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Show PHOTO ESSAY Bilateral Simultaneous Central Retinal Artery Occlusions in Wegener Granulomatosis Fiona Costello, MD, Steven Gilberg, MD, Jacob Karsh, MD, Bruce Burns, MD, and Brian Leonard, MD FIG. 1. Simultaneous central retinal artery occlusions OU. A46- year old woman noted acute visual loss in the OD. Immediately thereafter she took a 90- minute nap and upon awakening noted visual loss OU. Blood pressure was 130/ 70 and heart rate was 72/ min. There were splinter hemorrhages in the distal extremities and nail beds of all four limbs. Visual acuity was hand motions OU. The pupils measured 5 mm in darkness and constricted to 4 mm in bright light without afferent pupil defect. There was mild bilateral lacrimal gland enlargement, proptosis, and prominent injection of the superotemporal conjunctival and episcleral vessels. Slit lamp biomicroscopy was otherwise normal, and the intraocular pressures were 15 mm Hg OU. Ocular motility testing showed mild deficits of abduction OU. Dilated ophthalmoscopy demonstrated bilateral central retinal artery occlusions ( Fig. 1). Apart from hearing loss, the neurologic examination was normal. She denied systemic symptoms including those related to giant cell arteritis. But six years earlier she had been diagnosed with Sjogren syndrome when she presented with xerostomia, rash, and arthralgias. At that time, an erythrocyte serum sedimentation rate ( ESR) was 70 mm per Abstract: A 46- year old woman developed simultaneous central retinal artery occlusions ( CRAOs) in Wegener granulomatosis ( WG). She had presented six years earlier with xerostomia, skin rash, and arthralgias and received a diagnosis of Sjogren syndrome. Anti- neutrophilic cytoplasmic antibody ( ANCA) was negative. Months prior to the CRAOs, she had developed hearing loss, proptosis, and scleritis that were not responsive to prednisone 50 mg/ d. The CRAOs occurred while she was being treated at this dose level. ANCA was now positive. This is the 12th case of CRAO in WG and the 6th case of bilateral CRAOs reported in the English literature. It emphasizes that serious irreversible visual complications may occur even when the patient is being treated with substantial corticosteroid doses. ( J Neuro- Ophthalmol 2005; 25: 29- 32) From The Ottawa Hospital, Departments of Ophthalmology ( FC, SG, BL), Pathology ( BB) and Medicine ( FC, JK), University of Ottawa, Ottawa, Ontario. Address correspondence to Fiona Costello, MD, Division of Neurology, Room 6362, The Ottawa Hospital, General Campus, 501 Smyth Road, Ottawa, Ontario, Canada K1H 8L6; E- mail: fcostello@ ottawahospital. on. ca J Neuro- Ophthalmol, Vol. 25, No. 1, 2005 29 O TABLE 1. Visual loss secondary to central retinal artery occlusion in Wegener Granulomatosis 1' fi= Authors McDonald et al ( 7) 1960 Greenberger et al ( 9) 1967 Fauci et al ( 10) 1973 Haynes et al ( 6) 1977 Mizra et al ( 2) 1999 O'Gradaigh et al ( 8) 1999 O'Gradaigh et al ( 8) 1999 Lamprecht et al ( 5) 2000 Cases 1 1 1 1 1 2 1 Age/ Gender 58/ M 59/ M 66/ F 70/ F 58/ M 53/ F 55/ M 57/ M Ocular Arterial Event CRAOOD CRAO OD, impending CRAO OS Bilateral CRAOs Bilateral CRAOs CRAO OS, choroidal infarcts CRAO OD CRAO OS CRAO OS Lung Disease Pulmonary nodules, hemoptysis Apical infiltrates Hemoptysis NA Pleural effusion, cavitation Normal Hemoptysis Hemoptysis pulmonary infiltrates Renal Disease Albuminuria, Glomerulonephritis Proteinuria Proteinuria, hematuria, Glomerulonephritis Renal insufficiency Renal failure Hematuria, proteinuria, Glomerulonephritis Hematuria, Proteinuria, Glomerulonephritis Proteinuria, hematuria, renal insufficiency Other Disease Sinusitis, joint pain, orbitopathy, neuropathy Sinusitis, nasal ulcer Sinusitis, otitis, Budd Chiari syndrome, polyarthralgias. Sinusitis, joint pain, hearing loss, conjuctivitis Hearing loss, nasal congestion Tympanic inflammation Neuropathy, scleritis, splinter hemorrhages Nasal hemorrhage, deafness, sinusitis, arthralgias, neuropathy Serology ESR normal NA NA ESR elevated ESR, CRP elevated, C- ANCA+ ESR, CRP elevated, c- ANCA + CRP elevated, c- ANCA + ESR elevated, c- ANCA + Treatment Methylprednisolone 16 mg ( Further dosing details not available) Prednisone 100 mg orally 3 times daily Oral cyclophosphamide* Corticosteroid, cyclophosphamide* Prednisone 60 mg/ d, oral cyclophosphamide 100 mg/ d Methylprednisone 15 mg/ kg/ d, oral cyclophosphamide 15 mg/ kg/ d " Pulse therapy"* Intravenous corticosteroid lg for 3 days, prednisone 2 mg/ kg/ d and intravenous cyclophosphamide 4 mg/ kg Bilateral Simultaneous Central Retinal Artery Occlusions J Neuro- Ophthalmol, Vol. 25, No. 1, 2005 • S ,^ g § « „ 2 a a S « * « 5 ^ B&, gen i s: ••* a . a ss 5 8 a b - « =**) *•* < a a £ s&°. •^* ntra 2 S • b « " 3 « « s « * « >) 1 - it < a a Vis -- " w a « ) a • a « a < oi- ^ H H J « < H s< D B ca < D Hu >> 60 O O < uD t/ 3 < D M n) < D M Q f- H < D ^ o < D c « c3 < D c « s c3 < D c3 < D M 3 60 § hJ 5 < D w> ca • c < D 3 £ 3 o o f- H - S2 Td fl < D o ~ 0> 60 < M c3 U fc- H « o . g • 3 < £ £ £ " 3 B o 3 £ V Q O ^ O Q ' 3 RAO BRA Chor & OH O w £ 002 < N m n) < D - 3 200 • * " 3 < D 60 fl , P ~ 60 I o fl CM O O do I • z, ~ 3 < J a S 3 Pi OH £ OH ( S id fr - i ' a CM O 3? o • z, Q O 1 60 TS o a -^ o o o Td ^ 2 I 60 * V M 1 1- a 1 - a CM O h II hour, rheumatoid factor was 606 KU/ L, and serum creatinine kinase was 700 U/ L ( normal 15- 140 U/ L). Complete blood count, electrolytes, protein electrophoresis, anti- nuclear antibody titers ( ANA), hepatitis antibodies, anti- neutrophil cytoplasmic antibody ( ANCA), anti- DNA antibodies, complement levels, and Specific- specific antibodies ( SS- A and SS- B) were negative. Urinalysis showed trace protein and mild hematuria. Chest x- ray, abdominal ultrasound, nerve conduction studies, and electromyography were normal. The ophthalmic examination, including Schirmer testing, was normal. The patient was treated with prednisone 60 mg/ d with gradual taper and discontinuation over 18 months and her arthralgias resolved. Two years later, when the arthralgias returned, she underwent repeat testing with all of the aforementioned serological investigations, including ANCA, which were again normal. In the year prior to her bilateral visual loss, she had developed insidious bilateral hearing loss but had not undergone formal evaluation. Three months prior to the visual loss, she had developed bilateral periocular pain, proptosis, eyelid edema, and superior scleral injection. An orbital CT scan demonstrated enlarged lacrimal glands but no paranasal sinus disease. A biopsy of the left lacrimal gland showed acute neutrophilic infiltrates, necrosis, and chronic granulomatous inflammation. The patient was treated with oral prednisone 50 mg/ d but experienced no clinical improvement. At the time of the bilateral CRAOs, serum electrolytes and urinalysis testing were normal. The ESR was 60. Serological tests demonstrated normal ANA, ACE, and anti- phospholipid antibody titers. The c- ANCA level was now positive and the PR- 3 EIA titer was 100 units ( normal 0- 10). The p- ANCA and MPO EIA levels were negative. Chest x- ray, carotid Doppler ultrasound, cranial magnetic resonance imaging, and echocardiography were normal. The patient was diagnosed with limited Wegener granulomatosis ( WG). She was treated with intravenous methyrprednisolone and oral cyclophosphamide 150 mg/ day. The orbital and scleral inflammation rapidly improved, but there was no improvement in vision. Ocular involvement occurs in 40- 77% cases of WG ( 1- 3,5) and may be the presenting feature in 8- 16% of patients ( 1,4,11). The disease affects the orbit and eyes either by spread from the paranasal sinuses or by direct involvement ( 2,4). Visual loss is reported to occur in 8% of patients secondary to macular edema, neovascular glaucoma, or inflammation of the retina, optic nerve, or corneoscleral tissues ( 1,4- 6). Visual loss secondary to CRAO in WG has been infrequently reported in the English literature ( Table 1) ( 2- 11). Our patient was not so unusual in having simultaneous bilateral CRAOs, as this phenomenon has been reported in five other cases ( 3,4,6,9,10). The simultaneous involvement 31 J Neuro- Ophthalmol, Vol. 25, No. 1, 2005 Costello et al in our case was unique in that our patient developed bilateral CRAOs within 90 minutes. In one previously reported case ( 4), the interval was one day; in a second case ( 9), the interval was four days; in a third case ( 6), it was three months. In the remaining two cases ( 3,10), the interval was not specified. Our patient was relatively young ( the reported range is 33- 70 years) as was the patient reported by Peng et al ( 11). Our patient was on treatment of WG at the time of the CRAOs. In two previously reported cases ( 5,7), the patients experienced CRAO despite treatment with high dose corticosteroid therapy. In a case reported by Lamprecht et al ( 5) and Peng et al ( 11), the patients were also being treated with oral cyclophosphamide ( 5) when visual loss developed. In four other reports of CRAO and WG, visual improvement occurred with the initiation of corticosteroid and/ or cyclophosphamide therapy ( 4- 6,9). In two of these cases, the time course and degree of visual improvement is not specified ( 5,6). Greenberger ( 9) reported a case of bilateral CRAOS in which the visual acuity improved from 20/ 100 to 20/ 25 OS with initiation of prednisone therapy ( 100 mg po tid) but no improvement in the visual acuity OD, which progressed to no light perception. The OS was, however, considered an " impending" CRAO. Wong ( 4) reported a 58- year old man who developed a CRAO and hand motion vision OD. He received intravenous acetazolamide 500 mg, ocular massage, anterior chamber paracentesis and aspirin. The following morning he manifested a new CRAO OS, which was treated with the same regimen. Visual acuity had improved to 20/ 200 OD but had fallen to hand motion OS. He received oral prednisone 60 mg/ d and visual acuity gradually improved to 20/ 40 OD and 20/ 20 OS six days later, albeit with persistent " patchy peripheral field deficits." Our patient demonstrated no visual recovery after six months of follow up. In all six previously reported cases of CRAO and WG in which ANCA has been tested, it has always been positive ( Table 1). In ANCA positivity, alcohol- fixed neutrophils display either a diffusely granular or a perinuclear immu-nofluorescent cytoplasmic pattern. The diffusely granular pattern, corresponding to the distribution of the lysosomal antigen proteinase- 3 ( PR3), is referred to as c- ANCA. The perinuclear pattern, directed at myeloperoxidase ( MPO) ( 1), is referred to as p- ANCA. In serologically positive WG, 80- 95% of cases are c- ANCA ( anti- PR3) positive and 5- 20% are p- ANCA ( anti- MPO) positive ( 12). The ANCA titer may parallel the intensity of the disease, and a reversion to a normal titer may be associated with clinical remission. Patients who display negative or decreasing ANCA titers after therapy may be at lower risk for clinical relapses. However, in 1/ 3 of cases, the ANCA titer is poorly correlated with the intensity of the disease ( 12). Lack of c- ANCA positivity does not preclude the diagnosis of WG, as 5- 10% of cases may be c- ANCA negative, and these autoantibodies may be absent in up to 20% of limited forms of WG ( 1,12). In our case, c- ANCA was negative early in the disease course but positive at the time of visual loss. Our case emphasizes that serious visual complications may occur in WG treated with substantial doses of prednisone. The addition of cyclophosphamide may prevent such complications. Thus, an early diagnosis of WG becomes crucial. WG should not dismissed if c- ANCA is negative. REFERENCES 1. Harman LE, Margo CE. Wegener's Granulomatosis. Surv Ophthalmol. 1998; 42: 458- 80. 2. Mizra S, Raghu Ram AR, Bowling BS, et al. Central retinal artery occlusion and bilateral choroidal infarcts in Wegener's granulomatosis. Eye. 1999; 13: 374- 6. 3. Iida T, Spaide RF, Kantor J. Retinal and Choroidal Arterial Occlusion in Wegener's Granulomatosis. Am J Ophthalmol. 2002; 133: 151- 2. 4. Wong SC, Boyce RL, Dowd TC, et al. Bilateral central retinal artery occlusion in Wegener's granulomatosis and ai antitrypsin deficiency. Br J Ophthalmol. 2002; 86: 476. 5. Lamprecht P, Lerin- Lozano C, Reinhold- Keller E, et al. Retinal artery occlusion in Wegener's granulomatosis. Rheumatology. 2000; 39: 928- 9. 6. Haynes BF, Fishman ML, Fauci AS, et al. The ocular manifestations of Wegener's granulomatosis: fifteen years experience and review of the literature. Am J Med. 1977; 63: 131^ 1. 7. McDonald JB, Edwards RW Wegener's granulomatosis: a triad. JAMA. 1960; 173: 1205- 19. 8. O'Gradaigh D, Watts R, Glenn A, et al. An unusual cause of blindness in Wegener's Granulomatosis. Rheumatology. 1999; 38: 578- 9. 9. Greenberger MH. Central retinal artery closure in Wegener's granulomatosis. Am J Ophthalmol. 1967; 63: 515- 6. 10. Fauci AS, Wolff SM. Wegener's granulomatosis: studies in eighteen patients and a review of the literature. Medicine. 1973; 52: 535- 61. 11. Peng YJ, Fang PC, Huang WT. Central retinal artery occlusion in Wegener's granulomatosis: a case report and review of the literature. Can J Ophthalmol. 2004; 785- 9. 12. Valmaggia C, Neuweiler J. Orbital involvement as the first manifestation in classic Wegener's granulomatosis. Orbit. 2001; 20: 231- 7. 32 © 2005 Lippincott Williams & Wilkins |
