Management of ocular manifestations of Behcet's disease: outcome with cytotoxic drugs
Authors: DAVATCHI Fereydoun , SHAMS Hormoz , SHAHRAM Farhad , NADJI Abdol‐Hadi , JAMSHIDI Ahmad‐Reza , AKHLAGHI Ma'ssoomeh , ABDOLLAHI Bahar Sadeghi , ZIAIE Naghmeh , AKBARIAN Mahmood , GHARIBDOOST Farhad 
Published: August 2005

Background and aim:  Cytotoxic drugs, combined with steroids, are the first line of treatment for serious ocular manifestations in Behcet's disease (BD) such as uveitis and retinal vasculitis. If used judiciously, they are effective and safe, even in the long‐term. In our unit, the following cytotoxic drugs have been used for this purpose – oral or pulse cyclophosphamide, weekly methotrexate, chlorambucil, cyclosporin, azathioprine, or a combination of these. In our experience, these cytotoxic drugs had a similar range of efficacy regarding improvement in visual acuity. Having obtained the same treatment response, we pooled all our data together to evaluate the overall outcome of the eye complications in our cohort of BD patients.

Methods:  The treatment protocol was the same regardless of which cytotoxic drug was used. Prednisolone was given to all patients at an initial dose of 0.5 mg per kilogram of body weight per day. The dose was later tapered as necessary. If a patient was resistant to a given cytotoxic drug, the drug was changed to another. In pooled data, the results before the first treatment were compared with those after the last treatment. Visual acuity (VA) was measured using a Snellen chart (on a scale of 10). The Disease Activity Index (DAI) for anterior uveitis (AU), posterior uveitis (PU), and retinal vasculitis (RV) was measured according to the criteria of Ben Ezra. The Total Inflammatory Activity Index (TIAI) and the Total Adjusted Disease Activity Index (TADAI) were also calculated. Statistical analysis was performed using a Student's t‐test for paired samples comparing the data obtained before and after treatment.

Results:  At the last evaluation of our database (March 2004) on patients who had an active posterior uveitis and/or retinal vasculitis, 1104 were treated with cytotoxic drugs, of whom 290 patients received more than one treatment protocol. The mean duration of eye lesions was 32.8 months (SD 37.6). The mean treatment time was 20.1 months (SD 20.3). Overall, the VA of 70% of patients improved or maintained after treatment. The mean VA improved from 3.8 to 4.7 (t = 10.099, P < 0.000001). The mean DAI of AU improved from 2.5 to 0.8 (t = 19.575, P < 0.000001). The mean DAI of posterior uveitis improved from 2.1 to 0.9 (t = 28.616, P < 0.000001). The mean DAI of retinal vasculitis improved from 2.5 to 1.5 (t = 12.070, P < 0.000001). The mean TIAI improved from 16.5 to 7.9 (t = 20.13, P < 0.000001). The mean TADAI improved from 37.1 to 25.6 (t = 20.24, P < 0.000001). Further analysis showed methotrexate at a dose of 15 mg/week, and azathioprine at 2 mg/kg/day were preferred for posterior uveitis, while low dose pulsed cyclophosphamide (0.5 g/m2/month) – azathioprine combination therapy for retinal vasculitis.

Conclusion:  Cytotoxic drugs are efficacious in the treatment of serious ocular manifestations of BD.