CENTRAL RETINAL VEIN OCCLUSION IN PRIMARY ANTIPHOSPHOLIPID ANTIBODY SYNDROME Mamta Agarwal, MS, Jyotirmay Biswas, MS
Purpose: To report a case of a 20-year-old healthy patient with central retinal vein occlusion in his right eye attributable to primary antiphospholipid antibody syndrome. Methods: A 20-year-old man with poor vision in the right eye and diffuse retinal hemorrhages was investigated for infections, autoimmune disease, diabetes, and hypertension. Testing for homocysteine, anticardiolipin antibodies, lupus anticoagulant, and functional assays for protein S and protein C was performed to detect a hypercoagulable state. Results: Laboratory investigations revealed elevated levels of IgG and M anticardiolipin antibodies. Long-term oral anticoagulants were given to reduce the risk of future thromboses. Conclusion: Antiphospholipid antibodies play an important role in occlusive retinal vascular disorders, especially in young patients without any conventional risk factors. RETINAL CASES & BRIEF REPORTS 3:293–295, 2009
From the Medical and Vision Research Foundations, Sankara Nethralaya, Chennai, India.
Case Report A 20-year-old patient came to our clinic with a history of blurred vision in the right eye for 1 month. He denied any history of connective tissue disease or other systemic illness. On examination, his best corrected visual acuity in the right and left eye was 3/60 and 6/6, respectively. Ocular motility was normal. A relative afferent pupillary defect was seen in the right eye. Slit-lamp examination in both eyes was normal. Intraocular pressure by applanation tonometer was 12 mmHg in both eyes. Fundus examination by indirect ophthalmoscope in the right eye revealed severe disk edema and diffuse retinal hemorrhages associated with macular edema suggestive of central retinal vein occlusion (Figure 1). Laboratory investigations that included complete blood count, erythrocyte sedimentation rate, serum lipids, Venereal Disease Research Laboratory, rheumatoid factor, antinuclear antibodies, antineutrophillic cytoplasmic antibodies, coagulation profile, protein C, and protein S were done. All the investigations were normal except that the serum antibody profile revealed the presence of raised immunoglobulin G and M anticardiolipin antibodies. IgG was 12 GPLunits/mL (less than 10 negative), and IgM was 22.3 MPLunits/mL (less than 10 negative). The antibody assay for lupus anticoagulant was negative. A diagnosis of primary APS was made in view of no other systemic illness. The patient was referred to a hematologist. He was treated with long-term oral anticoagulants, including Acenocoumarol (Acitrom) at 3 mg per day and 150 mg aspirin per day. Prothrombin time was regularly monitored during his follow-up visits. After 1 month, his visual acuity improved to 6/18, N18 in the right eye. Fundus examination revealed partial resolution of disk edema and retinal hemorrhages. Fundus fluorescein angiogram at this visit was not suggestive of any neovascularization of the disk or retina. Patient was periodically reviewed every month. After 6 months, visual
T
he antiphospholipid antibody syndrome (APS) is defined as association of antiphospholipid antibodies with arterial or venous thrombosis, recurrent fetal loss, or thrombocytopenia. Primary APS occurs in patients with no autoimmune diseases, whereas secondary APS is seen most commonly in systemic lupus erythematosus and other conditions like infections, cancer, and drug-induced.1 Systemic manifestations in APS can be neurologic (stroke, migraine), dermatologic (livedo reticularis), cardiac (myocardial infarction, valvular heart disease), and renal (renal artery thrombosis).1 Ocular involvement in APS includes amaurosis fugax, ischemic optic neuropathy, retinal and choroidal vascular occlusion, visual field loss, diplopia, and proliferative retinopathy.2 We report a rare case of central retinal vein occlusion in a young patient who was diagnosed as having primary antiphospholipid syndrome without any underlying systemic disease. Reprint requests: Mamta Agarwal, MS, Medical and Vision Research Foundations, Sankara Nethralaya, 18, College Road, Chennai 600 006, Tamil Nadu, India; e-mail: [email protected]
293
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Fig. 1. Montage photograph of the right eye showing disk edema and scattered retinal hemorrhages in a patient with primary antiphospholipid antibody syndrome.
acuity improved to 6/6 in the right eye. There was no relative afferent pupillary defect and intraocular pressure was also normal. Fundus examination showed complete resolution of disk edema and retinal hemorrhages (Figure 2). No neovascularization of the fundus or iris was observed within 6 months of follow-up.
Discussion Retinal vascular occlusion is most commonly considered a disease of the elderly who have systemic hypertension, diabetes, coronary artery disease, or peripheral vascular disease. In patients younger than 40 years of age, it can be associated with Behcet’s disease, protein C and S deficiency, APS, hyperhomocysteinemia, or other hypercoagulable conditions like migraine, oral contraceptives, obesity, and smoking. Hyperhomocysteinemia is more frequent in young patients with central retinal vein occlusion than APS.
Fig. 2. Fundus photograph showing resolution of disk edema and hemorrhages after 4 months of anticoagulant therapy.
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2009
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NUMBER 3
Moreover, hyperhomocysteinemia is easily correctable with a vitamin supplement.3,4 Our patient was diagnosed to have central retinal vein occlusion in the presence of anticardiolipin antibodies without any underlying systemic illness. There are few studies in the literature that determine the association of retinal vessel occlusion and antiphospholipid syndrome. Cobo-Soriano et al studied 40 patients with retinal vessel occlusion and no conventional risk factors. They found significantly higher prevalence of anticardiolipin antibodies in patients with retinal vascular occlusion compared with control subjects (22.5% versus 5%).5 Bashahur et al also found higher levels of anticardiolipin antibodies in 10 of 43 patients (23%) with retinal vein occlusion who were free of other risk factors.6 Antiphospholipid syndrome is characterized by venous and arterial thrombosis and the presence of aPL that may occur as lupus anticoagulant or anticardiolipin antibodies, aCL. These antibodies are a family of immunoglobulins (IgG, IgM, IgA) with varying affinities for phospholipids–protein complexes. Lupus anticoagulant antibodies interfere with one or more of the in vitro phospholipids-dependent coagulation test (e.g., activated partial thromboplastin time, dilute prothrombin time, kaolin clotting time causing a prolongation of coagulation. CL antibodies crossreact with negatively charged phospholipids, including cardiolipin, phosphatidylserine, phosphatidylinositol, and phosphatic acid.7 However, the exact mechanism by which these inhibitors of coagulation promote thrombosis is still not clear. It has been suggested that these antibodies block the release of arachidonic acid from cell membrane-bound phospholipids in endothelial cells, thus decreasing prostacyclin production and promoting platelet aggregation. Other mechanisms causing thrombophilia include inhibition of protein C activation by endothelial cells, impaired fibrinolytic activity, and direct activation of platelets.8 However, treatment of this clinical condition is still controversial and includes prolonged use of anticoagulants and corticosteroids depending on the severity of thrombosis. Anticoagulants are given to reduce the risk of future thromboses. The diagnosis of this clinical entity is important because this disease, which usually affects young patients, may endanger ocular and vital prognosis. Our case indicates that presence of aPL is a notable risk factor for retinal vascular occlusive disease. It is important to look for all underlying risk factors in young patients presenting with retinal vessel occlusion, especially with no systemic illness. A prompt diagnosis is essential because this systemic syndrome is a threat to the contralateral eye and to the entire
295
PRIMARY ANTIPHOSPHOLIPID SYNDROME
brain because of the possibility of stroke. A diagnosis of primary APS implies a long-term anticoagulant therapy to reduce the risk of recurrent thrombotic events.
4.
5.
References 1.
2.
3.
Behbehani R, Sergott RC, Savino PJ. The antiphospholipid antibody syndrome: diagnostic aspects. Curr Opin Ophthalmol 2004;15:483– 485. Durrani OM, Gordon C, Murray PI. Primary antiphospholipid antibody syndrome (APS): current concepts. Surv Ophthalmol 2002;47:215–238. Salaun N, Delyfer MN, Rougier MB, Korobelnik JF. Assessment of risk factors for retinal vein occlusions in patients under 60 years of age. J Fr Ophtalmol 2007;30:918 –923.
6.
7.
8.
Ilhan F, Celiker U, Godekmerdan A, Kan E. The antiphospholipid antibody syndrome research in patients with retinal venous occlusion. Arch Med Res 2005;36:372–375. Cobo-Soriano R, Sanchez-Ramon 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. Bashshur ZF, Taher A, Masri AF, Najjar D, Arayssi TK, Noureddin BN. Anticardiolipin antibodies in patients with retinal vein occlusion and no risk factors. Retina 2003;23: 486 – 490. McNeil HP, Chesterman CN, Krilis SA. Immunology and clinical importance of antiphospholipid antibodies. Adv Immunol 1991;49:193–280. Petri M. Pathogenesis and treatment of the antiphospholipid antibody syndrome. Med Clin North Am 1997;81:151–177.
Purpose: To report a case of a 20-year-old healthy patient with central retinal vein occlusion in his right eye attributable to primary antiphospholipid antibody syndrome. Methods: A 20-year-old man with poor vision in the right eye and diffuse retinal hemorrhages was investigated for infections, autoimmune disease, diabetes, and hypertension. Testing for homocysteine, anticardiolipin antibodies, lupus anticoagulant, and functional assays for protein S and protein C was performed to detect a hypercoagulable state. Results: Laboratory investigations revealed elevated levels of IgG and M anticardiolipin antibodies. Long-term oral anticoagulants were given to reduce the risk of future thromboses. Conclusion: Antiphospholipid antibodies play an important role in occlusive retinal vascular disorders, especially in young patients without any conventional risk factors. RETINAL CASES & BRIEF REPORTS 3:293–295, 2009
From the Medical and Vision Research Foundations, Sankara Nethralaya, Chennai, India.
Case Report A 20-year-old patient came to our clinic with a history of blurred vision in the right eye for 1 month. He denied any history of connective tissue disease or other systemic illness. On examination, his best corrected visual acuity in the right and left eye was 3/60 and 6/6, respectively. Ocular motility was normal. A relative afferent pupillary defect was seen in the right eye. Slit-lamp examination in both eyes was normal. Intraocular pressure by applanation tonometer was 12 mmHg in both eyes. Fundus examination by indirect ophthalmoscope in the right eye revealed severe disk edema and diffuse retinal hemorrhages associated with macular edema suggestive of central retinal vein occlusion (Figure 1). Laboratory investigations that included complete blood count, erythrocyte sedimentation rate, serum lipids, Venereal Disease Research Laboratory, rheumatoid factor, antinuclear antibodies, antineutrophillic cytoplasmic antibodies, coagulation profile, protein C, and protein S were done. All the investigations were normal except that the serum antibody profile revealed the presence of raised immunoglobulin G and M anticardiolipin antibodies. IgG was 12 GPLunits/mL (less than 10 negative), and IgM was 22.3 MPLunits/mL (less than 10 negative). The antibody assay for lupus anticoagulant was negative. A diagnosis of primary APS was made in view of no other systemic illness. The patient was referred to a hematologist. He was treated with long-term oral anticoagulants, including Acenocoumarol (Acitrom) at 3 mg per day and 150 mg aspirin per day. Prothrombin time was regularly monitored during his follow-up visits. After 1 month, his visual acuity improved to 6/18, N18 in the right eye. Fundus examination revealed partial resolution of disk edema and retinal hemorrhages. Fundus fluorescein angiogram at this visit was not suggestive of any neovascularization of the disk or retina. Patient was periodically reviewed every month. After 6 months, visual
T
he antiphospholipid antibody syndrome (APS) is defined as association of antiphospholipid antibodies with arterial or venous thrombosis, recurrent fetal loss, or thrombocytopenia. Primary APS occurs in patients with no autoimmune diseases, whereas secondary APS is seen most commonly in systemic lupus erythematosus and other conditions like infections, cancer, and drug-induced.1 Systemic manifestations in APS can be neurologic (stroke, migraine), dermatologic (livedo reticularis), cardiac (myocardial infarction, valvular heart disease), and renal (renal artery thrombosis).1 Ocular involvement in APS includes amaurosis fugax, ischemic optic neuropathy, retinal and choroidal vascular occlusion, visual field loss, diplopia, and proliferative retinopathy.2 We report a rare case of central retinal vein occlusion in a young patient who was diagnosed as having primary antiphospholipid syndrome without any underlying systemic disease. Reprint requests: Mamta Agarwal, MS, Medical and Vision Research Foundations, Sankara Nethralaya, 18, College Road, Chennai 600 006, Tamil Nadu, India; e-mail: [email protected]
293
RETINAL CASES & BRIEF REPORTSℜ
294
Fig. 1. Montage photograph of the right eye showing disk edema and scattered retinal hemorrhages in a patient with primary antiphospholipid antibody syndrome.
acuity improved to 6/6 in the right eye. There was no relative afferent pupillary defect and intraocular pressure was also normal. Fundus examination showed complete resolution of disk edema and retinal hemorrhages (Figure 2). No neovascularization of the fundus or iris was observed within 6 months of follow-up.
Discussion Retinal vascular occlusion is most commonly considered a disease of the elderly who have systemic hypertension, diabetes, coronary artery disease, or peripheral vascular disease. In patients younger than 40 years of age, it can be associated with Behcet’s disease, protein C and S deficiency, APS, hyperhomocysteinemia, or other hypercoagulable conditions like migraine, oral contraceptives, obesity, and smoking. Hyperhomocysteinemia is more frequent in young patients with central retinal vein occlusion than APS.
Fig. 2. Fundus photograph showing resolution of disk edema and hemorrhages after 4 months of anticoagulant therapy.
●
2009
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VOLUME 3
●
NUMBER 3
Moreover, hyperhomocysteinemia is easily correctable with a vitamin supplement.3,4 Our patient was diagnosed to have central retinal vein occlusion in the presence of anticardiolipin antibodies without any underlying systemic illness. There are few studies in the literature that determine the association of retinal vessel occlusion and antiphospholipid syndrome. Cobo-Soriano et al studied 40 patients with retinal vessel occlusion and no conventional risk factors. They found significantly higher prevalence of anticardiolipin antibodies in patients with retinal vascular occlusion compared with control subjects (22.5% versus 5%).5 Bashahur et al also found higher levels of anticardiolipin antibodies in 10 of 43 patients (23%) with retinal vein occlusion who were free of other risk factors.6 Antiphospholipid syndrome is characterized by venous and arterial thrombosis and the presence of aPL that may occur as lupus anticoagulant or anticardiolipin antibodies, aCL. These antibodies are a family of immunoglobulins (IgG, IgM, IgA) with varying affinities for phospholipids–protein complexes. Lupus anticoagulant antibodies interfere with one or more of the in vitro phospholipids-dependent coagulation test (e.g., activated partial thromboplastin time, dilute prothrombin time, kaolin clotting time causing a prolongation of coagulation. CL antibodies crossreact with negatively charged phospholipids, including cardiolipin, phosphatidylserine, phosphatidylinositol, and phosphatic acid.7 However, the exact mechanism by which these inhibitors of coagulation promote thrombosis is still not clear. It has been suggested that these antibodies block the release of arachidonic acid from cell membrane-bound phospholipids in endothelial cells, thus decreasing prostacyclin production and promoting platelet aggregation. Other mechanisms causing thrombophilia include inhibition of protein C activation by endothelial cells, impaired fibrinolytic activity, and direct activation of platelets.8 However, treatment of this clinical condition is still controversial and includes prolonged use of anticoagulants and corticosteroids depending on the severity of thrombosis. Anticoagulants are given to reduce the risk of future thromboses. The diagnosis of this clinical entity is important because this disease, which usually affects young patients, may endanger ocular and vital prognosis. Our case indicates that presence of aPL is a notable risk factor for retinal vascular occlusive disease. It is important to look for all underlying risk factors in young patients presenting with retinal vessel occlusion, especially with no systemic illness. A prompt diagnosis is essential because this systemic syndrome is a threat to the contralateral eye and to the entire
295
PRIMARY ANTIPHOSPHOLIPID SYNDROME
brain because of the possibility of stroke. A diagnosis of primary APS implies a long-term anticoagulant therapy to reduce the risk of recurrent thrombotic events.
4.
5.
References 1.
2.
3.
Behbehani R, Sergott RC, Savino PJ. The antiphospholipid antibody syndrome: diagnostic aspects. Curr Opin Ophthalmol 2004;15:483– 485. Durrani OM, Gordon C, Murray PI. Primary antiphospholipid antibody syndrome (APS): current concepts. Surv Ophthalmol 2002;47:215–238. Salaun N, Delyfer MN, Rougier MB, Korobelnik JF. Assessment of risk factors for retinal vein occlusions in patients under 60 years of age. J Fr Ophtalmol 2007;30:918 –923.
6.
7.
8.
Ilhan F, Celiker U, Godekmerdan A, Kan E. The antiphospholipid antibody syndrome research in patients with retinal venous occlusion. Arch Med Res 2005;36:372–375. Cobo-Soriano R, Sanchez-Ramon 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. Bashshur ZF, Taher A, Masri AF, Najjar D, Arayssi TK, Noureddin BN. Anticardiolipin antibodies in patients with retinal vein occlusion and no risk factors. Retina 2003;23: 486 – 490. McNeil HP, Chesterman CN, Krilis SA. Immunology and clinical importance of antiphospholipid antibodies. Adv Immunol 1991;49:193–280. Petri M. Pathogenesis and treatment of the antiphospholipid antibody syndrome. Med Clin North Am 1997;81:151–177.
