Abstract
Paraneoplastic disorders are defined as syndromes in which the affected end organ is not a direct consequence of the mass or of distant metastasis. Instead, autoimmune response to the primary tumor causes end organ disorder and dysfunction. The temporal relationship of paraneoplastic illnesses can occur before, at the time of diagnosis, or after the identification of the primary malignancy, and in rare cases the primary malignancy may never be discovered.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Sawyer RA, Selhorst JB, Zimmerman LE, Hoyt WF. Blindness caused by photoreceptor degeneration as a remote effect of cancer. Am J Ophthalmol. 1976;81(5):606–13.
Chan JW. Paraneoplastic retinopathies and optic neuropathies. Surv Ophthalmol. 2003;48(1):12–38.
Chang PY, Yang CH, Yang CM. Cancer-associated retinopathy in a patient with hepatocellular carcinoma: case report and literature review. Retina. 2005;25(8):1093–6.
Katsuta H, Okada M, Nakauchi T, et al. Cancer-associated retinopathy associated with invasive thymoma. Am J Ophthalmol. 2002;134(3):383–9.
Tanaka A, Takase H, Adamus G, Mochizuki M. Cancer-associated retinopathy caused by benign thymoma. Br J Ophthalmol. 2010;94(4):526–8.
Hayashi M, Hatsukawa Y, Yasui M, et al. Cancer-associated retinopathy in a child with Langerhans cell histiocytosis. Jpn J Ophthalmol. 2007;51(5):393–6.
Adamus G. Autoantibody targets and their cancer relationship in the pathogenicity of paraneoplastic retinopathy. Autoimmun Rev. 2009;8(5):410–4.
Thirkill CE, Roth AM, Keltner JL. Cancer-associated retinopathy. Arch Ophthalmol. 1987;105(3):372–5.
Thirkill CE, Tait RC, Tyler NK, et al. The cancer-associated retinopathy antigen is a recoverin-like protein. Invest Ophthalmol Vis Sci. 1992;33(10):2768–72.
Shildkrot Y, Sobrin L, Gragoudas ES. Cancer-associated retinopathy: update on pathogenesis and therapy. Semin Ophthalmol. 2011;26(4–5):321–8.
Adamus G, Aptsiauri N, Guy J, et al. The occurrence of serum autoantibodies against enolase in cancer-associated retinopathy. Clin Immunol Immunopathol. 1996;78(2):120–9.
Maeda A, Ohguro H, Maeda T, et al. Aberrant expression of photoreceptor-specific calcium-binding protein (recoverin) in cancer cell lines. Cancer Res. 2000;60(7):1914–20.
Bazhin AV, Savchenko MS, Shifrina ON, et al. Recoverin as a paraneoplastic antigen in lung cancer: the occurrence of anti-recoverin autoantibodies in sera and recoverin in tumors. Lung Cancer. 2004;44(2):193–8.
Savchenko MS, Goncharskaia MA, Skorikova EE, et al. Autoantibodies against the Ca(2+)-binding protein recoverin in blood sera of patients with various oncological diseases. Oncol Lett. 2012;3(2):377–82.
Adamus G, Ortega H, Witkowska D, Polans A. Recoverin: a potent uveitogen for the induction of photoreceptor degeneration in Lewis rats. Exp Eye Res. 1994;59(4):447–55.
Ohguro H, Ogawa K, Maeda T, et al. Cancer-associated retinopathy induced by both anti-recoverin and anti-hsc70 antibodies in vivo. Invest Ophthalmol Vis Sci. 1999;40(13):3160–7.
Kim JH, Kim DH, Park WY, et al. Intravenously administered anti-recoverin antibody alone does not pass through the blood-retinal barrier. Korean J Ophthalmol. 2011;25(3):189–95.
Cao R, Cao Y. Cancer-associated retinopathy: a new mechanistic insight on vascular remodeling. Cell Cycle. 2010;9(10):1882–5.
Maeda A, Maeda T, Liang Y, et al. Effects of cytotoxic T lymphocyte antigen 4 (CTLA4) signaling and locally applied steroid on retinal dysfunction by recoverin, cancer-associated retinopathy antigen. Mol Vis. 2006;12:885–91.
Ohguro H, Rudnicka-Nawrot M, Buczylko J, et al. Structural and enzymatic aspects of rhodopsin phosphorylation. J Biol Chem. 1996;271(9):5215–24.
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(1–2):72–82.
Adamus G, Webb S, Shiraga S, Duvoisin RM. Anti-recoverin antibodies induce an increase in intracellular calcium, leading to apoptosis in retinal cells. J Autoimmun. 2006;26(2):146–53.
Weleber RG, Watzke RC, Shults WT, et al. Clinical and electrophysiologic characterization of paraneoplastic and autoimmune retinopathies associated with antienolase antibodies. Am J Ophthalmol. 2005;139(5):780–94.
Adamus G, Machnicki M, Seigel GM. Apoptotic retinal cell death induced by antirecoverin autoantibodies of cancer-associated retinopathy. Invest Ophthalmol Vis Sci. 1997;38(2):283–91.
Ohguro H, Yokoi Y, Ohguro I, et al. Clinical and immunologic aspects of cancer-associated retinopathy. Am J Ophthalmol. 2004;137(6):1117–9.
Scholl HP, Zrenner E. Electrophysiology in the investigation of acquired retinal disorders. Surv Ophthalmol. 2000;45(1):29–47.
Adamus G, Ren G, Weleber RG. Autoantibodies against retinal proteins in paraneoplastic and autoimmune retinopathy. BMC Ophthalmol. 2004;4:5.
Heckenlively JR, Fawzi AA, Oversier J, et al. Autoimmune retinopathy: patients with antirecoverin immunoreactivity and panretinal degeneration. Arch Ophthalmol. 2000;118(11):1525–33.
Masaoka N, Emoto Y, Sasaoka A, et al. Fluorescein angiographic findings in a case of cancer-associated retinopathy. Retina. 1999;19(5):462–4.
Mohamed Q, Harper CA. Acute optical coherence tomographic findings in cancer-associated retinopathy. Arch Ophthalmol. 2007;125(8):1132–3.
Abazari A, Allam SS, Adamus G, Ghazi NG. Optical coherence tomography findings in autoimmune retinopathy. Am J Ophthalmol. 2012;153(4):750–6, 6 e1.
Keltner JL, Thirkill CE, Tyler NK, Roth AM. Management and monitoring of cancer-associated retinopathy. Arch Ophthalmol. 1992;110(1):48–53.
Ferreyra HA, Jayasundera T, Khan NW, et al. Management of autoimmune retinopathies with immunosuppression. Arch Ophthalmol. 2009;127(4):390–7.
Guy J, Aptsiauri N. Treatment of paraneoplastic visual loss with intravenous immunoglobulin: report of 3 cases. Arch Ophthalmol. 1999;117(4):471–7.
Espandar L, O’Brien S, Thirkill C, et al. Successful treatment of cancer-associated retinopathy with alemtuzumab. J Neurooncol. 2007;83(3):295–302.
Mahdi N, Faia LJ, Goodwin J, et al. A case of autoimmune retinopathy associated with thyroid carcinoma. Ocul Immunol Inflamm. 2010;18(4):322–3.
Murphy MA, Thirkill CE, Hart Jr WM. Paraneoplastic retinopathy: a novel autoantibody reaction associated with small-cell lung carcinoma. J Neuroophthalmol. 1997;17(2):77–83.
Ohguro H, Ogawa K, Maeda T, et al. Retinal dysfunction in cancer-associated retinopathy is improved by Ca(2+) antagonist administration and dark adaptation. Invest Ophthalmol Vis Sci. 2001;42(11):2589–95.
Huynh N, Shildkrot Y, Lobo AM, Sobrin L. Intravitreal triamcinolone for cancer-associated retinopathy refractory to systemic therapy. J Ophthalmic Inflamm Infect. 2012;2(3):169–71.
Gass JD. Acute Vogt-Koyanagi-Harada-like syndrome occurring in a patient with metastatic cutaneous melanoma. In: Saari KM, editor. Uveitis update: proceedings of the First International Symposium on Uveitis held in Hanasaari, Espoo, Finland 1984. New York: Excerpta Medica; 1984. p. 407–8.
Berson EL, Lessell S. Paraneoplastic night blindness with malignant melanoma. Am J Ophthalmol. 1988;106(3):307–11.
Milam AH, Saari JC, Jacobson SG, et al. Autoantibodies against retinal bipolar cells in cutaneous melanoma-associated retinopathy. Invest Ophthalmol Vis Sci. 1993;34(1):91–100.
Hartmann TB, Bazhin AV, Schadendorf D, Eichmuller SB. SEREX identification of new tumor antigens linked to melanoma-associated retinopathy. Int J Cancer. 2005;114(1):88–93.
Lu Y, Jia L, He S, et al. Melanoma-associated retinopathy: a paraneoplastic autoimmune complication. Arch Ophthalmol. 2009;127(12):1572–80.
Dhingra A, Fina ME, Neinstein A, et al. Autoantibodies in melanoma-associated retinopathy target TRPM1 cation channels of retinal ON bipolar cells. J Neurosci. 2011;31(11):3962–7.
Koreen L, He SX, Johnson MW, et al. Anti-retinal pigment epithelium antibodies in acute exudative polymorphous vitelliform maculopathy: a new hypothesis about disease pathogenesis. Arch Ophthalmol. 2011;129(1):23–9.
Khurana RN, Wieland MR, Boldrey EE, et al. Vitelliform retinopathy in metastatic cutaneous melanoma with choroidal involvement. Arch Ophthalmol. 2011;129(11):1498–9.
Kim RY, Retsas S, Fitzke FW, et al. Cutaneous melanoma-associated retinopathy. Ophthalmology. 1994;101(11):1837–43.
Aronow ME, Adamus G, Abu-Asab M, et al. Paraneoplastic vitelliform retinopathy: clinicopathologic correlation and review of the literature. Surv Ophthalmol. 2012;57(6):558–64.
Keltner JL, 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(3):173–87.
Pfohler C, Haus A, Palmowski A, et al. Melanoma-associated retinopathy: high frequency of subclinical findings in patients with melanoma. Br J Dermatol. 2003;149(1):74–8.
Borkowski LM, Grover S, Fishman GA, Jampol LM. Retinal findings in melanoma-associated retinopathy. Am J Ophthalmol. 2001;132(2):273–5.
Al-Dahmash SA, Shields CL, Bianciotto CG, et al. Acute exudative paraneoplastic polymorphous vitelliform maculopathy in five cases. Ophthalmic Surg Lasers Imaging. 2012;43(5):366–73.
Ripps H, Carr RE, Siegel IM, Greenstein VC. Functional abnormalities in vincristine-induced night blindness. Invest Ophthalmol Vis Sci. 1984;25(7):787–94.
Monzon JG, Hammad N, Stevens SD, Dancey J. Retinopathy associated with adjuvant high-dose interferon-alpha2b in a patient with resected melanoma: a case report and review of the literature. Oncologist. 2012;17(3):384–7.
Powell SF, Dudek AZ. Treatment of melanoma-associated retinopathy. Curr Treat Options Neurol. 2010;12(1):54–63.
Jacobzone C, Cochard-Marianowski C, Kupfer I, et al. Corticosteroid treatment for melanoma-associated retinopathy: effect on visual acuity and electrophysiologic findings. Arch Dermatol. 2004;140(10):1258–61.
Subhadra C, Dudek AZ, Rath PP, Lee MS. Improvement in visual fields in a patient with melanoma-associated retinopathy treated with intravenous immunoglobulin. J Neuroophthalmol. 2008;28(1):23–6.
Bianciotto C, Shields CL, Thirkill CE, et al. Paraneoplastic retinopathy with multiple detachments of the neurosensory retina and autoantibodies against interphotoreceptor retinoid binding protein (IRBP) in cutaneous melanoma. Br J Ophthalmol. 2010;94(12):1684–5, 96.
Eksandh L, Adamus G, Mosgrove L, Andreasson S. Autoantibodies against bestrophin in a patient with vitelliform paraneoplastic retinopathy and a metastatic choroidal malignant melanoma. Arch Ophthalmol. 2008;126(3):432–5.
Jampol LM, Kim HH, Bryar PJ, et al. Multiple serous retinal detachments and subretinal deposits as the presenting signs of metastatic melanoma. Retina. 2004;24(2):320–2.
Nieuwendijk TJ, Hooymans JM. Paraneoplastic vitelliform retinopathy associated with metastatic choroidal melanoma. Eye. 2007;21(11):1436–7.
Sotodeh M, Paridaens D, Keunen J, et al. Paraneoplastic vitelliform retinopathy associated with cutaneous or uveal melanoma and metastases. Klin Monbl Augenheilkd. 2005;222(11):910–4.
Zacks DN, Pinnolis MK, Berson EL, Gragoudas ES. Melanoma-associated retinopathy and recurrent exudative retinal detachments in a patient with choroidal melanoma. Am J Ophthalmol. 2001;132(4):578–81.
Palmowski AM, Haus AH, Pfohler C, et al. Bilateral multifocal chorioretinopathy in a woman with cutaneous malignant melanoma. Arch Ophthalmol. 2002;120(12):1756–61.
Adamus G, Karren L. Autoimmunity against carbonic anhydrase II affects retinal cell functions in autoimmune retinopathy. J Autoimmun. 2009;32(2):133–9.
Wang Y, Abu-Asab MS, Li W, et al. Autoantibody against transient receptor potential M1 cation channels of retinal ON bipolar cells in paraneoplastic vitelliform retinopathy. BMC Ophthalmol. 2012;12:56.
Machemer R. On the pathogenesis of the flat malignant melanoma. Klin Monbl Augenheilkd. 1966;148(5):641–52.
Barr CC, Zimmerman LE, Curtin VT, Font RL. Bilateral diffuse melanocytic uveal tumors associated with systemic malignant neoplasms. A recently recognized syndrome. Arch Ophthalmol. 1982;100(2):249–55.
O’Neal KD, Butnor KJ, Perkinson KR, Proia AD. Bilateral diffuse uveal melanocytic proliferation associated with pancreatic carcinoma: a case report and literature review of this paraneoplastic syndrome. Surv Ophthalmol. 2003;48(6):613–25.
Mets RB, Golchet P, Adamus G, et al. Bilateral diffuse uveal melanocytic proliferation with a positive ophthalmoscopic and visual response to plasmapheresis. Arch Ophthalmol. 2011;129(9):1235–8.
Singh AD, Rundle PA, Slater DN, et al. Uveal and cutaneous involvement in paraneoplastic melanocytic proliferation. Arch Ophthalmol. 2003;121(11):1637–40.
Chahud F, Young RH, Remulla JF, et al. Bilateral diffuse uveal melanocytic proliferation associated with extraocular cancers: review of a process particularly associated with gynecologic cancers. Am J Surg Pathol. 2001;25(2):212–8.
Wu S, Slakter JS, Shields JA, Spaide RF. Cancer-associated nummular loss of the pigment epithelium. Am J Ophthalmol. 2005;139(5):933–5.
Gass JD, Gieser RG, Wilkinson CP, et al. Bilateral diffuse uveal melanocytic proliferation in patients with occult carcinoma. Arch Ophthalmol. 1990;108(4):527–33.
Besirli CG, Comer GM. High-resolution OCT imaging of RPE degeneration in bilateral diffuse uveal melanocytic proliferation. Ophthalmic Surg Lasers Imaging. 2010;41(Suppl):S96–100.
Ritland JS, Eide N, Tausjo J. Bilateral diffuse uveal melanocytic proliferation and uterine cancer. A case report. Acta Ophthalmol Scand. 2000;78(3):366–8.
Jaben EA, Pulido JS, Pittock S, et al. The potential role of plasma exchange as a treatment for bilateral diffuse uveal melanocytic proliferation: a report of two cases. J Clin Apher. 2011;26(6):356–61.
Ares-Luque A, Garcia-Tunon LA, Saiz A, et al. Isolated paraneoplastic optic neuropathy associated with small-cell lung cancer and anti-CV2 antibodies. J Neurol. 2007;254(8):1131–2.
Asproudis IC, Nikas AN, Psilas KG. Paraneoplastic optic neuropathy in a patient with a non-small cell lung carcinoma: a case report. Eur J Ophthalmol. 2005;15(3):420–3.
Carboni G, Forma G, Bond AD, et al. Bilateral paraneoplastic optic neuropathy and unilateral retinal compromise in association with prostate cancer: a differential diagnostic challenge in a patient with unexplained visual loss. Doc Ophthalmol. 2012;125(1):63–70.
Srikantha N, Goverdhan S, Evans A. Paraneoplastic optic neuropathy associated with papillary renal cell carcinoma. Br J Ophthalmol. 2011;95(3):429.
Slamovits TL, Posner JB, Reidy DL, et al. Pancreatic neuroendocrine paraneoplastic optic neuropathy: confirmation with antibody to optic nerve and hepatic metastasis. J Neuroophthalmol. 2013;33(1):21–5.
Cross SA, Salomao DR, Parisi JE, et al. Paraneoplastic autoimmune optic neuritis with retinitis defined by CRMP-5-IgG. Ann Neurol. 2003;54(12838519):38–50.
Calvert PC. A CR(I)MP in the optic nerve: recognition and implications of paraneoplastic optic neuropathy. J Neuroophthalmol. 2006;26(3):165–7.
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(3):178–81.
Sheorajpanday R, Slabbynck H, Van De Sompel W, et al. Small cell lung carcinoma presenting as collapsin response-mediating protein (CRMP) -5 paraneoplastic optic neuropathy. J Neuroophthalmol. 2006;26(3):168–72.
Waterston JA, Gilligan BS. Paraneoplastic optic neuritis and external ophthalmoplegia. Aust N Z J Med. 1986;16(5):703–4.
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(3):405–8.
Margolin E, Flint A, Trobe JD. High-titer collapsin response-mediating protein-associated (CRMP-5) paraneoplastic optic neuropathy and Vitritis as the only clinical manifestations in a patient with small cell lung carcinoma. J Neuroophthalmol. 2008;28(1):17–22.
Digre KB. Opsoclonus in adults. Report of three cases and review of the literature. Arch Neurol. 1986;43(11):1165–75.
Wray SH, Dalmau J, Chen A, et al. Paraneoplastic disorders of eye movements. Ann N Y Acad Sci. 2011;1233:279–84.
Pittock SJ, Kryzer TJ, Lennon VA. Paraneoplastic antibodies coexist and predict cancer, not neurological syndrome. Ann Neurol. 2004;56(5):715–9.
Luque FA, Furneaux HM, Ferziger R, et al. Anti-Ri: an antibody associated with paraneoplastic opsoclonus and breast cancer. Ann Neurol. 1991;29(3):241–51.
Singh AD, Milam AH, Shields CL, et al. Melanoma-associated retinopathy. Am J Ophthalmol. 1995;119:369–70.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2014 Springer-Verlag Berlin Heidelberg
About this chapter
Cite this chapter
Courtney, R.J., Singh, R.P., Aronow, M.B., Singh, A.D. (2014). Ocular Paraneoplastic Diseases. In: Singh, A., Damato, B. (eds) Clinical Ophthalmic Oncology. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-39489-8_10
Download citation
DOI: https://doi.org/10.1007/978-3-642-39489-8_10
Published:
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-642-39488-1
Online ISBN: 978-3-642-39489-8
eBook Packages: MedicineMedicine (R0)