Intravitreal chemotherapy in the treatment of primary vitreoretinal lymphoma_Chinese Journal of Ocular Fundus Diseases

Authors：

Department of Ophthalmology, Shanghai Eye & ENT Hospital of Fudan University, Shanghai, 200031, China;

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Keywords：

Eye neoplasms/drug therapy; Lymphoma/drug therapy; Chemotherapy; cancer; regional perfusion; Intravitreal injections; Review

DOI：

10.3760/cma.j.issn.1005-1015.2016.06.030

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Primary vitreoretinal lymphoma (PVRL) is a rare type of non-Hodgkin's lymphoma with poor prognosis and the optimal treatment has yet to be determined. Its treatment has evolved from enucleation to ocular radiotherapy, systemic chemotherapy and intravitreal chemotherapy. Radiotherapy can effectively eradicate tumor cells but ocular recurrences are common. Systemic chemotherapy has become the mainstream option but there are problems with only-partial response of PVRL and high rate of recurrence. Intravitreal chemotherapy, primarily used as adjunctive to systemic chemotherapy, has achieved high remission rate and low rate of recurrence as well as with limited ocular complications. The tumor cells were cleared and the visual function preserved. However, issues about the drug applied, treatment protocols and goals of intravitreal chemotherapy, whether for visual preservation or survival improvement, are worthy for further study.

Citation： ChenXiuju, ChangQing. Intravitreal chemotherapy in the treatment of primary vitreoretinal lymphoma. Chinese Journal of Ocular Fundus Diseases, 2016, 32(6): 667-670. doi: 10.3760/cma.j.issn.1005-1015.2016.06.030 Copy

1.	Cummings TJ, Stenzel TT, Klintworth G, et al.Primary intraocular T-cell-rich large B-cell lymphoma[J].Arch Pathol Lab Med, 2005, 129(8):1050-1053.
2.	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.DOI:10.1634/theoncologist.2011-0210.
3.	Coupland SE, Damato B.Understanding intraocular lymphomas[J].Clin Experiment Ophthalmol, 2008, 36(6):564-578.DOI:10.1111/j.1442-9071.2008.01843.x.
4.	Nussenblatt RB, Chan CC, Wilson WH, et al.International central nervous system and ocular lymphoma workshop:recommendations for the future[J]. Ocul Immunol Inflamm, 2006, 14(3):139-144.
5.	Coupland SE.Molecular pathology of lymphoma[J].Eye (Lond), 2013, 27(2):180-189.DOI:10.1038/eye. 2012.247.
6.	Pe'er J, Hochberg FH, Foster CS. Clinical review:treatment of vitreoretinal lymphoma[J].Ocul Immunol Inflamm, 2009, 17(5):299-306. DOI:10.3109/09273940903370755.
7.	Margolis L, Fraser R, Lichter A, et al.The role of radiation therapy in the management of ocular reticulum cell sarcoma[J].Cancer, 1980, 45(4):688-692.
8.	Char DH, Margolis L, Newman AB.Ocular reticulum cell sarcoma[J].Am J Ophthalmol, 1981, 91(4):480-483.
9.	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.
10.	De Angelis LM, Yahalom J, Heinemann MH, et al.Primary CNS lymphoma:combined treatment with chemotherapy and radiotherapy[J].Neurology, 1990, 40(1):80-86.
11.	McCann KJ, Ashton-Key M, Smith K, et al.Primary central nervous system lymphoma:tumor-related clones exist in the blood and bone marrow with evidence for separate development[J].Blood, 2009, 113(19):4677-4680.
12.	Sullivan SF, Dallow RI.Intraocular reticulum cell sarcoma:its dramatic response to systemic chemotherapy and its angiogenic potential[J].Ann Ophthalmol, 1977, 9(4):401-406.
13.	Strauchen JA, Dalton J, Friedman AH.Chemotherapy in the management of intraocular lymphoma[J].Cancer, 1989, 63(10):1918-1921.
14.	Batchelor TT, Kolak G, Ciordia R, et al.High-dose methotrexate for intraocular lymphoma[J].Clin Cancer Res, 2003, 9(2):711-715.
15.	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.
16.	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.
17.	Ericson L, Karlberg B, Rosengren BH.Trials of intravitreal injections of chemotherapeutic agents in rabbits[J]. Acta Ophthalmol (Copenh), 1964, 42(4):721-726.
18.	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.
19.	Velez G, Boldt HC, Whitcup SM.Local methotrexate and dexamethasone phosphate for the treatment of recurrent primary intraocular lymphoma[J].Ophthalmic Surg Lasers, 2002, 33(4):329-333.
20.	Fishburne BC, Wilson DJ, Rosenbaum JT, et al.Intravitreal methotrexate as an adjunctive treatment of intraocular lymphoma[J].Arch Ophthalmol, 1997, 115(9):1152-1156.
21.	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.
22.	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. DOI:10.1136/bjo.2007.127928.
23.	Henson JW, Yang J, Batchelor T.Intraocular methotrexate level after high-dose intravenous infusion[J].J Clin Oncol, 1999, 17(4):1329.
24.	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.
25.	Velez G, Yuan P, Sung C, et al.Pharmacokinetics and toxicity of intravitreal chemotherapy for primary intraocular lymphoma[J].Arch Ophthalmol, 2001, 119(10):1518-1524.
26.	Palakurthi NK, Krishnamoorthy M, Augsburger JJ, et al.Investigation of kinetics of methotrexate for therapeutic treatment of intraocular lymphoma[J].Curr Eye Res, 2010, 35(12):1105-1115. DOI:10.3109/02713683.2010.513089.
27.	Seregard S, Kock E, af Trampe E.Intravitreal chemotherapy for recurrent retinoblastoma in an only eye[J].Br J Ophthalmol, 1995, 79(2):194-195.
28.	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.
29.	Pulido JS, Bakri SJ, Valyi-Nagy T, et al.Rituximab penetrates full-thickness retina in contrast to tissue plasminogen activator control[J].Retina, 2007, 27(8):1071-1073.
30.	Hashida N, Ohguro N, Nishida K.Efficacy and complications of intravitreal rituximab injection for treating primary vitreoretinal lymphoma[J].Transl Vis Sci Technol, 2012, 1(3):1.
31.	Chan CC, Wallace DJ.Intraocular lymphoma:update on diagnosis and management[J].Cancer Control, 2004, 11(5):285-295.
32.	Guex-Crosier Y, Pittet N, Herbort CP.Evaluation of laser flare-cell photometry in the appraisal and management of intraocular inflammation in uveitis[J].Ophthalmology, 1994, 101(4):728-735.
33.	Nussenblatt RB, De Smet M, Podgor M, et al.The use of the flarephotometry in the detection of cytomegalic virus retinitis in AIDS patients[J].AIDS, 1994, 8(1):135-136.
34.	Salazar-Onfray F.Interleukin-10:a cytokine used by tumors to escape immunosurveillance[J].Med Oncol, 1999, 16(2):86-94.
35.	Cassoux N, Giron A, Bodaghi B, et al.IL-10 measurement in aqueous humor for screening patients with suspicion of primary intraocular lymphoma[J].Invest Ophthalmol Vis Sci, 2007, 48(7):3253-3259.
36.	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://www.ncbi.nlm.nih.gov/pmc/articles/PMC3672178/. DOI:10.1371/journal.pone.0065627.
37.	Kuiper J, Ten Dam-van Loon N, Domanian A, et al.Correlation between measurement of IL-10 and IL-6 in paired aqueous humour and vitreous fluid in primary vitreoretinal lymphoma[J].Acta Ophthalmol, 2015, 93(8):680-681. DOI:10.1111/aos.12733.
38.	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. DOI:10.1097/ICO.0b013e3182910106.
39.	van Oterendorp C, Ness T, Illerhaus G, et al.The trabectome as treatment option in secondary glaucoma due to intraocular lymphoma[J].J Glaucoma, 2014, 23(7):482-484. DOI:10.1097/IJG.0b013e31827a0875.

1. Cummings TJ, Stenzel TT, Klintworth G, et al.Primary intraocular T-cell-rich large B-cell lymphoma[J].Arch Pathol Lab Med, 2005, 129(8):1050-1053.
2. 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.DOI:10.1634/theoncologist.2011-0210.
3. Coupland SE, Damato B.Understanding intraocular lymphomas[J].Clin Experiment Ophthalmol, 2008, 36(6):564-578.DOI:10.1111/j.1442-9071.2008.01843.x.
4. Nussenblatt RB, Chan CC, Wilson WH, et al.International central nervous system and ocular lymphoma workshop:recommendations for the future[J]. Ocul Immunol Inflamm, 2006, 14(3):139-144.
5. Coupland SE.Molecular pathology of lymphoma[J].Eye (Lond), 2013, 27(2):180-189.DOI:10.1038/eye. 2012.247.
6. Pe'er J, Hochberg FH, Foster CS. Clinical review:treatment of vitreoretinal lymphoma[J].Ocul Immunol Inflamm, 2009, 17(5):299-306. DOI:10.3109/09273940903370755.
7. Margolis L, Fraser R, Lichter A, et al.The role of radiation therapy in the management of ocular reticulum cell sarcoma[J].Cancer, 1980, 45(4):688-692.
8. Char DH, Margolis L, Newman AB.Ocular reticulum cell sarcoma[J].Am J Ophthalmol, 1981, 91(4):480-483.
9. 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.
10. De Angelis LM, Yahalom J, Heinemann MH, et al.Primary CNS lymphoma:combined treatment with chemotherapy and radiotherapy[J].Neurology, 1990, 40(1):80-86.
11. McCann KJ, Ashton-Key M, Smith K, et al.Primary central nervous system lymphoma:tumor-related clones exist in the blood and bone marrow with evidence for separate development[J].Blood, 2009, 113(19):4677-4680.
12. Sullivan SF, Dallow RI.Intraocular reticulum cell sarcoma:its dramatic response to systemic chemotherapy and its angiogenic potential[J].Ann Ophthalmol, 1977, 9(4):401-406.
13. Strauchen JA, Dalton J, Friedman AH.Chemotherapy in the management of intraocular lymphoma[J].Cancer, 1989, 63(10):1918-1921.
14. Batchelor TT, Kolak G, Ciordia R, et al.High-dose methotrexate for intraocular lymphoma[J].Clin Cancer Res, 2003, 9(2):711-715.
15. 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.
16. 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.
17. Ericson L, Karlberg B, Rosengren BH.Trials of intravitreal injections of chemotherapeutic agents in rabbits[J]. Acta Ophthalmol (Copenh), 1964, 42(4):721-726.
18. 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.
19. Velez G, Boldt HC, Whitcup SM.Local methotrexate and dexamethasone phosphate for the treatment of recurrent primary intraocular lymphoma[J].Ophthalmic Surg Lasers, 2002, 33(4):329-333.
20. Fishburne BC, Wilson DJ, Rosenbaum JT, et al.Intravitreal methotrexate as an adjunctive treatment of intraocular lymphoma[J].Arch Ophthalmol, 1997, 115(9):1152-1156.
21. 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.
22. 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. DOI:10.1136/bjo.2007.127928.
23. Henson JW, Yang J, Batchelor T.Intraocular methotrexate level after high-dose intravenous infusion[J].J Clin Oncol, 1999, 17(4):1329.
24. 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.
25. Velez G, Yuan P, Sung C, et al.Pharmacokinetics and toxicity of intravitreal chemotherapy for primary intraocular lymphoma[J].Arch Ophthalmol, 2001, 119(10):1518-1524.
26. Palakurthi NK, Krishnamoorthy M, Augsburger JJ, et al.Investigation of kinetics of methotrexate for therapeutic treatment of intraocular lymphoma[J].Curr Eye Res, 2010, 35(12):1105-1115. DOI:10.3109/02713683.2010.513089.
27. Seregard S, Kock E, af Trampe E.Intravitreal chemotherapy for recurrent retinoblastoma in an only eye[J].Br J Ophthalmol, 1995, 79(2):194-195.
28. 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.
29. Pulido JS, Bakri SJ, Valyi-Nagy T, et al.Rituximab penetrates full-thickness retina in contrast to tissue plasminogen activator control[J].Retina, 2007, 27(8):1071-1073.
30. Hashida N, Ohguro N, Nishida K.Efficacy and complications of intravitreal rituximab injection for treating primary vitreoretinal lymphoma[J].Transl Vis Sci Technol, 2012, 1(3):1.
31. Chan CC, Wallace DJ.Intraocular lymphoma:update on diagnosis and management[J].Cancer Control, 2004, 11(5):285-295.
32. Guex-Crosier Y, Pittet N, Herbort CP.Evaluation of laser flare-cell photometry in the appraisal and management of intraocular inflammation in uveitis[J].Ophthalmology, 1994, 101(4):728-735.
33. Nussenblatt RB, De Smet M, Podgor M, et al.The use of the flarephotometry in the detection of cytomegalic virus retinitis in AIDS patients[J].AIDS, 1994, 8(1):135-136.
34. Salazar-Onfray F.Interleukin-10:a cytokine used by tumors to escape immunosurveillance[J].Med Oncol, 1999, 16(2):86-94.
35. Cassoux N, Giron A, Bodaghi B, et al.IL-10 measurement in aqueous humor for screening patients with suspicion of primary intraocular lymphoma[J].Invest Ophthalmol Vis Sci, 2007, 48(7):3253-3259.
36. 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://www.ncbi.nlm.nih.gov/pmc/articles/PMC3672178/. DOI:10.1371/journal.pone.0065627.
37. Kuiper J, Ten Dam-van Loon N, Domanian A, et al.Correlation between measurement of IL-10 and IL-6 in paired aqueous humour and vitreous fluid in primary vitreoretinal lymphoma[J].Acta Ophthalmol, 2015, 93(8):680-681. DOI:10.1111/aos.12733.
38. 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. DOI:10.1097/ICO.0b013e3182910106.
39. van Oterendorp C, Ness T, Illerhaus G, et al.The trabectome as treatment option in secondary glaucoma due to intraocular lymphoma[J].J Glaucoma, 2014, 23(7):482-484. DOI:10.1097/IJG.0b013e31827a0875.

Chinese Journal of Ocular Fundus Diseases

Intravitreal chemotherapy in the treatment of primary vitreoretinal lymphoma

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