Cancer-associated retinopathy (CAR) is caused by antiretinal antibodies cross-reacting with pathogens expressed by carcinoma cells. Cancer-associated retinopathy with antirecoverin antibody generally shows rapidly progressive visual deterioration.1- 3 Autoimmune retinopathy (AIR) is characterized by antiretinal antibody–positive serum in the absence of systemic carcinoma but with slowly progressive visual deterioration,1,3,4 although the pathogenic mechanism is uncertain. We describe a patient with CAR with antirecoverin antibody who had slowly progressive visual deterioration resembling AIR.
In 2004, we examined a 62-year-old woman with a 10-year history of progressive visual loss and night blindness. In 1994, Goldmann perimetry and electroretinography (ERG) at another hospital showed retinitis pigmentosa–like findings in the right eye and a normal appearance in the left. In 2000, ERG response showed further deterioration in the right eye and a normal response in the left. In 2002, the left eye also exhibited a visual field defect and ERG abnormality. The patient had no history of carcinoma or ocular trauma.
When examined in 2004, our patient's visual acuities were 20/30 OD and 20/20 OS. Slitlamp examination demonstrated mild iridocyclitis and nuclear cataract bilaterally. Funduscopic examination results demonstrated optic disc pallor, retinal artery whitening, and retinal pigment epithelial atrophy with partial pigmentation in the midperipheral area across 360° (Figure 1A). Fluorescein angiography demonstrated a window defect corresponding to the retinal degeneration (Figure 1B) and late leakage from retinal capillary vessels. Goldmann perimetry demonstrated central and temporal islands in the right eye and a ring scotoma in the left. Results of single bright-flash ERG were unrecordable bilaterally. Western blot analysis detected no serum autoantibodies. One year later, a visual field defect developed in the left eye. Western blot analysis detected serum autoantibody against a 23-kDa protein (recoverin) (Figure 2A). Although the slowly progressive visual dysfunction suggested AIR, systemic screening detected a 2-mm bronchioloalveolar carcinoma without metastasis, and the patient was treated with lobectomy. Subsequently, CAR was diagnosed. A few carcinoma cells exhibited cytoplasmic immunoreactivity for recoverin (Figure 2C). One month after the lobectomy, the patient's visual acuity decreased and late-phase fluorescein angiography demonstrated cystoid macular edema in the left eye and marked leakage from retinal capillary vessels bilaterally. Oral administration of prednisolone, 40 mg/d, was initiated and then tapered across 5 months. At the last follow-up examination, the patient's visual acuity remained unchanged (20/30 OD and 20/20 OS), with no further progression of the visual field defect.
Fundus photographs of the right eye on the initial visit in 2004. A, Fundus photograph demonstrates optic disc pallor, retinal artery whitening, and retinal pigment epithelial atrophy with partial pigmentation in the midperipheral area. B, Fluorescein angiography (42 seconds after dye injection) demonstrates a window defect corresponding to retinal degeneration.
Western blot analysis using bovine retinal soluble fractions in the patient's serum (A) and immunohistochemistry performed on the resected lung sample (B and C) 1 year after the initial examination. A, Antibody to soluble 23-kDa (recoverin) protein was probed with the patient's serum (lane A, 1:200 dilution). Lane B shows human recombinant recoverin. B and C, Hematoxylin-eosin staining (B) and immunodetection of recoverin (C) in bronchioloalveolar carcinoma. Cytoplasmic immunoreactivity for recoverin was noted in a few carcinoma cells (C) (original magnification ×200).
Patients with AIR exhibit slowly progressive visual deterioration mimicking retinitis pigmentosa, cystoid macular edema, and retinal vascular edema on fluorescein angiography.1,4 Some patients have systemic benign tumors.4 The patient we describe was diagnosed as having CAR with antirecoverin antibody 11 years after the initial visual symptoms appeared despite clinical features resembling AIR.
Our group previously described a patient with CAR who had aberrant expression of recoverin in many carcinoma cells.2 In the current patient the causative tumor was quite small and only a few carcinoma cells expressed the recoverin antigen, suggesting that the slow clinical course correlated with the low number of recoverin-immunopositive tumor cells, unlike patients in previously reported cases.1,2
Based on the clinical course and immunohistochemical findings, we infer that lung adenocarcinoma or preneoplastic lesions, such as atypical adenomatous hyperplasia5 expressing recoverin, were present when the initial visual symptoms were noticed, suggesting that some patients with AIR have an occult preneoplastic or malignant tumor expressing recoverin. We conclude that regular screening for systemic cancer may be necessary to save the lives and vision of patients with presumed AIR.
Correspondence: Dr Saito, Department of Ophthalmology and Visual Sciences, Hokkaido University Graduate School of Medicine, Nishi 7 chome, Kita 15 jou, Kita-ku, Sapporo 060-8638, Japan (firstname.lastname@example.org).
Financial Disclosure: None reported.
Saito W, Kase S, Ohguro H, Furudate N, Ohno S. Slowly Progressive Cancer-Associated Retinopathy. Arch Ophthalmol. 2007;125(10):1431-1433. doi:10.1001/archopht.125.10.1431