Japanese Journal of Ophthalmology

, Volume 56, Issue 4, pp 383–389 | Cite as

Clinical features and diagnostic significance of the intraocular fluid of 217 patients with intraocular lymphoma

  • Keisuke Kimura
  • Yoshihiko Usui
  • Hiroshi Goto
  • The Japanese Intraocular Lymphoma Study Group
Clinical Investigation

Abstract

Purpose

Intraocular lymphoma is a rare disease with a poor prognosis. Early diagnosis and early treatment greatly influence the survival prognosis of this disease. This retrospective study aimed to clarify the clinical features of patients diagnosed with intraocular lymphoma, and the diagnostic significance of results from analysis of vitreous samples including cytology, cytokine measurements, and the IgH gene rearrangement test.

Methods

We reviewed 217 patients with intraocular lymphoma diagnosed at 25 medical institutions in Japan. Together with clinical observation, cytological analysis, determination of the levels of cytokines, and/or detection of IgH gene rearrangements were conducted using vitreous fluid specimens. The results were studied in conjunction with clinical findings of intraocular lymphoma. Survival curves were estimated by use of the Kaplan–Meier method.

Results

The subjects comprised 85 men and 132 women, with a mean age at first ophthalmological examination of 63.4 years. The mean observation period was 41.3 months. During the observation period, 69 patients had onset of lymphoma in one eye and 148 had onset in both eyes. Intraocular lymphoma with involvement of the central nervous system (CNS) was most common, found in 60.8 % of the patients, whereas intraocular lymphoma without involvement of other organs was found in 28.1 % of patients. With respect to onset patterns, 82.5 % of patients developed primary ocular lesions whereas 16.1 % developed primary CNS lesions preceding intraocular lymphoma. Blurred vision and ataxia were the most common ocular and extra-ocular symptoms that prompted patients to seek medical examination. Vitreous opacification was the most common ocular finding. The detection rates of malignant cytology, IL-10/IL-6 ratio greater than 1.0, and IgH gene rearrangements in vitreous specimens were 44.5, 91.7, and 80.6 %, respectively, of patients tested. IL-10/IL-6 ratio greater than 1.0 had the highest overall detection rate, and was extremely high (≥90 %) in patients with or without vitreous opacification. The 5-year survival rate was 61.1 %.

Conclusion

Cytokine analysis of vitreous biopsy had the highest detection rate for intraocular lymphoma. This supplementary diagnostic test should be performed frequently to confirm a diagnosis of intraocular lymphoma.

Keywords

Intraocular lymphoma Clinical features Multicenter study 

References

  1. 1.
    Bardenstein DS. Intraocular Lymphoma. Cancer Control. 1998;5:317–25.PubMedGoogle Scholar
  2. 2.
    Goto H, Mochizuki M, Yamaki K, Kotake S, Usui M, Ohno S. Epidemiological survey of intraocular inflammation in Japan. Jpn J Ophthalmol. 2007;51:41–4.PubMedCrossRefGoogle Scholar
  3. 3.
    Whitcup SM, de Smet MD, Rubin BI, Palestine AG, Martin DF, Burnier M Jr, et al. Intraocular lymphoma. Clinical and histopathologic diagnosis. Ophthalmology. 1993;100:1399–406.PubMedGoogle Scholar
  4. 4.
    Wakefield D, Zierhut M. Intraocular lymphoma: more questions than answers. Ocul Immunol Inflamm. 2009;17:6–10.PubMedCrossRefGoogle Scholar
  5. 5.
    Char DH, Ljung BM, Miller T, Phillips T. Primary intraocular lymphoma (ocular reticulum cell sarcoma) diagnosis and management. Ophthalmology. 1988;95:625–30.PubMedGoogle Scholar
  6. 6.
    Whitcup SM, Stark-Vancs V, Wittes RE, Solomon D, Podgor MJ, Nussenblatt RB, et al. Association of interleukin 10 in the vitreous and cerebrospinal fluid and primary central nervous system lymphoma. Arch Ophthalmol. 1997;115:1157–60.PubMedCrossRefGoogle Scholar
  7. 7.
    Baehring JM, Androudi S, Longtine JJ, Betensky RA, Sklar J, Foster CS, et al. Analysis of clonal immunoglobulin heavy chain rearrangements in ocular lymphoma. Cancer. 2005;104:591–7.PubMedCrossRefGoogle Scholar
  8. 8.
    Sugita S, Takase H, Sugamoto Y, Arai A, Miura O, Mochizuki M. Diagnosis of intraocular lymphoma by polymerase chain reaction analysis and cytokine profiling of the vitreous fluid. Jpn J Ophthalmol. 2009;53:209–14.PubMedCrossRefGoogle Scholar
  9. 9.
    Ohta K, Sano K, Suzuki T, Hidaka E, Yoshida A, Kikuchi T. B cell clonality of primary central nervous system and primary intraocular lymphomas. Jpn J Ophthalmol. 2007;51:147–9.PubMedCrossRefGoogle Scholar
  10. 10.
    Shen DF, Zhuang Z, LeHoang P, Boni R, Zheng S, Nussenblatt RB, et al. Utility of microdissection and polymerase chain reaction for the detection of immunoglobulin gene rearrangement and translocation in primary intraocular lymphoma. Ophthalmology. 1998;105:1664–9.PubMedCrossRefGoogle Scholar
  11. 11.
    Raparia K, Chang CC, Chevez-Barrios P. Intraocular lymphoma: diagnostic approach and immunophenotypic findings in vitrectomy specimens. Arch Pathol Lab Med. 2009;133:1233–7.PubMedGoogle Scholar
  12. 12.
    Chan CC, Gonzales JA. Primary intraocular lymphoma. Singapore: World Scientific; 2007. p. 19–42.Google Scholar
  13. 13.
    Freeman LN, Schachat AP, Knox DL, Michels RG, Green WR. Clinical features, laboratory investigations, and survival in ocular reticulum cell sarcoma. Ophthalmology. 1987;94:1631–9.PubMedGoogle Scholar
  14. 14.
    Grimm SA, Pulido JS, Jahnke K, Schiff D, Hall AJ, Shenkier TN, et al. Primary intraocular lymphoma: an International Primary Central Nervous System Lymphoma Collaborative Group Report. Ann Oncol. 2007;18:1851–5.PubMedCrossRefGoogle Scholar
  15. 15.
    Jahnke K, Korfel A, Komm J, Bechrakis NE, Stein H, Thiel E, et al. Intraocular lymphoma 2000–2005: results of a retrospective multicentre trial. Graefes Arch Clin Exp Ophthalmol. 2006;244:663–9.PubMedCrossRefGoogle Scholar
  16. 16.
    Hoffman PM, McKelvie P, Hall AJ, Stawell RJ, Santamaria JD. Intraocular lymphoma: a series of 14 patients with clinicopathological features and treatment outcomes. Eye (Lond). 2003;17:513–21.CrossRefGoogle Scholar
  17. 17.
    Cooper EL, Riker JL. Malignant lymphoma of the uveal tract. Am J Ophthalmol. 1951;34:1153–8.PubMedGoogle Scholar
  18. 18.
    Schabet M. Epidemiology of primary CNS lymphoma. J Neurooncol. 1999;43:199–201.PubMedCrossRefGoogle Scholar
  19. 19.
    Kim SK, Chan CC, Wallace DJ. Management of primary intraocular lymphoma. Curr Oncol Rep. 2005;7:74–9.PubMedCrossRefGoogle Scholar
  20. 20.
    Coupland SE, Heimann H, Bechrakis NE. Primary intraocular lymphoma: a review of the clinical histopathological and molecular biological features. Graefes Arch Clin Exp Ophthalmol. 2004;242:901–13.PubMedCrossRefGoogle Scholar
  21. 21.
    Grimm SA, McCannel CA, Omuro AM, Ferreri AJ, Blay JY, Neuwelt EA, et al. Primary CNS lymphoma with intraocular involvement: International PCNSL Collaborative Group Report. Neurology. 2008;71:1355–60.PubMedCrossRefGoogle Scholar
  22. 22.
    Klingele TG, Hogan MJ. Ocular reticulum cell sarcoma. Am J Ophthalmol. 1975;79:39–47.PubMedGoogle Scholar
  23. 23.
    Michels RG, Knox DL, Erozan YS, Green WR. Intraocular reticulum cell sarcoma. Diagnosis by pars plana vitrectomy. Arch Ophthalmol. 1975;93:1331–5.PubMedCrossRefGoogle Scholar
  24. 24.
    Merle-Beral H, Davi F, Cassoux N, Baudet S, Colin C, Gourdet T, et al. Biological diagnosis of primary intraocular lymphoma. Br J Haematol. 2004;124:469–73.PubMedCrossRefGoogle Scholar
  25. 25.
    Wolf LA, Reed GF, Buggage RR, Nussenblatt RB, Chan CC. Vitreous cytokine levels. Ophthalmology. 2003;110:1671–2.PubMedCrossRefGoogle Scholar
  26. 26.
    Levy-Clarke GA, Byrnes GA, Buggage RR, Shen DF, Filie AC, Caruso RC, et al. Primary intraocular lymphoma diagnosed by fine needle aspiration biopsy of a subretinal lesion. Retina. 2001;21:281–4.PubMedCrossRefGoogle Scholar
  27. 27.
    Sen HN, Bodaghi B, Hoang PL, Nussenblatt R. Primary intraocular lymphoma: diagnosis and differential diagnosis. Ocul Immunol Inflamm. 2009;17:133–41.PubMedCrossRefGoogle Scholar
  28. 28.
    Isobe K, Ejima Y, Tokumaru S, Shikama N, Suzuki G, Takemoto M, et al. Treatment of primary intraocular lymphoma with radiation therapy: a multi-institutional survey in Japan. Leuk Lymphoma. 2006;47:1800–5.PubMedCrossRefGoogle Scholar
  29. 29.
    Fishburne BC, Wilson DJ, Rosenbaum JT, Neuwelt EA. Intravitreal methotrexate as an adjunctive treatment of intraocular lymphoma. Arch Ophthalmol. 1997;115:1152–6.PubMedCrossRefGoogle Scholar
  30. 30.
    Wang JK, Yang CM, Lin CP, Shan YD, Lo AY, Tien HF. An Asian patient with intraocular lymphoma treated by intravitreal methotrexate. Jpn J Ophthalmol. 2006;50:474–8.PubMedCrossRefGoogle Scholar
  31. 31.
    Sou R, Ohguro N, Maeda T, Saishin Y, Tano Y. Treatment of primary intraocular lymphoma with intravitreal methotrexate. Jpn J Ophthalmol. 2008;52:167–74.PubMedCrossRefGoogle Scholar
  32. 32.
    Batchelor TT, Kolak G, Ciordia R, Foster CS, Henson JW. High-dose methotrexate for intraocular lymphoma. Clin Cancer Res. 2003;9:711–5.PubMedGoogle Scholar

Copyright information

© Japanese Ophthalmological Society 2012

Authors and Affiliations

  • Keisuke Kimura
    • 1
  • Yoshihiko Usui
    • 1
  • Hiroshi Goto
    • 1
  • The Japanese Intraocular Lymphoma Study Group
  1. 1.Department of OphthalmologyTokyo Medical University HospitalTokyoJapan

Personalised recommendations