Update on Diagnosis and Treatment of Primary Vitreoretinal Lymphoma

  • Xiao Zhang
  • Meifen Zhang
Part of the Advances in Visual Science and Eye Diseases book series (AVSED, volume 3)


Primary vitreoretinal lymphoma (PVRL) is one manifestation of primary central nervous system lymphoma (PCNSL) and typically a systemic disease. It often masquerades as chronic uveitis, especially posterior and pan-uveitis, and is frequently misdiagnosed at first. The golden standard for diagnosis is malignant lymphoid cells from the eye. Cytology and immunohistochemistry could confirm the diagnosis of PVRL. Flow cytometry, gene rearrangement, and intraocular cytokine detection are important auxiliary examinations. New methods using microRNA, gene mutation, and SNP might be helpful in the diagnosis and treatment response monitoring. Treatments of PVRL include systemic and local therapy. Intravitreal methotrexate and ocular radiotherapy are used for PVRL patients without brain involvement. Intravitreal anti-CD20 agent is a relatively new therapy, and seems to be safe and effective.


  1. 1.
    Givner I. Malignant lymphoma with ocular involvement: clinicopathologic report. Bull N Y Acad Med. 1954;30(9):721–2.PubMedGoogle Scholar
  2. 2.
    Chan CC, Fisson S, Bodaghi B. The future of primary intraocular lymphoma (retinal lymphoma). Ocul Immunol Inflamm. 2009;17(6):375–9.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Chan CC, Rubenstein JL, Coupland SE, Davis JL, Harbour JW, Johnston PB, et al. Primary vitreoretinal lymphoma: a report from an International Primary Central Nervous System Lymphoma Collaborative Group symposium. Oncologist. 2011;16(11):1589–99.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Chan CC, Sen HN. Current concepts in diagnosing and managing primary vitreoretinal (intraocular) lymphoma. Discov Med. 2013;15(81):93–100.PubMedPubMedCentralGoogle Scholar
  5. 5.
    Sagoo MS, Mehta H, Swampillai AJ, Cohen VM, Amin SZ, Plowman PN, et al. Primary intraocular lymphoma. Surv Ophthalmol. 2014;59(5):503–16.CrossRefPubMedGoogle Scholar
  6. 6.
    Grange LK, Kouchouk A, Dalal MD, Vitale S, Nussenblatt RB, Chan CC, et al. Neoplastic masquerade syndromes in patients with uveitis. Am J Ophthalmol. 2014;157(3):526–31.CrossRefPubMedGoogle Scholar
  7. 7.
    Faia LJ, Chan CC. Primary intraocular lymphoma. Arch Pathol Lab Med. 2009;133(8):1228–32.PubMedPubMedCentralGoogle Scholar
  8. 8.
    Rajagopal R, Harbour JW. Diagnostic testing and treatment choices in primary vitreoretinal lymphoma. Retina. 2011;31(3):435–40.CrossRefPubMedGoogle Scholar
  9. 9.
    Mudhar HS, Sheard R. Diagnostic cellular yield is superior with full pars plana vitrectomy compared with core vitreous biopsy. Eye (Lond). 2013;27(1):50–5.CrossRefGoogle Scholar
  10. 10.
    Levasseur SD, Wittenberg LA, White VA. Vitreoretinal lymphoma: a 20-year review of incidence, clinical and cytologic features, treatment, and outcomes. JAMA Ophthalmol. 2013;131(1):50–5.CrossRefPubMedGoogle Scholar
  11. 11.
    Kinoshita Y, Takasu K, Kobayashi TK, Yuri T, Tsubura A, Shikata N. Diagnosis of intraocular lesions using vitreous humor and intraocular perfusion fluid cytology: experience with 83 cases. Diagn Cytopathol. 2015;43(5):353–9.CrossRefPubMedGoogle Scholar
  12. 12.
    Coupland SE, Bechrakis NE, Anastassiou G, Foerster AM, Heiligenhaus A, Pleyer U, et al. Evaluation of vitrectomy specimens and chorioretinal biopsies in the diagnosis of primary intraocular lymphoma in patients with Masquerade syndrome. Graefes Arch Clin Exp Ophthalmol. 2003;241(10):860–70.CrossRefPubMedGoogle Scholar
  13. 13.
    Ranty ML, Laurent C, Aziza J, Mahieu L, Olle P, Quintyn JC, et al. Improving the cytological diagnosis of intraocular lymphoma from vitreous fluid. Histopathology. 2015;67(1):48–61.CrossRefPubMedGoogle Scholar
  14. 14.
    Sen HN, Bodaghi B, Hoang PL, Nussenblatt R. Primary intraocular lymphoma: diagnosis and differential diagnosis. Ocul Immunol Inflamm. 2009;17(3):133–41.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Coupland SE. Molecular pathology of lymphoma. Eye (Lond). 2013;27(2):180–9.CrossRefGoogle Scholar
  16. 16.
    Zaldivar RA, Martin DF, Holden JT, Grossniklaus HE. Primary intraocular lymphoma: clinical, cytologic, and flow cytometric analysis. Ophthalmology. 2004;111(9):1762–7.PubMedGoogle Scholar
  17. 17.
    Chan CC. Molecular pathology of primary intraocular lymphoma. Trans Am Ophthalmol Soc. 2003;101:275–92.PubMedPubMedCentralGoogle Scholar
  18. 18.
    Wang Y, Shen D, Wang VM, Sen HN, Chan CC. Molecular biomarkers for the diagnosis of primary vitreoretinal lymphoma. Int J Mol Sci. 2011;12(9):5684–97.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Chan CC, Whitcup SM, Solomon D, Nussenblatt RB. Interleukin-10 in the vitreous of primary intraocular lymphoma. Am J Ophthalmol. 1995;120(5):671–3.CrossRefPubMedGoogle Scholar
  20. 20.
    Kimura K, Usui Y, Goto H, Japanese Intraocular Lymphoma Study Group. Clinical features and diagnostic significance of the intraocular fluid of 217 patients with intraocular lymphoma. Jpn J Ophthalmol. 2012;56(4):383–9.CrossRefPubMedGoogle Scholar
  21. 21.
    Fisson S, Ouakrim H, Touitou V, Baudet S, Ben Abdelwahed R, Donnou S, et al. Cytokine profile in human eyes: contribution of a new cytokine combination for differential diagnosis between intraocular lymphoma or uveitis. PLoS One. 2013;8(2):e52385.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Usui Y, Wakabayashi Y, Okunuki Y, Kimura K, Tajima K, Matsuda R, et al. Immune mediators in vitreous fluids from patients with vitreoretinal B-cell lymphoma. Invest Ophthalmol Vis Sci. 2012;53(9):5395–402.CrossRefPubMedGoogle Scholar
  23. 23.
    Ecker S, Hines JC, Pfahler SM, Glaser BM. Aqueous cytokine and growth factor levels do not reliably reflect those levels found in the vitreous. Mol Vis. 2011;17:2856–63.PubMedPubMedCentralGoogle Scholar
  24. 24.
    Cassoux N, Giron A, Bodaghi B, Tran TH, Baudet S, Davy F, et al. IL-10 measurement in aqueous humor for screening patients with suspicion of primary intraocular lymphoma. Invest Ophthalmol Vis Sci. 2007;48(7):3253–9.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Saleh M, Nikolitch K, Bourcier T, Speeg C, Gaucher D. Repeated IL-10 measurement in aqueous humor and OCT imaging are valuable tools to monitor intraocular lymphoma treated with intravitreal injections of methotrexate. Graefes Arch Clin Exp Ophthalmol. 2012;250(5):761–4.CrossRefPubMedGoogle Scholar
  26. 26.
    Tuo J, Shen D, Yang HH, Chan CC. Distinct microRNA-155 expression in the vitreous of patients with primary vitreoretinal lymphoma and uveitis. Am J Ophthalmol. 2014;157(3):728–34.CrossRefPubMedGoogle Scholar
  27. 27.
    Pulido JS, Salomao DR, Frederick LA, Viswanatha DS. MyD-88 L265P mutations are present in some cases of vitreoretinal lymphoma. Retina. 2015;35(4):624–7.CrossRefPubMedGoogle Scholar
  28. 28.
    Bonzheim I, Giese S, Deuter C, Süsskind D, Zierhut M, Waizel M, et al. High frequency of MYD88 mutations in vitreoretinal B-cell lymphoma: a valuable tool to improve diagnostic yield of vitreous aspirates. Blood. 2015;126(1):76–9.CrossRefPubMedGoogle Scholar
  29. 29.
    Ramkumar HL, Shen de F, Tuo J, Braziel RM, Coupland SE, Smith JR, et al. IL-10-1082 SNP and IL-10 in primary CNS and vitreoretinal lymphomas. Graefes Arch Clin Exp Ophthalmol. 2012;250(10):1541–8.CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Hoang-Xuan K, Bessell E, Bromberg J, Hottinger AF, Preusser M, Rudà R, et al., European Association for Neuro-Oncology Task Force on Primary CNS Lymphoma. Diagnosis and treatment of primary CNS lymphoma in immunocompetent patients: guidelines from the European Association for Neuro-Oncology. Lancet Oncol. 2015;16(7):e322–32.CrossRefPubMedGoogle Scholar
  31. 31.
    Bessell EM, Hoang-Xuan K, Ferreri AJ, Reni M. Primary central nervous system lymphoma: biological aspects and controversies in management. Eur J Cancer. 2007;43(7):1141–52.CrossRefPubMedGoogle Scholar
  32. 32.
    Frenkel S, Hendler K, Siegal T, Shalom E, Pe’er J. Intravitreal methotrexate for treating vitreoretinal lymphoma: 10 years of experience. Br J Ophthalmol. 2008;92(3):383–8.CrossRefPubMedGoogle Scholar
  33. 33.
    STuraka K, Bryan JS, De Souza S, Gordon AJ, Kwong HM Jr, Ziemianski MC, et al. Vitreoretinal lymphoma: changing trends in diagnosis and local treatment modalities at a single institution. Clin Lymphoma Myeloma Leuk. 2012;12(6):412–7.CrossRefGoogle Scholar
  34. 34.
    Chu LC, Eberhart CG, Grossman SA, Herman JG. Epigenetic silencing of multiple genes in primary CNS lymphoma. Int J Cancer. 2006;119(10):2487–91.CrossRefPubMedGoogle Scholar
  35. 35.
    Gorovoy I, Prechanond T, Abia M, Afshar AR, Stewart JM. Toxic corneal epitheliopathy after intravitreal methotrexate and its treatment with oral folic acid. Cornea. 2013;32(8):1171–3.CrossRefPubMedGoogle Scholar
  36. 36.
    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(9):1800–5.CrossRefPubMedGoogle Scholar
  37. 37.
    Mikami R, Nakayama H, Goto H, Kimura K, Usui Y, Nogi S, et al. Preliminary results of radiotherapy for primary intraocular non-Hodgkin lymphoma. Leuk Lymphoma. 2013;54(10):2181–4.CrossRefPubMedGoogle Scholar
  38. 38.
    Manna S, Banerjee RK, Augsburger JJ, Al-Rjoub MF, Donnell A, Correa ZM. Biodegradable chitosan and polylactic acid-based intraocular micro-implant for sustained release of methotrexate into vitreous: analysis of pharmacokinetics and toxicity in rabbit eyes. Graefes Arch Clin Exp Ophthalmol. 2015;253(8):1297–305.CrossRefPubMedGoogle Scholar
  39. 39.
    Siegal T. Primary central nervous system lymphoma: current state of anti-CD20 therapy and appraisal of reported response criteria. J Clin Neurosci. 2014;21(5):709–15.CrossRefPubMedGoogle Scholar
  40. 40.
    Kitzmann AS, Pulido JS, Mohney BG, Baratz KH, Grube T, Marler RJ, et al. Intraocular use of rituximab. Eye (Lond). 2007;21(12):1524–7.CrossRefGoogle Scholar
  41. 41.
    Mineo JF, Scheffer A, Karkoutly C, Nouvel L, Kerdraon O, Trauet J, et al. Using human CD20-transfected murine lymphomatous B cells to evaluate the efficacy of intravitreal and intracerebral rituximab injections in mice. Invest Ophthalmol Vis Sci. 2008;49(11):4738–45.CrossRefPubMedGoogle Scholar
  42. 42.
    Larkin KL, Saboo US, Comer GM, Forooghian F, Mackensen F, Merrill P, et al. Use of intravitreal rituximab for treatment of vitreoretinal lymphoma. Br J Ophthalmol. 2014;98(1):99–103.CrossRefPubMedGoogle Scholar
  43. 43.
    Ben Abdelwahed R, Donnou S, Ouakrim H, Crozet L, Cosette J, Jacquet A, et al. Preclinical study of Ublituximab, a Glycoengineered anti-human CD20 antibody, in murine models of primary cerebral and intraocular B-cell lymphomas. Invest Ophthalmol Vis Sci. 2013;54(5):3657–65.CrossRefPubMedGoogle Scholar
  44. 44.
    Galand C, Donnou S, Crozet L, Brunet S, Touitou V, Ouakrim H, et al. Th17 cells are involved in the local control of tumor progression in primary intraocular lymphoma. PLoS One. 2011;6(9):e24622.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. and People's Medical Publishing House, PR of China 2020

Authors and Affiliations

  • Xiao Zhang
    • 1
  • Meifen Zhang
    • 1
  1. 1.Department of OphthalmologyPeking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina

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