原发性眼内淋巴瘤_Chinese Journal of Ocular Fundus Diseases

Authors：

王敏 ,  张美芬

100730 中国医学科学院北京协和医学院北京协和医院眼科;

Corresponding author：

张美芬, Email: meifen_zhang@hotmail.com

Keywords：

淋巴瘤, 非霍奇金/病因学; 淋巴瘤, 非霍奇金/诊断; 淋巴瘤, 非霍奇金/治疗; 中枢神经系统肿瘤/并发症; 综述

DOI：

10.3760/cma.j.issn.1005-1015.2015.02.030

Video：

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原发性眼内淋巴瘤(PIOL)多为弥漫大B细胞淋巴瘤, 好发于中老年人, 且女性较男性更多见。其典型表现类似葡萄膜炎, 常被延误诊断。根据不同眼后节表现可将PIOL分为玻璃体型及玻璃体视网膜型。玻璃体病理检查是确立PIOL诊断的金标准, 免疫组织化学、流式细胞技术、细胞因子检测及聚合酶链反应技术在一定程度上有助于提高PIOL的诊断率。PIOL主要采用甲氨蝶呤及阿糖胞苷等药物进行全身化学治疗, 同时可辅以放射治疗及玻璃体腔注药等局部化学药物治疗。PIOL预后不佳, 初次确诊后的平均生存期为1~3年。大多数患者在确诊后2年内能发现中枢神经系统受累。中枢神经系统受累是导致患者死亡的最重要原因。

Citation： 王敏, 张美芬. 原发性眼内淋巴瘤. Chinese Journal of Ocular Fundus Diseases, 2015, 31(2): 208-211. doi: 10.3760/cma.j.issn.1005-1015.2015.02.030 Copy

1.	Sagoo MS, Mehta H, Swampillai AJ, et al. Primary intraocular lymphoma[J]. Surv Ophthalmol, 2014, 59(5):503-516.
2.	Jahnke K, Korfel A, Komm J, et al. Intraocular lymphoma 2000-2005:results of a retrospective multicentre trial[J]. Graefe's Arch Clin Exp Ophthalmol, 2006, 244(6):663-669.
3.	Freeman LN, Schachat AP, Knox DL, et al. Clinical features, laboratory investigations, and survival in ocular reticulum cell sarcoma[J]. Ophthalmology, 1987, 94(12):1631-1639.
4.	Chan CC. Molecular pathology of primary intraocular lymphoma[J]. Trans Am Ophthalmol Soc, 2003, 101:275-292.
5.	Goto H, Mochizuki M, Yamaki K, et al. Epidemiological survey of intraocular inflammation in Japan[J]. Jpn J Ophthalmol, 2007, 51(1):41-44.
6.	Davis JL. Intraocular lymphoma:a clinical perspective[J]. Eye (Lond), 2013, 27(2):153-162.
7.	Chan CC, Rubenstein JL, Coupland SE, et al. Primary vitreoretinal lymphoma:a report from an International Primary Central Nervous System Lymphoma Collaborative Group symposium[J]. Oncologist, 2011, 16(11):1589-1599.
8.	Mochizuki M, Singh AD. Epidemiology and clinical features of intraocular lymphoma[J]. Ocul Immunol Inflamm, 2009, 17(2):69-72.
9.	Harris NL, Jaffe ES, Diebold J, et al. The World Health Organization classification of neoplastic diseases of the hematopoietic and lymphoid tissues. Report of the Clinical Advisory Committee meeting, Airlie House, Virginia, November, 1997[J]. Ann Oncol, 1999, 10(12):1419-1432.
10.	Sauer TC, Meyers SM, Shen D, et al. Primary intraocular (retinal) lymphoma following ocular toxoplasmosis[J]. Retin Cases Brief Rep, 2010, 4(2):160-163.
11.	Chan CC, Shen D, Hackett JJ, et al. Expression of chemokine receptors, CXCR4 and CXCR5, and chemokines, BLC and SDF-1, in the eyes of patients with primary intraocular lymphoma[J]. Ophthalmology, 2003, 110(2):421-426.
12.	Kimura K, Usui Y, Goto H. Clinical features and diagnostic significance of the intraocular fluid of 217 patients with intraocular lymphoma[J]. Jpn J Ophthalmol, 2012, 56(4):383-389.
13.	周旻, 江睿, 张艳琼, 等.原发性眼内淋巴瘤13例[J].中华眼底病杂志, 2012, 28(3):245-248.
14.	Vollmer L. The diagnosis and management of ocular lymphoma[J]. Optom Vis Sci, 2013, 90(2):56-62.
15.	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.
16.	Aronow ME, Singh AD. The use of imaging in the diagnosis and management of intraocular lymphoma[J]. Int Ophthalmol Clin, 2012, 52(4):199-208.
17.	Fardeau C, Lee CP, Merle-Beral H, et al. Retinal fluorescein, indocyanine green angiography, and optic coherence tomography in non-Hodgkin primary intraocular lymphoma[J]. Am J Ophthalmol, 2009, 147(5):886-894.
18.	Egawa M, Mitamura Y, Hayashi Y, et al. Changes of fundus autofluorescence and spectral-domain optical coherence tomographic findings after treatment of primary intraocular lymphoma[J]. J Ophthalmic Inflamm Infect, 2014, 4(1):7.
19.	Davis JL. Diagnosis of intraocular lymphoma[J]. Ocul Immunol Inflamm, 2004, 12(1):7-16.
20.	Sen HN, Bodaghi B, Hoang PL, et al. Primary intraocular lymphoma:diagnosis and differential diagnosis[J]. Ocul Immunol Inflamm, 2009, 17(3):133-141.
21.	Hwang CS, Yeh S, Bergstrom CS. Diagnostic vitrectomy for primary intraocular lymphoma:when, why, how?[J]. Int Ophthalmol Clin, 2014, 54(2):155-171.
22.	Kanavi MR, Soheilian M, Hosseini SB, et al. 25-gauge transconjunctival diagnostic vitrectomy in suspected cases of intraocular lymphoma:a case series and review of the literature[J]. Int J Ophthalmol, 2014, 7(3):577-581.
23.	Wakefield D, Zierhut M. Intraocular lymphoma:more questions than answers[J]. Ocul Immunol Inflamm, 2009, 17(1):6-10.
24.	Coupland SE, Bechrakis NE, Anastassiou G, et al. Evaluation of vitrectomy specimens and chorioretinal biopsies in the diagnosis of primary intraocular lymphoma in patients with Masquerade syndrome[J]. Graefe's Arch Clin Exp Ophthalmol, 2003, 241(10):860-870.
25.	Chan CC, Sen HN. Current concepts in diagnosing and managing primary vitreoretinal (intraocular) lymphoma[J]. Discov Med, 2013, 15(81):93-100.
26.	Nasir S, Deangelis LM. Update on the management of primary CNS lymphoma[J]. Oncology (Williston Park), 2000, 14(2):228-234.
27.	Rodriguez EF, Sepah YJ, Jang HS, et al. Cytologic features in vitreous preparations of patients with suspicion of intraocular lymphoma[J]. Diagn Cytopathol, 2014, 42(1):37-44.
28.	Davis JL, Viciana AL, Ruiz P. Diagnosis of intraocular lymphoma by flow cytometry[J]. Am J Ophthalmol, 1997, 124(3):362-372.
29.	Wang Y, Shen D, Wang VM, et al. Molecular biomarkers for the diagnosis of primary vitreoretinal lymphoma[J]. Int J Mol Sci, 2011, 12(9):5684-5697.
30.	Davis JL, Ruiz PJ, Shah M, et al. Evaluation of the reactive T-cell infiltrate in uveitis and intraocular lymphoma with flow cytometry of vitreous fluid (an American Ophthalmological Society thesis)[J]. Trans Am Ophthalmol Soc, 2012, 110(12):117-129.
31.	Ohta K, Sano K, Imai H, et al. Cytokine and molecular analyses of intraocular lymphoma[J]. Ocul Immunol Inflamm, 2009, 17(3):142-147.
32.	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):65627[2013-06-04].http://dx.plos.org/10.1371/journal.pone.0065627..
33.	Chan CC, Buggage RR, Nussenblatt RB. Intraocular lymphoma[J]. Curr Opin Ophthalmol, 2002, 13(6):411-418.
34.	Teckie S, Yahalom J. Primary intraocular lymphoma:treatment outcomes with ocular radiation therapy alone[J]. Leuk Lymphoma, 2014, 55(4):795-801.
35.	Rajagopal R, Harbour JW. Diagnostic testing and treatment choices in primary vitreoretinal lymphoma[J]. Retina, 2011, 31(3):435-440.
36.	Pe'Er J, Hochberg FH, Foster CS. Clinical review:treatment of vitreoretinal lymphoma[J]. Ocul Immunol Inflamm, 2009, 17(5):299-306.
37.	Berenbom A, Davila RM, Lin HS, et al. Treatment outcomes for primary intraocular lymphoma:implications for external beam radiotherapy[J]. Eye (Lond), 2007, 21(9):1198-1201.
38.	Soussain C, Choquet S, Fourme E, et al. Intensive chemotherapy with thiotepa, busulfan and cyclophosphamide and hematopoietic stem cell rescue in relapsed or refractory primary central nervous system lymphoma and intraocular lymphoma:a retrospective study of 79 cases[J]. Haematologica, 2012, 97(11):1751-1756.
39.	Mason JO, Fischer DH. Intrathecal chemotherapy for recurrent central nervous system intraocular lymphoma[J]. Ophthalmology, 2003, 110(6):1241-1244.
40.	Itty S, Olson JH, O'Connell DJ, et al. Treatment of primary intraocular lymphoma (PIOL) has involved systemic, intravitreal or intrathecal chemotherapy and/or radiotherapy[J]. Retina, 2009, 29(3):415-416.
41.	Frenkel S, Hendler K, Siegal T, et al. Intravitreal methotrexate for treating vitreoretinal lymphoma:10 years of experience[J]. Br J Ophthalmol, 2008, 92(3):383-388.
42.	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.
43.	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.
44.	Gorovoy I, Prechanond T, Abia M, et al. Toxic corneal epitheliopathy after intravitreal methotrexate and its treatment with oral folic acid[J]. Cornea, 2013, 32(8):1171-1173.
45.	Manna S, Augsburger JJ, Correa ZM, et al. Development of chitosan and polylactic acid based methotrexate intravitreal micro-implants to treat primary intraocular lymphoma:an in vitro study[J/OL]. J Biomech Eng, 2014, 136(2):21018[2014-02-05].http://biomechanical.asmedigitalcollection.asme.org/article.aspx?articleid=1789067..
46.	Siegal T. Primary central nervous system. lymphoma:current state of anti-CD20 therapy and appraisal of reported response criteria[J]. J Clin Neurosci, 2014, 21(5):709-715.
47.	Soussain C, Suzan F, Hoang-Xuan K, et al. Results of intensive chemotherapy followed by hematopoietic stem-cell rescue in 22 patients with refractory or recurrent primary CNS lymphoma or intraocular lymphoma[J]. J Clin Oncol, 2001, 19(3):742-749.
48.	Li Z, Mahesh SP, Shen DF, et al.Eradication of tumor colonization and invasion by a B cell-specific immunotoxin in a murine model for human primary intraocular lymphoma[J]. Cancer Res, 2006, 66(21):10586-10593.
49.	Deangelis LM, Yahalom J, Thaler HT, et al. Combined modality therapy for primary CNS lymphoma[J]. J Clin Oncol, 1992, 10(4):635-643.

1. Sagoo MS, Mehta H, Swampillai AJ, et al. Primary intraocular lymphoma[J]. Surv Ophthalmol, 2014, 59(5):503-516.
2. Jahnke K, Korfel A, Komm J, et al. Intraocular lymphoma 2000-2005:results of a retrospective multicentre trial[J]. Graefe's Arch Clin Exp Ophthalmol, 2006, 244(6):663-669.
3. Freeman LN, Schachat AP, Knox DL, et al. Clinical features, laboratory investigations, and survival in ocular reticulum cell sarcoma[J]. Ophthalmology, 1987, 94(12):1631-1639.
4. Chan CC. Molecular pathology of primary intraocular lymphoma[J]. Trans Am Ophthalmol Soc, 2003, 101:275-292.
5. Goto H, Mochizuki M, Yamaki K, et al. Epidemiological survey of intraocular inflammation in Japan[J]. Jpn J Ophthalmol, 2007, 51(1):41-44.
6. Davis JL. Intraocular lymphoma:a clinical perspective[J]. Eye (Lond), 2013, 27(2):153-162.
7. Chan CC, Rubenstein JL, Coupland SE, et al. Primary vitreoretinal lymphoma:a report from an International Primary Central Nervous System Lymphoma Collaborative Group symposium[J]. Oncologist, 2011, 16(11):1589-1599.
8. Mochizuki M, Singh AD. Epidemiology and clinical features of intraocular lymphoma[J]. Ocul Immunol Inflamm, 2009, 17(2):69-72.
9. Harris NL, Jaffe ES, Diebold J, et al. The World Health Organization classification of neoplastic diseases of the hematopoietic and lymphoid tissues. Report of the Clinical Advisory Committee meeting, Airlie House, Virginia, November, 1997[J]. Ann Oncol, 1999, 10(12):1419-1432.
10. Sauer TC, Meyers SM, Shen D, et al. Primary intraocular (retinal) lymphoma following ocular toxoplasmosis[J]. Retin Cases Brief Rep, 2010, 4(2):160-163.
11. Chan CC, Shen D, Hackett JJ, et al. Expression of chemokine receptors, CXCR4 and CXCR5, and chemokines, BLC and SDF-1, in the eyes of patients with primary intraocular lymphoma[J]. Ophthalmology, 2003, 110(2):421-426.
12. Kimura K, Usui Y, Goto H. Clinical features and diagnostic significance of the intraocular fluid of 217 patients with intraocular lymphoma[J]. Jpn J Ophthalmol, 2012, 56(4):383-389.
13. 周旻, 江睿, 张艳琼, 等.原发性眼内淋巴瘤13例[J].中华眼底病杂志, 2012, 28(3):245-248.
14. Vollmer L. The diagnosis and management of ocular lymphoma[J]. Optom Vis Sci, 2013, 90(2):56-62.
15. 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.
16. Aronow ME, Singh AD. The use of imaging in the diagnosis and management of intraocular lymphoma[J]. Int Ophthalmol Clin, 2012, 52(4):199-208.
17. Fardeau C, Lee CP, Merle-Beral H, et al. Retinal fluorescein, indocyanine green angiography, and optic coherence tomography in non-Hodgkin primary intraocular lymphoma[J]. Am J Ophthalmol, 2009, 147(5):886-894.
18. Egawa M, Mitamura Y, Hayashi Y, et al. Changes of fundus autofluorescence and spectral-domain optical coherence tomographic findings after treatment of primary intraocular lymphoma[J]. J Ophthalmic Inflamm Infect, 2014, 4(1):7.
19. Davis JL. Diagnosis of intraocular lymphoma[J]. Ocul Immunol Inflamm, 2004, 12(1):7-16.
20. Sen HN, Bodaghi B, Hoang PL, et al. Primary intraocular lymphoma:diagnosis and differential diagnosis[J]. Ocul Immunol Inflamm, 2009, 17(3):133-141.
21. Hwang CS, Yeh S, Bergstrom CS. Diagnostic vitrectomy for primary intraocular lymphoma:when, why, how?[J]. Int Ophthalmol Clin, 2014, 54(2):155-171.
22. Kanavi MR, Soheilian M, Hosseini SB, et al. 25-gauge transconjunctival diagnostic vitrectomy in suspected cases of intraocular lymphoma:a case series and review of the literature[J]. Int J Ophthalmol, 2014, 7(3):577-581.
23. Wakefield D, Zierhut M. Intraocular lymphoma:more questions than answers[J]. Ocul Immunol Inflamm, 2009, 17(1):6-10.
24. Coupland SE, Bechrakis NE, Anastassiou G, et al. Evaluation of vitrectomy specimens and chorioretinal biopsies in the diagnosis of primary intraocular lymphoma in patients with Masquerade syndrome[J]. Graefe's Arch Clin Exp Ophthalmol, 2003, 241(10):860-870.
25. Chan CC, Sen HN. Current concepts in diagnosing and managing primary vitreoretinal (intraocular) lymphoma[J]. Discov Med, 2013, 15(81):93-100.
26. Nasir S, Deangelis LM. Update on the management of primary CNS lymphoma[J]. Oncology (Williston Park), 2000, 14(2):228-234.
27. Rodriguez EF, Sepah YJ, Jang HS, et al. Cytologic features in vitreous preparations of patients with suspicion of intraocular lymphoma[J]. Diagn Cytopathol, 2014, 42(1):37-44.
28. Davis JL, Viciana AL, Ruiz P. Diagnosis of intraocular lymphoma by flow cytometry[J]. Am J Ophthalmol, 1997, 124(3):362-372.
29. Wang Y, Shen D, Wang VM, et al. Molecular biomarkers for the diagnosis of primary vitreoretinal lymphoma[J]. Int J Mol Sci, 2011, 12(9):5684-5697.
30. Davis JL, Ruiz PJ, Shah M, et al. Evaluation of the reactive T-cell infiltrate in uveitis and intraocular lymphoma with flow cytometry of vitreous fluid (an American Ophthalmological Society thesis)[J]. Trans Am Ophthalmol Soc, 2012, 110(12):117-129.
31. Ohta K, Sano K, Imai H, et al. Cytokine and molecular analyses of intraocular lymphoma[J]. Ocul Immunol Inflamm, 2009, 17(3):142-147.
32. 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):65627[2013-06-04].http://dx.plos.org/10.1371/journal.pone.0065627..
33. Chan CC, Buggage RR, Nussenblatt RB. Intraocular lymphoma[J]. Curr Opin Ophthalmol, 2002, 13(6):411-418.
34. Teckie S, Yahalom J. Primary intraocular lymphoma:treatment outcomes with ocular radiation therapy alone[J]. Leuk Lymphoma, 2014, 55(4):795-801.
35. Rajagopal R, Harbour JW. Diagnostic testing and treatment choices in primary vitreoretinal lymphoma[J]. Retina, 2011, 31(3):435-440.
36. Pe'Er J, Hochberg FH, Foster CS. Clinical review:treatment of vitreoretinal lymphoma[J]. Ocul Immunol Inflamm, 2009, 17(5):299-306.
37. Berenbom A, Davila RM, Lin HS, et al. Treatment outcomes for primary intraocular lymphoma:implications for external beam radiotherapy[J]. Eye (Lond), 2007, 21(9):1198-1201.
38. Soussain C, Choquet S, Fourme E, et al. Intensive chemotherapy with thiotepa, busulfan and cyclophosphamide and hematopoietic stem cell rescue in relapsed or refractory primary central nervous system lymphoma and intraocular lymphoma:a retrospective study of 79 cases[J]. Haematologica, 2012, 97(11):1751-1756.
39. Mason JO, Fischer DH. Intrathecal chemotherapy for recurrent central nervous system intraocular lymphoma[J]. Ophthalmology, 2003, 110(6):1241-1244.
40. Itty S, Olson JH, O'Connell DJ, et al. Treatment of primary intraocular lymphoma (PIOL) has involved systemic, intravitreal or intrathecal chemotherapy and/or radiotherapy[J]. Retina, 2009, 29(3):415-416.
41. Frenkel S, Hendler K, Siegal T, et al. Intravitreal methotrexate for treating vitreoretinal lymphoma:10 years of experience[J]. Br J Ophthalmol, 2008, 92(3):383-388.
42. 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.
43. 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.
44. Gorovoy I, Prechanond T, Abia M, et al. Toxic corneal epitheliopathy after intravitreal methotrexate and its treatment with oral folic acid[J]. Cornea, 2013, 32(8):1171-1173.
45. Manna S, Augsburger JJ, Correa ZM, et al. Development of chitosan and polylactic acid based methotrexate intravitreal micro-implants to treat primary intraocular lymphoma:an in vitro study[J/OL]. J Biomech Eng, 2014, 136(2):21018[2014-02-05].http://biomechanical.asmedigitalcollection.asme.org/article.aspx?articleid=1789067..
46. Siegal T. Primary central nervous system. lymphoma:current state of anti-CD20 therapy and appraisal of reported response criteria[J]. J Clin Neurosci, 2014, 21(5):709-715.
47. Soussain C, Suzan F, Hoang-Xuan K, et al. Results of intensive chemotherapy followed by hematopoietic stem-cell rescue in 22 patients with refractory or recurrent primary CNS lymphoma or intraocular lymphoma[J]. J Clin Oncol, 2001, 19(3):742-749.
48. Li Z, Mahesh SP, Shen DF, et al.Eradication of tumor colonization and invasion by a B cell-specific immunotoxin in a murine model for human primary intraocular lymphoma[J]. Cancer Res, 2006, 66(21):10586-10593.
49. Deangelis LM, Yahalom J, Thaler HT, et al. Combined modality therapy for primary CNS lymphoma[J]. J Clin Oncol, 1992, 10(4):635-643.

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原发性眼内淋巴瘤

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