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Year : 2015  |  Volume : 11  |  Issue : 3  |  Page : 668

Therapeutic vitrectomy for vitreal recurrence of intraocular lymphoma resistant to intravitreal methotrexate post systemic chemotherapy

1 Department of Ophthalmology, Dr. Rajendra Prasad Centre for Ophthalmic Sciences, New Delhi, India
2 Department of Medical Oncology, Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, India

Date of Web Publication9-Oct-2015

Correspondence Address:
Varun Gogia
Retina and Uvea Services, Dr. Rajendra Prasad Centre, All India Institute of Medical Sciences, New Delhi
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0973-1482.140824

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 > Abstract 

A 49-year-old female with biopsy proven primary vitreoretinal lymphoma and primary central nervous system lymphoma (PCNSL) presented with asymmetric involvement of both eyes. Right eye had primarily retinal and optic nerve involvement with no light perception while the left eye had purely vitreal form of the disease with visual acuity of 6/18. She was treated with recommended DeAngelis protocol for PCNSL and achieved complete remission of CNS disease and in the right eye and responded only partially to the systemic chemotherapy in the left eye. She received multiple intravitreal methotrexate injections (400 ∝g/0.1 ml) for persisting disease in the left eye. However, she developed resistance to the same after repeated injections for which therapeutic vitrectomy was performed. She achieved final visual acuity of 6/12 in the right eye and 6/18 in the left eye and did not relapse until last follow-up of 2 years.

Keywords: Intraocular lymphoma, intravitreal methotrexate, vitrectomy

How to cite this article:
Venkatesh P, Gogia V, Khanduja S, Gupta S, Kumar L, Garg S. Therapeutic vitrectomy for vitreal recurrence of intraocular lymphoma resistant to intravitreal methotrexate post systemic chemotherapy. J Can Res Ther 2015;11:668

How to cite this URL:
Venkatesh P, Gogia V, Khanduja S, Gupta S, Kumar L, Garg S. Therapeutic vitrectomy for vitreal recurrence of intraocular lymphoma resistant to intravitreal methotrexate post systemic chemotherapy. J Can Res Ther [serial online] 2015 [cited 2020 Jul 16];11:668. Available from: http://www.cancerjournal.net/text.asp?2015/11/3/668/140824

 > Introduction Top

Primary vitreoretinal lymphoma (PVRL) is the most common ocular masquerade syndrome. [1] It is rare non-Hodgkin lymphoma and subtype of primary central nervous system lymphoma (PCNSL). [1] Vitritis, sub retinal and sub retinal pigment epithelial yellowish infiltrates are most common presenting signs. We report a case of PVRL with PCNSL who presented with asymmetric involvement in both eyes and each eye responded to different management strategies. To the best of our knowledge, this is also the first report to highlight the management of intraocular lymphoma by therapeutic vitrectomy.

 > Case report Top

A 49-year-old female patient was referred with diagnosis of biopsy proven primary intraocular lymphoma. She also had a history of behavior and cognition dysfunction, loss of appetite, weight loss and right side facial palsy and hemiparesis. Her best corrected visual acuity was no light perception and 6/18 in right and left eye respectively. Ocular adnexa, ocular motility and anterior segment examination in both eyes was normal but for retrolental cells and membranes in the left eye. Fundus examination of the right eye revealed marked blurring of disc margins and areas with subretinal creamy infiltrates [Figure 1]a. There was also a scar from previous subretinal biopsy undertaken at another center. Left eye had Grade 2 media haze with no retinal or disc involvement [Figure 1]b. Fluorescein angiography revealed disc leakage along with venous beading along inferior arcades in the right eye and with no retinal or disc involvement in the left eye [Figure 1]c and d. Neurological examination revealed right upper motor neuron facial palsy and increased tone in right upper limb and lower limb.
Figure 1: Fundus photograph of the right eye (a) shows optic disc infiltration and sub retinal infiltration with vascular changes while that of the left eye (b) shows significant vitreous membranes and no involvement of the optic disc, sub retinal space and retinal vessels. (c and d) The above features are highlighted in the corresponding fluorescein angiographic images. (e and f) Show complete resolution of the optic nerve and retinochoroidal involvement in the right eye and of vitreous membranes in the left eye respectively

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Brain magnetic resonance imaging showed multiple, nonenhancing, focal and confluent areas of T2-weighted/fluid-attenuated inversion recovery hyper-intense lesions in bilateral periventricular and sub-cortical white matter, left thalamocapsular region and left cerebral peduncle. Cerebrospinal fluid cytology showed clusters of lymphoid cells with high nuclear-cytoplasmic ratio and were CD3+, CD22−. Blood count, chemistry, serum lactate dehydrogenase, antinuclear antibodies were within normal limits and serology for HIV was negative. Computed tomography of chest, abdomen and pelvis and bone marrow biopsy were negative for involvement by lymphoma. A clinical diagnosis of PVRL with PCNSL was made, and the patient was treated with recommended DeAngelis et al. protocol. [2]

Following treatment with above protocol, there was complete resolution of the CNS as well as intraocular involvement in both eyes [Figure 1]e and f. At 3 months of follow-up, right eye showed complete remission and the visual acuity had improved to 6/18. In the left eye, however, severe recurrence was noted with the formation of extensive vitreous membranes that reduced the vision to 3/60 [Figure 2]a with no retinochoroidal involvement and absence of any signs of intraocular inflammation. Fluorescein angiography also confirmed any inflammatory component to recurrence of vitreal haze with the absence of cystoid macular edema and any paravascular or disk leak. As there was only vitreal recurrence in the left eye we decided to treat this with intravitreal methotrexate (MTX) injections. She received nine intravitreal MTX injections (400 μg/0.1 ml) depending on activity (based on vitreous haze) over 15 months. With this treatment, patient was in clinical remission with no disease activity in both eyes after 18 months of initial presentation [Figure 2]b. Three months after her 9 th injection of intravitreal MTX, she again developed vitreal relapse in the left eye. Despite two further intravitreal injections of MTX, no significant resolution of the vitreous membranes was noted [Figure 2]c. We related lack of response to be possibly being an indication of resistance to MTX and so performed a complete therapeutic vitrectomy using 23-gauge vitrectomy system. After 2 years of vitrectomy, no relapse has been observed [Figure 2]d and patient maintains visual acuity of 6/18 and 6/12 in right and left eye, respectively.
Figure 2: (a) Severe relapse of vitreous membranes in the left eye 3 months after systemic therapy. (b) Partial resolution following the third intravitreal methotrexate (MTX) injection. (c) Shows fundus appearance immediately prior to vitrectomy (as a manifestation of relapse of vitreal lymphoma and resistance to further MTX injections). (d) Shows clear media and absence of any vitreous relapse following therapeutic vitrectomy

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 > Discussion Top

Primary vitreoretinal lymphoma typically presents as posterior uveitis with nonspecific findings of vitreous debris, optic nerve infiltration, subretinal infiltration, elevated chorioretinal lesions and retinal detachment. [3] It is usually bilateral, and CNS is involved in 56-85% of cases. [4],[5] So far, there are three main treatment options for PVRL; systemic high-dose MTX injection, orbital irradiation, and intravitreal chemotherapy with MTX injections. [6],[7]

Our patient had bilateral but asymmetric involvement with retinal and optic nerve involvement in the right eye and only vitreal involvement in the left eye. She received standard management for PCNSL including systemic chemotherapy and cranial irradiation (excluding the eye fields). Initial response was noted in both eyes; however, right eye with predominant retinal disease resolved completely and left eye continued showing activity. This highlighted the fact that retinal and optic nerve involvement paralleled CNS disease and due to significantly lower levels of chemotherapeutic agent in the vitreous cavity, remission could not be sustained in the left eye. Chan and Wallace have reported therapeutic levels of MTX for up to 5 days as compared to few hours with systemic route. [8] Various reports have also described poor response to systemic MTX based regimens due to poor penetrance in ocular tissues and recommended intravitreal MTX as a treatment modality for PVRL with good response and fewer complications. [9],[10],[11],[12] In view of incomplete response and involvement limited to vitreous only, we treated our patient with multiple intravitreal MTX injections in the left eye. Frenkel et al. have demonstrated clinical remission after a mean of 6.4 ± 3.4 (range: 2-16) injections of MTX. [9] In our patient after an initial satisfactory response to nine intravitreal MTX injections, there was a severe relapse that was resistant to further MTX injections. In view of the disease primarily limited to vitreous we hence decided to do a complete pars plana vitrectomy and could achieve complete remission of disease after surgery.

While diagnostic vitreous biopsy is routinely performed to confirm the suspicion of intraocular lymphoma, to the best of our knowledge, complete vitrectomy as a treatment modality for PVRL has not been described earlier. Diagnostic vitreous biopsy has been in use for several decades in the management algorithm of intraocular lymphomas and no concerns of systemic spread has been raised, unlike with retinoblastoma. The prolonged remission seen in our patient following complete vitrectomy prompts us to wonder if microincisional therapeutic vitrectomy should become the treatment of choice in patients with vitreal form of intraocular lymphoma. We understand that observations from more number of patients following such intervention would be necessary before coming to the firm conclusion, and despite successful therapeutic vitrectomy, patients with PVRL must continue to be systemically monitored for CNS involvement.

 > References Top

Pe'er J, Hochberg FH, Foster CS. Clinical review: Treatment of vitreoretinal lymphoma. Ocul Immunol Inflamm 2009;17:299-306.  Back to cited text no. 1
DeAngelis LM, Seiferheld W, Schold SC, Fisher B, Schultz CJ, Radiation Therapy Oncology Group Study 93-10. Combination chemotherapy and radiotherapy for primary central nervous system lymphoma: Radiation Therapy Oncology Group Study 93-10. J Clin Oncol 2002;20:4643-8.  Back to cited text no. 2
Choi JY, Kafkala C, Foster CS. Primary intraocular lymphoma: A review. Semin Ophthalmol 2006;21:125-33.  Back to cited text no. 3
Peterson K, Gordon KB, Heinemann MH, DeAngelis LM. The clinical spectrum of ocular lymphoma. Cancer 1993;72:843-9.  Back to cited text no. 4
Cassoux N, Merle-Beral H, Leblond V, Bodaghi B, Miléa D, Gerber S, et al. Ocular and central nervous system lymphoma: Clinical features and diagnosis. Ocul Immunol Inflamm 2000;8:243-50.  Back to cited text no. 5
Nelson DF, Martz KL, Bonner H, Nelson JS, Newall J, Kerman HD, et al. Non-Hodgkin's lymphoma of the brain: Can high dose, large volume radiation therapy improve survival? Report on a prospective trial by the radiation therapy oncology group (RTOG): RTOG 8315. Int J Radiat Oncol Biol Phys 1992;23:9-17.  Back to cited text no. 6
Batchelor TT, Kolak G, Ciordia R, Foster CS, Henson JW. High-dose methotrexate for intraocular lymphoma. Clin Cancer Res 2003;9:711-5.  Back to cited text no. 7
Chan CC, Wallace DJ. Intraocular lymphoma: Update on diagnosis and management. Cancer Control 2004;11:285-95.  Back to cited text no. 8
Frenkel S, Hendler K, Siegal T, Shalom E, Pe'er J. Intravitreal methotrexate for treating vitreoretinal lymphoma: 10 years of experience. Br J Ophthalmol 2008;92:383-8.  Back to cited text no. 9
Whitcup SM, de Smet MD, Rubin BI, Palestine AG, Martin DF, Burnier M Jr, et al. Intraocular lymphoma. Clinical and histopathologic diagnosis. Ophthalmology 1993;100:1399-406.  Back to cited text no. 10
de Smet MD, Vancs VS, Kohler D, Solomon D, Chan CC. Intravitreal chemotherapy for the treatment of recurrent intraocular lymphoma. Br J Ophthalmol 1999;83:448-51.  Back to cited text no. 11
Henson JW, Yang J, Batchelor T. Intraocular methotrexate level after high-dose intravenous infusion. J Clin Oncol 1999;17:1329.  Back to cited text no. 12


  [Figure 1], [Figure 2]


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