- Email: [email protected]
Early clinical experience with leflunomide in uveitis
Correspondence
corneal angles and helped in monitoring the improvement (Fig. 1). This can be done by adjusting the focus adjustment knob of the Stratus OCT III (placed on the side of the patient module) to the maximum hyperopic position, not to set the patient’s refractive correction but to move the focal plane of the engine towards the ocular surface. REFERENCES 1. Rhee DJ, Goldberg MJ, Parrish RK. Bilateral angle-closure glaucoma and cilliary body swelling from topiramate. Arch Ophthalmol 2001;119(11):1721–3. 2. Lachkar Y, Bowassida W. Drug-induced acute angle closure glaucoma. Curr Opin Ophthalmol 2007;18(2):129–33. 3. Levy J, Yagev R, Petrova A, Lifshitz T. Topiramate-induced bilateral angle-closure glaucoma. Can J Ophthalmol 2006;41(2):221–5. 4. Viet Tran H, Ravinet E, Schnyder C, Reichhart M, GuexCroisier Y. Blood-brain barrier disruption associated with topiramate-induced angle-closure glaucoma of acute onset. Klin Monatsbl Augenheilkd 2006;223(5):425–7. 5. Chen TC, C W Chao, J A Sorkin. Topiramate induced myopic shift and angle closure glaucoma. Br J Ophthalmol 2003;87:648–9.
Paula Palomares, Luis Amselem, Manuel Diaz-Llopis Department of Ophthalmology Consorcio Hospital General Universitario de Valencia Valencia, Spain [email protected] Can J Ophthalmol 2007;42:633–4 doi: 10.3129/can.j.ophthalmol.i07-092
Early clinical experience with leflunomide in uveitis
L
eflunomide (LEF), a pyrimidine synthesis inhibitor, exerts immunosuppressive, anti-inflammatory, and antiproliferative effects. LEF inhibits T-cell proliferation, possibly through inhibitory responses to interleukins (IL)-2, -6, and -1β, tumour necrosis factor (TNF)-α, intercellular adhesion molecule (ICAM)-1, cyclooxygenase (COX)-1, COX-2, NF-κβ complex, and nitric oxide. Multiple trials have demonstrated the efficacy and safety of LEF in psoriatic and rheumatoid arthritis.1 Despite its known immunomodulatory effects, there are very few studies regarding the role of LEF in uveitis. One report of LEF use in sarcoidosis cited cases of both ocular and pulmonary involvement.2 The author was unable to document any other published reports specifically concerning LEF use in human uveitis patients. A 19-year-old male with stable juvenile idiopathic arthritis had been followed for 5 years with chronic bilateral nongranulomatous anterior uveitis poorly controlled with topical and systemic corticosteroids, nonsteroidal anti-inflammatory
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drugs, methotrexate (MTX), and cyclosporine. LEF was initiated at 20 mg orally daily. Concurrent medications, including alternate-day oral prednisone 30 mg, MTX, and topical corticosteroids, were maintained. Corrected visual acuity was 20/15 bilaterally with 1⁄2 + anterior chamber (AC) flare and 1 ⁄2–1+ AC cells bilaterally. At 2 month follow-up, uveitis activity had increased bilaterally, with 1–2+ AC flare and 1+ cells OD, and 1+ flare and 1+ cells OS. By 4 months, the uveitis had resolved OD and improved OS to 1⁄2+ flare and 1⁄2–1+ AC cells. Oral prednisone was tapered to 10 mg every other day, and other therapy remained unchanged. At 6-month follow-up the OD demonstrated no active uveitis, and the OS had improved further, with 1⁄2+ flare and 1⁄2+ AC cells. The vision remained good. There were no identified adverse effects from LEF. LEF affects multiple inflammatory mediators, such as ICAM-1, IL-6, nitric oxide, and NF-κβ, in addition to preventing antigen presentation by inhibition of T-cell interaction with antigen-presenting cells,3 all of which have been implicated in uveitic inflammation.4 Furthermore, LEF is able to inhibit disease in the experimental autoimmune uveitis rat model.5 LEF may play a role in the management of some uveitides. Further studies are required to critically evaluate the role of LEF in the management of uveitis. REFERENCES 1. Litinsky I, Paran D, Levartovsky D, et al. The effects of leflunomide on clinical parameters and serum levels of IL-6, IL-10, MMP-1 and MMP-3 in patients with resistant rheumatoid arthritis. Cytokine 2006;33:106–10. 2. Baughman RP, Lower EE. Leflunomide for chronic sarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis 2004;21:43–8. 3. Zeyda M, Poglitsch M, Geyeregger R, et al. Disruption of the interaction of T cells with antigen-presenting cells by the active leflunomide metabolite teriflunomide: involvement of impaired integrin activation and immunologic synapse formation. Arthritis Rheum 2005;52:2730–9. 4. Deschenes JD, Roy M, Rocha G. Immunology of uveitis. In: Tasman W, Jaeger E, eds. Duane’s Foundations of Clinical Ophthalmology. Philadelphia: Lippincott-Raven; 1997:1–13. 5. Robertson SM, Lang LS. Leflunomide: inhibition of S-antigen induced autoimmune uveitis in Lewis rats. Agents Actions 1994;42:167–72.
Mili Roy, MD, BSc(MED), FRCSC Department of Ophthalmology University of Manitoba, Winnipeg, Man. [email protected] Can J Ophthalmol 2007;42:634 doi: 10.3129/can.j.ophthalmol.i07-085
corneal angles and helped in monitoring the improvement (Fig. 1). This can be done by adjusting the focus adjustment knob of the Stratus OCT III (placed on the side of the patient module) to the maximum hyperopic position, not to set the patient’s refractive correction but to move the focal plane of the engine towards the ocular surface. REFERENCES 1. Rhee DJ, Goldberg MJ, Parrish RK. Bilateral angle-closure glaucoma and cilliary body swelling from topiramate. Arch Ophthalmol 2001;119(11):1721–3. 2. Lachkar Y, Bowassida W. Drug-induced acute angle closure glaucoma. Curr Opin Ophthalmol 2007;18(2):129–33. 3. Levy J, Yagev R, Petrova A, Lifshitz T. Topiramate-induced bilateral angle-closure glaucoma. Can J Ophthalmol 2006;41(2):221–5. 4. Viet Tran H, Ravinet E, Schnyder C, Reichhart M, GuexCroisier Y. Blood-brain barrier disruption associated with topiramate-induced angle-closure glaucoma of acute onset. Klin Monatsbl Augenheilkd 2006;223(5):425–7. 5. Chen TC, C W Chao, J A Sorkin. Topiramate induced myopic shift and angle closure glaucoma. Br J Ophthalmol 2003;87:648–9.
Paula Palomares, Luis Amselem, Manuel Diaz-Llopis Department of Ophthalmology Consorcio Hospital General Universitario de Valencia Valencia, Spain [email protected] Can J Ophthalmol 2007;42:633–4 doi: 10.3129/can.j.ophthalmol.i07-092
Early clinical experience with leflunomide in uveitis
L
eflunomide (LEF), a pyrimidine synthesis inhibitor, exerts immunosuppressive, anti-inflammatory, and antiproliferative effects. LEF inhibits T-cell proliferation, possibly through inhibitory responses to interleukins (IL)-2, -6, and -1β, tumour necrosis factor (TNF)-α, intercellular adhesion molecule (ICAM)-1, cyclooxygenase (COX)-1, COX-2, NF-κβ complex, and nitric oxide. Multiple trials have demonstrated the efficacy and safety of LEF in psoriatic and rheumatoid arthritis.1 Despite its known immunomodulatory effects, there are very few studies regarding the role of LEF in uveitis. One report of LEF use in sarcoidosis cited cases of both ocular and pulmonary involvement.2 The author was unable to document any other published reports specifically concerning LEF use in human uveitis patients. A 19-year-old male with stable juvenile idiopathic arthritis had been followed for 5 years with chronic bilateral nongranulomatous anterior uveitis poorly controlled with topical and systemic corticosteroids, nonsteroidal anti-inflammatory
634
CAN J OPHTHALMOL—VOL. 42, NO. 4, 2007
drugs, methotrexate (MTX), and cyclosporine. LEF was initiated at 20 mg orally daily. Concurrent medications, including alternate-day oral prednisone 30 mg, MTX, and topical corticosteroids, were maintained. Corrected visual acuity was 20/15 bilaterally with 1⁄2 + anterior chamber (AC) flare and 1 ⁄2–1+ AC cells bilaterally. At 2 month follow-up, uveitis activity had increased bilaterally, with 1–2+ AC flare and 1+ cells OD, and 1+ flare and 1+ cells OS. By 4 months, the uveitis had resolved OD and improved OS to 1⁄2+ flare and 1⁄2–1+ AC cells. Oral prednisone was tapered to 10 mg every other day, and other therapy remained unchanged. At 6-month follow-up the OD demonstrated no active uveitis, and the OS had improved further, with 1⁄2+ flare and 1⁄2+ AC cells. The vision remained good. There were no identified adverse effects from LEF. LEF affects multiple inflammatory mediators, such as ICAM-1, IL-6, nitric oxide, and NF-κβ, in addition to preventing antigen presentation by inhibition of T-cell interaction with antigen-presenting cells,3 all of which have been implicated in uveitic inflammation.4 Furthermore, LEF is able to inhibit disease in the experimental autoimmune uveitis rat model.5 LEF may play a role in the management of some uveitides. Further studies are required to critically evaluate the role of LEF in the management of uveitis. REFERENCES 1. Litinsky I, Paran D, Levartovsky D, et al. The effects of leflunomide on clinical parameters and serum levels of IL-6, IL-10, MMP-1 and MMP-3 in patients with resistant rheumatoid arthritis. Cytokine 2006;33:106–10. 2. Baughman RP, Lower EE. Leflunomide for chronic sarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis 2004;21:43–8. 3. Zeyda M, Poglitsch M, Geyeregger R, et al. Disruption of the interaction of T cells with antigen-presenting cells by the active leflunomide metabolite teriflunomide: involvement of impaired integrin activation and immunologic synapse formation. Arthritis Rheum 2005;52:2730–9. 4. Deschenes JD, Roy M, Rocha G. Immunology of uveitis. In: Tasman W, Jaeger E, eds. Duane’s Foundations of Clinical Ophthalmology. Philadelphia: Lippincott-Raven; 1997:1–13. 5. Robertson SM, Lang LS. Leflunomide: inhibition of S-antigen induced autoimmune uveitis in Lewis rats. Agents Actions 1994;42:167–72.
Mili Roy, MD, BSc(MED), FRCSC Department of Ophthalmology University of Manitoba, Winnipeg, Man. [email protected] Can J Ophthalmol 2007;42:634 doi: 10.3129/can.j.ophthalmol.i07-085