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      Recent progress in the diagnosis and treatment of primary vitreoretinal lymphoma

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      Author(s): a , a , b , *
      Publication date (Electronic):
      Journal: Taiwan Journal of Ophthalmology
      Publisher: Medknow Publications & Media Pvt Ltd
      Keywords: lymphoma, primary, retina, vitreous

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          Abstract

          Primary vitreoretinal lymphoma (PVRL) was previously termed primary intraocular lymphoma. PVRL is a potentially fatal intraocular malignancy, and 65–90% of PVRL cases eventually involve the central nervous system (CNS). The incidence of PVRL has been rising in both immunocompromised and immuno-competent populations worldwide. PVRL frequently masquerades as chronic uveitis. Advanced auxiliary examinations, such as optical coherence tomography and fundus autofluorescence have been applied in the diagnosis of PVRL. Histology and immunohistochemistry in combination with molecular tests and interleukin-10 analysis have been demonstrated as reliable in diagnosing PVRL. Despite early initiation of treatment, mortality is high with PVRL associated with CNS involvement and relapses are common. The use of systemic chemotherapy has not been proven to prevent CNS involvement; however, local therapies including intravitreal injections of methotrexate and/or rituximab and low-dose radiotherapy to the eye, has shown to be extremely effective in controlling intraocular lymphoma with encouraging results.

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          Primary vitreoretinal lymphoma: a report from an International Primary Central Nervous System Lymphoma Collaborative Group symposium.

          Nathalie Cassoux, J. Rubenstein, Sarah E Coupland … (2010)
          Primary vitreoretinal lymphoma (PVRL), also known as primary intraocular lymphoma, is a rare malignancy typically classified as a diffuse large B-cell lymphoma and most frequently develops in elderly populations. PVRL commonly masquerades as posterior uveitis and has a unique tropism for the retina and central nervous system (CNS). Over 15% of primary CNS lymphoma patients develop intraocular lymphoma, usually occurring in the retina and/or vitreous. Conversely, 65%-90% of PVRL patients develop CNS lymphoma. Consequently, PVRL is often fatal because of ultimate CNS association. Current PVRL animal models are limited and require further development. Typical clinical findings include vitreous cellular infiltration (lymphoma and inflammatory cells) and subretinal tumor infiltration as determined using dilated fundoscopy, fluorescent angiography, and optical coherent tomography. Currently, PVRL is most often diagnosed using both histology to identify lymphoma cells in the vitreous or retina and immunohistochemistry to indicate monoclonality. Additional adjuncts in diagnosing PVRL exist, including elevation of interleukin-10 levels in ocular fluids and detection of Ig(H) or T-cell receptor gene rearrangements in malignant cells. The optimal therapy for PVRL is not defined and requires the combined effort of oncologists and ophthalmologists. PVRL is sensitive to radiation therapy and exhibits high responsiveness to intravitreal methotrexate or rituximab. Although systemic chemotherapy alone can result in high response rates in patients with PVRL, there is a high relapse rate. Because of the disease rarity, international, multicenter, collaborative efforts are required to better understand the biology and pathogenesis of PVRL as well as to define both diagnostic markers and optimal therapies.
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            Intravitreal methotrexate for treating vitreoretinal lymphoma: 10 years of experience.

            S Frenkel, T Siegal, E. Shalom-Paz … (2008)
            To describe our experience in treating vitreoretinal involvement of primary central nervous system lymphoma, by intravitreal injections of methotrexate (MTX). Patients with suspected intraocular lymphoma underwent a diagnostic vitrectomy. Samples were sent for cytology, genetic evaluation and for interleukin level measurements. Treatment protocol included injection of 400 microg/0.1 ml MTX intravitreally twice weekly for 4 weeks, once weekly for 8 weeks, and then once monthly for 9 months, for a total of 25 injections. Data were collected from the patients' records and included, inter alia, response to intravitreal MTX measured by time to disappearance of vitreal cells and retinal infiltrates, changes in visual acuity, and clinical recurrence rate. In the past 10 years we have treated 44 eyes of 26 patients; seven patients had monocular involvement, and 19 binocular. Six patients were initially diagnosed as having a non-responsive uveitis, and 16 with either CNS or systemic lymphoma with later involvement of the eye. Four patients had systemic lymphoma; one of them was found to have CNS lymphoma after the ocular involvement. Three patients had T cell lymphoma, and the rest had B cell lymphoma. Clinical remission was reached after 6.4 (3.4) (2-16) injections of MTX (mean (SD) (range)), with 95% of the eyes needing 13 injections or less to be cleared of malignant cells. None of the patients had an intraocular recurrence. Among the side effects, the most common was corneal epitheliopathy, which usually appeared after the third injection and began to subside when the intervals between injections increased. Vitreoretinal involvement of lymphoma can be controlled effectively and without serious adverse reactions by intravitreal MTX injections. The treatment protocol described herein has resulted in no intraocular recurrence so far and has had bearable side effects. The accumulating clinical results bring us to propose the consideration of this protocol as a good first-line treatment option for intraocular lymphoma.
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              Clinical features and diagnostic significance of the intraocular fluid of 217 patients with intraocular lymphoma.

              Hiroshi Goto, , Yoshihiko Usui … (2012)
              Intraocular lymphoma is a rare disease with a poor prognosis. Early diagnosis and early treatment greatly influence the survival prognosis of this disease. This retrospective study aimed to clarify the clinical features of patients diagnosed with intraocular lymphoma, and the diagnostic significance of results from analysis of vitreous samples including cytology, cytokine measurements, and the IgH gene rearrangement test. We reviewed 217 patients with intraocular lymphoma diagnosed at 25 medical institutions in Japan. Together with clinical observation, cytological analysis, determination of the levels of cytokines, and/or detection of IgH gene rearrangements were conducted using vitreous fluid specimens. The results were studied in conjunction with clinical findings of intraocular lymphoma. Survival curves were estimated by use of the Kaplan-Meier method. The subjects comprised 85 men and 132 women, with a mean age at first ophthalmological examination of 63.4 years. The mean observation period was 41.3 months. During the observation period, 69 patients had onset of lymphoma in one eye and 148 had onset in both eyes. Intraocular lymphoma with involvement of the central nervous system (CNS) was most common, found in 60.8 % of the patients, whereas intraocular lymphoma without involvement of other organs was found in 28.1 % of patients. With respect to onset patterns, 82.5 % of patients developed primary ocular lesions whereas 16.1 % developed primary CNS lesions preceding intraocular lymphoma. Blurred vision and ataxia were the most common ocular and extra-ocular symptoms that prompted patients to seek medical examination. Vitreous opacification was the most common ocular finding. The detection rates of malignant cytology, IL-10/IL-6 ratio greater than 1.0, and IgH gene rearrangements in vitreous specimens were 44.5, 91.7, and 80.6 %, respectively, of patients tested. IL-10/IL-6 ratio greater than 1.0 had the highest overall detection rate, and was extremely high (≥90 %) in patients with or without vitreous opacification. The 5-year survival rate was 61.1 %. Cytokine analysis of vitreous biopsy had the highest detection rate for intraocular lymphoma. This supplementary diagnostic test should be performed frequently to confirm a diagnosis of intraocular lymphoma.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Taiwan J Ophthalmol
                Journal ID (iso-abbrev): Taiwan J Ophthalmol
                Journal ID (publisher-id): TJO
                Title: Taiwan Journal of Ophthalmology
                Publisher: Medknow Publications & Media Pvt Ltd (India )
                ISSN (Print): 2211-5056
                ISSN (Electronic): 2211-5072
                Publication date (Print): Oct-Dec 2016
                Publication date (Electronic): 27 June 2016
                Volume: 6
                Issue: 4
                Pages: 170-176
                Affiliations
                [a ] Department of Ophthalmology, Fudan University Eye and ENT Hospital, Fudan University, Shanghai, PR China
                [b ] Shanghai Key Laboratory of Visual Impairment and Restoration, Fudan University, Shanghai, PR China
                Author notes
                [* ] Corresponding author. Department of Ophthalmology, Fudan University Eye and ENT Hospital, Fudan University, 83 Fenyang Road, Shanghai, PR China. E-mail address: xugezhi@ 123456sohu.com (G. Xu).
                Article
                Publisher ID: TJO-6-170
                DOI: 10.1016/j.tjo.2016.05.002
                PMC ID: 5525622
                SO-VID: b58c4560-b271-4aa3-a9d0-793961c08f15
                Copyright © Copyright: © 2016, The Ophthalmologic Society of Taiwan
                License:

                This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                Date received : 18 January 2016
                Date revision received : 03 May 2016
                Date accepted : 10 May 2016
                Categories
                Subject: Review Article

                Keywords: lymphoma,primary,retina,vitreous
                Data availability:
                Keywords: lymphoma, primary, retina, vitreous

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