A 46-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 Sjögren syndrome when she presented with xerostomia, rash, and arthralgias. At that time, an erythrocyte serum sedimentation rate (ESR) was 70 mm per 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 anti-bodies (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 methylprednisolone 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 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 cyclo-phosphamide 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 immunofluorescent 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) positiveand 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.
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