Adalimumab has recently been reported to maintain disease remission in three patients with Behçet’s uveitis with no recurrence and stable visual acuities during the follow-up after being switched from infliximab to adalimumab [81].

The most common adverse events are upper respiratory tract infection and headache. Hypertension, autoantibody production, infusion reaction, rash, eczema, contact dermatitis, pruritus, and lower back pain are uncommon side effects.

The recommendations for the optimal use of anti-TNF agents are given in an excellent review by Sfikakis et al. [82].

Cytotoxic and Other Immunosuppressive Agents

Antimetabolites such as azathioprine and methotrexate and less frequently alkylating agents such as cyclophosphamide and chlorambucil are being used for the refractory cases of ocular Behçet’s disease.

Azathioprine, at 2.5 mg/kg/day, has been shown to be effective in preventing the development of new eye diseases in patients with Behçet’s who do not have eye involvement in a randomized, placebo-controlled, double-blind study restricted to male patients [83]. This study also showed that azathioprine was effective in maintaining visual acuity, reducing the number of hypopyon attacks, and reducing the steroid requirement. The patients taking azathioprine also had less frequent oral ulcers, genital ulcers, and arthritis.

A combination of azathioprine and cyclosporine or triple drug therapy combining corticosteroids, cyclosporine, and azathioprine may be more effective than monotherapy with either agent and has been reported to successfully induce remission in some patients [84].

Methotrexate may be used in refractory uveitis especially in children with Behçet’s disease or as a steroid sparing treatment and may reduce ocular inflammation.

Cyclophosphamide and chlorambucil are used more for the nervous system involvement and much less for ocular involvement in patients who

are refractory to other agents at doses of 1 g intravenous pulsed cyclophosphamide and 2–12 mg/ day chlorambucil.

The side effects of cytotoxic drugs and other immunosuppressive agents can be serious and include bone marrow suppression, hepatotoxicity, secondary malignancies, and decreased fertility. In the light of these potential side effects, these agents are usually reserved for the most desperate cases that have failed treatment with other medications [60].

Tolerization Therapy

As mentioned in the etiopathogenesis, crossreactivity between microbial HSP65 and human HSP60 has been hypothesized to trigger the disease in predisposed hosts by stimulating T cells and by inducing TNF-a(alpha) by various cell types [70, 85]. Uveitis, induced by the human HSP60, could be inhibited with the peptide linked to recombinant cholera toxin B subunit in Lewis rats [86]. This strategy was adopted in a phase I/ II clinical trial by oral administration of p336- 351-CTB, three times weekly, followed by gradual withdrawal of all immunosuppressive drugs used to control the disease in eight patients with Behçet’s disease [87]. Although the efficacy of this therapy needs to be confirmed in phase III trials and randomized controlled studies, tolerization therapy seems to be promising in the management of Behçet’s disease as well as other autoimmune diseases.

Laser Treatment

The characteristic occlusive retinal vasculitis may result in ischemic changes that may lead to retinal and/or disc neovascularization. Left untreated, retinal and/or disc neovascularization may induce further complications such as vitreous hemorrhage, tractional retinal detachment, and neovascular glaucoma. While medical treatment is necessary to suppress inflammation, it has no effect on capillary non-perfusion and neovascularization. Therefore, laser photocoagulation should be performed in areas of capillary non-perfusion and retinal neovascularization (Fig. 12.29) [88]. In the presence of disc

neovascularization, panretinal photocoagulation should be performed.

Photocoagulation is well tolerated and does not induce postoperative inflammation. Nevertheless, it is not an alternative to medical treatment and systemic medication must continue. Photocoagulation should not be performed during an inflammatory attack and should not be directed toward edema, and topical steroids should be given after photocoagulation [89].

Plasmapheresis

Studies indicate neutrophil hyperactivity in Behçet’s disease. Neutrophils and monocytes produce inflammatory cytokines that promote further neutrophil activity [90, 91]. Therefore, neutrophil apheresis can decrease the severity and frequency of attacks in Behçet’s disease as shown by two small open-label trials [91, 92]. However, this procedure does not extensively deplete T cells [91], which are thought to have a significant role in the posterior ocular attacks.

Surgical Management of Ocular

Complications

surgery to reduce postoperative inflammation, and surgery should be deferred until the eyes are free of active inflammation for at least 2–3 months.

Cataract Surgery

Cataract formation is very common in Behçet’s disease due to multiple factors, including recurrent intraocular inflammation, posterior synechia formation, and corticosteroid therapy. Cataract surgery in uveitic eyes may lead to severe postoperative complications such as recurrent intraocular inflammation, posterior synechia formation, cystoid macular edema, and optic atrophy and requires special attention. However, it is generally a safe procedure with favorable visual results in patients with Behçet’s disease [93]. Nevertheless, the visual result after cataract surgery depends on the preoperative status of the posterior segment [94]. The phacoemulsification technique seems to be superior to other techniques due to minimal surgical trauma. It is important to insert the intraocular lens into the capsular bag, which reduces the postoperative inflammation risk by avoiding contact of the intraocular lens with the iris and ciliary body [93, 95]. Foldable acrylic posterior chamber intraocular lenses are recommended for these patients [96, 97].

Trabeculectomy

Patients with Behçet’s uveitis should receive immunosuppressive therapy prior to any ocular

Trabeculectomy and intraoperative application of mitomycin C appear to provide long-term safety