PULSED INTRAVENOUS CYCLOPHOSPHAMIDE FOR SLE RETINAL VASCULITIS Jern Yee Chen, MBBS,* Vidya S. Limaye, MBBS, FRACP, PhD,†‡ Rajeev Jain, MD,* Tim Y. Lu, FRACP,† Susanna M. Proudman, MBBS, FRACP,†‡ Grant L. Raymond, FRANZCO*
Purpose: To report a case of systemic lupus erythematosus vaso-occlusive retinopathy with severe visual loss treated with intravenous pulsed cyclophosphamide. Methods: Retrospective interventional case report. Results: A 20-year-old Cambodian woman with newly diagnosed systemic lupus erythematosus presented with acute visual loss. Fluorescein fundus angiography demonstrated occlusive retinal vasculitis. Treatment with pulsed intravenous cyclophosphamide, intravenous methylprednisolone, and anticoagulation resulted in recovery of vision from count fingers to 6/6 in both eyes. Conclusion: Early aggressive immunosuppression and anticoagulation for systemic lupus erythematosus retinal vasculitis can be beneficial in preventing disease progression and restoring vision. Further studies are needed to compare dosage regimens. RETINAL CASES & BRIEF REPORTS 6:111–115, 2012
From the Departments of *Ophthalmology and †Rheumatology, Royal Adelaide Hospital, Adelaide, South Australia, Australia; and ‡Department of Medicine, University of Adelaide, Adelaide, South Australia, Australia.
In the management of SLE, the choice of immunosuppressive regimen is dictated by the severity and extent of organ involvement, with aggressive immunosuppressive drugs, such as cyclophosphamide, and high doses of steroids reserved for the most severe or potential organ-damaging disease. When complicated by secondary antiphospholipid antibody syndrome, long-term anticoagulation is generally instituted for the prevention of future thrombotic episodes. The rarity of retinal vasculitis in SLE, especially in the presence of antiphospholipid antibodies, has hindered the development of clear management guidelines and as such, visual prognosis is extremely poor, with up to 50% of patients achieving final visual acuity of 20/200 or less.3 The severity of retinal manifestations tends to correlate with systemic disease activity and has been documented in association with lupus cerebritis.1 Accordingly, those with vascular retinopathy have a significantly higher mortality.4 We report a case of retinal vasculitis in a patient with newly diagnosed SLE and lupus anticoagulant, in whom aggressive cyclophosphamide, steroids, and anticoagulation resulted in an excellent visual outcome, associated with reversal of angiographically demonstrable pathology.
S
ystemic lupus erythematosus (SLE) is the prototype autoimmune disease in which polyclonal B-cell activation and resulting autoantibodies lead to diverse clinical manifestations, which may affect any organ system including the eyes.1,2 Ocular manifestations vary from relatively benign sicca syndrome to potentially blinding retinal vasculitis.1 As with much of the pathology in SLE, immune complex deposition is thought to play an important role in the pathogenesis of retinal vasculitis.1 Of note, severe vaso-occlusive retinopathy is a rare manifestation in SLE. Affected patients are also reported to have a higher incidence of antiphospholipid antibodies (77% vs. 29%).2
The authors report no financial or conflicts of interest to disclose. Reprint requests: Jern Yee Chen, MBBS, Department of Ophthalmology, Wellington Hospital, Riddiford Street, Newtown, Wellington 6021, New Zealand; e-mail: [email protected]
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Case Report A 20-year-old Cambodian woman presented with fever, photosensitivity, lethargy, polyarthralgia, and weight loss of 10 kg. Systemic examination revealed tachycardia and hypotension with a systolic blood pressure of 90 mmHg. She was cachexic and had synovitis of the small joints of the hands. Blood cultures were negative as were hepatitis B surface antigen and hepatitis C antibody, Epstein–Barr virus IgM, and cytomegalovirus IgM. Tests for human immunodeficiency virus, Mycobacterium tuberculosis, and Leptospira were negative. Immunologic screenings revealed positive antinuclear antibody homogenous titer (1/2,560), speckled titer (1/640), positive ENA anti-SSA (Ro) 218 Elisa units and ENA anti-SSB (La) 218 Elisa units, elevated anti–double-stranded DNA .100 IU/mL (,8.0), and reduced complement C3 0.43 g/L (0.6–1.2 g/L). Renal biopsy showed mesangioproliferative glomerulonephritis consistent with lupus nephritis. Lupus anticoagulant was strongly positive (Russell’s viper venom time screening test, 75.4 [30–45]; DRVVT lupus ratio, 1.87 [,1.1]; positive platelet neutralization APTT, 86 [24–38]; and prothrombin INR, 1.0 [0.8–1.2]). There was a negative result for cardiolipin antibody 7 GPL units (,9) and b2-glycoprotein I. A diagnosis of SLE was made, and she started on with 200 mg of hydroxychloroquine 2 times a day, 7.5 mg of methotrexate daily, and 30 mg of prednisolone daily. After 1 week, she developed bilateral blurred vision with headache. Her best-corrected visual acuities were 6/36 in the right eye and 6/18 in the left eye. There was no relative afferent pupillary defect. Dilated fundoscopy examination showed posterior pole ischemia with evolving retinal nerve fiber layer infarcts in the right eye (Figure 1). Fundus fluorescein angiography showed bilateral delayed perfusion more marked in the right eye, with significant vaso-occlusive disease involving the right macula suggesting microthrombotic lesions. There was peripheral capillary dropout and some peripheral vascular sclerosis (Figure 2). Magnetic resonance imaging of the brain did not show changes suggestive of central nervous system lupus or optic neuritis. Given sight-threatening retinal vasculitis, she was started on with intravenous (IV) 500 mg of cyclophosphamide (pulsed 2 weekly), 1 g of IV methylprednisolone for 3 days. Given the appearance of angiographic thrombotic lesions with a strongly positive lupus anticoagulant, she was also treated with aspirin. Within 3 days, there was a rapid and dramatic improvement in visual acuity and resolution of the headaches. One week after clinical improvement, she was discharged home with 25 mg of oral prednisolone daily, 200 mg of oral hydroxychloroquine 2 times a day, and 100 mg of oral aspirin daily. However, after 3 days, she experienced further acute visual deterioration to count fingers vision bilaterally, with exacerbation of her systemic symptoms. Dilated fundoscopy showed worsening vaso-occlusive disease with attenuated arterioles and extensive retinal nerve fiber layer infarcts, more prominent in the right eye. Review after 24 hours showed that the best-corrected visual acuities had improved to 6/24 in the right eye and 6/18 in the left eye. Repeat fundus fluorescein angiography showed some persistent areas of vasoocclusion but also now reperfusion in some areas of previous vasoocclusion in the right eye and one area of persistent occlusion in the left eye (Figure 3). It was thought that the transient acute loss of vision was most likely related to posterior ischemic optic neuropathy of vasculitic origin because there was no significant increase in the vasculitis affecting the macula circulation in either eye. Additional treatment of 500 mg of IV cyclophosphamide and 1 g of IV methylprednisolone pulsing and 1 mg/kg of subcutaneous enoxaparin 2 times a day resulted in marked improvement in visual acuity and resolution of abdominal pain, fever, and arthralgias. Before discharge, warfarin was initiated with cessation of enoxaparin.
Fig. 1. Color fundus photographs. A. Retinal nerve ischemia at posterior pole on first presentation. B. Evolving localized areas of retinal nerve fiber layer infarcts, particularly superonasally. C. Four months after the treatment, fundus appeared normal.
SLE RETINAL VASCULITIS TREATMENT
Fig. 2. Fluorescein fundus angiography at initial presentation. A. Early venous phase showing delayed filling of superotemporal retinal vein. B. Later venous phase showing poor posterior pole retinal perfusion, particularly at superior and temporal aspects of the right macula (arrows).
Remission from lupus, based on resolution of fever, lethargy, photosensitivity, and arthralgias, was achieved after the administration of 3 g of IV cyclophosphamide over 6 cycles and was followed by a slow taper of oral prednisolone and maintenance with 50 mg of azathioprine 2 times a day. Serological response improved with treatment (Figure 4). On review after 9 months, she has maintained visual acuities of 6/6 in both eyes and fundoscopy examination revealed no active retinal vasculitis and healthy optic disks.
Discussion We present a patient with recently diagnosed SLE who developed occlusive retinal vasculitis in association with antiphospholipid antibodies. Management was directed to the plausible underlying pathogenic
113
Fig. 3. Repeat fluorescein fundus angiography. A. Areas of poor retinal perfusion on initial presentation. Arrows in figure A highlight the areas where the blood vessels were blocked on presentation. In figure B, the arrows highlight the same areas that are now perfused. B. Several weeks later, fundus fluorescein angiography showed areas of retinal reperfusion (arrows) and less leakage. Additionally, staining of vessel walls superonasal to macula was evident.
mechanisms, namely, immune complex deposition resulting from SLE disease activity and thrombosis resulting from lupus anticoagulant. Both mechanisms were likely contributors to the clinical presentation, and indeed, the fundus fluorescein angiography demonstrated both leakage (consistent with vasculitis) and occlusive lesions (suggestive of thrombosis). The combination of high doses of pulsed IV corticosteroids, aggressive pulsed two weekly IV cyclophosphamide, and anticoagulation halted the progression of the lesions and moreover resulted in angiographically demonstrable reversal of the pathology. This case highlights the benefits of this treatment strategy
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Fig. 4. Improvement in anti–double-stranded DNA titers with treatment.
in a condition, which frequently has a poor visual prognosis. Cyclophosphamide is a cytotoxic alkylating agent. There is a substantial body of evidence supporting the use of cyclophosphamide in the treatment of severe organ threatening renal and central nervous system lupus. Furthermore, it is regarded as the ‘‘gold standard’’ treatment to which other immunosuppressants are compared.5 However, cyclophosphamide has significant toxicities, which include cytopenias, infections, gonadal failure, and risk of malignancy.5 Consequently, various dosing regimes have been trialed to reduce this risk, and it has been found that
lower-dose IV pulsed regimens are as effective as high-dose regimens, with additional advantages of excellent immediate tolerance without the need for IV antiemetics and forced hydration, and reduced costs.6 There is a paucity of evidence in the ophthalmic literature for the use of cyclophosphamide in the treatment of SLE retinal vasculitis. A recent review by Au and O’Day2 reported 47 cases of lupus microangiopathy. Only 11 cases were treated with cyclophosphamide, of which 3 were treated with pulsed IV cyclophosphamide (Table 1). One patient reported by El-Asrar et al7 was treated initially with pulsed IV cyclophosphamide with chloroquine but subsequently
Table 1. Literature Review on IV Cyclophosphamide in the Treatment of SLE Retinal Vasculitis
Authors
Total SLE Cases; CP-Treated Cases
El-Asrar et al7
1;1
Read et al8
1;1
Au and O’Day2
1;1
Initial VA
Final VA
Tx Before Visual Symptoms
Additional Tx After Development of Visual Symptoms
20/30 OD Not reported Pulse IV CP 10 mg/kg Not reported 20/20 OS monthly, chloroquine 250 mg daily 20/30 OU 3/200 OD Prednisolone 60 mg IV CP (first episode) 20/30 OS daily, HCQ ! VA 20/20 OU ! 7 months later relapse: Tx 40 mg sub-Tenon triamcinolone + PPV + endolaser OU CF OU 20/200 OU Prednisolone 50 mg IV streptokinase, heparin, warfarin, daily pulse methylprednisolone, cyclosporine, oral steroids ! 2 weeks later VA 1/60 OU ! 1 week later pulsed IV CP ! 2 months later neovasc: Tx bilateral PRP ! Bilateral VH: Tx bilateral vitrectomies ! VA 6/60 OU
OS, left eye; OD, right eye; OU, both eyes; VA, visual acuity; PPV, pars plana vitrectomy; Tx, treatment; HCQ, hydroxychloroquine; PRP, panretinal photocoagulation; VH, vitreous haemorrhage; CP, cyclophosphamide.
115
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experienced ciliary retinal artery occlusion on cessation of chloroquine. Further treatment and final visual acuities were not reported. The case reported by Read et al8 retained 20/20 in both eyes after treatment with pulsed IV cyclophosphamide and prednisolone for relapse of SLE with vasculitis. However, subsequent relapse of lupus vasculitis was only treated with subTenon triamcinolone acetonide and not cyclophosphamide. Resultant visual loss was 3/200 in the right eye and 20/30 in the left eye. In the case reported by Au and O’Day,2 pulsed IV cyclophosphamide was delayed 3 weeks until after the initial onset of lupus vasculitis. Eventual visual acuities in this case were 6/60 in both eyes. Regarding the use of anticoagulation in this case, the literature suggests that there is a significant increase in thrombotic events in patients with both SLE and antiphospholipid antibodies.9 Consequently, to minimize the vaso-occlusive risk, we advocate the use of adjunctive anticoagulation. In summary, this patient with SLE and antiphospholipid syndrome presented with severe acute visual loss associated with retinal vasculitis. The excellent visual outcome demonstrated the potential benefits from early institution of a treatment regimen that included pulsed IV cyclophosphamide given every 2 weeks (as distinct from conventional monthly dosing) together with methylprednisolone and anticoagulation treatment. Further study is required regarding dosing regimens.
Key words: intravenous pulsed cyclophosphamide, retinal vasculitis, systemic lupus erythematosus. References 1. Neumann R, Foster S. Corticosteroid-sparing strategies in the treatment of retinal vasculitis in systemic lupus erythematosus. Retina 1995;15:206–212. 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. Jabs DA, Fine SL. Severe retinal vaso-occlusive disease in systemic lupus syndrome. Arch Ophthalmol 1986;104: 558–563. 4. Stafford-Brady FJ, Urowitz MB, Gladman DD, Easterbrook M. Lupus retinopathy: patterns, associations, and prognosis. Arthritis Rheum 1988;31:1105–1110. 5. Petri M. Cylcophosphamide: new approaches for systemic lupus erythematosus. Lupus 2004;13:366–371. 6. Houssiau FA, Vasconcelos C, D’Cruz D, et al. Immunosuppressive therapy in lupus nephritis: The Euro-Lupus Nephritis Trial, a randomized trial of low-dose versus high-dose intravenous cyclophosphamide. Arthritis Rheum 2002;46: 2121–2131. 7. El-Asrar AMA, Naddaf HO, Al-Momen A, Al-Balla SR. Systemic lupus erythematosus flare-up manifesting as a cilioretinal artery occlusion. Lupus 1995;4:158–160. 8. Read RW, Chong LP, Rao NA. Occlusive retinal vasculitis associated with systemic lupus erythematosus. Arch Ophthalmol 2000;118:588–589. 9. Laskin CA, Clark CA, Spitzer KA. Antiphospholipid syndrome in SLE: is the whole greater than the sum of its parts? Rheum Dis Clin North Am 2005;31:255–272.
Purpose: To report a case of systemic lupus erythematosus vaso-occlusive retinopathy with severe visual loss treated with intravenous pulsed cyclophosphamide. Methods: Retrospective interventional case report. Results: A 20-year-old Cambodian woman with newly diagnosed systemic lupus erythematosus presented with acute visual loss. Fluorescein fundus angiography demonstrated occlusive retinal vasculitis. Treatment with pulsed intravenous cyclophosphamide, intravenous methylprednisolone, and anticoagulation resulted in recovery of vision from count fingers to 6/6 in both eyes. Conclusion: Early aggressive immunosuppression and anticoagulation for systemic lupus erythematosus retinal vasculitis can be beneficial in preventing disease progression and restoring vision. Further studies are needed to compare dosage regimens. RETINAL CASES & BRIEF REPORTS 6:111–115, 2012
From the Departments of *Ophthalmology and †Rheumatology, Royal Adelaide Hospital, Adelaide, South Australia, Australia; and ‡Department of Medicine, University of Adelaide, Adelaide, South Australia, Australia.
In the management of SLE, the choice of immunosuppressive regimen is dictated by the severity and extent of organ involvement, with aggressive immunosuppressive drugs, such as cyclophosphamide, and high doses of steroids reserved for the most severe or potential organ-damaging disease. When complicated by secondary antiphospholipid antibody syndrome, long-term anticoagulation is generally instituted for the prevention of future thrombotic episodes. The rarity of retinal vasculitis in SLE, especially in the presence of antiphospholipid antibodies, has hindered the development of clear management guidelines and as such, visual prognosis is extremely poor, with up to 50% of patients achieving final visual acuity of 20/200 or less.3 The severity of retinal manifestations tends to correlate with systemic disease activity and has been documented in association with lupus cerebritis.1 Accordingly, those with vascular retinopathy have a significantly higher mortality.4 We report a case of retinal vasculitis in a patient with newly diagnosed SLE and lupus anticoagulant, in whom aggressive cyclophosphamide, steroids, and anticoagulation resulted in an excellent visual outcome, associated with reversal of angiographically demonstrable pathology.
S
ystemic lupus erythematosus (SLE) is the prototype autoimmune disease in which polyclonal B-cell activation and resulting autoantibodies lead to diverse clinical manifestations, which may affect any organ system including the eyes.1,2 Ocular manifestations vary from relatively benign sicca syndrome to potentially blinding retinal vasculitis.1 As with much of the pathology in SLE, immune complex deposition is thought to play an important role in the pathogenesis of retinal vasculitis.1 Of note, severe vaso-occlusive retinopathy is a rare manifestation in SLE. Affected patients are also reported to have a higher incidence of antiphospholipid antibodies (77% vs. 29%).2
The authors report no financial or conflicts of interest to disclose. Reprint requests: Jern Yee Chen, MBBS, Department of Ophthalmology, Wellington Hospital, Riddiford Street, Newtown, Wellington 6021, New Zealand; e-mail: [email protected]
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Case Report A 20-year-old Cambodian woman presented with fever, photosensitivity, lethargy, polyarthralgia, and weight loss of 10 kg. Systemic examination revealed tachycardia and hypotension with a systolic blood pressure of 90 mmHg. She was cachexic and had synovitis of the small joints of the hands. Blood cultures were negative as were hepatitis B surface antigen and hepatitis C antibody, Epstein–Barr virus IgM, and cytomegalovirus IgM. Tests for human immunodeficiency virus, Mycobacterium tuberculosis, and Leptospira were negative. Immunologic screenings revealed positive antinuclear antibody homogenous titer (1/2,560), speckled titer (1/640), positive ENA anti-SSA (Ro) 218 Elisa units and ENA anti-SSB (La) 218 Elisa units, elevated anti–double-stranded DNA .100 IU/mL (,8.0), and reduced complement C3 0.43 g/L (0.6–1.2 g/L). Renal biopsy showed mesangioproliferative glomerulonephritis consistent with lupus nephritis. Lupus anticoagulant was strongly positive (Russell’s viper venom time screening test, 75.4 [30–45]; DRVVT lupus ratio, 1.87 [,1.1]; positive platelet neutralization APTT, 86 [24–38]; and prothrombin INR, 1.0 [0.8–1.2]). There was a negative result for cardiolipin antibody 7 GPL units (,9) and b2-glycoprotein I. A diagnosis of SLE was made, and she started on with 200 mg of hydroxychloroquine 2 times a day, 7.5 mg of methotrexate daily, and 30 mg of prednisolone daily. After 1 week, she developed bilateral blurred vision with headache. Her best-corrected visual acuities were 6/36 in the right eye and 6/18 in the left eye. There was no relative afferent pupillary defect. Dilated fundoscopy examination showed posterior pole ischemia with evolving retinal nerve fiber layer infarcts in the right eye (Figure 1). Fundus fluorescein angiography showed bilateral delayed perfusion more marked in the right eye, with significant vaso-occlusive disease involving the right macula suggesting microthrombotic lesions. There was peripheral capillary dropout and some peripheral vascular sclerosis (Figure 2). Magnetic resonance imaging of the brain did not show changes suggestive of central nervous system lupus or optic neuritis. Given sight-threatening retinal vasculitis, she was started on with intravenous (IV) 500 mg of cyclophosphamide (pulsed 2 weekly), 1 g of IV methylprednisolone for 3 days. Given the appearance of angiographic thrombotic lesions with a strongly positive lupus anticoagulant, she was also treated with aspirin. Within 3 days, there was a rapid and dramatic improvement in visual acuity and resolution of the headaches. One week after clinical improvement, she was discharged home with 25 mg of oral prednisolone daily, 200 mg of oral hydroxychloroquine 2 times a day, and 100 mg of oral aspirin daily. However, after 3 days, she experienced further acute visual deterioration to count fingers vision bilaterally, with exacerbation of her systemic symptoms. Dilated fundoscopy showed worsening vaso-occlusive disease with attenuated arterioles and extensive retinal nerve fiber layer infarcts, more prominent in the right eye. Review after 24 hours showed that the best-corrected visual acuities had improved to 6/24 in the right eye and 6/18 in the left eye. Repeat fundus fluorescein angiography showed some persistent areas of vasoocclusion but also now reperfusion in some areas of previous vasoocclusion in the right eye and one area of persistent occlusion in the left eye (Figure 3). It was thought that the transient acute loss of vision was most likely related to posterior ischemic optic neuropathy of vasculitic origin because there was no significant increase in the vasculitis affecting the macula circulation in either eye. Additional treatment of 500 mg of IV cyclophosphamide and 1 g of IV methylprednisolone pulsing and 1 mg/kg of subcutaneous enoxaparin 2 times a day resulted in marked improvement in visual acuity and resolution of abdominal pain, fever, and arthralgias. Before discharge, warfarin was initiated with cessation of enoxaparin.
Fig. 1. Color fundus photographs. A. Retinal nerve ischemia at posterior pole on first presentation. B. Evolving localized areas of retinal nerve fiber layer infarcts, particularly superonasally. C. Four months after the treatment, fundus appeared normal.
SLE RETINAL VASCULITIS TREATMENT
Fig. 2. Fluorescein fundus angiography at initial presentation. A. Early venous phase showing delayed filling of superotemporal retinal vein. B. Later venous phase showing poor posterior pole retinal perfusion, particularly at superior and temporal aspects of the right macula (arrows).
Remission from lupus, based on resolution of fever, lethargy, photosensitivity, and arthralgias, was achieved after the administration of 3 g of IV cyclophosphamide over 6 cycles and was followed by a slow taper of oral prednisolone and maintenance with 50 mg of azathioprine 2 times a day. Serological response improved with treatment (Figure 4). On review after 9 months, she has maintained visual acuities of 6/6 in both eyes and fundoscopy examination revealed no active retinal vasculitis and healthy optic disks.
Discussion We present a patient with recently diagnosed SLE who developed occlusive retinal vasculitis in association with antiphospholipid antibodies. Management was directed to the plausible underlying pathogenic
113
Fig. 3. Repeat fluorescein fundus angiography. A. Areas of poor retinal perfusion on initial presentation. Arrows in figure A highlight the areas where the blood vessels were blocked on presentation. In figure B, the arrows highlight the same areas that are now perfused. B. Several weeks later, fundus fluorescein angiography showed areas of retinal reperfusion (arrows) and less leakage. Additionally, staining of vessel walls superonasal to macula was evident.
mechanisms, namely, immune complex deposition resulting from SLE disease activity and thrombosis resulting from lupus anticoagulant. Both mechanisms were likely contributors to the clinical presentation, and indeed, the fundus fluorescein angiography demonstrated both leakage (consistent with vasculitis) and occlusive lesions (suggestive of thrombosis). The combination of high doses of pulsed IV corticosteroids, aggressive pulsed two weekly IV cyclophosphamide, and anticoagulation halted the progression of the lesions and moreover resulted in angiographically demonstrable reversal of the pathology. This case highlights the benefits of this treatment strategy
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Fig. 4. Improvement in anti–double-stranded DNA titers with treatment.
in a condition, which frequently has a poor visual prognosis. Cyclophosphamide is a cytotoxic alkylating agent. There is a substantial body of evidence supporting the use of cyclophosphamide in the treatment of severe organ threatening renal and central nervous system lupus. Furthermore, it is regarded as the ‘‘gold standard’’ treatment to which other immunosuppressants are compared.5 However, cyclophosphamide has significant toxicities, which include cytopenias, infections, gonadal failure, and risk of malignancy.5 Consequently, various dosing regimes have been trialed to reduce this risk, and it has been found that
lower-dose IV pulsed regimens are as effective as high-dose regimens, with additional advantages of excellent immediate tolerance without the need for IV antiemetics and forced hydration, and reduced costs.6 There is a paucity of evidence in the ophthalmic literature for the use of cyclophosphamide in the treatment of SLE retinal vasculitis. A recent review by Au and O’Day2 reported 47 cases of lupus microangiopathy. Only 11 cases were treated with cyclophosphamide, of which 3 were treated with pulsed IV cyclophosphamide (Table 1). One patient reported by El-Asrar et al7 was treated initially with pulsed IV cyclophosphamide with chloroquine but subsequently
Table 1. Literature Review on IV Cyclophosphamide in the Treatment of SLE Retinal Vasculitis
Authors
Total SLE Cases; CP-Treated Cases
El-Asrar et al7
1;1
Read et al8
1;1
Au and O’Day2
1;1
Initial VA
Final VA
Tx Before Visual Symptoms
Additional Tx After Development of Visual Symptoms
20/30 OD Not reported Pulse IV CP 10 mg/kg Not reported 20/20 OS monthly, chloroquine 250 mg daily 20/30 OU 3/200 OD Prednisolone 60 mg IV CP (first episode) 20/30 OS daily, HCQ ! VA 20/20 OU ! 7 months later relapse: Tx 40 mg sub-Tenon triamcinolone + PPV + endolaser OU CF OU 20/200 OU Prednisolone 50 mg IV streptokinase, heparin, warfarin, daily pulse methylprednisolone, cyclosporine, oral steroids ! 2 weeks later VA 1/60 OU ! 1 week later pulsed IV CP ! 2 months later neovasc: Tx bilateral PRP ! Bilateral VH: Tx bilateral vitrectomies ! VA 6/60 OU
OS, left eye; OD, right eye; OU, both eyes; VA, visual acuity; PPV, pars plana vitrectomy; Tx, treatment; HCQ, hydroxychloroquine; PRP, panretinal photocoagulation; VH, vitreous haemorrhage; CP, cyclophosphamide.
115
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experienced ciliary retinal artery occlusion on cessation of chloroquine. Further treatment and final visual acuities were not reported. The case reported by Read et al8 retained 20/20 in both eyes after treatment with pulsed IV cyclophosphamide and prednisolone for relapse of SLE with vasculitis. However, subsequent relapse of lupus vasculitis was only treated with subTenon triamcinolone acetonide and not cyclophosphamide. Resultant visual loss was 3/200 in the right eye and 20/30 in the left eye. In the case reported by Au and O’Day,2 pulsed IV cyclophosphamide was delayed 3 weeks until after the initial onset of lupus vasculitis. Eventual visual acuities in this case were 6/60 in both eyes. Regarding the use of anticoagulation in this case, the literature suggests that there is a significant increase in thrombotic events in patients with both SLE and antiphospholipid antibodies.9 Consequently, to minimize the vaso-occlusive risk, we advocate the use of adjunctive anticoagulation. In summary, this patient with SLE and antiphospholipid syndrome presented with severe acute visual loss associated with retinal vasculitis. The excellent visual outcome demonstrated the potential benefits from early institution of a treatment regimen that included pulsed IV cyclophosphamide given every 2 weeks (as distinct from conventional monthly dosing) together with methylprednisolone and anticoagulation treatment. Further study is required regarding dosing regimens.
Key words: intravenous pulsed cyclophosphamide, retinal vasculitis, systemic lupus erythematosus. References 1. Neumann R, Foster S. Corticosteroid-sparing strategies in the treatment of retinal vasculitis in systemic lupus erythematosus. Retina 1995;15:206–212. 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. Jabs DA, Fine SL. Severe retinal vaso-occlusive disease in systemic lupus syndrome. Arch Ophthalmol 1986;104: 558–563. 4. Stafford-Brady FJ, Urowitz MB, Gladman DD, Easterbrook M. Lupus retinopathy: patterns, associations, and prognosis. Arthritis Rheum 1988;31:1105–1110. 5. Petri M. Cylcophosphamide: new approaches for systemic lupus erythematosus. Lupus 2004;13:366–371. 6. Houssiau FA, Vasconcelos C, D’Cruz D, et al. Immunosuppressive therapy in lupus nephritis: The Euro-Lupus Nephritis Trial, a randomized trial of low-dose versus high-dose intravenous cyclophosphamide. Arthritis Rheum 2002;46: 2121–2131. 7. El-Asrar AMA, Naddaf HO, Al-Momen A, Al-Balla SR. Systemic lupus erythematosus flare-up manifesting as a cilioretinal artery occlusion. Lupus 1995;4:158–160. 8. Read RW, Chong LP, Rao NA. Occlusive retinal vasculitis associated with systemic lupus erythematosus. Arch Ophthalmol 2000;118:588–589. 9. Laskin CA, Clark CA, Spitzer KA. Antiphospholipid syndrome in SLE: is the whole greater than the sum of its parts? Rheum Dis Clin North Am 2005;31:255–272.
