Unusual presentation of cornea verticillata with intravitreal methotrexate in a case of primary intraocular lymphoma

A 56-year-old woman presented with floaters and diminution of vision in the right eye for 1 week. On examination, visual acuity was 20/400 in the right eye and 20/60 in the left eye. Indirect ophthalmoscopy revealed vitritis in the right eye and subretinal deposits in both eyes. Vitreous biopsy of the right eye revealed large B-cell-type primary intraocular lymphoma and the patient underwent multiple intravitreal methotrexate injections (400 μg/0.1 mL) in the right eye and systemic chemotherapy for bilateral disease. Following biweekly injections of methotrexate, her visual acuity improved considerably from 20/400 to 20/60 with resolution of vitritis. However, following eighth dose of intravitreal methotrexate, she experienced visual decline to 20/120 along with photophobia, redness and watering. Whorl-shaped opacities, limbitis and corneal haze were noted on slit-lamp examination. Intravitreal methotrexate was stopped, and the patient was started on frequent topical lubricants, loteprednol, topical folinic acid and oral folic acid. Complete resolution of corneal toxicity was observed at 3 weeks and the injections were suspended as there was no recurrence at 6 months follow-up.

Primary Intraocular Lymphoma: The Masquerade Syndrome

This chapter aims to provide a complete knowledge over the primary intraocular lymphoma (PIOL) and a correct clinical approach towards this rare condition, to avoid delays in diagnosis, which is considered the most important prognostic factor. A PIOL arises with no specific symptoms and could mimic both inflammatory and non-inflammatory ocular conditions. Also known as reticulum cell sarcoma in the past, PIOL is an ocular malignant condition, with a strong bond with primary central system lymphoma (PCNSL). This linkage is underlined by the fact that approximately 30% of the patients with PIOL have also PCNSL at presentation, while 45–90% will develop PCSNL in the following months. A correct diagnosis is currently achieved by the means of many different techniques: cytology, flow cytometry, immunohistochemistry, molecular analysis, and cytokines assay. Treatment of this condition has been completely revolutionized with the introduction of monoclonal antibodies directed against specific proteins present on the surface of lymphomatous cells.

Primary Intraocular Lymphoma in a Patient with Bilateral Epstein-Barr Virus Panuveitis

Purpose. Herein, we report a case of primary intraocular lymphoma (PIOL) with the first presentation of bilateral Epstein-Barr virus- (EBV-) associated panuveitis. Case Presentation. A 69-year-old male was referred with a three-day history of blurred vision and pain and redness in his left eye following cataract surgery. Examination revealed panuveitis, vitritis, and necrotizing retinitis with retinal hemorrhage. A month later, the right eye was also involved. Polymerase chain reaction-based analysis of the vitreous sample was positive for EBV, and cytological evaluation was compatible with the diagnosis of B-cell lymphoma. A significant improvement was observed following serial intravitreal rituximab and methotrexate injections. The central nervous system and lungs were involved after 6 months, and the patient expired despite systemic chemotherapy. Conclusion. There may be an association between EBV panuveitis and primary intraocular B-cell lymphoma.

Primary Intraocular Lymphoma in a Patient with Bilateral Epstein-Barr Virus Panuveitis: A Case Report

Purpose: Herein, we report a case of primary intraocular lymphoma (PIOL) with the first presentation of bilateral Epstein-Barr virus (EBV)-associated panuveitis and retinitis.Case presentation: A 69-year-old male was referred with a three-day history of blurred vision and pain and redness in his left eye following cataract surgery. Ophthalmic examination revealed panuveitis, vitritis, and necrotizing retinitis with retinal hemorrhage. A month later, the right eye was also involved. Initially, the clinical diagnosis of acute retinal necrosis was made based on clinical manifestation; however, the partial response to intravenous and intravitreal antiviral treatment in the left eye and involvement of the right eye resulted in further investigation of masquerade syndromes. Polymerase chain reaction-based analysis of vitreous sample was positive for EBV, and cytological evaluation was compatible with the diagnosis of B-cell lymphoma. A significant improvement was observed following serial intravitreal rituximab and methotrexate injections. The central nervous system and lungs were involved after 6 months, and the patient expired despite treatment with systemic chemotherapy. Conclusion: There may be an association between EBV panuveitis and primary intraocular B-cell lymphoma.

Comparative DNA Flow Cytometric Study of Primary Intraocular and Central Nervous System Lymphomas

Primary intraocular lymphoma is generally considered as a subset of primary CNS lymphoma. This study attempts to show that they may in fact represent distinct entities by comparing their respective proliferation rates using DNA flow cytometry. Four samples of primary intraocular lymphoma and seven samples of primary CNS lymphoma were analyzed, all from paraffin-embedded tissue. All tumors were of the large B-cell type. A normal human tonsil sample was used as a control. Tissue samples were analyzed by DNA flow cytometry, which is a precise and objective method to measure DNA content and cell proliferation of a tumor. S-phase fraction (SPF) and DNA content were measured for each sample. The average SPF for primary intraocular lymphoma was significantly higher than that of primary CNS lymphoma, 23.8 (range: 18.9 to 29.6) versus 15.1 (range: 1.1 to 25.1) respectively. Of the 11 tumors analyzed, 2 brain tumors were aneuploid and 1 eye tumor was peridiploid. All other tumors were diploid. Thus, no significant pattern was detected in the DNA content of the tumors. This lack of clinical significance of tumor aneuploidy is consistent with data reported in the literature. The results of this study indicate that primary intraocular lymphoma is more aggressive and of higher grade than primary CNS lymphoma. The different proliferation rates of intraocular and CNS lymphomas may be explained by either their different spatial location or a distinct genetic composition, the latter reinforcing the hypothesis that the two are fundamentally different entities

Outcomes of intravitreal methotrexate to salvage eyes with relapsed primary intraocular lymphoma

PurposeTo report the outcomes of intravitreal methotrexate (MTX) injections to rescue eyes with relapsed primary intraocular lymphoma (PIOL).MethodsRetrospective case series of patients with ocular relapse of PIOL who had initially received systemic chemotherapy (all five cases) and external beam radiotherapy (EBRT) to brain and orbits (two cases). Injections of MTX (400 µg/0.1 mL) were given one time per week for 1 month, every other week for 4 months, followed by a maintenance phase of one injection one time per month for 8 months (total of 20 injections in a year).ResultsFrom April 2008 to February 2016, there were nine eyes of five patients (three men; average age at first presentation 62 years) treated with our rescue protocol of intravitreal MTX injections. Ocular relapse occurred at a mean interval of 15 months (range 5–34 months) after the completion of initial systemic treatment. At mean follow-up of 31 months (range 5–104 months), tumour control was achieved in eight out of nine eyes (89%); one eye failed, with persistent retinal infiltrates despite increasing the frequency of injections, resulting in severe keratopathy. The only other complication occurred in one eye, developing cystoid macular oedema from MTX injections that resolved with topical anti-inflammatory medications and reduced frequency of MTX. There were no cases of reduced vision or ocular relapse, but two patients died (one of central nervous system lymphoma).ConclusionsIntravitreal MTX was a safe and effective treatment modality for relapsed PIOL after systemic chemotherapy and radiotherapy, achieving local tumour control in 89%, and hence represents an optimal choice. However, given the rare nature of PIOL, larger collaborative studies with longer follow-up are needed to corroborate this.