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Factors related to central nervous system involvement of primary vitreoretinal lymphoma

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Abstract

Purpose

This single center retrospective study aimed to investigate the factors associated with central nervous system (CNS) involvement of primary vitreoretinal lymphoma (PVRL).

Methods

Clinical features of patients with PVRL (Group 1), those diagnosed with vitreoretinal lymphoma (VRL) after primary CNS lymphoma diagnosis (Group 2), and those concurrently diagnosed with CNS lymphoma and VRL (Group 3), were compared. The main outcomes included sex, age, types of treatment, survival, visual acuity, diagnostic methods, VRL recurrence, ocular manifestations, and interleukin levels in the aqueous humor.

Results

Groups 1, 2, and 3 included 66 eyes in 38 patients, 29 eyes in 18 patients, and 14 eyes in 8 patients, respectively. Group 3 had shorter overall survival (OS) than Groups 1 and 2 (P = 0.042 and P = 0.009, respectively). The three groups did not differ in progression-free survival (P = 0.060). The 5-year survival rates of Groups 1, 2, and 3 were 56.5%, 44.0%, and 25.0%, respectively (P = 0.001). Patients with CNS involvement in Group 1 exhibited VRL recurrence (P < 0.001), high interleukin-10 (P = 0.024), and sub-retinal pigment epithelium (RPE) infiltration (P = 0.009). Patients experiencing VRL recurrence in Group 1 tended to show CNS involvement (P < 0.001).

Conclusion

Patients concurrently diagnosed with CNS lymphoma and VRL had a shorter OS and a lower 5-year survival rate. In patients with PVRL, the recurrence of VRL, high interleukin-10, and sub-RPE infiltration were associated with CNS involvement.

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References

  1. Levasseur SD, Wittenberg LA, White VA (2013) Vitreoretinal lymphoma: a 20-year review of incidence, clinical and cytologic features, treatment, and outcomes. JAMA Ophthalmol 131:50–55. https://doi.org/10.1001/jamaophthalmol.2013.569

    Article  PubMed  Google Scholar 

  2. Pe’er J, Hochberg FH, Foster CS (2009) Clinical review: treatment of vitreoretinal lymphoma. Ocul Immunol Inflamm 17:299–306. https://doi.org/10.3109/09273940903370755

    Article  CAS  PubMed  Google Scholar 

  3. Soussain C, Malaise D, Cassoux N (2021) Primary vitreoretinal lymphoma: a diagnostic and management challenge. Blood 138:1519–1534. https://doi.org/10.1182/blood.2020008235

    Article  CAS  PubMed  Google Scholar 

  4. Chan CC, Shen D, Hackett JJ, Buggage RR, Tuaillon N (2003) Expression of chemokine receptors, CXCR4 and CXCR5, and chemokines, BLC and SDF-1, in the eyes of patients with primary intraocular lymphoma. Ophthalmology 110:421–426. https://doi.org/10.1016/S0161-6420(02)01737-2

    Article  PubMed  Google Scholar 

  5. Shiels MS, Pfeiffer RM, Besson C, Clarke CA, Morton LM, Nogueira L, Pawlish K, Yanik EL, Suneja G, Engels EA (2016) Trends in primary central nervous system lymphoma incidence and survival in the U.S. Br J Haematol 174:417–424. https://doi.org/10.1111/bjh.14073

    Article  PubMed  PubMed Central  Google Scholar 

  6. Venkatesh R, Bavaharan B, Mahendradas P, Yadav NK (2019) Primary vitreoretinal lymphoma: prevalence, impact, and management challenges. Clin Ophthalmol 13:353–364. https://doi.org/10.2147/OPTH.S159014

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Cassoux N, Merle-Beral H, Leblond V, Bodaghi B, Milea D, Gerber S, Fardeau C, Reux I, Xuan KH, Chan CC, LeHoang P (2000) Ocular and central nervous system lymphoma: clinical features and diagnosis. Ocul Immunol Inflamm 8:243–250. https://doi.org/10.1076/ocii.8.4.243.6463

    Article  CAS  PubMed  Google Scholar 

  8. Jahnke K, Korfel A, Komm J, Bechrakis NE, Stein H, Thiel E, Coupland SE (2006) Intraocular lymphoma 2000–2005: results of a retrospective multicentre trial. Graefes Arch Clin Exp Ophthalmol 244:663–669. https://doi.org/10.1007/s00417-005-0138-9

    Article  PubMed  Google Scholar 

  9. Raval V, Binkley E, Aronow ME, Valenzuela J, Peereboom DM, Singh AD (2021) Primary central nervous system lymphoma - ocular variant: an interdisciplinary review on management. Surv Ophthalmol 66:1009–1020. https://doi.org/10.1016/j.survophthal.2021.03.004

    Article  PubMed  Google Scholar 

  10. Grimm SA, Pulido JS, Jahnke K, Schiff D, Hall AJ, Shenkier TN, Siegal T, Doolittle ND, Batchelor T, Herrlinger U, Neuwelt EA, Laperriere N, Chamberlain MC, Blay JY, Ferreri AJ, Omuro AM, Thiel E, Abrey LE (2007) Primary intraocular lymphoma: an International Primary Central Nervous System Lymphoma Collaborative Group Report. Ann Oncol 18:1851–1855. https://doi.org/10.1093/annonc/mdm340

    Article  CAS  PubMed  Google Scholar 

  11. Missotten T, Tielemans D, Bromberg JE, van Hagen PM, van Lochem EG, van Dongen JJM, Baarsma GS, Langerak AW (2013) Multicolor flowcytometric immunophenoty** is a valuable tool for detection of intraocular lymphoma. Ophthalmology 120:991–996. https://doi.org/10.1016/j.ophtha.2012.11.007

    Article  PubMed  Google Scholar 

  12. Davis JL, Miller DM, Ruiz P (2005) Diagnostic testing of vitrectomy specimens. Am J Ophthalmol 140:822–829. https://doi.org/10.1016/j.ajo.2005.05.032

    Article  PubMed  Google Scholar 

  13. Frenkel S, Pe’er J, Kaufman R, Maly B, Habot-Wilner Z (2020) The importance of cytokines analysis in the diagnosis of vitreoretinal lymphoma. Acta Ophthalmol 98:e668–e673. https://doi.org/10.1111/aos.14347

    Article  CAS  PubMed  Google Scholar 

  14. Cassoux N, Giron A, Bodaghi B, Tran TH, Baudet S, Davy F, Chan CC, Lehoang P, Merle-Beral H (2007) IL-10 measurement in aqueous humor for screening patients with suspicion of primary intraocular lymphoma. Invest Ophthalmol Vis Sci 48:3253–3259. https://doi.org/10.1167/iovs.06-0031

    Article  PubMed  Google Scholar 

  15. Whitcup SM, Stark-Vancs V, Wittes RE, Solomon D, Podgor MJ, Nussenblatt RB, Chan CC (1997) Association of interleukin 10 in the vitreous and cerebrospinal fluid and primary central nervous system lymphoma. Arch Ophthalmol 115:1157–1160. https://doi.org/10.1001/archopht.1997.01100160327010

    Article  CAS  PubMed  Google Scholar 

  16. Fend F, Ferreri AJM, Coupland SE (2016) How we diagnose and treat vitreoretinal lymphoma. Br J Haematol 173:680–692. https://doi.org/10.1111/bjh.14025

    Article  PubMed  Google Scholar 

  17. Miserocchi E, Ferreri AJM, Giuffre C, Cangi MG, Francaviglia I, Calimeri T, Ponzoni M, Pecciarini L, Bandello FM, Modorati GM (2019) Myd88 L265p mutation detection in the aqueous humor of patients with vitreoretinal lymphoma. Retina 39:679–684. https://doi.org/10.1097/IAE.0000000000002319

    Article  CAS  PubMed  Google Scholar 

  18. Frenkel S, Hendler K, Siegal T, Shalom E, Pe’er J (2008) Intravitreal methotrexate for treating vitreoretinal lymphoma: 10 years of experience. Br J Ophthalmol 92:383–388. https://doi.org/10.1136/bjo.2007.127928

    Article  CAS  PubMed  Google Scholar 

  19. Cheng CL, Yeh PT, Fang WQ, Ma WL, Hou HA, Tsai CH, Lin CP, Tien HF (2023) Long-term outcomes of combined intravitreal methotrexate and systemic high-dose methotrexate therapy in vitreoretinal lymphoma. Cancer Med 12:8102–8111. https://doi.org/10.1002/cam4.5609

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Cho BJ, Kim DY, Park UC, Lee JY, Yoon YH, Yu HG (2018) Clinical features and treatment outcomes of vitreoretinal lymphoma according to its association with CNS lymphoma. Ocul Immunol Inflamm 26:365–371. https://doi.org/10.1080/09273948.2017.1421669

    Article  PubMed  Google Scholar 

  21. Castellino A, Pulido JS, Johnston PB, Ristow KM, Nora Bennani N, Inwards DJ, Macon WR, Micallef INM, King RL, Salomao DR, Witzig TE, Habermann TM, Nowakowski GS (2019) Role of systemic high-dose methotrexate and combined approaches in the management of vitreoretinal lymphoma: a single center experience 1990–2018. Am J Hematol 94:291–298. https://doi.org/10.1002/ajh.25350

    Article  CAS  PubMed  Google Scholar 

  22. Abrey LE, Ben-Porat L, Panageas KS, Yahalom J, Berkey B, Curran W, Schultz C, Leibel S, Nelson D, Mehta M, DeAngelis LM (2006) Primary central nervous system lymphoma: the Memorial Sloan-Kettering Cancer Center prognostic model. J Clin Oncol 24:5711–5715. https://doi.org/10.1200/JCO.2006.08.2941

    Article  PubMed  Google Scholar 

  23. Kim GH, Kwak JH, Park YH (2023) Elevated interleukin-10 levels in patients with ocular toxoplasmosis. Parasites Hosts Dis 61:310–316. https://doi.org/10.3347/PHD.22172

    Article  PubMed  PubMed Central  Google Scholar 

  24. Khatri VP, Caligiuri MA (1998) A review of the association between interleukin-10 and human B-cell malignancies. Cancer Immunol Immun 46:239–244. https://doi.org/10.1007/s002620050483

    Article  CAS  Google Scholar 

  25. Coupland SE, Chan CC, Smith J (2009) Pathophysiology of retinal lymphoma. Ocul Immunol Inflamm 17:227–237. https://doi.org/10.1080/09273940903168696

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Sasayama T, Nakamizo S, Nishihara M, Kawamura A, Tanaka H, Mizukawa K, Miyake S, Taniguchi M, Hosoda K, Kohmura E (2012) Cerebrospinal fluid interleukin-10 is a potentially useful biomarker in immunocompetent primary central nervous system lymphoma (PCNSL). Neuro Oncol 14:368–380. https://doi.org/10.1093/neuonc/nor203

    Article  CAS  PubMed  Google Scholar 

  27. Song Y, Zhang W, Zhang L, Wu W, Zhang Y, Han X, Yang C, Zhang L, Zhou DB (2016) Cerebrospinal fluid IL-10 and IL-10/IL-6 as accurate diagnostic biomarkers for primary central nervous system large B-cell lymphoma. Sci Rep 6:38671. https://doi.org/10.1038/srep38671

    Article  CAS  PubMed  PubMed Central  ADS  Google Scholar 

  28. Dalvin LA, Lim LS, Ancona-Lezama D, Mazloumi M, Chang M, Porcu P, Martinez NL, Glass J, Mashayekhi A, Shields CL (2020) Clinical features predictive of survival in patients with vitreoretinal lymphoma: analysis of 70 patients at a single ocular oncology center. Asia Pac J Ophthalmol (Phila) 9:110–116. https://doi.org/10.1097/APO.0000000000000274

    Article  PubMed  Google Scholar 

  29. Dalvin LA, Pulido JS, Shields CL, Marchese A, Miserocchi E, Frenkel S, Pe’er J (2023) Vitreoretinal lymphoma: central nervous system lymphoma risk with unilateral or bilateral ocular tumour. A multicentre collaboration. Eye (Lond) 37:54–61. https://doi.org/10.1038/s41433-021-01887-2

    Article  PubMed  Google Scholar 

  30. Chan CC, Rubenstein JL, Coupland SE, Davis JL, Harbour JW, Johnston PB, Cassoux N, Touitou V, Smith JR, Batchelor TT, Pulido JS (2011) Primary vitreoretinal lymphoma: a report from an International Primary Central Nervous System Lymphoma Collaborative Group symposium. Oncologist 16:1589–1599. https://doi.org/10.1634/theoncologist.2011-0210

    Article  PubMed  PubMed Central  Google Scholar 

  31. Kimura K, Usui Y, Goto H, Japanese Intraocular Lymphoma Study G (2012) Clinical features and diagnostic significance of the intraocular fluid of 217 patients with intraocular lymphoma. Jpn J Ophthalmol 56:383–389. https://doi.org/10.1007/s10384-012-0150-7

    Article  Google Scholar 

  32. Tanaka R, Kaburaki T, Taoka K, Karakawa A, Tsuji H, Nishikawa M, Yatomi Y, Shinozaki-Ushiku A, Ushiku T, Araki F (2022) More accurate diagnosis of vitreoretinal lymphoma using a combination of diagnostic test results: a prospective observational study. Ocul Immunol Inflamm 30:1354–1360. https://doi.org/10.1080/09273948.2021.1873394

    Article  CAS  PubMed  Google Scholar 

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Funding

This study was supported by the National Research Foundation of Korea grant funded by the Korea government (MSIT)(RS-2023-00253065).

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Authors and Affiliations

  1. Department of Ophthalmology and Visual Science, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-Gu, Seoul, 06591, Korea

    Joo Young Kim, Jae Jung Kim, Rae Young Kim, Mirinae Kim, Young Gun Park & Young-Hoon Park

  2. Catholic Institute for Visual Science, College of Medicine, The Catholic University of Korea, Seoul, Korea

    Joo Young Kim, Rae Young Kim, Mirinae Kim, Young Gun Park & Young-Hoon Park

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  1. Joo Young Kim
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Correspondence to Young-Hoon Park.

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All procedures performed in the study involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.

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The IRB waived the requirement for informed consent because of the retrospective nature of this study.

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Kim, J.Y., Kim, J.J., Kim, R.Y. et al. Factors related to central nervous system involvement of primary vitreoretinal lymphoma. Graefes Arch Clin Exp Ophthalmol (2024). https://doi.org/10.1007/s00417-024-06434-9

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