- Email: [email protected]
Optical coherence tomography for diagnosis and monitoring of angle-closure glaucoma induced by topiramate
Correspondence
tion by activated PC. Synergistic interaction of these 2 different thrombophilic factors might have played a role in the development of the RVT. Since RVT is reported to recur in 10% of patients within 4 years5 and because of the high incidence of neovascularization, proliferative retinopathy, and neovascular glaucoma in patients with RVT associated with FVL,6 it seemed reasonable to treat the patient with anticoagulants. In conclusion, despite prevailing reports questioning the role of protein S deficiency and FVL per se in the etiology of RVT, their coexistence, especially in young patients, might play a role in the pathogenesis of RVT. REFERENCES 1. Fegan CD. Central retinal vein occlusion and thrombophilia. Eye 2002;16:98–106. 2. Adamczuk YP, Iglesias Varela ML, Martinuzzo ME, Cerrato GS, Forastiero RR. Central retinal vein occlusion and thrombophilia risk factors. Blood Coag Fibrinol 2002;13:623–6. 3. Arsene S, Delahousse B, Regina S, Le Lez ML, Pisella PJ, Gruel Y. Increased prevalence of factor V Leiden in patients with retinal vein occlusion and under 60 years of age. Thromb Haemost 2005;94:101–6. 4. Filho PP, Pierre MM, Nascimento MA, Marcondes MA. Central retinal vein prethrombosis as an initial manifestation of protein S deficiency. Sau Paulo Med J 2004;122:134–5. 5. Backhouse O, Parapia L, Mahomed I, Lee D. Familial thrombophlia and retinal vein occlusion. Eye 2000;14:13–7. 6. Hvarfner C, Hillarp A, Larsson J. Influence of factor V Leiden on the development of neovascularization secondary to central retinal vein occlusion. Br J Ophthalmol 2003;87:305–6.
G.T. Sucak, Z. Aki, M. Or Departments of Hematology and Ophthalmology Gazi University Faculty of Medicine, Besevler Ankara, Turkey [email protected]
glaucoma 1 week after topiramate treatment was started for migraine. In our case, the diagnosis and monitoring of bilateral angle-closure glaucoma were accomplished mainly with optical coherence tomography (OCT; Stratus OCT III, Carl Zeiss, Germany). A 29-year-old woman undergoing treatment with topiramate for migraine presented with a complaint of blurred distance vision in both eyes. Her symptoms began 1 week after starting topiramate and progressed for 12 hours. Before the onset of symptoms, she had had excellent uncorrected vision. Initial examination revealed a visual acuity of 20/200 OU with a –7 diopter (D) of myopic correction. Intraocular pressures (IOP) were 32 mm Hg OD and 30 mm Hg OS. Anterior chambers were shallow, and angles were closed on gonioscopy. OCT demonstrated closed iridocorneal angles (Fig. 1A). Topiramate was discontinued, and topical 0.5% timolol maleate and 250 mg acetazolamide taken orally 3 times daily were introduced. The first day after discontinuing topiramate the patient’s pressures decreased to 10 mm Hg in both eyes. Visual acuity was 20/200 OU with a –7 D correction, and angles were still narrow on OCT. Five days after stopping topiramate, visual acuity was 20/20 OU without correction, IOP was 8 mm Hg OU, the anterior chamber depth was normal, and iridocorneal angles seen with OCT were opened (Fig. 1B). Acute myopia is a rare, idiosyncratic reaction to sulfonamides.3 Although controversy exists regarding the exact mechanism of acute myopia and angle-closure glaucoma after sulfonamide use, most authors have attributed this to ciliary body swelling secondary to blood barrier disruption. Ocular examination before starting topiramate use cannot identify eyes at risk. Acute bilateral angleclosure is usually reversible if the drug is discontinued. Other authors have used gonioscopy and ultrasound biomicroscopy.4–5 In our case, OCT confirmed narrow irido-
Can J Ophthalmol 2007;42:632–3 doi: 10.3129/can.j.ophthalmol.i07-107
Optical coherence tomography for diagnosis and monitoring of angle-closure glaucoma induced by topiramate
T
opiramate is an oral sulfonamide medication used primarily for seizure treatment that also demonstrates preliminary efficacy in the treatment of bipolar disorders and control of migraine pain. Topiramate may be associated with ciliochoroidal effusion with forward displacement of the lens–iris diaphragm and anterior chamber shallowing, resulting in acute myopia and angle-closure glaucoma.1–2 We present a rare case of acute, bilateral angle-closure
Fig. 1—Monitoring iridocorneal angle by optical coherence tomography. (A) Optical coherence tomography of the right eye at initial examination showing a closed iridocorneal angle. (B) Five days after discontinuing topiramate, iridocorneal angle was wider.
CAN J OPHTHALMOL—VOL. 42, NO. 4, 2007
633
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
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
tion by activated PC. Synergistic interaction of these 2 different thrombophilic factors might have played a role in the development of the RVT. Since RVT is reported to recur in 10% of patients within 4 years5 and because of the high incidence of neovascularization, proliferative retinopathy, and neovascular glaucoma in patients with RVT associated with FVL,6 it seemed reasonable to treat the patient with anticoagulants. In conclusion, despite prevailing reports questioning the role of protein S deficiency and FVL per se in the etiology of RVT, their coexistence, especially in young patients, might play a role in the pathogenesis of RVT. REFERENCES 1. Fegan CD. Central retinal vein occlusion and thrombophilia. Eye 2002;16:98–106. 2. Adamczuk YP, Iglesias Varela ML, Martinuzzo ME, Cerrato GS, Forastiero RR. Central retinal vein occlusion and thrombophilia risk factors. Blood Coag Fibrinol 2002;13:623–6. 3. Arsene S, Delahousse B, Regina S, Le Lez ML, Pisella PJ, Gruel Y. Increased prevalence of factor V Leiden in patients with retinal vein occlusion and under 60 years of age. Thromb Haemost 2005;94:101–6. 4. Filho PP, Pierre MM, Nascimento MA, Marcondes MA. Central retinal vein prethrombosis as an initial manifestation of protein S deficiency. Sau Paulo Med J 2004;122:134–5. 5. Backhouse O, Parapia L, Mahomed I, Lee D. Familial thrombophlia and retinal vein occlusion. Eye 2000;14:13–7. 6. Hvarfner C, Hillarp A, Larsson J. Influence of factor V Leiden on the development of neovascularization secondary to central retinal vein occlusion. Br J Ophthalmol 2003;87:305–6.
G.T. Sucak, Z. Aki, M. Or Departments of Hematology and Ophthalmology Gazi University Faculty of Medicine, Besevler Ankara, Turkey [email protected]
glaucoma 1 week after topiramate treatment was started for migraine. In our case, the diagnosis and monitoring of bilateral angle-closure glaucoma were accomplished mainly with optical coherence tomography (OCT; Stratus OCT III, Carl Zeiss, Germany). A 29-year-old woman undergoing treatment with topiramate for migraine presented with a complaint of blurred distance vision in both eyes. Her symptoms began 1 week after starting topiramate and progressed for 12 hours. Before the onset of symptoms, she had had excellent uncorrected vision. Initial examination revealed a visual acuity of 20/200 OU with a –7 diopter (D) of myopic correction. Intraocular pressures (IOP) were 32 mm Hg OD and 30 mm Hg OS. Anterior chambers were shallow, and angles were closed on gonioscopy. OCT demonstrated closed iridocorneal angles (Fig. 1A). Topiramate was discontinued, and topical 0.5% timolol maleate and 250 mg acetazolamide taken orally 3 times daily were introduced. The first day after discontinuing topiramate the patient’s pressures decreased to 10 mm Hg in both eyes. Visual acuity was 20/200 OU with a –7 D correction, and angles were still narrow on OCT. Five days after stopping topiramate, visual acuity was 20/20 OU without correction, IOP was 8 mm Hg OU, the anterior chamber depth was normal, and iridocorneal angles seen with OCT were opened (Fig. 1B). Acute myopia is a rare, idiosyncratic reaction to sulfonamides.3 Although controversy exists regarding the exact mechanism of acute myopia and angle-closure glaucoma after sulfonamide use, most authors have attributed this to ciliary body swelling secondary to blood barrier disruption. Ocular examination before starting topiramate use cannot identify eyes at risk. Acute bilateral angleclosure is usually reversible if the drug is discontinued. Other authors have used gonioscopy and ultrasound biomicroscopy.4–5 In our case, OCT confirmed narrow irido-
Can J Ophthalmol 2007;42:632–3 doi: 10.3129/can.j.ophthalmol.i07-107
Optical coherence tomography for diagnosis and monitoring of angle-closure glaucoma induced by topiramate
T
opiramate is an oral sulfonamide medication used primarily for seizure treatment that also demonstrates preliminary efficacy in the treatment of bipolar disorders and control of migraine pain. Topiramate may be associated with ciliochoroidal effusion with forward displacement of the lens–iris diaphragm and anterior chamber shallowing, resulting in acute myopia and angle-closure glaucoma.1–2 We present a rare case of acute, bilateral angle-closure
Fig. 1—Monitoring iridocorneal angle by optical coherence tomography. (A) Optical coherence tomography of the right eye at initial examination showing a closed iridocorneal angle. (B) Five days after discontinuing topiramate, iridocorneal angle was wider.
CAN J OPHTHALMOL—VOL. 42, NO. 4, 2007
633
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
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