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Elderly woman with prominent temporal arteries referred for sudden, painless vision loss
The left eye had retinal whitening of the macula with dot hemorrhage and attenuated arteries, an attenuated inner retina and a thin ganglion cell layer.
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An 88-year-old woman was referred urgently by rheumatology to our neuro-ophthalmology clinic due to “going blind” in her left eye starting 3 weeks before presentation in the setting of very prominent temporal arteries. She reported that her vision loss was sudden and painless and that it did not fluctuate after the initial drastic decline. She denied any prior transient vision loss, diplopia, other visual disturbances or trauma. She denied any associated headaches, fevers, chills, night sweats, jaw claudication, scalp tenderness or proximal muscle weakness. She denied any visual disturbances in her right eye.
The patient’s daughter felt that her mother’s temporal arteries appeared “particularly prominent” in the previous month. The patient’s weight reportedly fluctuated between 95 lb and 106 lb, which her daughter attributed to “being slender all her life” and a poor appetite. Due to these observations, the patient’s rheumatologist checked a C-reactive protein test, which was normal. A temporal artery biopsy was discussed at that time but deferred by the patient given her lack of associated systemic symptoms.
Her ocular history was remarkable only for refractive error, and the patient did not have an established ophthalmologist before presentation. Her medical history was significant for sarcoidosis without extrapulmonary findings, stage IV chronic renal disease, hypertension, carpal tunnel syndrome, two ankle fractures, lumbar laminectomy and atrial fibrillation controlled on amiodarone.
Examination
The patient’s uncorrected visual acuity was 20/25-2 in the right eye and hand motion in the left eye. Pupils were round and reactive to light with a 2+ relative afferent pupillary defect in the left eye. IOPs were 10 mm Hg and 11 mm Hg. External exam revealed prominent, non-tender temporal arteries bilaterally. Anterior segment exam by slit lamp was remarkable only for mild cataracts in each eye. Dilated funduscopy revealed asymmetric optic nerves with a cup-to-disc ratio of 0.6 in the right eye and 0.85 in the left eye. The left optic nerve was pale, and the right optic nerve had a disc hemorrhage. The left eye had retinal whitening of the macula with dot hemorrhage and attenuated arteries with beading (Figure 1). The fundus in the right eye was otherwise unremarkable.
Figure 1. Color fundus photo of left eye. Optic disc pallor with cup-to-disc ratio of 0.85. Whitening of macula. Attenuated arteries throughout.
Images: Wright E, Athappilly G
Figure 2. Macular OCT (left) of left eye shows marked attenuation of inner retina. Ganglion cell analysis (right) demonstrates marked attenuation of the left eye.
Figure 3. Fluorescein angiography of left eye. Patchy choroidal filling and very early arterial filling (a). Laminar venous filling noted at 1:04 (b). Delayed filling of inferior venules, with no filling of superior venules (c). ‘Boxcarring’ of arteries (d).
A 30-2 Humphrey visual field was unreliable due to high fixation losses and high false negative errors. Optical coherence tomography of the macula and ganglion cell layer was normal for the right eye. In the left eye, OCT revealed an attenuated inner retina and severely thin ganglion cell layer (Figure 2). OCT of the nerve fiber layer revealed normal thickness in both eyes but was limited due to poor signal strength. Fluorescein angiography was normal in the right eye but revealed patchy choroidal filling and delayed, incomplete arterial and venous filling in the left eye. There was no leakage or neovascularization on fluorescein angiography in the left eye (Figure 3).
What is your diagnosis?
Sudden, painless vision loss
The differential diagnosis of isolated, sudden and painless vision loss includes retinal artery or vein occlusion, ischemic optic neuropathy, vitreous hemorrhage, retinal detachment, optic neuritis and, less commonly, cerebral vascular accident and toxic poisoning such as methanol. For our patient, the combined dilated funduscopy and fluorescein angiography findings in the left eye were characteristic of a central retinal artery occlusion.
The etiology of central retinal artery occlusion can be broken down into embolic phenomena, trauma, hypercoagulopathy, ocular conditions associated with retinal arterial obstruction, collagen vascular diseases and other vasculitides. Given the patient’s age, history and examination findings, the most likely causes considered were vasculitic (giant cell arteritis, systemic lupus erythematosus, polyarteritis nodosa, amyloidosis, sarcoidosis) and embolic (cardiac thrombus, atherosclerotic disease).
At the time of the patient’s initial presentation, a stat C-reactive protein was found to be minimally elevated at 7.7 mg/L (normal: less than 5 mg/L). She was initially started on steroids for presumed giant cell arteritis (GCA), and a rush temporal artery biopsy was performed and appeared grossly nodular so she was treated with a 3-day course of intravenous methylprednisolone.
One day after completion of the intravenous steroids, the final pathology results of the patient’s temporal artery biopsy revealed marked depositional disruption of the elastic lamina by congophilic material, consistent with amyloid vasculopathy. No arterial inflammation was seen (Figure 4).
Figure 4. Amyloid fibril deposition in temporal artery with no evidence of inflammation (top left, bottom left). Congo red stain (top right) and pathognomonic apple-green birefringence under polarized light microscopy (bottom right).
Discussion
Amyloidosis is a disease entity that involves the extracellular tissue deposition of fibrils composed of low molecular weight subunits of a variety of proteins, many of which circulate in the plasma. These deposits may result in a wide range of clinical manifestations depending on their type, location and amount of deposition. A variety of human proteins have been identified as precursors of amyloid fibrils, all of them undergoing conformational changes that lead to an anti-parallel beta-pleated sheet configuration. The characteristic and pathognomonic pathologic appearance of amyloid is apple-green birefringence of Congo red-stained tissue under polarized light microscopy.
The clinical manifestations most commonly associated with amyloidosis include nephropathy, cardiomyopathy, hepatomegaly with or without splenomegaly, cerebral amyloid angiopathy, musculoskeletal disease, bleeding disorders due to reduced factor X activity and pulmonary disease.
Occasionally, patients with light chain amyloidosis present with atypical symptoms that can mimic GCA, including scalp tenderness, jaw claudication, myalgias and weight loss. A few reports have described cases in which biopsy-proven amyloid involvement of the temporal arteries clinically mimicked GCA in patients who developed sudden onset, painless vision loss. Most of these cases have been associated with primary systemic or light chain amyloidosis, which is characterized by a clonal population of plasma cells in the bone marrow that produce monoclonal light chains of the kappa or lambda type. Like GCA, these patients can have elevated inflammatory markers and anemia, further confusing the picture. In these cases, the temporal artery biopsy was critical in making the diagnosis, as in the present case.
Occult GCA was defined by Hayreh as sudden, painless vision loss without any systemic symptoms or signs typical of GCA. The incidence of occult GCA reported in the literature varies from 5% to 38%. Hayreh performed a prospective study from 1973 to 1985 involving 85 patients who had ocular involvement and GCA confirmed on temporal artery biopsy. In his study, 21.2% of patients presented without any symptoms or signs of GCA.
A few cases in the literature have also reported a possible association between GCA and amyloidosis. In these cases, patients had symptoms of GCA and amyloidosis, with pathologic findings of both granulomatous inflammation and amyloid deposits.
Follow-up
The patient was quickly tapered off of steroids and is currently followed by hematology, with plans for a bone marrow biopsy and treatment with melphalan or lenalidomide plus dexamethasone.
Our case highlights the importance of keeping in mind the possibility of amyloidosis mimicking temporal arteritis, especially in patients with a normal ESR or CRP and pertinent comorbidities of systemic amyloidosis. Likewise, patients with a standing diagnosis of amyloidosis should be warned of the possibility of developing sudden, painless vision loss as a rare manifestation of the disease.
References:
Emmungil H, et al. Case Rep Rheumatol. 2014;doi:10.1155/2014/549641.Hamidou M, et al. Rev Med Intern. 1991;12(4):306-308.
Hayreh SS, et al. Am J Ophthalmol. 1998;doi:10.1016/S0002-9394(99)80193-7.
Ing EB, et al. Ophthalmic Surg Lasers. 1997;doi:10.3928/1542-8877-19970401-14.
Sharma S, Brown GC. Retina, volume 2. 4th ed. Elsevier; 2006:1323-1332.
Simmons RJ, et al. Arch Ophthalmol. 1962;doi:10.1001/archopht.1962.00960030012 004.
For more information:
Emily Wright, MD, and Geetha Athappilly, MD can be reached at New England Eye Center, Tufts University School of Medicine, 750 Washington St., Box 450, Boston, MA 02111; 617-636-4219; website: www.neec.com.Edited by Gregory D. Lee, MD, and Nora W. Muakkassa, MD. They can be reached at New England Eye Center, Tufts University School of Medicine, 750 Washington St., Box 450, Boston, MA 02111; 617-636-4219; website: www.neec.com.