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Paraneoplastic retinopathy/ optic neuropathy

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Opinion statement

Paraneoplastic retinopathy and paraneoplastic optic neuropathy comprise a heterogeneous group of ocular syndromes associated with various clinical symptoms and multiple circulating antiretinal antibodies. Current evidence supports an underlying autoimmune mediated process, which is the rationale for the provision of immuno-suppressive therapy in addition to antitumor treatment. There are no controlled clinical trials that address the treatment of paraneoplastic retinopathy and/or optic neuropathy. Management decisions must be based on a relatively small number of case reports. There have been no reports of spontaneous visual improvement in these disorders. Therefore, any improvement after treatment is attributable to the therapeutic intervention. With the exception of the paraneoplastic optic neuropathy patient group, most patients show little or no response to immunosuppressive therapy, and only a small percentage of patients have dramatic improvement. However, modest improvements in visual function can improve patient quality of life and functional independence. Prompt diagnosis and initiation of therapy before significant visual loss is seen seems to be a critical factor in treatment success. An increase in serial autoantibody titers may serve as a marker of disease activity and allow initiation of therapeutic interventions before symptomatic visual decline.

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References and Recommended Reading

  1. Chan JW: Paraneoplastic retinopathies and optic neuropathies. Surv Ophthalmol 2003, 48:12–38. This is a comprehensive review of clinical syndromes, associated antibodies and histopathology, pathogenesis, and treatment outcome of paraneoplastic retinopathy and optic neuropathy.

    Article  PubMed  Google Scholar 

  2. Sawyer RA, Selhorst JB, Zimmerman LE, Hoyt WF: Blindness caused by photoreceptor degeneration as a remote effect of cancer. Am J Ophthalmol 1976, 81:606–613.

    PubMed  CAS  Google Scholar 

  3. Klingele TG, Burde RM, Rappazzo JA, et al.: Paraneoplastic retinopathy. J Clin Neuroophthalmol 1984, 4:239–245.

    PubMed  CAS  Google Scholar 

  4. Keltner JL, Roth AM, Chang RS: Photoreceptor degeneration. Possible autoimmune disorder. Arch Ophthalmol 1983, 101:564–569.

    PubMed  CAS  Google Scholar 

  5. Thirkill CE, Roth AM, Keltner JL: Cancer-associated retinopathy. Arch Ophthalmol 1987, 105:372–375.

    PubMed  CAS  Google Scholar 

  6. Polans AS, Witkowska D, Haley TL, et al.: Recoverin, a photoreceptor-specific calcium-binding protein, is expressed by the tumor of a patient with cancerassociated retinopathy. Proc Natl Acad Sci U S A 1995, 92:9176–9180.

    Article  PubMed  CAS  Google Scholar 

  7. Yamaji Y, Matsubara S, Yamadori I, et al.: Characterization of a small-cell-lung-carcinoma cell line from a patient with cancer-associated retinopathy. Int J Cancer 1996, 65:671–676.

    Article  PubMed  CAS  Google Scholar 

  8. Matsubara S, Yamaji Y, Sato M, et al.: Expression of a photoreceptor protein, recoverin, as a cancer-associated retinopathy autoantigen in human lung cancer cell lines. Br J Cancer 1996, 74:1419–1422.

    PubMed  CAS  Google Scholar 

  9. Ohguro H, Marayuma I, Nakzawa M, Oohira A: Antirecoverin antibody in the aqueous humor of a patient with cancer-associated retinopathy. Am J Ophthalmol 2002, 134:605–607.

    Article  PubMed  Google Scholar 

  10. Shiraga S, Adamus G: Mechanism of CAR syndrome: anti-recoverin antibodies are the inducers of retinal cell apoptotic death via the caspase 9- and caspase 3-dependent pathway. J Neuroimmunol 2002, 132:72–82.

    Article  PubMed  CAS  Google Scholar 

  11. Chen W, Elias RV, Bao W, Lerious, et al.: Anti-recoverin antibodies cause the apoptotic death of mammalian photoreceptor cells in vitro. J Neurosci Res 1999, 57:706–718.

    Article  PubMed  CAS  Google Scholar 

  12. Chen W, Cao W, Achyuthan AM, McGinnis JF: In vitro inhibition of antirecoverin immunoglobulinmediated death of mammalian photoreceptor cells. J Neurosci Res 2001, 63:116–123.

    Article  PubMed  CAS  Google Scholar 

  13. Adamus G, Maachnicki M, Seigel GM: Apoptotic retinal cell death induced by autoantibodies of cancer associated retinopathy. Invest Ophthal Vis Sci 1997, 38:283–291.

    PubMed  CAS  Google Scholar 

  14. Bazhin AV, Shifrina ON, Savchenko MS, et al.: Low titre autoantibodies against recoverin in sera of patients with small cell lung cancer but without a loss of vision. Lung Cancer 2001, 34:99–104.

    Article  PubMed  CAS  Google Scholar 

  15. Heckenlively JR, Fawzi AA, Oversier J, et al.: Autoimmune retinopathy: patients with antirecoverin immunoreactivity and panretinal degeneration. Arch Ophthalmol 2000, 118:1525–1533.

    PubMed  CAS  Google Scholar 

  16. Ohguro H, Yokoi Y, Ohguro I, et al.: Clinical and immunological aspects of cancer-associated retinopathy. Am J Ophthalmol 2004, 137:1117–1119.

    Article  PubMed  Google Scholar 

  17. Keltner JL, Thirkill CE, Tyler NK, Roth A: Management and monitoring of cancer-associated retinopathy. Arch Ophthalmol 1992, 110:48–53.

    PubMed  CAS  Google Scholar 

  18. Kornguth SE, Klein R, Appen R, Choate J: Occurrence of anti-retinal ganglion cell antibodies in patients with small cell carcinoma of the lung. Cancer 1982, 50:1289–1293.

    Article  PubMed  CAS  Google Scholar 

  19. Buchanan RA, Gardiner TA, Aracher DB: An ultrastructural study of retinal photoreceptor degeneration associated with bronchial carcinoma. Am J Ophthalmol 1984, 97:277–287.

    PubMed  CAS  Google Scholar 

  20. Gehrs K, Tiedeman J: Hemeralopia in an older adult. Surv Ophthalmol 1992, 37:185–189.

    Article  PubMed  CAS  Google Scholar 

  21. Jacobson DM, Adamus G: Retinal anti-bipolar cell antibodies in a patient with paraneoplastic retinopathy and colon carcinoma. Am J Ophthalmol 2001, 131:806–808.

    Article  PubMed  CAS  Google Scholar 

  22. Rizzo JF, Gittinger JW: Selective immunohistochemical staining in the paraneoplastic retinopathy syndrome. Ophthalmology 1992, 99:1286–1295.

    PubMed  Google Scholar 

  23. Ohnishi Y, Ohara S, Sakamoto T, et al.: Cancer-associated retinopathy with retinal phlebitis. Br J Ophthalmol 1993, 77:795–798.

    PubMed  CAS  Google Scholar 

  24. Eltabbakh GH, Hoogerland DL, Kay MC: Paraneoplasticd retinopathy associated with uterine sarcoma. Gynecol Oncol 1995, 58:120–123.

    Article  PubMed  CAS  Google Scholar 

  25. Boucher MC, Allaire GS: Cancer-associated retinopathy: a clinicopathological case report. Can J Ophthalmol 1997, 32:46–49.

    PubMed  CAS  Google Scholar 

  26. Adamus G, Amundson D, MacKay C, Gouras P: Long-term persistence of antirecoverin antibodies in endometrial cancer-associated retinopathy. Arch Ophthalmol 1998, 116:251–253.

    PubMed  CAS  Google Scholar 

  27. Salgia R, Hedges TR, Rizk M, et al.: Cancer-associated retinopathy in a patient with non-small-cell lung carcinoma. Lung Cancer 1998, 22:149–152.

    Article  PubMed  CAS  Google Scholar 

  28. Crofts JW, Bachynski BN, Odel JG: Visual paraneoplastic syndrome associated with undifferentiated endometrial carcinoma. Can J Ophthalmol 1988, 23:128–132.

    PubMed  CAS  Google Scholar 

  29. Ing EB, Augsburger JJ, Eagle RC: Lung cancer with visual loss. Surv Ophthalmol 1996, 40:505–510.

    Article  PubMed  CAS  Google Scholar 

  30. Suzuki T, Ohara Y, Sato Y, et al.: Cancer-associated retinopathy with presumed vasculitis. Am J Ophthalmol 1996, 122:125–127.

    PubMed  CAS  Google Scholar 

  31. Campo E, Brunier MN, Merino MJ: Small cell carcinoma of the endometrium with associated ocular paraneoplastic syndrome. Cancer 1992, 69:2283–2288.

    Article  PubMed  CAS  Google Scholar 

  32. Guy J, Aptsiauri N: Treatment of paraneoplastic visual loss with intravenous immunoglobulin. Arch Ophthalmol 1999, 117:471–477.

    PubMed  CAS  Google Scholar 

  33. Murphy MA, Thirkill CE, Hart WM: Paraneoplastic retinopathy: a novel autoantibody reaction associated with small cell lung carcinoma. J Neuroophthalmol 1996, 17:77–83.

    Google Scholar 

  34. Thirkill CE, FitzGerald P, Sergott RC, et al.: Cancerassociated retinopathy (CAR syndrome) with antibodies reacting with retinal, optic-nerve, and cancer cells. N Engl J Med 1989, 321:1589–1594.

    Article  PubMed  CAS  Google Scholar 

  35. Berson EL, Lessell S: Paraneoplastic night blindness with malignant melanoma. Am J Ophthalmol 1988, 106:307–311.

    Article  PubMed  CAS  Google Scholar 

  36. Milam AH, Saari JC, Jacobson SG, et al.: Autoantibodies against retinal bipolar cells in cutaneous melanomaassociated retinopathy. Invest Ophthalmol Vis Sci 1993, 34:91–100.

    PubMed  CAS  Google Scholar 

  37. Potter MJ, Thirkill CE, Dam OM, et al.: Clinical and immunocytochemical findings in a case of melanoma-associated retinopathy. Ophthalmology 1999, 16:2121–2125.

    Article  Google Scholar 

  38. Alexander KR, Fishman GA, Peachey NS, et al.: On response defect in paraneoplastic night blindness with cutaneous malignant melanoma. Invest Ophthalmol Vis Sci 1992, 33:477–483.

    PubMed  CAS  Google Scholar 

  39. Kiratli H, Thirkill CE, Bilgic S, et al.: Paraneoplastic retinopathy associated with metastatic cutaneous melanoma of unknown primary site. Eye 1997, 11:889–892.

    PubMed  Google Scholar 

  40. Pfohler C, Haus A, Palmowski A, et al.: Melanomaassociated retinopathy: high frequency of subclinical findings in patients with melanoma. Br J Dermatol 2003, 49:74–78.

    Article  Google Scholar 

  41. Kellner U, Bornfeld N, Foerster MH: Severe course of cutaneous melanoma associated retinopathy. Invest Ophthalmol Vis Sci 1994, 35:2117.

    Google Scholar 

  42. Remulla JF, Pineda R, Gaudio AR, Milam AH: Cutaneous melanoma-associated retinopathy with retinal periphlebitis. Arch Ophthalmol 1995, 113:854–855.

    PubMed  CAS  Google Scholar 

  43. Keltner JK, Thirkill CE, Yip PT: Clinical and immunologic characteristics of melanoma-associated retinopathy syndrome: eleven new cases and a review of 51 previously published cases. J Neuroophthalmol 2001, 21:173–187.

    PubMed  CAS  Google Scholar 

  44. Vaphiades MS, Brown H, Whitcup SM: Node way out. Surv Ophthalmol 2000, 45:77–83.

    Article  PubMed  CAS  Google Scholar 

  45. Milam AH: Clinical aspects: paraneoplastic retinopathy. In Neurobiology and Clinical Aspects of the Outer Retina. Edited by Djamgoz MBA, Archer SN, Vallerga S. London: Chapman and Hall; 1995:461–471.

    Google Scholar 

  46. Cross SA, Salomao DR, Parisi JE, et al.: Paraneoplastic autoimmune optic neuritis with retinitis defined by CRMP-5-IgG. Ann Neurol 2003, 54:38–50. The authors review the paraneoplastic optic neuropathy literature, add an additional 16 cases, and propose expansion of the clinical and neuropathological features of the syndrome to include retinopathy.

    Article  PubMed  Google Scholar 

  47. Waterston JA, Gilligan BS: Paraneoplastic optic neuritis and external ophthalmoplegia. Aust NZ J Med 1986, 16:703–704.

    CAS  Google Scholar 

  48. Luiz JE, Lee AG, Keltner JL, et al.: Paraneoplastic optic neuropathy and autoantibody production in small-cell carcinoma of the lung. J Neuroophthalmol 1998, 18:178–181.

    PubMed  CAS  Google Scholar 

  49. Malik S, Furlan AJ, Sweeney PJ, et al.: Optic neuropathy: a rare paraneoplastic syndrome. J Clin Neuroophthalmol 1992, 12:137–141.

    PubMed  CAS  Google Scholar 

  50. Blumenthal D, Schochet S Jr, Gutmann L, et al.: Smallcell carcinoma of the lung presenting with paraneoplastic peripheral nerve microvasuclitis and optic neuropathy. Muscle Nerve 1998, 21:1358–1359.

    Article  PubMed  CAS  Google Scholar 

  51. de la Sayette V, Bertran F, Honnorat J, et al.: Paraneoplastic cerebellar syndrome and optic neuritis with anti-CV2 antibodies: clinical response to excision of the primary tumor. Arch Neurol 1998, 55:405–408.

    Article  PubMed  Google Scholar 

  52. Kennedy MJ, Eustace P, OBriain DS, Daly PA: Paraneoplastic papilladema in neuroblastoma. Postgrad Med J 1987, 873–876.

  53. Coppeto JR, Monteiro ML, Cannarozzi DB: Optic neuropathy associated with chronic lymphomatous meningitis. J Clin Neuroophthalmol 1988, 8:39–45.

    PubMed  CAS  Google Scholar 

  54. Adamus G, Sugden B, Shiraga S, et al.: Anti-apoptotic effects of CNTF gene transfer on photoreceptor degeneration in experimental antibody-induced retinopathy. Journal of Autoimmunity 2003, 21:121–129.

    Article  PubMed  CAS  Google Scholar 

  55. Chen W, Cao W, Achyuthan AM, McGinnis JF: In vitro inhibition of antirecoverin immunoglobulinmediated death of mammalian photoreceptor cells. J Neurosci Res 2001, 63:116–12

    Article  PubMed  CAS  Google Scholar 

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  1. Department of Neurology, University of Colorado Health Sciences Center, 1635 North Ursula Street, 80010, Aurora, CO, USA

    Denise M. Damek MD

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Damek, D.M. Paraneoplastic retinopathy/ optic neuropathy. Curr Treat Options Neurol 7, 57–67 (2005). https://doi.org/10.1007/s11940-005-0007-1

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  • DOI: https://doi.org/10.1007/s11940-005-0007-1

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