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Intralesional Rituximab for Primary Iris Lymphoma

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Intralesional Rituximab for Primary Iris Lymphoma Letters Laboratories, Allergan, Inspire, Ista Pharmaceuticals, and LUX Biosciences; injection, the tumor shrank and completely disappeared on and having stock or stock options in Eyegate. No other disclosures were slitlamp, gonioscopic, and ultrasonographic biomicroscopic reported. examinations by 5 months (Figure, G-I). There were no ante- 1. Teichmann L. Das Saugader System. Leipzig, Germany: Engelmann; 1861:1-121. rior segment toxic effects or recurrence 8 months after the 2. Busacca A. Les vaisseaux lymphatiques de la conjonctive bulbaire humaine last injection and no evidence of systemic lymphoma based étudiés par la méthode des injections vitales de bleutripan. Arch d’opht. 1948; 8:10. on examination and fludeoxyglucose F 18 positron emission 3. Nakao S, Hafezi-Moghadam A, Ishibashi T. Lymphatics and tomography. lymphangiogenesis in the eye. J Ophthalmol. 2012;2012:783163. 4. Mihara M, Hara H, Araki J, et al. Indocyanine green (ICG) lymphography is Discussion | Intralesional rituximab injection is used success- superior to lymphoscintigraphy for diagnostic imaging of early lymphedema of fully to treat ocular lymphomas. Savino et al4 described 7 pa- the upper limbs. PLoS One. 2012;7(6):e38182. tients with adnexal MALT lymphomas, treated with 4 weekly 5. Rayes A, Oréfice F, Rocha H. Distribuição da rede linfática da conjuntiva bulbar humana normal, estudada através de injeções conjuntivais de azul de injections and followed up for more than 1 year, who had com- tripan a 1%. Arq Bras Oftalmol. 1980;43(5):188-200. plete remission (4 patients [57%]), partial response (2 pa- 6. Singh D. Conjunctival lymphatic system. J Cataract Refract Surg. 2003;29(4): tients [29%]), or no response (1 patient [14%]); the disease re- 632-633. mained stable for 4 years in the patients with partial responses. Ferrerietal5 reported complete responses to rituximab injec- OBSERVATION tions for 2 of 3 conjunctival MALT lymphomas, without ad- verse effects. Intralesional Rituximab for Primary Iris Lymphoma We found intralesional rituximab to be an effective treat- Primary B-cell mucosa-associated lymphoid tissue (MALT) ment for primary iris lymphoma, but long-term effective- lymphoma of the iris is rare. The largest published series of 14 ness is unknown. Reduced effectiveness might occur for iris lymphomas included 3 such lymphomas.1 Thus, data con- high-grade lymphomas or those with ciliary body and cho- cerning the effectiveness of treatment of these tumors are lim- roidal involvement. Potential complications of intralesional ited. External radiotherapy (the main treatment), resection, and injection are hyphema, cataract, increased intraocular pres- systemic chemotherapy can cause substantial morbidity. Ri- sure, dispersion of tumor cells, and corneal toxic effects. Our tuximab monoclonal antibody, targeting CD20 on B cells, has case was diagnosed using fine-needle aspiration biopsy, been used systemically and intralesionally to treat orbital and which has not been shown to increase the risk of seeding or primary intraocular lymphomas and ocular inflammatory metastasis.1 diseases.2,3 To our knowledge, we report the first case of pri- We used the same dose and frequency of rituximab as used mary iris MALT lymphoma treated with intralesional ritux- for primary intraocular lymphoma. Pharmacokinetics in rab- imab injection. bits show that rituximab’s half-life is 4.7 days in the vitreous and 5.3 days in the aqueous humor after an intravitreal injec- Report of a Case | A man in his late 60s presented for evalua- tion, indicating that at least 10 μg remains in the eye 30 days tion of a right iris lesion that had been noted during routine after a 1-mg injection,6 with the actual amount being even examination. Visual acuity was 20/25 OU. Slitlamp examina- greater in eyes with B-cell lymphoma that sequesters the an- tion showed a 10×9×3.5-mm, well-delineated, bilobed, tibody by antigen binding. Because rituximab preferentially vascularized, tan, peripheral iris nodule between the 3- and binds to malignant B cells expressing CD20 antigen, it is pos- 6-o’clock positions (Figure, A). There were episcleral sentinel sible that simple rituximab injection into the vitreous or aque- vessels and anterior chamber angle involvement but no ous humor may be as effective as intralesional treatment for visible iris seeding or aqueous cells (Figure, B). The eye B-cell lymphoma. was pseudophakic. Ciliary body involvement was seen on ultrasonographic biomicroscopy (Figure, C). Fine-needle Hakan Demirci, MD aspiration biopsy showed a monomorphic population of Joshua S. Grant, MD + small to medium-sized hyperchromatic, CD20 lymphocytes Victor M. Elner, MD, PhD of MALT lymphoma (Figure, D and E). Few CD3+, reactive T lymphocytes were present (Figure, F). Systemic evaluation Author Affiliations: Department of Ophthalmology and Visual Sciences, W. K. showed no other involvement. The tumor was staged as Kellogg Eye Center, University of Michigan, Ann Arbor. T2N0M0. Corresponding Author: Hakan Demirci, MD, Department of Ophthalmology Treatment options of external radiotherapy, brachy- and Visual Sciences, W. K. Kellogg Eye Center, University of Michigan, 1000 Wall therapy, and excision were discussed, but the patient elected St, Ann Arbor, MI 48105 ([email protected]). intralesional rituximab based on successful treatments of Published Online: September 11, 2014. primary intraocular and orbital lymphomas with rituximab doi:10.1001/jamaophthalmol.2014.3303. injections. Using a 32-gauge needle, an anterior chamber tap Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were was performed to release 0.05 mL of aqueous humor. Using reported. another 32-gauge needle, 0.1 mL of rituximab (1 mg/0.1 mL) Funding/Support: This work was supported by a donation from Mrs and Mr was injected into the tumor through the cornea infratempo- Witham. rally under slitlamp visualization. In total, 3 injections, Role of the Sponsor: The funder had no role in the design and conduct of the repeated monthly, were performed. Beginning with the first study; collection, management, analysis, and interpretation of the data; 104 JAMA Ophthalmology January 2015 Volume 133, Number 1 jamaophthalmology.com Copyright 2014 American Medical Association. All rights reserved. Downloaded From: http://archopht.jamanetwork.com/ by Sociedad Mexicana de Oftalmologia on 02/11/2015 Letters Figure. Iris Lymphoma of the Right Eye Before and After Therapy A B C D E F A, Well-delineated, bilobed, vascularized, tan iris lesion. B, Anterior chamber angle involvement on gonioscopy. C, Ciliary body involvement on ultrasonographic biomicroscopy. D, Aspiration biopsy showing neoplastic medium-sized lymphocytes with hyperchromatic nuclei containing prominent nucleoli that contrast with small, reactive lymphocytes (hematoxylin-eosin, original magnification ×60). E, Numerous cells are CD20+ neoplastic B lymphocytes (immunohistochemistry, original G H I magnification ×60). F, Few cells are reactive CD3+ T lymphocytes (immunohistochemistry, original magnification ×60). G, After 3 monthly intralesional rituximab injections, the tumor disappeared completely. H, The anterior chamber angle was free of tumor. I, No tumor was found on ultrasonographic biomicroscopy. preparation, review, or approval of the manuscript; and decision to submit Conjunctival Pseudotumor Caused the manuscript for publication. by Herpes Simplex Virus Infection 1. Mashayekhi A, Shields CL, Shields JA. Iris involvement by A conjunctival mass in a patient with human immunodefi- lymphoma: a review of 13 cases. Clin Experiment Ophthalmol. 2013;41(1): 19-26. ciency virus (HIV) can have a long differential diagnosis, rang- 2. Larkin KL, Saboo US, Comer GM, et al. Use of intravitreal rituximab for ing from opportunistic infections to malignant neoplasms. Given treatment of vitreoretinal lymphoma. Br J Ophthalmol. 2014;98(1): that patients in this population may have atypical presenta- 99-103. tions, the benefit of invasive biopsy often outweighs surgical 3. Laurenti L, De Padua L, Battendieri R, et al. Intralesional administration of risk and can help guide treatment. We report 2 cases of pa- rituximab for treatment of CD20 positive orbital lymphoma: safety and tients referred to our ocular oncology services with herpetic con- efficacy evaluation. Leuk Res. 2011;35(5):682-684. junctivitis that masqueraded as conjunctival tumors. 4. Savino G, Battendieri R, Gari M, Caputo CG, Laurenti L, Blasi MA. Long-term outcomes of primary ocular adnexal lymphoma treatment with intraorbital rituximab injections. J Cancer Res Clin Oncol. 2013;139(7): Report of Cases |Case 1. A man in his early 50s with a history of her- 1251-1255. pes simplex virus (HSV) keratouveitis presented with increasing 5. Ferreri AJ, Govi S, Colucci A, Crocchiolo R, Modorati G. Intralesional left eye pain for 2 months. His medical history was significant for rituximab: a new therapeutic approach for patients with conjunctival HIV (CD4 lymphocyte count, 525/μL [to convert to ×109 per liter, lymphomas. Ophthalmology. 2011;118(1):24-28. multiply by 0.001]; viral load undetectable) and hepatitis C. On 6. Kim H, Csaky KG, Chan CC, et al. The pharmacokinetics of rituximab following an intravitreal injection. Exp Eye Res. 2006;82(5): examination, a fleshy yellow conjunctival lesion with subconjunc- 760-766. tival hemorrhage was noted (Figure 1A), with a follicular reaction jamaophthalmology.com JAMA Ophthalmology January 2015 Volume 133, Number 1 105 Copyright 2014 American Medical Association. All rights reserved. Downloaded From: http://archopht.jamanetwork.com/ by Sociedad Mexicana de Oftalmologia on 02/11/2015.
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