Download PDF
Klin Monbl Augenheilkd 2000; 216(1): 17-24
DOI: 10.1055/s-2000-10511
Übersicht

Georg Thieme Verlag Stuttgart · New York

Karzinomassoziierte Retinopathie: Eine Übersicht mit klinischen Beispielen[*]

Cancer-associated retinopathyBeate Sobottka1 , Torsten Schlote2 , Dorothea Besch3 , Tzonka Djelebova3 , Helmut Wilhelm3 , Eberhart Zrenner3
  • Univ.-Augenklinik Tübingen, Schleichstr. 12, D-72076 Tübingen
  • 1 Abteilung III: Glaskörper- und Netzhautchirurgie (Direktorin: Prof. Dr. I. Kreissig)
  • 2 Abteilung I: Allgemeine Augenheilkunde mit Poliklinik (Kommissarischer Direktor: Prof. Dr. M. Zierhut)
  • 3 Abteilung II: Pathophysiologie des Sehens und Neuroophthalmologie (Direktor: Prof. Dr. E. Zrenner)
Further Information

Publication History

Publication Date:
31 December 2000 (online)

Also available at
    Permissions and Reprints

Zusammenfassung

Die karzinomassoziierte Retinopathie (CAR) ist ein seltenes paraneoplastisches Syndrom. Innerhalb weniger Monate konnten zwei Patienten mit einer CAR an der Univ.-Augenklinik Tübingen diagnostiziert werden, über die im Rahmen dieser Übersicht berichtet wird.

Am häufigsten wurde die CAR beim kleinzelligen Bronchialkarzinom, in Einzelfällen beim Rhabdomyosarkom, Gebärmutter-, Prostata- und Mammakarzinom beschrieben. Die genaue Pathogenese der CAR ist unbekannt. Eine wichtige Rolle scheint die tumorinduzierte, spezifische Immunreaktion gegen das Photorezeptorprotein Recoverin („23-kd retinal CAR antigen”) zu spielen, die sich nicht bei jedem Patienten nachweisen lässt. Vermutlich sind weitere retinale Antigene an der Pathogenese beteiligt. Symptome machen sich in der Regel bereits vor der Diagnose des Primärtumors bemerkbar. Es kommt zu einer schnell progredienten, meist asymmetrischen Visusminderung, der oft Photopsien und eine vermehrte Blendungsempfindlichkeit vorausgehen. Gesichtsfelddefekte können sehr heterogen sein, häufiger sind Skotome in der mittleren Peripherie oder parazentral. Im ERG zeigen sich typischerweise reduzierte Antworten, obwohl auch von normalen ERG-Befunden bei sonst typischer CAR berichtet wird. Funduskopisch kann sich ein unauffälliger Netzhautbefund zeigen, häufiger sind jedoch Veränderungen des retinalen Pigmentepithels, Einscheidungen der retinalen Gefäße und eine Verengung der retinalen Arteriolen. Die Prognose muss als schlecht eingestuft werden. In den wenigen dokumentierten Verlaufsbeobachtungen in der Literatur kam es ohne Therapie innerhalb von 6 bis 18 Monaten zur Erblindung. Obwohl systemische Kortikosteroide bei einigen Patienten als hilfreich beschrieben wurden, ist ein allgemein anerkanntes und in seiner Wirksamkeit belegtes Therapiekonzept bislang nicht verfügbar.

Als Literatursuche wurden die Datenbanken Medline und Current Contents Search verwendet.

Cancer-associated retinopathy (CAR) is a rare paraneoplastic syndrome. In this survey we report about two further patients with CAR, who were referred to the University Eye Hospital of Tuebingen within a few months. The most common primary tumor associated with CAR is small cell carcinoma of the lung. Case reports about rhabdomyosarcoma, carcinoma of the endometrium, prostate and mamma were also described. The exact pathogenesis of CAR is still unknown. Specific autoantibodies were found against the photoreceptor protein recoverin (23-kd retinal CAR antigen). However, this reaction is not present in all patients, and probably other antigens are also involved. Most of the patients experience symptoms of CAR before the primary tumor is detected. Besides glare sensitivity and flashing lights, a rapidly progressive, often asymmetric visual loss may occur. Although paracentral and midperipheral scotomas can be found frequently, visual field defects are often quite heterogeneous. Typically, the responses in the electroretinogram (ERG) are markedly reduced, but normal ERGs were also described. The fundus picture in CAR shows sheathing of the retinal vessels, narrowing of the arterioles and clumbing of the retinal pigment epithelium. The prognosis is poor. Frequently there is progression to bilateral loss of vision within a few months. Treatment of the primary tumor does not seem to alter the ocular prognosis. Systemic corticosteroids may be helpful in some patients. Nevertheless, no proven therapeutic regimen is currently available.

Literature search was done by Medline and Current Contents Search.

Schlüsselwörter

paraneoplastische Syndrome - karzinomassoziierte Retinopathie - paraneoplastische Optikusneuropathie - Mammakarzinom - Karzinom des Corpus uteri - paraneoplastische Syndrome des zentralen Nervensystems

Key words

paraneoplastic syndrome - cancer-associated retinopathy - paraneoplastic optic neuropathy - mamma carcinoma - carcinoma of the endometrium - paraneoplastic neurological syndromes

1 Manuskript erstmalig eingereicht am 18. 8. 99 und in der vorliegenden Form angenommen am 28. 10. 99.

Literatur

1 Manuskript erstmalig eingereicht am 18. 8. 99 und in der vorliegenden Form angenommen am 28. 10. 99.

  • 01 Adamus  G, Guy  J, Dchmied  J L, et al. Role of Anti-recoverin autoantibodies in cancer-associated retinopathy.  Invest Ophthalmol Vis Sci. 1993;  34 2626-2633
    Google Scholar
  • 02 Aptsiauri  N, Jordan  B I, Heckenlively  J. Anti-recoverin immunoreactivity in patients with retinal degeneration without systemic malignancy. ARVO abstracts.  Invest Ophthalmol Vis Sci. 1998;  39(4, Suppl.) 363
    Google Scholar
  • 03 Bearse  M A, Sutter  E E. Imaging localized retinal dysfunction with the multi-focal electroretinogram.  Opt Soc Am J A. 1996;  13 634-640
    Google Scholar
  • 04 Berson  E L, Lessell  S. Paraneoplastic night blindness with malignant melanoma.  Am J Ophthalmol. 1988;  106 307-311
    Google Scholar
  • 05 Boghen  D, Sebag  M, Michaud  J. Paraneoplastic optic neuritis and encephalomyelitis: report of a case.  Arch Neurol. 1988;  45 353-356
    Google Scholar
  • 06 Boucher  M A, Allaire  G S. Cancer-associated retinopathy: a clinicopathological case report.  Can J Ophthalmol. 1997;  32 46-49
    Google Scholar
  • 07 Brink  H, Deutmann  A, Beex  L. Unusual retinal pigment epitheliopathy and choroidopathy in carcinomatosis: a rare cae of cancer-associated retinopathy.  Graefe's Arch Clin Exp Ophthalmol. 1997;  235 59-61
    Google Scholar
  • 08 Buchanan  T AS, Gardiner  T A, Archer  D B. An ultrastructural study of retinal photoreceptor degeneration associated with bronchial carcinoma.  Am J Ophthalmol. 1984;  97 277-287
    Google Scholar
  • 09 Campo  E, Brunier  M N, Merino  M J. Small cell carcinoma of the endometrium with associated ocular paraneoplastic syndrome.  Cancer. 1992;  69 2283-2288
    Google Scholar
  • 10 Christian  C L, Elkon  K B. Autoantibodies to intracellular proteins. Clinical and biological significance.  Am J Med. 1986;  80 53-61
    PubMedGoogle Scholar
  • 11 Cogan  D G, Kuwabara  T, Currie  J, Kattah  J. Paraneoplastische Retinopathie unter dem klinischen Bild einer Zapfendystrophie und Achromatopsie.  Klin Monatsbl Augenheilkd. 1990;  197 156-158
    PubMedGoogle Scholar
  • 12 Crofts  J W, Bachynski  B N, Odel  J G. Visual paraneoplastic syndrome associated with undifferentiated endometrial carcinoma.  Can J Ophthalmol. 1988;  23 128-132
    PubMedGoogle Scholar
  • 13 Dizhoor  A M, Ray  S, Kumar  S, et al. Recoverin: a calcium sensitive activator of retinal rod guaylate cyclase.  Science. 1991;  251 915-918
    PubMedGoogle Scholar
  • 14 Gehrs  K, Tiedemann  J. Hemeralopia in an older adult.  Surv Ophthalmol. 1992;  37 185-189
    PubMedGoogle Scholar
  • 15 Grunwald  G B, Klein  R, Simmonds  M A, Kornguth  S E. Autoimmune basis for visual paraneoplastic syndrome in patients with small cell lung carcinoma.  Lancet. 1985;  1 658-661
    PubMedGoogle Scholar
  • 16 Grunwald  G B, Kornguth  S E, Towfighi  J, et al. Autoimmune basis for visual paraneoplastic syndrome in patients with small cell lung carcinoma: retinal immune deposits and ablation of retinal ganglion cells.  Cancer. 1987;  60 780-786
    PubMedGoogle Scholar
  • 17 Guy  J R, Adamus  G, Aptsiauri  N, et al. Cancer associated retinopathy: a new antibody.  Invest Ophthalmol Vis Sci. 1993;  100 (Suppl) 116
    PubMedGoogle Scholar
  • 18 Guy  J, Aptsiauri  N. IVIg protocol: reversal of carcinoma ssociated retinopathy (CAR) induced blindness with IVIg.  Neurology. 1997;  48 (Suppl) A329-A330
    PubMedGoogle Scholar
  • 19 Hammerstein  W, Jurgens  H, Gobel  U. Retinadegeneration und embryonales Rhabdomyosarkom des Thorax.  Fortschr Ophthalmol. 1991;  88 463-465
    PubMedGoogle Scholar
  • 20 Hararda  T, Fukami  H, Takeuchi  T, et al. Interferone-assoziierte Retinopathie.  Klin Monatsbl Augenheilkd. 1995;  207 302-304
    PubMedGoogle Scholar
  • 21 Heckenlively  J R, Oversier  J J, Jordan  B, Aptsiauri  N. CAR-like syndrome: progressive panretinal degenerations not associated with cancer but with anti-recoverin (and other) anti-retinal antibodies. ARVO abstracts.  Invest Ophthalmol Vis Sci. 1998;  39 (4, suppl) S216
    PubMedGoogle Scholar
  • 22 Henson  R A, Russel  D S, Wilkinson  M. Carcinomatous neuropathy and myopathy: a clinical and pathological study.  Brain. 1954;  77 82-121
    PubMedGoogle Scholar
  • 23 Honorat  J, Antoine  J C, Derringto  E, et al. Antibodies to a subpopulation of glial cells and a 66kDa developmental protein in patients with paraneoplastic neurological syndromes.  J Neurol Neurosurg Psychiatry. 1996;  61 270-278
    PubMedGoogle Scholar
  • 24 Jacobsen  D M, Thirkill  C E, Tipping  S J. A clinical triad to diagnose paraneoplastic retinopathy.  Ann Neurol. 1990;  28 162-167
    CrossrefPubMedGoogle Scholar
  • 25 Jordan  B L, Dawson  W W, Weeks  C L, Tahir  R, Hazariwala  K, Marsh  R D. Anti-retina antibody responses in patients with cancer associated retinal deficit (CARD). ARVO abstracts.  Invest Ophthalmol Vis Sci. 1999;  40(4,suppl) S153
    PubMedGoogle Scholar
  • 26 Keltner  J L, Roth  A M, Chang  R S. Photoreceptor degeneration: possible autoimmune disorder.  Arch Ophthalmol. 1983;  101 564-569
    PubMedGoogle Scholar
  • 27 Keltner  J L, Thirkill  C E, Tyler  N K, Roth  A M. Management and monitoring of cancer-associated retinopathy.  Arch Ophthalmol. 1992;  110 48-53
    PubMedGoogle Scholar
  • 28 Klingele  T G, Burde  R M, Rappazzo  J A, et al. Paraneoplastic retinopathy.  J Clin Neuro Ophthalmol. 1984;  4 239-245
    PubMedGoogle Scholar
  • 29 Kornguth  S E. Neuronal proteins and paraneoplastic syndromes.  N Eng J Med. 1989;  321 1607-1608
    PubMedGoogle Scholar
  • 30 Kornguth  S E, Kalinke  T, Grunwald  G B, et al. Antineurofilament antibodies in the sera of patients with small cell carcinoma of the lung and visual paraneoplastic syndrome.  Cancer Res. 1986;  46 2588-2593
    PubMedGoogle Scholar
  • 31 Kornguth  S E, Klein  R, Appen  R, Choate  J. Occurrence of antiretinal ganglion cell antibodies in patiens with small cell carcinoma of the lung.  Cancer. 1982;  50 1289-1293
    PubMedGoogle Scholar
  • 32 Kretschmann  U, Rüther  K, Usui  T, Zrenner  E. ERG campimetry using a multi-input stimulation technique for mapping of retinal function in the central visual field.  Ophthalmic Res. 1996;  160 303-311
    PubMedGoogle Scholar
  • 33 Kretschmann  U, Schlote  T, Stübiger  N, et al. Multifokale Elektroretinographie bei erworbenen Makulafunktionsstörungen.  Klin Monatsbl Augenheilkd. 1998;  212 93-100
    PubMedGoogle Scholar
  • 34 Kupersmith  M J, Seiple  W H, Holopigian  K, et al. Maculopathy caused by intra-arterially administered cisplatin and intravenously administered carmustine.  Am J Ophthalmol. 1992;  113 435-438
    PubMedGoogle Scholar
  • 35 Malik  S, Furlan  A J, Sweeney  P J, et al. Optic neuropathy a rare paraneoplsatic syndrome.  J Clin Neuroophthalmol. 1992;  12 137-141
    PubMedGoogle Scholar
  • 36 Marmor  M F, Zrenner  E. Standard for clinical electroretinography (1994 upgrade).  Doc Ophthalmol. 1995;  89 199-210
    CrossrefPubMedGoogle Scholar
  • 37 Matsui  Y, Mehta  M C, Katsumi  O, et al. Electrophysiological findings in paraneoplastic retinopathy.  Graefe's Arch Clin Exp Ophthalmol. 1992;  230 324-328
    PubMedGoogle Scholar
  • 38 Milam  A H, Dacey  D M, Dizhoor  D M. Recoverin immunoreactivity in mammalian cone bipolar cells.  Vis Neurosci. 1992;  0 1-2
    PubMedGoogle Scholar
  • 39 Milam  A H, Saari  J C, Jacobson  S G, Lubinski  W P, Feun  L G, Alexander  K R. Autoantibodies against retinal bipolar cells in cutaneous melanoma-associated retinopathy.  Invest Ophthalmol Vis Sci. 1993;  34 91-99
    PubMedGoogle Scholar
  • 40 Mizener  J B, Kimura  A E, Adamus  G, et al. Autoimmune retinopathy in the absence of cancer.  Am J Ophthalmol. 1997;  123 607-618
    PubMedGoogle Scholar
  • 41 Murphy  M A, Thirkill  C E, Hart  W M. Paraneoplastic retinopathy: a novel auto-antibody reaction associated with small cell lung carcinoma.  J Neuroophthalmol. 1996;  17 77-83
    PubMedGoogle Scholar
  • 42 Oohira  A, Tamaki  Y, Nagahara  K. A case of paraneoplastic retinopathy.  Jpn J Ophthalmol. 1993;  37 28-31
    PubMedGoogle Scholar
  • 43 Ohnishi  Y, Ohara  S, Sakamoto  T, et al. Cancer-associated retinopathy with retinal phlebitis.  Br J Ophthalmol. 1993;  77 795-798
    PubMedGoogle Scholar
  • 44 Ojeda  V J. The classification of spinal cord disorders in patients with cancer.  Pathology. 1983;  5 122-124
    PubMedGoogle Scholar
  • 45 Pepkowitz  S, Reader  A, Jacobs  A, et al. Paraneoplastic retinopathy: resolution with plasmapheresis.  Transfusion. 1993;  33 (Suppl) S275
    PubMedGoogle Scholar
  • 46 Pillay  N, Gibert  J J, Ebers  G C, Brown  J D. Internuclear ophthalmoplegia and optic neuritis: paraneoplastic effects of bronchial carcinoma.  Neurology. 1984;  34 788-791
    PubMedGoogle Scholar
  • 47 van der Pol  B AE, Planten  J TJ. A non-metastatic remote effect of lung carcinoma.  Doc Ophthalmol. 1997;  67 89-94
    PubMedGoogle Scholar
  • 48 Polans  A S, Burton  M D, Haley  T L, et al. Recoverin, but not visinin, is an autoantigen in the human retina identified with a cancer-associated retinopathy.  Invest Ophthalmol Vis Sci. 1993;  34 81-90
    PubMedGoogle Scholar
  • 49 Polans  A S, Buczylko  J, Crabb  J, Palczewski  K. A photoreceptor calcium binding protein is recognized by autoantibodies obtained from patients with cancer-associated ertinopathy.  J Cell Biol. 1991;  112 981-989
    CrossrefPubMedGoogle Scholar
  • 50 Purvin  V A. Anterior ischemic optic neuropathy secondary to interferon alfa.  Arch Ophthalmol. 1995;  113 1041-1044
    PubMedGoogle Scholar
  • 51 Ripps  H, Carr  R E, Siegel  I M, Greenstein  V C. Functional abnormalities in vincristine-induced nicht blindness.  Invest Ophthalmol Vis Sci. 1984;  25 787-794
    PubMedGoogle Scholar
  • 52 Rizzo  J F, Gittinger  J W. Selective immunohistochemical staining in the paraneoplastic retinopathy syndrome.  Ophthalmology. 1992;  99 1286-1295
    PubMedGoogle Scholar
  • 53 Rizzo  J F, Volpe  N F. Cancer-associated retinopathy. In: Pepose JS, Holland GN, Wilhelmus KR (Hrsg.). Ocular infection and immunity. Mosby ; 1996: 585-599
    Google Scholar
  • 54 Rowe  S E, Trobe  J D, Sieving  P A. Idiopathic photoreceptor dysfunction causes unexplained visual acuity loss in later adulthood.  Ophthalmology. 1990;  97 1632-1637
    PubMedGoogle Scholar
  • 55 Rudge  P. Optic neuritis as a complication of carcinoma of the breast.  Proc R Soc Med. 1973;  66 1106-1107
    PubMedGoogle Scholar
  • 56 Sawyer  R A, Selhorst  J B, Zimmerman  L E, Hoyt  W F. Blindness caused by photoreceptor degeneration as a remote effect of cancer.  Am J Ophthalmol. 1976;  81 606-613
    PubMedGoogle Scholar
  • 57 de la Sayette  V, Bertran  F, Honnorat  J, et al. Paraneoplastic cerebellar syndrome and optic neuritis with anti-CV2 antibodies.  Arch Neurol. 1998;  55 405-408
    CrossrefPubMedGoogle Scholar
  • 58 Spence  A M, Sumi  S M, Ruff  R. Paraneoplastic syndromes that involve the nervous system.  Curr Probl Cancer. 1983;  8 4-43
    PubMedGoogle Scholar
  • 59 Steffansson  K, Marton  L S, Dieperink  M E, et al. Circulating autonatibodies to the 200,000-dalton protein of neurofilaments in the serum of healthy individuals.  Science. 1985;  228 1117-1119
    PubMedGoogle Scholar
  • 60 Suzuki  T, Obara  Y, Sato  Y, et al. Cancer-associated retinopathy with presumed vasculitis.  Am J Ophthalmol. 1996;  122 125-127
    PubMedGoogle Scholar
  • 61 Thirkill  C E. Experimental, cancer-induced retinopathy.  Ocular Imunol Inflamm. 1997;  5 55-65
    PubMedGoogle Scholar
  • 62 Thirkill  C E, FitzGerald  P, Sergott  R C, et al. Cancer associated retinopathy (CAR syndrome) with antibodies reacting with retinal, optic nerve, and cancer cells.  N Engl J Med. 1989;  321 1589-1594
    PubMedGoogle Scholar
  • 63 Thirkill  C E, Roth  A M, Keltner  J L. Cancer associated retinopathy.  Arch Ophthalmol. 1987;  105 372-375
    PubMedGoogle Scholar
  • 64 Thirkill  C E, Keltner  J L, Tyler  N K, Roth  A M. Antibody reactions with retina and cancer-associated antigens in 10 patients with cancer-associated retinopathy.  Arch Ophthalmol. 1993;  111 931-937
    PubMedGoogle Scholar
  • 65 Thirkill  C E, Tait  R C, Tyler  N K, et al. The cancer-associated retinopathy antigen is a recoverin-like protein.  Invest Ophthalmol Vis Sci. 1992;  33 2768-2772
    PubMedGoogle Scholar
  • 66 Thirkill  C E, Tait  R C, Tyler  N K, et al. Intraperitoneal cultivation of small-cell carcinoma induces expression of the retinal cancer-associated retinopathy antigen.  Arch Ophthalmol. 1993;  111 974-978
    PubMedGoogle Scholar
  • 67 Vargas Nunez  J A, Bonilla Velasco  F, Casas Fernandez-Tjerina  J, Vaquero Ruano  M. Degeneracion retiniana paraneoplasica.  Med Clin. 1987;  88 431-435
    PubMedGoogle Scholar
  • 68 Whitcup  S M, Vistica  B P, Milam  A H, et al. Recoverin-associated retinopathy: a clinically and immunologically distinctive disease.  Am J Ophthalmol. 1998;  126 230-237
    CrossrefPubMedGoogle Scholar