ReviewAnti-CD 20 monoclonal antibody (rituximab) treatment for inflammatory ocular diseases
Section snippets
Rituximab
Anti CD20 Rituximab is a chimeric (murine and human) monoclonal antibody directed against the CD20 molecule, a tetraspan membrane protein found only on the surface of mature B cells [1], [2], [3], [4], [5], [6]. The CD20 molecule displays a dynamic appearance first evolving in the immature B cell stage and later disappearing when B cells differentiate into plasma cells. By targeting CD20 the killing of B-cell precursor stem cells is avoided. Long-lived plasma cells residing in the bone marrow
Drug safety and adverse events
The tolerability and safety of Rituximab has been well described in the clinical trials of patients with RA and review articles on non-Hodgkin's lymphoma [4], [7], [8], [9], [10]. The most frequent adverse events are infusion reactions (30–35% with the first infusion). Patients may experience immediate infusion reactions of mild and transient character [4], [7], [8], [9], [10], [11]. Nevertheless, severe infusion reactions are uncommon and their frequency is reduced by the use of concomitant
Rituximab in systemic autoimmune diseases
Several clinical studies have demonstrated the substantial impact of rituximab for treatment of various systemic autoimmune diseases [1], [2], [3], [4], [5], [6], [7], [8], [10], [11], [12], [13], [14], [15], [16], [17]. Evidence of therapeutic effect is also mounting for numerous autoimmune conditions such as rheumatoid arthritis, systemic lupus erythematosus (SLE), Wegener's granulomatosis and anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis, idiopathic thrombocytopenic
Rituximab in inflammatory eye diseases
Rituximab has been successfully used for the treatment of refractory keratoconjunctivitis, scleritis [18], [19], [20], [21], [22], [23], peripheral ulcerative keratitis [24], [25], uveitis [26], [27], [28], [29] and ocular surface inflammatory diseases such as cicatricial pemphigoid [30], [31] also when associated with systemic diseases. Experience in inflammatory ocular diseases is still scarce with few case reports on its efficacy.
Scleritis and orbital inflammation
Necrotizing scleritis and peripheral ulcerative keratitis are destructive forms of ocular inflammation of Wegener's granulomatosis usually associated with active systemic vasculitis and can result in profound visual loss. Successful effectiveness with Rituximab has been reported on three patients with scleritis and peripherative ulcerative keratitis associated with Wegener's granulomatosis [18], [20], [21], [22], [23]. Another case of peripherative ulcerative keratitis associated to Wegener's
Sjogren's syndrome
Keratoconjunctivitis sicca (KCS) is the most common ocular manifestation of Sjogren's syndrome; sicca syndrome, secondary to lacrimal gland inflammation and reduction of lacrimal tear secretion can induce severe corneal complications and may eventually lead to bilateral blindness.
Preliminary experiences of Rituximab therapy in Sjogren's syndrome patients suggest that patients with more residual exocrine gland function might better benefit from treatment. Sicca syndrome responded much better in
Ocular cicatricial pemphigoid
Ocular cicatricial pemphigoid (OCP) is one of the subsets within the spectrum of mucous membrane pemphigoid, a family of autoimmune blistering diseases with autoantibodies targeting various glycoproteins in skin and/or mucous membranes [30]. The disease is relentlessly progressive, usually slow, and often resulting in profound visual disability. Foster and colleagues reported effective results on twelve patients with OCP treated with a combination of Rituximab and intravenous immunoglobulin
Intraocular lymphoma
Primary intraocular lymphoma, is a hematopoietic tumor that arises within the retina, vitreous, subretinal pigment epithelial space or optic nerve head. Intraocular lymphoma may manifest with different forms of uveitis called “masquerade syndrome”. The malignancy is considered a subset of primary central nervous system lymphoma, which is a variant of extra-nodal non Hodgkin lymphoma. Malignant lymphocytes present in intraocular lymphoma express certain B cell markers including CD 20 [32].
Uveitis
Rituximab may be helpful in selected patients with chronic uveitis refractory to corticosteroid and conventional immunosuppressants. Tappeiner and colleagues reported improvement of endogenous uveitis and associated cystoid macular edema in an adult patient treated with Rituximab; the treatment also displayed a steroid-sparing effect. However, the B-cell depletion in the peripheral blood and the positive effect on uveitis were transient, since there was a recurrence of inflammation after 6 and 9
Children with juvenile idiopathic arthritis associated uveitis: personal experience
Juvenile idiopathic arthritis (JIA) is the most common systemic disorder associated with uveitis in childhood, accounting for approximately 75% of all pediatric anterior uveitis cases. Long-term ocular complications of uveitis such as cataract, band keratopathy, posterior synechia, glaucoma and maculopathy can lead to severe visual impairment in about 38% of patients [34]. Visual outcome in long-term follow-up of patients suffering from JIA-associated uveitis has been described as poor, with
Take-home messages
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Rituximab, a humanized monoclonal antibody targeted to CD20, has been used extensively for treating systemic lymphoma, rheumatoid arthritis and other autoimmune diseases.
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Rituximab may be effective in the treatment of ocular inflammatory diseases in particular the most aggressive, recalcitrant and sight-threatening forms of inflammation such as uveitis in children associated with JIA, as well as diseases not responsive to anti-TNF alpha blocking agents.
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Inflammatory ocular diseases treated with
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