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Vision Loss With Postmenopausal Bleeding

Vision Loss With Postmenopausal Bleeding Case A woman in her 50s presented with painless bilateral vision loss that developed over a period of 2 weeks to the point that she was unable to appreciate light in either eye. Two weeks prior to her visual symptoms, she had noticed intermittent painless, postmenopausal vaginal bleeding. Her medical and ocular history were unremarkable. Her examination reults 2 years prior were normal, with a visual acuity of 20/20 OU. In the emergency department, the patient had a computed tomographic scan of the brain and orbits that was normal, and she was referred to Ophthalmology. Ophthalmologic examination revealed a visual acuity of no light perception OU. Pupils were unreactive to light but constricted to a near target. Extraocular movements were full. Slitlamp examination of the anterior chamber revealed mild nuclear sclerosis in each eye and quiet anterior chambers. A dilated fundus examination is shown in the Figure. Neurological examination results were within normal limits. Figure. View LargeDownload Color fundus photographs of both eyes revealed bilateral optic nerve pallor and significantly attenuated retinal vessels. Box Section Ref ID What Would You Do Next? Magnetic resonance imaging of the brain and orbits with gadolinium Test for antiretinal antibodies Syphilis and tuberculosis testing Obtain erythrocyte sedimentation rate and C-reactive protein level Read the Discussion. Discussion Diagnosis Cancer-associated retinopathy (CAR) associated with ovarian carcinoma What To Do Next B. Test for antiretinal antibodies Discussion Cancer-associated retinopathy is the most common intraocular paraneoplastic syndrome but is a rare cause of vision loss with no sex predilection.1 Patients develop vision loss over a period of weeks to months, which precedes the diagnosis of an underlying malignancy in about half of the cases.2 Fundus examination varies from normal early on in the disease to retinal pigment epithelial thinning and mottling in the later stages. In this patient, there were findings of optic nerve pallor and significantly attenuated retinal arterioles. These clinical features prompted further investigations, including testing for specific autoantibodies, which led to the diagnosis of CAR and necessitated an expedited referral to gynecology given her postmenopausal bleeding. Diagnostic workup of patients suspected of having CAR should include a full electroretinogram and testing for antiretinal antibodies including antirecoverin, α-enolase, carbonic anhydrase II, and aldolase.2 These antibodies may be detected even before a cancer becomes detectable but should be interpreted in the right clinical context because they may also be seen to a lesser extent in patients with cancer without visual symptoms or even less commonly in healthy individuals.3 Finally, the workup should include a thorough evaluation for an underlying malignancy directed toward clinical symptoms, if present. The pathogenic mechanism driving CAR is the molecular mimicry of protein antigens expressed by various carcinomas that are the same as or similar to retinal proteins, which leads to cross-reactivity.1,2,4 The most commonly associated retinal antigens that have been implicated in CAR are recoverin and α-enolase, which have unique clinical presentations. Cancer-associated retinopathy with positive antirecoverin titers is associated with an underlying malignancy in essentially 100% of cases and widespread retinal dysfunction because rods and cones are affected equally.5 α-Enolase is less predictive of an associated neoplasm, and symptoms are usually related to cone dysfunction.5 After small-cell lung carcinoma, gynecologic cancers (ovarian, endometrial, and cervical) account for most primary tumors associated with CAR.1 In 15 of 28 cases (54%) previously described in a 2011 review of the literature,6 the primary tumor was diagnosed after the onset of visual symptoms, with the longest reported interval at 36 months. Both antirecoverin and antienolase antibodies have been reported with gynecological malignancies.3 The treatment of the underlying malignancy with surgery, chemotherapy, and radiation does not improve vision. Long-term immunosuppression remains the favored therapeutic approach, but visual prognosis is poor, despite aggressive immunosuppression.2 Some benefit has been reported from combinations of systemic corticosteroids, plasmapheresis, and intravenous immunoglobulins that aim to decrease the circulating autoantibodies and the destruction of photoreceptors.7 Steroid-sparing immunomodulatory therapy including azathioprine, cyclosporine, or mycophenolate mofetil, either alone or in combination, have been reported to improve visual acuity and visual fields in a small cohort of patients.8 In addition, successful reports of monoclonal antibodies targeting B cells have been reported including alemtuzumab9 (anti-CD52, panlymphocytic marker) and rituximab10 (anti-CD20, B-cell marker). Both of the aforementioned patients showed no previous response to prednisone or other steroid-sparing agents. Patient Outcome In this patient, further investigation of her visual loss included an electroretinogram that demonstrated extinguished scotopic and photopic a- and b-waves. Testing for the presence of antirecoverin antibodies was positive. A systemic workup directed toward her postmenopausal bleeding with ultrasonography demonstrated a very large mass replacing the cervix and lower uterine segment. Hysterectomy and bilateral salpingo-oophorectomy were performed with the final pathological diagnosis of high-grade ovarian carcinoma with endometrial and lymph node involvement. She started chemotherapy with carboplatin and paclitaxel. A diagnosis of CAR-associated retinopathy secondary to ovarian carcinoma was made. The patient was treated with a prolonged course of intravenous and oral corticosteroids, which did not lead to any improvement of her vision. Back to top Article Information Corresponding Author: Jonathan A. Micieli, MD, CM, Department of Ophthalmology and Vision Sciences, University of Toronto, 340 College St, Ste 400, Toronto, ON M5T 2S8, Canada (jonathan.micieli@utoronto.ca). Published Online: May 5, 2016. doi:10.1001/jamaophthalmol.2015.5005. Conflict Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported. References 1. Chan JW. Paraneoplastic retinopathies and optic neuropathies. Surv Ophthalmol. 2003;48(1):12-38.PubMedGoogle ScholarCrossref 2. Rahimy E, Sarraf D. Paraneoplastic and non-paraneoplastic retinopathy and optic neuropathy: evaluation and management. Surv Ophthalmol. 2013;58(5):430-458.PubMedGoogle ScholarCrossref 3. Adamus G, Choi D, Raghunath A, Schiffman J. Significance of anti-retinal autoantibodies in cancer-associated retinopathy with gynecological cancers. J Clin Exp Ophthalmol. 2013;4(6):307.PubMedGoogle ScholarCrossref 4. Albert LJ, Inman RD. Molecular mimicry and autoimmunity. N Engl J Med. 1999;341(27):2068-2074.PubMedGoogle ScholarCrossref 5. Ohguro H, Yokoi Y, Ohguro I, et al. Clinical and immunologic aspects of cancer-associated retinopathy. Am J Ophthalmol. 2004;137(6):1117-1119.PubMedGoogle ScholarCrossref 6. Cybulsak P, Navajas EV, Altomare F, Bernardini MQ. Clear cell carcinoma of the endometrium causing paraneoplastic retinopathy: case report and review of the literature. Case Rep Obstet Gynecol.2011;631929. PubMedGoogle Scholar 7. Keltner JL, Thirkill CE, Tyler NK, Roth AM. Management and monitoring of cancer-associated retinopathy. Arch Ophthalmol. 1992;110(1):48-53.PubMedGoogle ScholarCrossref 8. Ferreyra HA, Jayasundera T, Khan NW, He S, Lu Y, Heckenlively JR. Management of autoimmune retinopathies with immunosuppression. Arch Ophthalmol. 2009;127(4):390-397.PubMedGoogle ScholarCrossref 9. Espandar L, O’Brien S, Thirkill C, Lubecki LA, Esmaeli B. Successful treatment of cancer-associated retinopathy with alemtuzumab. J Neurooncol. 2007;83(3):295-302.PubMedGoogle ScholarCrossref 10. Mahdi N, Faia LJ, Goodwin J, Nussenblatt RB, Sen HN. A case of autoimmune retinopathy associated with thyroid carcinoma. Ocul Immunol Inflamm. 2010;18(4):322-323.PubMedGoogle ScholarCrossref http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png JAMA Ophthalmology American Medical Association

Vision Loss With Postmenopausal Bleeding

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Publisher
American Medical Association
Copyright
Copyright © 2016 American Medical Association. All Rights Reserved.
ISSN
2168-6165
eISSN
2168-6173
DOI
10.1001/jamaophthalmol.2015.5005
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Abstract

Case A woman in her 50s presented with painless bilateral vision loss that developed over a period of 2 weeks to the point that she was unable to appreciate light in either eye. Two weeks prior to her visual symptoms, she had noticed intermittent painless, postmenopausal vaginal bleeding. Her medical and ocular history were unremarkable. Her examination reults 2 years prior were normal, with a visual acuity of 20/20 OU. In the emergency department, the patient had a computed tomographic scan of the brain and orbits that was normal, and she was referred to Ophthalmology. Ophthalmologic examination revealed a visual acuity of no light perception OU. Pupils were unreactive to light but constricted to a near target. Extraocular movements were full. Slitlamp examination of the anterior chamber revealed mild nuclear sclerosis in each eye and quiet anterior chambers. A dilated fundus examination is shown in the Figure. Neurological examination results were within normal limits. Figure. View LargeDownload Color fundus photographs of both eyes revealed bilateral optic nerve pallor and significantly attenuated retinal vessels. Box Section Ref ID What Would You Do Next? Magnetic resonance imaging of the brain and orbits with gadolinium Test for antiretinal antibodies Syphilis and tuberculosis testing Obtain erythrocyte sedimentation rate and C-reactive protein level Read the Discussion. Discussion Diagnosis Cancer-associated retinopathy (CAR) associated with ovarian carcinoma What To Do Next B. Test for antiretinal antibodies Discussion Cancer-associated retinopathy is the most common intraocular paraneoplastic syndrome but is a rare cause of vision loss with no sex predilection.1 Patients develop vision loss over a period of weeks to months, which precedes the diagnosis of an underlying malignancy in about half of the cases.2 Fundus examination varies from normal early on in the disease to retinal pigment epithelial thinning and mottling in the later stages. In this patient, there were findings of optic nerve pallor and significantly attenuated retinal arterioles. These clinical features prompted further investigations, including testing for specific autoantibodies, which led to the diagnosis of CAR and necessitated an expedited referral to gynecology given her postmenopausal bleeding. Diagnostic workup of patients suspected of having CAR should include a full electroretinogram and testing for antiretinal antibodies including antirecoverin, α-enolase, carbonic anhydrase II, and aldolase.2 These antibodies may be detected even before a cancer becomes detectable but should be interpreted in the right clinical context because they may also be seen to a lesser extent in patients with cancer without visual symptoms or even less commonly in healthy individuals.3 Finally, the workup should include a thorough evaluation for an underlying malignancy directed toward clinical symptoms, if present. The pathogenic mechanism driving CAR is the molecular mimicry of protein antigens expressed by various carcinomas that are the same as or similar to retinal proteins, which leads to cross-reactivity.1,2,4 The most commonly associated retinal antigens that have been implicated in CAR are recoverin and α-enolase, which have unique clinical presentations. Cancer-associated retinopathy with positive antirecoverin titers is associated with an underlying malignancy in essentially 100% of cases and widespread retinal dysfunction because rods and cones are affected equally.5 α-Enolase is less predictive of an associated neoplasm, and symptoms are usually related to cone dysfunction.5 After small-cell lung carcinoma, gynecologic cancers (ovarian, endometrial, and cervical) account for most primary tumors associated with CAR.1 In 15 of 28 cases (54%) previously described in a 2011 review of the literature,6 the primary tumor was diagnosed after the onset of visual symptoms, with the longest reported interval at 36 months. Both antirecoverin and antienolase antibodies have been reported with gynecological malignancies.3 The treatment of the underlying malignancy with surgery, chemotherapy, and radiation does not improve vision. Long-term immunosuppression remains the favored therapeutic approach, but visual prognosis is poor, despite aggressive immunosuppression.2 Some benefit has been reported from combinations of systemic corticosteroids, plasmapheresis, and intravenous immunoglobulins that aim to decrease the circulating autoantibodies and the destruction of photoreceptors.7 Steroid-sparing immunomodulatory therapy including azathioprine, cyclosporine, or mycophenolate mofetil, either alone or in combination, have been reported to improve visual acuity and visual fields in a small cohort of patients.8 In addition, successful reports of monoclonal antibodies targeting B cells have been reported including alemtuzumab9 (anti-CD52, panlymphocytic marker) and rituximab10 (anti-CD20, B-cell marker). Both of the aforementioned patients showed no previous response to prednisone or other steroid-sparing agents. Patient Outcome In this patient, further investigation of her visual loss included an electroretinogram that demonstrated extinguished scotopic and photopic a- and b-waves. Testing for the presence of antirecoverin antibodies was positive. A systemic workup directed toward her postmenopausal bleeding with ultrasonography demonstrated a very large mass replacing the cervix and lower uterine segment. Hysterectomy and bilateral salpingo-oophorectomy were performed with the final pathological diagnosis of high-grade ovarian carcinoma with endometrial and lymph node involvement. She started chemotherapy with carboplatin and paclitaxel. A diagnosis of CAR-associated retinopathy secondary to ovarian carcinoma was made. The patient was treated with a prolonged course of intravenous and oral corticosteroids, which did not lead to any improvement of her vision. Back to top Article Information Corresponding Author: Jonathan A. Micieli, MD, CM, Department of Ophthalmology and Vision Sciences, University of Toronto, 340 College St, Ste 400, Toronto, ON M5T 2S8, Canada (jonathan.micieli@utoronto.ca). Published Online: May 5, 2016. doi:10.1001/jamaophthalmol.2015.5005. Conflict Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported. References 1. Chan JW. Paraneoplastic retinopathies and optic neuropathies. Surv Ophthalmol. 2003;48(1):12-38.PubMedGoogle ScholarCrossref 2. Rahimy E, Sarraf D. Paraneoplastic and non-paraneoplastic retinopathy and optic neuropathy: evaluation and management. Surv Ophthalmol. 2013;58(5):430-458.PubMedGoogle ScholarCrossref 3. Adamus G, Choi D, Raghunath A, Schiffman J. Significance of anti-retinal autoantibodies in cancer-associated retinopathy with gynecological cancers. J Clin Exp Ophthalmol. 2013;4(6):307.PubMedGoogle ScholarCrossref 4. Albert LJ, Inman RD. Molecular mimicry and autoimmunity. N Engl J Med. 1999;341(27):2068-2074.PubMedGoogle ScholarCrossref 5. Ohguro H, Yokoi Y, Ohguro I, et al. Clinical and immunologic aspects of cancer-associated retinopathy. Am J Ophthalmol. 2004;137(6):1117-1119.PubMedGoogle ScholarCrossref 6. Cybulsak P, Navajas EV, Altomare F, Bernardini MQ. Clear cell carcinoma of the endometrium causing paraneoplastic retinopathy: case report and review of the literature. Case Rep Obstet Gynecol.2011;631929. PubMedGoogle Scholar 7. Keltner JL, Thirkill CE, Tyler NK, Roth AM. Management and monitoring of cancer-associated retinopathy. Arch Ophthalmol. 1992;110(1):48-53.PubMedGoogle ScholarCrossref 8. Ferreyra HA, Jayasundera T, Khan NW, He S, Lu Y, Heckenlively JR. Management of autoimmune retinopathies with immunosuppression. Arch Ophthalmol. 2009;127(4):390-397.PubMedGoogle ScholarCrossref 9. Espandar L, O’Brien S, Thirkill C, Lubecki LA, Esmaeli B. Successful treatment of cancer-associated retinopathy with alemtuzumab. J Neurooncol. 2007;83(3):295-302.PubMedGoogle ScholarCrossref 10. Mahdi N, Faia LJ, Goodwin J, Nussenblatt RB, Sen HN. A case of autoimmune retinopathy associated with thyroid carcinoma. Ocul Immunol Inflamm. 2010;18(4):322-323.PubMedGoogle ScholarCrossref

Journal

JAMA OphthalmologyAmerican Medical Association

Published: Jul 1, 2016

Keywords: blindness,visual acuity,ovarian cancer,postmenopausal bleeding,eye

References