- Department of Ophthalmology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China;
Zhang Meifen,
Email: zhangmeifen@pumch.cn
Primary vitreoretinal lymphoma (PVRL) represents the most prevalent subtype of primary intraocular lymphoma, predominantly exhibiting diffuse large B-cell lymphoma histopathology. This malignancy is characterized by poor prognosis and frequent central nervous system involvement. Current therapeutic strategies for PVRL are diverse, including local chemotherapy, systemic chemotherapy, targeted therapy, and autologous stem cell transplantation, yet marked by significant therapeutic heterogeneity and lack of standardized protocols. In recent years, clinical advancements have been achieved with local therapies (e.g., intravitreal methotrexate and rituximab and systemic treatments (e.g., Bruton's tyrosine kinase inhibitors). However, the absence of standardized treatment protocols remains a significant clinical challenge. Recent years have witnessed notable progress in both local and systemic treatment modalities. Nevertheless, existing evidence is primarily derived from small-scale retrospective studies with inherent limitations, including suboptimal study designs, therapeutic heterogeneity, and insufficient patient stratification. These constraints have hindered the establishment of evidence-based treatment consensus. Future research should focus on conducting multicenter prospective studies, establishing international collaborative networks, and implementing long-term follow-up protocols to facilitate precision medicine approaches. Concurrent exploration of novel therapeutic targets and pharmacological agents is imperative to transform PVRL management from empirical practice to evidence-based personalized medicine, ultimately improving clinical outcomes.
Copyright © the editorial department of Chinese Journal of Ocular Fundus Diseases of West China Medical Publisher. All rights reserved
| 1. | Min GJ, Kim TY, Jeon YW, et al. Diagnosis, treatment, and prognosis of primary intraocular lymphoma: single-center real-world clinical experience[J]. Cancer Med, 2023, 12(7): 7911-7922. DOI: 10.1002/cam4.5567. |
| 2. | Kang H, Tao Y. Clinical utility of cytokine analysis in the diagnosis and efficacy monitoring of vitreoretinal lymphoma[J]. Int J Ophthalmol, 2022, 15(12): 1893-1902. DOI: 10.18240/ijo.2022.12.01. |
| 3. | Cheng CL, Yeh PT, Fang WQ, et al. Long-term outcomes of combined intravitreal methotrexate and systemic high-dose methotrexate therapy in vitreoretinal lymphoma[J]. Cancer Med, 2023, 12(7): 8102-8111. DOI: 10.1002/cam4.5609. |
| 4. | Farrall AL, Smith JR. Eye involvement in primary central nervous system lymphoma[J]. Surv Ophthalmol, 2020, 65(5): 548-561. DOI: 10.1016/j.survophthal.2020.02.001. |
| 5. | International Vitreoretinal B-Cell Lymphoma Registry Investigator Group. Presentation, diagnostic testing and initial treatment of vitreoretinal lymphoma[J]. Ophthalmol Retina, 2024, 8(1): 72-80. DOI: 10.1016/j.oret.2023.08.012. |
| 6. | Jiang T, Gu J, Liu S, et al. Retinal changes of primary vitreoretinal lymphoma after intravitreal methotrexate[J/OL]. BMC Ophthalmol, 2022, 22(1): 375[2022-09-20]. https://pubmed.ncbi.nlm.nih.gov/36127675/. DOI: 10.1186/s12886-022-02604-7. |
| 7. | Riemens A, Bromberg J, Touitou V, et al. Treatment strategies in primary vitreoretinal lymphoma: a 17-center European collaborative study[J]. JAMA Ophthalmol, 2015, 133(2): 191-197. DOI: 10.1001/jamaophthalmol.2014.4755. |
| 8. | Soussain C, Malaise D, Cassoux N. Primary vitreoretinal lymphoma: a diagnostic and management challenge[J]. Blood, 2021, 138(17): 1519-1534. DOI: 10.1182/blood.2020008235. |
| 9. | Gu J, Jiang T, Liu S, et al. Longitudinal analysis of ocular manifestation and interleukin during intravitreal treatment of vitreoretinal lymphoma with methotrexate[J]. Am J Ophthalmol, 2023, 251: 189-196. DOI: 10.1016/j.ajo.2023.03.010. |
| 10. | Raja H, Snyder MR, Johnston PB, et al. Effect of intravitreal methotrexate and rituximab on interleukin-10 levels in aqueous humor of treated eyes with vitreoretinal lymphoma[J/OL]. PLoS One, 2013, 8(6): e65627[2013-06-04]. https://pubmed.ncbi.nlm.nih.gov/23750271/. DOI: 10.1371/journal.pone.0065627. |
| 11. | Jeong Y, Ryu JS, Park UC, et al. Corneal epithelial toxicity after intravitreal methotrexate injection for vitreoretinal lymphoma: clinical and in vitro studies[J/OL]. J Clin Med, 2020, 9(8): 2672[2020-08-18]. https://pubmed.ncbi.nlm.nih.gov/32824794/. DOI: 10.3390/jcm9082672. |
| 12. | de Smet MD, Vancs VS, Kohler D, et al. Intravitreal chemotherapy for the treatment of recurrent intraocular lymphoma[J]. Br J Ophthalmol, 1999, 83(4): 448-451. DOI: 10.1136/bjo.83.4.448. |
| 13. | Habot-Wilner Z, Frenkel S, Pe'er J. Efficacy and safety of intravitreal methotrexate for vitreo-retinal lymphoma-20 years of experience[J]. Br J Haematol, 2021, 194(1): 92-100. DOI: 10.1111/bjh.17451. |
| 14. | Fishburne BC, Wilson DJ, Rosenbaum JT, et al. Intravitreal methotrexate as an adjunctive treatment of intraocular lymphoma[J/OL]. Arch Ophthalmol, 1997, 115(9): 1152[1997-09-01]. https://pubmed.ncbi.nlm.nih.gov/9298056/. DOI: 10.1001/archopht.1997.01100160322009. |
| 15. | Smith JR, Rosenbaum JT, Wilson DJ, et al. Role of intravitreal methotrexate in the management of primary central nervous system lymphoma with ocular involvement[J]. Ophthalmology, 2002, 109(9): 1709-1716. DOI: 10.1016/s0161-6420(02)01125-9. |
| 16. | Zhang Y, Zhang X, Zou D, et al. Lenalidomide and Rituximab regimen combined with intravitreal methotrexate followed by lenalidomide maintenance for primary vitreoretinal lymphoma: a prospective phase II study[J/OL]. Front Oncol, 2021, 11: 701507[2021-06-24]. https://pubmed.ncbi.nlm.nih.gov/34249763/. DOI: 10.3389/fonc.2021.701507. |
| 17. | Kim RY, Park JH, Kim M, et al. Changes in choroidal vascular structure from vitreoretinal lymphoma and the intraocular cytokine level associated with clinical resolution after intravitreal methotrexate treatment[J/OL]. PLoS One, 2021, 16(11): e0260469[2021-11-23]. https://pubmed.ncbi.nlm.nih.gov/34813633/. DOI: 10.1371/journal.pone.0260469. |
| 18. | Gozzi F, Aldigeri R, Mastrofilippo V, et al. Survival and recurrence in vitreoretinal lymphoma simulating uveitis at presentation: the possible role of combined chemotherapy[J]. Ocul Immunol Inflamm, 2022, 30(7-8): 1833-1841. DOI: 10.1080/09273948.2021.1962916. |
| 19. | Jiang TT, Li RW, Liu SX, et al. The diagnosis and treatment of primary vitreoretinal lymphoma: 10 years of experience[J]. Chin J Ocul Fundus Dis, 2022, 38(5): 376-381. DOI: 10.3760/cma.j.cn511434-20220310-00126. |
| 20. | Zhou N, Xu X, Liu Y, et al. A proposed protocol of intravitreal injection of methotrexate for treatment of primary vitreoretinal lymphoma[J]. Eye (Lond), 2022, 36(7): 1448-1455. DOI: 10.1038/s41433-021-01657-0. |
| 21. | Zhou X, Zhou X, Shi H, et al. Reduced frequency of intravitreal methotrexate injection lowers the risk of keratopathy in vitreoretinal lymphoma patients[J/OL]. BMC Ophthalmol, 2020, 20(1): 189[2020-05-12]. https://pubmed.ncbi.nlm.nih.gov/32397978/. DOI: 10.1186/s12886-020-01464-3. |
| 22. | Kim H, Csaky KG, Chan CC, et al. The pharmacokinetics of rituximab following an intravitreal injection[J]. Exp Eye Res, 2006, 82(5): 760-766. DOI: 10.1016/j.exer.2005.09.018. |
| 23. | Kitzmann AS, Pulido JS, Mohney BG, et al. Intraocular use of rituximab[J]. Eye (Lond), 2007, 21(12): 1524-1527. DOI: 10.1038/sj.eye.6702804. |
| 24. | Ohguro N, Hashida N, Tano Y. Effect of intravitreous rituximab injections in patients with recurrent ocular lesions associated with central nervous system lymphoma[J]. Arch Ophthalmol, 2008, 126(7): 1002-1003. DOI: 10.1001/archopht.126.7.1002. |
| 25. | Hashida N, Ohguro N, Nishida K. Efficacy and complications of intravitreal Rituximab injection for treating primary vitreoretinal lymphoma[J/OL]. Transl Vis Sci Technol, 2012, 1(3): 1[2012-10-22]. https://pubmed.ncbi.nlm.nih.gov/24049708/. DOI: 10.1167/tvst.1.3.1. |
| 26. | Larkin KL, Saboo US, Comer GM, et al. Use of intravitreal Rituximab for treatment of vitreoretinal lymphoma[J]. Br J Ophthalmol, 2014, 98(1): 99-103. DOI: 10.1136/bjophthalmol-2013-304043. |
| 27. | Kakkassery V, Heindl LM, Rokohl AC, et al. Primary vitreoretinal lymphoma therapy monitoring: significant vitreous haze reduction after intravitreal Rituximab[J]. Neurosignals, 2021, 29(S1): 1-7. DOI: 10.33594/000000367. |
| 28. | Rishi P, Manchegowda PT, Gondhale HP, et al. Intravitreal rituximab monotherapy for management of eyes with vitreoretinal lymphoma: initial experience from India[J]. Int Ophthalmol, 2021, 41(7): 2495-2504. DOI: 10.1007/s10792-021-01805-1. |
| 29. | Pulido JS, Johnston PB, Nowakowski GS, et al. The diagnosis and treatment of primary vitreoretinal lymphoma: a review[J/OL]. Int J Retina Vitr, 2018, 4: 18[2018-05-07]. https://pubmed.ncbi.nlm.nih.gov/29760948/. DOI: 10.1186/s40942-018-0120-4. |
| 30. | Trudeau M, Shepherd FA, Blackstein ME, et al. Intraocular lymphoma: report of three cases and review of the literature[J]. Am J Clin Oncol, 1988, 11(2): 126-130. DOI: 10.1097/00000421-198804000-00008. |
| 31. | Strauchen JA, Dalton J, Friedman AH. Chemotherapy in the management of intraocular lymphoma[J]. Cancer, 1989, 63(10): 1918-1921. DOI: 10.1002/1097-0142(19890515)63:10<1918::aid-cncr2820631008>3.0.co;2-d. |
| 32. | Grimm SA, McCannel CA, Omuro AM, et al. Primary CNS lymphoma with intraocular involvement International PCNSL Collaborative Group Report[J]. Neurology, 2008, 71(17): 1355-1360. DOI: 10.1212/01.wnl.0000327672.04729.8c. |
| 33. | Stefanovic A, Davis J, Murray T, et al. Treatment of isolated primary intraocular lymphoma with high-dose methotrexate-based chemotherapy and binocular radiation therapy: a single-institution experience[J]. Br J Haematol, 2010, 151(1): 103-106. DOI: 10.1111/j.1365-2141.2010.08321.x. |
| 34. | Mikami R, Nakayama H, Goto H, et al. Preliminary results of radiotherapy for primary intraocular non-Hodgkin lymphoma[J]. Leuk Lymphoma, 2013, 54(10): 2181-2184. DOI: 10.3109/10428194.2013.769216. |
| 35. | Teckie S, Yahalom J. Primary intraocular lymphoma: treatment outcomes with ocular radiation therapy alone[J]. Leuk Lymphoma, 2014, 55(4): 795-801. DOI: 10.3109/10428194.2013.819576. |
| 36. | Milgrom SA, Cheah CY, Pinnix CC, et al. Acute and late toxicity of bilateral orbital irradiation in the management of primary intraocular lymphoma[J]. Leuk Lymphoma, 2016, 57(11): 2612-2618. DOI: 10.3109/10428194.2016.1166490. |
| 37. | Steffanoni S, Calimeri T, Marktel S, et al. Diagnosis and treatment using autologous stem-cell transplantation in primary central nervous system lymphoma: a systematic review[J/OL]. Cancers, 2023, 15(2): 526[2023-01-15]. https://pubmed.ncbi.nlm.nih.gov/36672475/. DOI: 10.3390/cancers15020526. |
| 38. | Shields CL, Sioufi K, Mashayekhi A, et al. Intravitreal melphalan for treatment of primary vitreoretinal lymphoma: a new indication for an old drug[J]. JAMA Ophthalmol, 2017, 135(7): 815-818. DOI: 10.1001/jamaophthalmol.2017.1810. |
| 39. | Damato B, Bever GJ, Kim DJ, et al. An audit of retinal lymphoma treatment at the University of California San Francisco[J]. Eye, 2020, 34(3): 515-522. DOI: 10.1038/s41433-019-0539-3. |
| 40. | Liberman P, Francis JH, Mehrotra K, et al. Clinical outcomes in vitrectomized versus non-vitrectomized eyes in patients with primary vitreoretinal lymphoma[J]. Ocul Immunol Inflamm, 2023, 31(3): 496-500. DOI: 10.1080/09273948.2022.2033794. |
| 41. | de Smet MD, Stark-Vancs V, Kohler DR, et al. Intraocular levels of methotrexate after intravenous administration[J]. Am J Ophthalmol, 1996, 121(4): 442-444. DOI: 10.1016/s0002-9394(14)70444-1. |
| 42. | Shi YH, Tao Y, Wang DS. Past, present and future of primary vitreoretinal lymphoma[J]. Chin J Ophthalmol, 2021, 11(1): 54-59. DOI: 10.3877/cma.j.issn.2095-2007.2021.01.009. |
| 43. | Hashida N, Nakai K, Saitoh N, et al. Association between ocular findings and preventive therapy with onset of central nervous system involvement in patients with primary vitreoretinal lymphoma[J]. Graefe's Arch Clin Exp Ophthalmol, 2014, 252(4): 687-693. DOI: 10.1007/s00417-014-2584-8. |
| 44. | Zhang X, Zhang Y, Zhuang Z, et al. Cerebrospinal fluid interleukin-10 biomarker for vitreoretinal lymphoma[J]. Am J Ophthalmol, 2023, 246: 242-250. DOI: 10.1016/j.ajo.2022.10.009. |
| 45. | Ferreri AJ, Blay JY, Reni M, et al. Relevance of intraocular involvement in the management of primary central nervous system lymphomas[J]. Ann Oncol, 2002, 13(4): 531-538. DOI: 10.1093/annonc/mdf080. |
| 46. | Cho BJ, Kim DY, Park UC, et al. Clinical features and treatment outcomes of vitreoretinal lymphoma according to its association with CNS lymphoma[J]. Ocul Immunol Inflamm, 2018, 26(3): 365-371. DOI: 10.1080/09273948.2017.1421669. |
| 47. | Kreher S, Strehlow F, Martus P, et al. Prognostic impact of intraocular involvement in primary CNS lymphoma: experience from the G-PCNSL-SG1 trial[J]. Ann Hematol, 2015, 94(3): 409-414. DOI: 10.1007/s00277-014-2212-z. |
| 48. | Kaburaki T, Taoka K, Matsuda J, et al. Combined intravitreal methotrexate and immunochemotherapy followed by reduced-dose whole-brain radiotherapy for newly diagnosed B-cell primary intraocular lymphoma[J]. Br J Haematol, 2017, 179(2): 246-255. DOI: 10.1111/bjh.14848. |
| 49. | Jahnke K, Wagner T, Bechrakis NE, et al. Pharmacokinetics and efficacy of ifosfamide and trofosfamide in patients with intraocular lymphoma[J]. Ann Oncol, 2005, 16(12): 1974-1978. DOI: 10.1093/annonc/mdi409. |
| 50. | Jahnke K, Thiel E, Bechrakis NE, et al. Ifosfamide or trofosfamide in patients with intraocular lymphoma[J]. J Neurooncol, 2009, 93(2): 213-217. DOI: 10.1007/s11060-008-9761-8. |
| 51. | Baron M, Belin L, Cassoux N, et al. Temozolomide is effective and well tolerated in patients with primary vitreoretinal lymphoma[J]. Blood, 2020, 135(20): 1811-1815. DOI: 10.1182/blood.2019003073. |
| 52. | Kim YR, Cho H, Kim SJ, et al. Clinical outcomes of etoposide and cytarabine as consolidation in elderly patients with primary CNS lymphoma[J/OL]. Oncologist, 2024, 29(6): e796-e802[2024-06-03]. https://pubmed.ncbi.nlm.nih.gov/38581718/. DOI: 10.1093/oncolo/oyae059. |
| 53. | Ma WL, Hou HA, Hsu YJ, et al. Clinical outcomes of primary intraocular lymphoma patients treated with front-line systemic high-dose methotrexate and intravitreal methotrexate injection[J]. Ann Hematol, 2016, 95(4): 593-601. DOI: 10.1007/s00277-015-2582-x. |
| 54. | Wilson WH, Young RM, Schmitz R, et al. Targeting B cell receptor signaling with ibrutinib in diffuse large B cell lymphoma[J]. Nat Med, 2015, 21(8): 922-926. DOI: 10.1038/nm.3884. |
| 55. | Wilson WH, Wright GW, Huang DW, et al. Effect of ibrutinib with R-CHOP chemotherapy in genetic subtypes of DLBCL[J]. Cancer Cell, 2021, 39(12): 1643-1653. DOI: 10.1016/j.ccell.2021.10.006. |
| 56. | Soussain C, Choquet S, Blonski M, et al. Ibrutinib monotherapy for relapse or refractory primary CNS lymphoma and primary vitreoretinal lymphoma: Final analysis of the phase II 'proof-of-concept' iLOC study by the Lymphoma study association (LYSA) and the French oculo-cerebral lymphoma (LOC) network[J]. Eur J Cancer, 2019, 117: 121-130. DOI: 10.1016/j.ejca.2019.05.024. |
| 57. | Wang L, Guan W, Peng X. Targeting bruton tyrosine kinase for the treatment of vitreoretinal lymphoma: report of 11 consecutive patients[J/OL]. Blood, 2021, 11: 676792[2021-03-23]. https://pubmed.ncbi.nlm.nih.gov/33968786/. DOI: 10.3389/fonc.2021.676792. |
| 58. | Chen H, Zhuang Z, Zhang X, et al. Relapses and outcomes of systemic chemo-free therapies combined with intravitreous methotrexate in isolated primary vitreoretinal lymphoma: an analysis based on two prospective cohort studies[J/OL]. Ann Hematol, 2025, 2025: E1(2025-03-24)[2025-05-26]. https://pubmed.ncbi.nlm.nih.gov/40415007/. DOI: 10.1007/s00277-025-06414-x. [published online ahead of print]. |
| 59. | Ghesquieres H, Chevrier M, Laadhari M, et al. Lenalidomide in combination with intravenous rituximab (REVRI) in relapsed/refractory primary CNS lymphoma or primary intraocular lymphoma: a multicenter prospective 'proof of concept' phase II study of the French Oculo-Cerebral lymphoma (LOC) Network and the Lymphoma Study Association (LYSA)†[J]. Ann Oncol, 2019, 30(4): 621-628. DOI: 10.1093/annonc/mdz032. |
| 60. | Seidel S, Nilius-Eliliwi V, Kowalski T, et al. High-dose chemotherapy with autologous hematopoietic stem cell transplantation in relapsed or refractory primary CNS lymphoma: a retrospective monocentric analysis of long-term outcome, prognostic factors, and toxicity[J/OL]. Cancers, 2022, 14(9): 2100[2022-04-23]. https://pubmed.ncbi.nlm.nih.gov/35565230/. DOI: 10.3390/cancers14092100. |
| 61. | Liu J, Wang H, Li X, et al. Impact of autologous stem cell transplantation on primary central nervous system lymphoma in first-line and relapse settings: a retrospective study in China[J/OL]. Ann Transpl, 2023, 28: e938467[2023-01-03]. https://pubmed.ncbi.nlm.nih.gov/36593744/. DOI: 10.12659/AOT.938467. |
| 62. | Chen T, Liu Y, Wang Y, et al. Evidence-based expert consensus on the management of primary central nervous system lymphoma in China[J]. J Hematol Oncol, 2022, 15(1): 136. DOI: 10.1186/s13045-022-01356-7. |
| 63. | Ophthalmic Tumor Expert Committee of China Anti-Cancer Association, Ophthalmology Expert Committee of China Medical Education Society. Chinese expert consensus recommendations for the diagnosis and treatment of vitreoretinal lymphoma (2024)[J]. Chin J Exp Ophthalmol, 2024, 42(3): 209-218. DOI: 10.3760/cma.j.cn115989-20231204-00195. |
| 64. | Ferreri AJM, Calimeri T, Cwynarski K, et al. Primary central nervous system lymphoma[J/OL]. Nat Rev Dis Primers, 2023, 9(1): 29[2023-07-15]. https://pubmed.ncbi.nlm.nih.gov/37322012/. DOI: 10.1038/s41572-023-00439-0. |
- 1. Min GJ, Kim TY, Jeon YW, et al. Diagnosis, treatment, and prognosis of primary intraocular lymphoma: single-center real-world clinical experience[J]. Cancer Med, 2023, 12(7): 7911-7922. DOI: 10.1002/cam4.5567.
- 2. Kang H, Tao Y. Clinical utility of cytokine analysis in the diagnosis and efficacy monitoring of vitreoretinal lymphoma[J]. Int J Ophthalmol, 2022, 15(12): 1893-1902. DOI: 10.18240/ijo.2022.12.01.
- 3. Cheng CL, Yeh PT, Fang WQ, et al. Long-term outcomes of combined intravitreal methotrexate and systemic high-dose methotrexate therapy in vitreoretinal lymphoma[J]. Cancer Med, 2023, 12(7): 8102-8111. DOI: 10.1002/cam4.5609.
- 4. Farrall AL, Smith JR. Eye involvement in primary central nervous system lymphoma[J]. Surv Ophthalmol, 2020, 65(5): 548-561. DOI: 10.1016/j.survophthal.2020.02.001.
- 5. International Vitreoretinal B-Cell Lymphoma Registry Investigator Group. Presentation, diagnostic testing and initial treatment of vitreoretinal lymphoma[J]. Ophthalmol Retina, 2024, 8(1): 72-80. DOI: 10.1016/j.oret.2023.08.012.
- 6. Jiang T, Gu J, Liu S, et al. Retinal changes of primary vitreoretinal lymphoma after intravitreal methotrexate[J/OL]. BMC Ophthalmol, 2022, 22(1): 375[2022-09-20]. https://pubmed.ncbi.nlm.nih.gov/36127675/. DOI: 10.1186/s12886-022-02604-7.
- 7. Riemens A, Bromberg J, Touitou V, et al. Treatment strategies in primary vitreoretinal lymphoma: a 17-center European collaborative study[J]. JAMA Ophthalmol, 2015, 133(2): 191-197. DOI: 10.1001/jamaophthalmol.2014.4755.
- 8. Soussain C, Malaise D, Cassoux N. Primary vitreoretinal lymphoma: a diagnostic and management challenge[J]. Blood, 2021, 138(17): 1519-1534. DOI: 10.1182/blood.2020008235.
- 9. Gu J, Jiang T, Liu S, et al. Longitudinal analysis of ocular manifestation and interleukin during intravitreal treatment of vitreoretinal lymphoma with methotrexate[J]. Am J Ophthalmol, 2023, 251: 189-196. DOI: 10.1016/j.ajo.2023.03.010.
- 10. Raja H, Snyder MR, Johnston PB, et al. Effect of intravitreal methotrexate and rituximab on interleukin-10 levels in aqueous humor of treated eyes with vitreoretinal lymphoma[J/OL]. PLoS One, 2013, 8(6): e65627[2013-06-04]. https://pubmed.ncbi.nlm.nih.gov/23750271/. DOI: 10.1371/journal.pone.0065627.
- 11. Jeong Y, Ryu JS, Park UC, et al. Corneal epithelial toxicity after intravitreal methotrexate injection for vitreoretinal lymphoma: clinical and in vitro studies[J/OL]. J Clin Med, 2020, 9(8): 2672[2020-08-18]. https://pubmed.ncbi.nlm.nih.gov/32824794/. DOI: 10.3390/jcm9082672.
- 12. de Smet MD, Vancs VS, Kohler D, et al. Intravitreal chemotherapy for the treatment of recurrent intraocular lymphoma[J]. Br J Ophthalmol, 1999, 83(4): 448-451. DOI: 10.1136/bjo.83.4.448.
- 13. Habot-Wilner Z, Frenkel S, Pe'er J. Efficacy and safety of intravitreal methotrexate for vitreo-retinal lymphoma-20 years of experience[J]. Br J Haematol, 2021, 194(1): 92-100. DOI: 10.1111/bjh.17451.
- 14. Fishburne BC, Wilson DJ, Rosenbaum JT, et al. Intravitreal methotrexate as an adjunctive treatment of intraocular lymphoma[J/OL]. Arch Ophthalmol, 1997, 115(9): 1152[1997-09-01]. https://pubmed.ncbi.nlm.nih.gov/9298056/. DOI: 10.1001/archopht.1997.01100160322009.
- 15. Smith JR, Rosenbaum JT, Wilson DJ, et al. Role of intravitreal methotrexate in the management of primary central nervous system lymphoma with ocular involvement[J]. Ophthalmology, 2002, 109(9): 1709-1716. DOI: 10.1016/s0161-6420(02)01125-9.
- 16. Zhang Y, Zhang X, Zou D, et al. Lenalidomide and Rituximab regimen combined with intravitreal methotrexate followed by lenalidomide maintenance for primary vitreoretinal lymphoma: a prospective phase II study[J/OL]. Front Oncol, 2021, 11: 701507[2021-06-24]. https://pubmed.ncbi.nlm.nih.gov/34249763/. DOI: 10.3389/fonc.2021.701507.
- 17. Kim RY, Park JH, Kim M, et al. Changes in choroidal vascular structure from vitreoretinal lymphoma and the intraocular cytokine level associated with clinical resolution after intravitreal methotrexate treatment[J/OL]. PLoS One, 2021, 16(11): e0260469[2021-11-23]. https://pubmed.ncbi.nlm.nih.gov/34813633/. DOI: 10.1371/journal.pone.0260469.
- 18. Gozzi F, Aldigeri R, Mastrofilippo V, et al. Survival and recurrence in vitreoretinal lymphoma simulating uveitis at presentation: the possible role of combined chemotherapy[J]. Ocul Immunol Inflamm, 2022, 30(7-8): 1833-1841. DOI: 10.1080/09273948.2021.1962916.
- 19. Jiang TT, Li RW, Liu SX, et al. The diagnosis and treatment of primary vitreoretinal lymphoma: 10 years of experience[J]. Chin J Ocul Fundus Dis, 2022, 38(5): 376-381. DOI: 10.3760/cma.j.cn511434-20220310-00126.
- 20. Zhou N, Xu X, Liu Y, et al. A proposed protocol of intravitreal injection of methotrexate for treatment of primary vitreoretinal lymphoma[J]. Eye (Lond), 2022, 36(7): 1448-1455. DOI: 10.1038/s41433-021-01657-0.
- 21. Zhou X, Zhou X, Shi H, et al. Reduced frequency of intravitreal methotrexate injection lowers the risk of keratopathy in vitreoretinal lymphoma patients[J/OL]. BMC Ophthalmol, 2020, 20(1): 189[2020-05-12]. https://pubmed.ncbi.nlm.nih.gov/32397978/. DOI: 10.1186/s12886-020-01464-3.
- 22. Kim H, Csaky KG, Chan CC, et al. The pharmacokinetics of rituximab following an intravitreal injection[J]. Exp Eye Res, 2006, 82(5): 760-766. DOI: 10.1016/j.exer.2005.09.018.
- 23. Kitzmann AS, Pulido JS, Mohney BG, et al. Intraocular use of rituximab[J]. Eye (Lond), 2007, 21(12): 1524-1527. DOI: 10.1038/sj.eye.6702804.
- 24. Ohguro N, Hashida N, Tano Y. Effect of intravitreous rituximab injections in patients with recurrent ocular lesions associated with central nervous system lymphoma[J]. Arch Ophthalmol, 2008, 126(7): 1002-1003. DOI: 10.1001/archopht.126.7.1002.
- 25. Hashida N, Ohguro N, Nishida K. Efficacy and complications of intravitreal Rituximab injection for treating primary vitreoretinal lymphoma[J/OL]. Transl Vis Sci Technol, 2012, 1(3): 1[2012-10-22]. https://pubmed.ncbi.nlm.nih.gov/24049708/. DOI: 10.1167/tvst.1.3.1.
- 26. Larkin KL, Saboo US, Comer GM, et al. Use of intravitreal Rituximab for treatment of vitreoretinal lymphoma[J]. Br J Ophthalmol, 2014, 98(1): 99-103. DOI: 10.1136/bjophthalmol-2013-304043.
- 27. Kakkassery V, Heindl LM, Rokohl AC, et al. Primary vitreoretinal lymphoma therapy monitoring: significant vitreous haze reduction after intravitreal Rituximab[J]. Neurosignals, 2021, 29(S1): 1-7. DOI: 10.33594/000000367.
- 28. Rishi P, Manchegowda PT, Gondhale HP, et al. Intravitreal rituximab monotherapy for management of eyes with vitreoretinal lymphoma: initial experience from India[J]. Int Ophthalmol, 2021, 41(7): 2495-2504. DOI: 10.1007/s10792-021-01805-1.
- 29. Pulido JS, Johnston PB, Nowakowski GS, et al. The diagnosis and treatment of primary vitreoretinal lymphoma: a review[J/OL]. Int J Retina Vitr, 2018, 4: 18[2018-05-07]. https://pubmed.ncbi.nlm.nih.gov/29760948/. DOI: 10.1186/s40942-018-0120-4.
- 30. Trudeau M, Shepherd FA, Blackstein ME, et al. Intraocular lymphoma: report of three cases and review of the literature[J]. Am J Clin Oncol, 1988, 11(2): 126-130. DOI: 10.1097/00000421-198804000-00008.
- 31. Strauchen JA, Dalton J, Friedman AH. Chemotherapy in the management of intraocular lymphoma[J]. Cancer, 1989, 63(10): 1918-1921. DOI: 10.1002/1097-0142(19890515)63:10<1918::aid-cncr2820631008>3.0.co;2-d.
- 32. Grimm SA, McCannel CA, Omuro AM, et al. Primary CNS lymphoma with intraocular involvement International PCNSL Collaborative Group Report[J]. Neurology, 2008, 71(17): 1355-1360. DOI: 10.1212/01.wnl.0000327672.04729.8c.
- 33. Stefanovic A, Davis J, Murray T, et al. Treatment of isolated primary intraocular lymphoma with high-dose methotrexate-based chemotherapy and binocular radiation therapy: a single-institution experience[J]. Br J Haematol, 2010, 151(1): 103-106. DOI: 10.1111/j.1365-2141.2010.08321.x.
- 34. Mikami R, Nakayama H, Goto H, et al. Preliminary results of radiotherapy for primary intraocular non-Hodgkin lymphoma[J]. Leuk Lymphoma, 2013, 54(10): 2181-2184. DOI: 10.3109/10428194.2013.769216.
- 35. Teckie S, Yahalom J. Primary intraocular lymphoma: treatment outcomes with ocular radiation therapy alone[J]. Leuk Lymphoma, 2014, 55(4): 795-801. DOI: 10.3109/10428194.2013.819576.
- 36. Milgrom SA, Cheah CY, Pinnix CC, et al. Acute and late toxicity of bilateral orbital irradiation in the management of primary intraocular lymphoma[J]. Leuk Lymphoma, 2016, 57(11): 2612-2618. DOI: 10.3109/10428194.2016.1166490.
- 37. Steffanoni S, Calimeri T, Marktel S, et al. Diagnosis and treatment using autologous stem-cell transplantation in primary central nervous system lymphoma: a systematic review[J/OL]. Cancers, 2023, 15(2): 526[2023-01-15]. https://pubmed.ncbi.nlm.nih.gov/36672475/. DOI: 10.3390/cancers15020526.
- 38. Shields CL, Sioufi K, Mashayekhi A, et al. Intravitreal melphalan for treatment of primary vitreoretinal lymphoma: a new indication for an old drug[J]. JAMA Ophthalmol, 2017, 135(7): 815-818. DOI: 10.1001/jamaophthalmol.2017.1810.
- 39. Damato B, Bever GJ, Kim DJ, et al. An audit of retinal lymphoma treatment at the University of California San Francisco[J]. Eye, 2020, 34(3): 515-522. DOI: 10.1038/s41433-019-0539-3.
- 40. Liberman P, Francis JH, Mehrotra K, et al. Clinical outcomes in vitrectomized versus non-vitrectomized eyes in patients with primary vitreoretinal lymphoma[J]. Ocul Immunol Inflamm, 2023, 31(3): 496-500. DOI: 10.1080/09273948.2022.2033794.
- 41. de Smet MD, Stark-Vancs V, Kohler DR, et al. Intraocular levels of methotrexate after intravenous administration[J]. Am J Ophthalmol, 1996, 121(4): 442-444. DOI: 10.1016/s0002-9394(14)70444-1.
- 42. Shi YH, Tao Y, Wang DS. Past, present and future of primary vitreoretinal lymphoma[J]. Chin J Ophthalmol, 2021, 11(1): 54-59. DOI: 10.3877/cma.j.issn.2095-2007.2021.01.009.
- 43. Hashida N, Nakai K, Saitoh N, et al. Association between ocular findings and preventive therapy with onset of central nervous system involvement in patients with primary vitreoretinal lymphoma[J]. Graefe's Arch Clin Exp Ophthalmol, 2014, 252(4): 687-693. DOI: 10.1007/s00417-014-2584-8.
- 44. Zhang X, Zhang Y, Zhuang Z, et al. Cerebrospinal fluid interleukin-10 biomarker for vitreoretinal lymphoma[J]. Am J Ophthalmol, 2023, 246: 242-250. DOI: 10.1016/j.ajo.2022.10.009.
- 45. Ferreri AJ, Blay JY, Reni M, et al. Relevance of intraocular involvement in the management of primary central nervous system lymphomas[J]. Ann Oncol, 2002, 13(4): 531-538. DOI: 10.1093/annonc/mdf080.
- 46. Cho BJ, Kim DY, Park UC, et al. Clinical features and treatment outcomes of vitreoretinal lymphoma according to its association with CNS lymphoma[J]. Ocul Immunol Inflamm, 2018, 26(3): 365-371. DOI: 10.1080/09273948.2017.1421669.
- 47. Kreher S, Strehlow F, Martus P, et al. Prognostic impact of intraocular involvement in primary CNS lymphoma: experience from the G-PCNSL-SG1 trial[J]. Ann Hematol, 2015, 94(3): 409-414. DOI: 10.1007/s00277-014-2212-z.
- 48. Kaburaki T, Taoka K, Matsuda J, et al. Combined intravitreal methotrexate and immunochemotherapy followed by reduced-dose whole-brain radiotherapy for newly diagnosed B-cell primary intraocular lymphoma[J]. Br J Haematol, 2017, 179(2): 246-255. DOI: 10.1111/bjh.14848.
- 49. Jahnke K, Wagner T, Bechrakis NE, et al. Pharmacokinetics and efficacy of ifosfamide and trofosfamide in patients with intraocular lymphoma[J]. Ann Oncol, 2005, 16(12): 1974-1978. DOI: 10.1093/annonc/mdi409.
- 50. Jahnke K, Thiel E, Bechrakis NE, et al. Ifosfamide or trofosfamide in patients with intraocular lymphoma[J]. J Neurooncol, 2009, 93(2): 213-217. DOI: 10.1007/s11060-008-9761-8.
- 51. Baron M, Belin L, Cassoux N, et al. Temozolomide is effective and well tolerated in patients with primary vitreoretinal lymphoma[J]. Blood, 2020, 135(20): 1811-1815. DOI: 10.1182/blood.2019003073.
- 52. Kim YR, Cho H, Kim SJ, et al. Clinical outcomes of etoposide and cytarabine as consolidation in elderly patients with primary CNS lymphoma[J/OL]. Oncologist, 2024, 29(6): e796-e802[2024-06-03]. https://pubmed.ncbi.nlm.nih.gov/38581718/. DOI: 10.1093/oncolo/oyae059.
- 53. Ma WL, Hou HA, Hsu YJ, et al. Clinical outcomes of primary intraocular lymphoma patients treated with front-line systemic high-dose methotrexate and intravitreal methotrexate injection[J]. Ann Hematol, 2016, 95(4): 593-601. DOI: 10.1007/s00277-015-2582-x.
- 54. Wilson WH, Young RM, Schmitz R, et al. Targeting B cell receptor signaling with ibrutinib in diffuse large B cell lymphoma[J]. Nat Med, 2015, 21(8): 922-926. DOI: 10.1038/nm.3884.
- 55. Wilson WH, Wright GW, Huang DW, et al. Effect of ibrutinib with R-CHOP chemotherapy in genetic subtypes of DLBCL[J]. Cancer Cell, 2021, 39(12): 1643-1653. DOI: 10.1016/j.ccell.2021.10.006.
- 56. Soussain C, Choquet S, Blonski M, et al. Ibrutinib monotherapy for relapse or refractory primary CNS lymphoma and primary vitreoretinal lymphoma: Final analysis of the phase II 'proof-of-concept' iLOC study by the Lymphoma study association (LYSA) and the French oculo-cerebral lymphoma (LOC) network[J]. Eur J Cancer, 2019, 117: 121-130. DOI: 10.1016/j.ejca.2019.05.024.
- 57. Wang L, Guan W, Peng X. Targeting bruton tyrosine kinase for the treatment of vitreoretinal lymphoma: report of 11 consecutive patients[J/OL]. Blood, 2021, 11: 676792[2021-03-23]. https://pubmed.ncbi.nlm.nih.gov/33968786/. DOI: 10.3389/fonc.2021.676792.
- 58. Chen H, Zhuang Z, Zhang X, et al. Relapses and outcomes of systemic chemo-free therapies combined with intravitreous methotrexate in isolated primary vitreoretinal lymphoma: an analysis based on two prospective cohort studies[J/OL]. Ann Hematol, 2025, 2025: E1(2025-03-24)[2025-05-26]. https://pubmed.ncbi.nlm.nih.gov/40415007/. DOI: 10.1007/s00277-025-06414-x. [published online ahead of print].
- 59. Ghesquieres H, Chevrier M, Laadhari M, et al. Lenalidomide in combination with intravenous rituximab (REVRI) in relapsed/refractory primary CNS lymphoma or primary intraocular lymphoma: a multicenter prospective 'proof of concept' phase II study of the French Oculo-Cerebral lymphoma (LOC) Network and the Lymphoma Study Association (LYSA)†[J]. Ann Oncol, 2019, 30(4): 621-628. DOI: 10.1093/annonc/mdz032.
- 60. Seidel S, Nilius-Eliliwi V, Kowalski T, et al. High-dose chemotherapy with autologous hematopoietic stem cell transplantation in relapsed or refractory primary CNS lymphoma: a retrospective monocentric analysis of long-term outcome, prognostic factors, and toxicity[J/OL]. Cancers, 2022, 14(9): 2100[2022-04-23]. https://pubmed.ncbi.nlm.nih.gov/35565230/. DOI: 10.3390/cancers14092100.
- 61. Liu J, Wang H, Li X, et al. Impact of autologous stem cell transplantation on primary central nervous system lymphoma in first-line and relapse settings: a retrospective study in China[J/OL]. Ann Transpl, 2023, 28: e938467[2023-01-03]. https://pubmed.ncbi.nlm.nih.gov/36593744/. DOI: 10.12659/AOT.938467.
- 62. Chen T, Liu Y, Wang Y, et al. Evidence-based expert consensus on the management of primary central nervous system lymphoma in China[J]. J Hematol Oncol, 2022, 15(1): 136. DOI: 10.1186/s13045-022-01356-7.
- 63. Ophthalmic Tumor Expert Committee of China Anti-Cancer Association, Ophthalmology Expert Committee of China Medical Education Society. Chinese expert consensus recommendations for the diagnosis and treatment of vitreoretinal lymphoma (2024)[J]. Chin J Exp Ophthalmol, 2024, 42(3): 209-218. DOI: 10.3760/cma.j.cn115989-20231204-00195.
- 64. Ferreri AJM, Calimeri T, Cwynarski K, et al. Primary central nervous system lymphoma[J/OL]. Nat Rev Dis Primers, 2023, 9(1): 29[2023-07-15]. https://pubmed.ncbi.nlm.nih.gov/37322012/. DOI: 10.1038/s41572-023-00439-0.