BILATERAL CENTRAL RETINAL ARTERY OCCLUSIONS AND HUGHES SYNDROME Saumil Sheth, MD, Ryan B. Rush, MD
Purpose: The purpose of this study to report a case of bilateral retinal artery occlusions in a patient with systemic lupus erythematosus and antiphospholipid antibodies. Methods: A 28-year-old woman with systemic lupus erythematosus presented with sudden painless bilateral vision loss. Clinical examination and flourescein angiography were performed, and a diagnosis of bilateral central retinal artery occlusions was made. Laboratory evaluations were ordered. Results: Laboratory evaluation revealed the presence of antiphospholipid antibodies. The patient was treated with corticosteroids, azathioprine, aspirin, and warfarin. The patient’s visual acuity gradually improved over 2 weeks and then remained stable for 6 months without any further thrombotic events. Conclusion: The presence of bilateral retinal artery occlusions in a young patient should prompt an immediate evaluation for antiphospholipid antibodies, especially if the patient has been previously diagnosed with systemic lupus erythematosus. Correctly diagnosing patients with antiphospholipid antibodies is important because it implies the need for longterm anticoagulative and antiaggregative therapies to reduce the patient’s risk of recurrent, life-threatening, thrombotic events. RETINAL CASES & BRIEF REPORTS 6:304–306, 2012
eye. The external and anterior segments were within normal limits. The posterior segments of both eyes had clear media, and there were no appreciable vitreous cells. The posterior poles of each eye showed multiple intraretinal hemorrhages and cotton wool spots. Confluent retinal whitening, arterial attenuation, blood column segmentation, and a “cherry-red spot” were present in both eyes (Figures 1 and 2). Flourescein angiography demonstrated delayed arteriovenous transit time, reversal of flow in the branch retinal arteries, and late staining of the retinal blood vessels bilaterally. The patient was diagnosed with bilateral central retinal artery occlusions with SLE-associated retinal vasculitis. The patient was admitted into the hospital and started on 1 g of intravenous methylprednisolone daily. Serology for antiphospholipid antibodies was performed, and the patient was found to be positive for the lupus anticoagulant. The patient was then started on oral aspirin and warfarin. Once adequately anticoagulated, the patient was discharged on oral prednisone 1 mgkg−1d−1, azathioprine 1 mgkg−1d−1, 325 mg of aspirin, and a variable dosing schedule of warfarin. Two weeks after discharge, the patient’s best-corrected visual acuity improved to 20/200 in each eye. The prednisone was tapered slowly after 6 weeks, and the patient was maintained on azathioprine, lowdose aspirin, and warfarin indefinitely. Her best-corrected visual acuity remained stable at 20/200 at the 6-month follow-up visit. No additional thrombotic events occurred during the follow-up period.
From the Sydney Eye Hospital, Sydney, Australia. Case Report A 28-year-old woman recently diagnosed with systemic lupus erythematosus (SLE) presented with a 1-day history of sudden painless bilateral vision loss. There was no history of trauma and her ocular history was unremarkable. Two months earlier, she developed an erythematous rash involving her face and torso and was subsequently diagnosed with SLE by her health care provider. Her medical history was negative for diabetes mellitus, hypertension, and heart disease. She did have a history of a second trimester spontaneous abortion as well as an intrauterine fetal death. She had been undergoing treatment with systemic corticosteroids since her diagnosis with SLE and was on oral prednisolone 20 mg daily upon presentation. On clinical examination, her best-corrected visual acuity was hand movements at 2 m in both eyes. There was no relative afferent pupillary defect, and her intraocular pressure was 12 mmHg in each
The authors report no conflicts of interest. Reprint requests: Ryan B. Rush, MD, Sydney Eye Hospital, 8 Macquarie Street, Sydney, New South Wales, Australia 2000; e-mail: [email protected]
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Fig. 1. Right fundus photograph of the posterior pole.
Discussion Systemic lupus erythematosus–associated retinal vasculitis occurs in 23% of patients with SLE during the initial onset of symptoms and increases to 29% during periods of SLE activity after onset.1 Systemic lupus erythematosus antibodies primarily target the antigenic components of medium-sized blood vessels, resulting in a paucicellular vasculopathy with gradual deposition of hyaline within the vessel walls. Manifestations of SLE-associated retinal vasculitis are generally confined to the retinal arterioles and venules of the posterior pole, clinically appearing as cotton wool spots (or nerve fiber layer axoplasmic stasis) and blot or flame-shaped hemorrhages.2 Unlike giant cell arteritis, SLE-associated retinal vasculitis does not result in a hypercellular inflammatory reaction with rapid vessel occlusion by endothelial activation, vasospasm, and secondary thrombus formation, which can directly occlude large-sized vessels like the central retinal artery.3 Therefore, SLE-associated retinal vasculitis alone does not account for the development of a central
retinal artery occlusion. Systemic lupus erythematosus is associated with heart valve vegetations known as Libman–Sacks endocarditis, but these vegetations only rarely embolize. However, when antiphospholipid antibodies such as the lupus anticoagulant or anticardiolipin antibodies are present, a hypercoagulable state develops and the retinal circulation becomes predisposed to large-sized vessel thrombus formation.4 Antiphospholipid antibodies are found in 30% of patients with SLE and in 84% of all cases of idiopathic retinal thrombosis.5 When antiphospholipid antibodies, SLE, and retinal thromboses occur together, this entity becomes known as Hughes syndrome. Life-threatening thromboembolic complications have been reported to be as high as 73% in cases of Hughes syndrome. This risk is reduced to 19% when antithrombotic and antiplatelet agents are given prophylactically.6 Before the occurrence of the first thrombotic episode, some investigators recommend the use of aspirin and warfarin, whereas others suggest only low-dose aspirin. However, after the first thrombotic episode, the combined regimen of antithrombotic and antiplatelet agents becomes essential (international normalized ratio [INR] $ 3, Stroke Prevention in Reversible Ischemia Trial, INR 2–3).7 Numerous case studies have reported on the link between retinal vascular occlusions and antiphospholipid antibodies.8–10 The presence of bilateral retinal vascular occlusions in a young patient should prompt an immediate evaluation for antiphospholipid antibodies, especially if the patient has been previously diagnosed with SLE. Correctly diagnosing Hughes syndrome is important clinically because it implies the need for long-term anticoagulative and antiaggregative therapies to reduce the patient’s risk of recurrent even life-threatening thrombotic events. Key words: central retinal artery occlusion, Hughes syndrome. References
Fig. 2. Left fundus photograph of the posterior pole.
1. Read RW. Clinical mini-review: systemic lupus erythematosus and the eye. Ocul Immunol Inflamm 2004;12:87–99. 2. Au A, O’Day J. Review of severe vaso-occlusive retinopathy in systemic lupus erythematosus and the antiphospholipid syndrome: associations, visual outcomes, complications and treatment. Clin Experiment Ophthalmol 2004;32:87–100. 3. Nag TC, Wadhwa S. Histopathological changes in the eyes in systemic lupus erythematosus: an electron microscope and immunohistochemical study. Histol Histopathol 2005;20:373–382. 4. Durrani OM, Gordon C, Murray PI. Primary anti-phospholipid antibody syndrome (APS): current concepts. Surv Ophthalmol 2002;47:215–238.
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5. Cobo-Soriano R, Sánchez-Ramón S, Aparicio MJ, et al. Antiphospholipid antibodies and retinal thrombosis in patients without risk factors: a prospective case-control study. Am J Ophthalmol 1999;128:725–732. 6. Greaves M, Cohen H, MacHin SJ, Mackie I. Guidelines on the investigation and management of the antiphospholipid syndrome. Br J Haematol 2000;109:704–715. 7. A randomized trial of anticoagulants versus aspirin after cerebral ischemia of presumed arterial origin. The Stroke Prevention in Reversible Ischemia Trial (SPIRIT) Study Group. Ann Neurol 1997;42:857–865.
8. Chang PC, Chen WS, Lin HY, et al. Combined central retinal artery and vein occlusion in a patient with systemic lupus erythematosus and anti-phospholipid syndrome. Lupus 2010;19:206–209. 9. Trojet S, Loukil I, El Afrit MA, et al. Bilateral retinal vascular occlusion during antiphospholipid antibody syndrome: a case report. J Fr Ophtalmol 2005;28:503–507. 10. Durukan AH, Akar Y, Bayraktar MZ, et al. Combined retinal artery and vein occlusion in a patient with systemic lupus erythematosus and antiphospholipid syndrome. Can J Ophthalmol 2005;40:87–89.
Purpose: The purpose of this study to report a case of bilateral retinal artery occlusions in a patient with systemic lupus erythematosus and antiphospholipid antibodies. Methods: A 28-year-old woman with systemic lupus erythematosus presented with sudden painless bilateral vision loss. Clinical examination and flourescein angiography were performed, and a diagnosis of bilateral central retinal artery occlusions was made. Laboratory evaluations were ordered. Results: Laboratory evaluation revealed the presence of antiphospholipid antibodies. The patient was treated with corticosteroids, azathioprine, aspirin, and warfarin. The patient’s visual acuity gradually improved over 2 weeks and then remained stable for 6 months without any further thrombotic events. Conclusion: The presence of bilateral retinal artery occlusions in a young patient should prompt an immediate evaluation for antiphospholipid antibodies, especially if the patient has been previously diagnosed with systemic lupus erythematosus. Correctly diagnosing patients with antiphospholipid antibodies is important because it implies the need for longterm anticoagulative and antiaggregative therapies to reduce the patient’s risk of recurrent, life-threatening, thrombotic events. RETINAL CASES & BRIEF REPORTS 6:304–306, 2012
eye. The external and anterior segments were within normal limits. The posterior segments of both eyes had clear media, and there were no appreciable vitreous cells. The posterior poles of each eye showed multiple intraretinal hemorrhages and cotton wool spots. Confluent retinal whitening, arterial attenuation, blood column segmentation, and a “cherry-red spot” were present in both eyes (Figures 1 and 2). Flourescein angiography demonstrated delayed arteriovenous transit time, reversal of flow in the branch retinal arteries, and late staining of the retinal blood vessels bilaterally. The patient was diagnosed with bilateral central retinal artery occlusions with SLE-associated retinal vasculitis. The patient was admitted into the hospital and started on 1 g of intravenous methylprednisolone daily. Serology for antiphospholipid antibodies was performed, and the patient was found to be positive for the lupus anticoagulant. The patient was then started on oral aspirin and warfarin. Once adequately anticoagulated, the patient was discharged on oral prednisone 1 mgkg−1d−1, azathioprine 1 mgkg−1d−1, 325 mg of aspirin, and a variable dosing schedule of warfarin. Two weeks after discharge, the patient’s best-corrected visual acuity improved to 20/200 in each eye. The prednisone was tapered slowly after 6 weeks, and the patient was maintained on azathioprine, lowdose aspirin, and warfarin indefinitely. Her best-corrected visual acuity remained stable at 20/200 at the 6-month follow-up visit. No additional thrombotic events occurred during the follow-up period.
From the Sydney Eye Hospital, Sydney, Australia. Case Report A 28-year-old woman recently diagnosed with systemic lupus erythematosus (SLE) presented with a 1-day history of sudden painless bilateral vision loss. There was no history of trauma and her ocular history was unremarkable. Two months earlier, she developed an erythematous rash involving her face and torso and was subsequently diagnosed with SLE by her health care provider. Her medical history was negative for diabetes mellitus, hypertension, and heart disease. She did have a history of a second trimester spontaneous abortion as well as an intrauterine fetal death. She had been undergoing treatment with systemic corticosteroids since her diagnosis with SLE and was on oral prednisolone 20 mg daily upon presentation. On clinical examination, her best-corrected visual acuity was hand movements at 2 m in both eyes. There was no relative afferent pupillary defect, and her intraocular pressure was 12 mmHg in each
The authors report no conflicts of interest. Reprint requests: Ryan B. Rush, MD, Sydney Eye Hospital, 8 Macquarie Street, Sydney, New South Wales, Australia 2000; e-mail: [email protected]
304
305
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Fig. 1. Right fundus photograph of the posterior pole.
Discussion Systemic lupus erythematosus–associated retinal vasculitis occurs in 23% of patients with SLE during the initial onset of symptoms and increases to 29% during periods of SLE activity after onset.1 Systemic lupus erythematosus antibodies primarily target the antigenic components of medium-sized blood vessels, resulting in a paucicellular vasculopathy with gradual deposition of hyaline within the vessel walls. Manifestations of SLE-associated retinal vasculitis are generally confined to the retinal arterioles and venules of the posterior pole, clinically appearing as cotton wool spots (or nerve fiber layer axoplasmic stasis) and blot or flame-shaped hemorrhages.2 Unlike giant cell arteritis, SLE-associated retinal vasculitis does not result in a hypercellular inflammatory reaction with rapid vessel occlusion by endothelial activation, vasospasm, and secondary thrombus formation, which can directly occlude large-sized vessels like the central retinal artery.3 Therefore, SLE-associated retinal vasculitis alone does not account for the development of a central
retinal artery occlusion. Systemic lupus erythematosus is associated with heart valve vegetations known as Libman–Sacks endocarditis, but these vegetations only rarely embolize. However, when antiphospholipid antibodies such as the lupus anticoagulant or anticardiolipin antibodies are present, a hypercoagulable state develops and the retinal circulation becomes predisposed to large-sized vessel thrombus formation.4 Antiphospholipid antibodies are found in 30% of patients with SLE and in 84% of all cases of idiopathic retinal thrombosis.5 When antiphospholipid antibodies, SLE, and retinal thromboses occur together, this entity becomes known as Hughes syndrome. Life-threatening thromboembolic complications have been reported to be as high as 73% in cases of Hughes syndrome. This risk is reduced to 19% when antithrombotic and antiplatelet agents are given prophylactically.6 Before the occurrence of the first thrombotic episode, some investigators recommend the use of aspirin and warfarin, whereas others suggest only low-dose aspirin. However, after the first thrombotic episode, the combined regimen of antithrombotic and antiplatelet agents becomes essential (international normalized ratio [INR] $ 3, Stroke Prevention in Reversible Ischemia Trial, INR 2–3).7 Numerous case studies have reported on the link between retinal vascular occlusions and antiphospholipid antibodies.8–10 The presence of bilateral retinal vascular occlusions in a young patient should prompt an immediate evaluation for antiphospholipid antibodies, especially if the patient has been previously diagnosed with SLE. Correctly diagnosing Hughes syndrome is important clinically because it implies the need for long-term anticoagulative and antiaggregative therapies to reduce the patient’s risk of recurrent even life-threatening thrombotic events. Key words: central retinal artery occlusion, Hughes syndrome. References
Fig. 2. Left fundus photograph of the posterior pole.
1. Read RW. Clinical mini-review: systemic lupus erythematosus and the eye. Ocul Immunol Inflamm 2004;12:87–99. 2. Au A, O’Day J. Review of severe vaso-occlusive retinopathy in systemic lupus erythematosus and the antiphospholipid syndrome: associations, visual outcomes, complications and treatment. Clin Experiment Ophthalmol 2004;32:87–100. 3. Nag TC, Wadhwa S. Histopathological changes in the eyes in systemic lupus erythematosus: an electron microscope and immunohistochemical study. Histol Histopathol 2005;20:373–382. 4. Durrani OM, Gordon C, Murray PI. Primary anti-phospholipid antibody syndrome (APS): current concepts. Surv Ophthalmol 2002;47:215–238.
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5. Cobo-Soriano R, Sánchez-Ramón S, Aparicio MJ, et al. Antiphospholipid antibodies and retinal thrombosis in patients without risk factors: a prospective case-control study. Am J Ophthalmol 1999;128:725–732. 6. Greaves M, Cohen H, MacHin SJ, Mackie I. Guidelines on the investigation and management of the antiphospholipid syndrome. Br J Haematol 2000;109:704–715. 7. A randomized trial of anticoagulants versus aspirin after cerebral ischemia of presumed arterial origin. The Stroke Prevention in Reversible Ischemia Trial (SPIRIT) Study Group. Ann Neurol 1997;42:857–865.
8. Chang PC, Chen WS, Lin HY, et al. Combined central retinal artery and vein occlusion in a patient with systemic lupus erythematosus and anti-phospholipid syndrome. Lupus 2010;19:206–209. 9. Trojet S, Loukil I, El Afrit MA, et al. Bilateral retinal vascular occlusion during antiphospholipid antibody syndrome: a case report. J Fr Ophtalmol 2005;28:503–507. 10. Durukan AH, Akar Y, Bayraktar MZ, et al. Combined retinal artery and vein occlusion in a patient with systemic lupus erythematosus and antiphospholipid syndrome. Can J Ophthalmol 2005;40:87–89.
