg, once weekly. There are various reports about effects of MTX on inflammation control. Samson et al revealed that intraocular inflammation was controlled with MTX in 76% of patients [8]. Other studies showed that MTX was able to suppress inflammation at the ratio ranging from 45% to 72.6% [17-19]. There are other smaller retrospective studies inflammation reduction was achieved in 60% to 100% of patients [20-23].It is difficult to compare our results with these reports, because this study include small case series, but it showed that 5mg/week MTX was able to sufficiently suppress inflammation in our people.
One of the purposes of using IMT is to reduce prolonged systemic corticosteroids use which frequently results in serious side effects including gastritis, pepticulcer, diabetes, osteoporosis, hypertension, aseptic necrosis of the femoral head, etc. Steroids also affect visual acuity by causing cataracts orglaucoma in uveitic eyes. Many ophthalmologists reported that oral methotrexate showed steroid-sparing effect in uveitis patients. Samson et al revealed that MTX had steroid-sparing effect in approximately 70% of patients at dose of 7.5~40mg [8]. There are other reports revealed that MTX showed corticosteroid reduction in 50% to 100% of patients [17, 18, 24]. In this study, for 48.2% of patients corticosteroids could be ceased at 6 months of MTX therapy and 37.0% at 1 year of therapy, consequently the discontinuation of steroids was achieved in 85.2%. This result suggested that 5mg per week MTX therapy also had sufficient steroid-sparing effect. We suppose that the main reason to allow discontinuation of steroids was associated with decreased relapse rate.
In this study, except 4 patients, 85.2% of patients showed no relapse from 6 months after MTX therapy and there was no need to continue corticosteroids.
Visual acuity is one of the most important matters for patients and ophthalmologists. When initiating MTX therapy, most of patients included in this study showed poor visual acuity because of severe inflammation or frequent relapse or complications including cataract and floaters. Compared with visual acuity at initiation of therapy, it showed improvement in 29 eyes (82.9%) and there was no significant difference in 2 eyes (5.7%). To be more exact, 3 patients had already developed complicated cataract at the time of initiating therapy and showed no improvement of VA with use of MTX. But 6 months after starting MTX, inflammation was efficiently controlled and showed no relapse, so the patients were allowed to receive ECCE and IOL implantation to finally result in significant improvement of visual outcome. 2 cases whose visual acuity showed no improvement had iridocyclitis with sclerits and idiopathic anterior uveitis, respectively. However, 7.4% of patient included in this study showed decrease in visual outcome. They were diagnosed as Behcet’s disease and VKH syndrome.
Generally, MTX is safe medication but still shows serious adverse effects including elevated liver enzymes, leukopenia, nausea, malaise and so on, which sometimes prompt discontinuation of therapy. Samson et al reported that in 18 % of patients had to stop medication because of serious side effects and 43% developed common adverse reactions [8]. In current study, no one developed severe side effect, consequently no one stopped MTX therapy. Only mild to moderate adverse reactions including fatigue, stomatitis, diarrhea and leukopenia were noted in 22.2% of patients.