Use of intravitreal rituximab for treatment of vitreoretinal lymphoma

Larkin, Kelly L.; Saboo, Ujwala S.; Comer, Grant M.; Forooghian, Farzin; Mackensen, Friederike; Merrill, Pauline T.; Sen, H. Nida; Singh, Arun D.; Essex, Rohan W.; Lake, Stewart; Lim, Lyndell L; Vasconcelos-Santos, Daniel Vítor; Foster, C. Stephen; Wilson, David J.; Smith, Justine R.

doi:10.1136/bjophthalmol-2013-304043

Cited by 68 publications

(42 citation statements)

References 30 publications

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“…Since a different pH and components of drug solutions may lead to changes in the buffering capacity of the human vitreous, the purpose of this study was to evaluate the pH changes of the human vitreous after the administration of intravitreous drugs. The effects of rituximab, used for treatment of intraocular lymphoma, were also characterized [3]. …”

Section: Introductionmentioning

confidence: 99%

pH of anti-VEGF agents in the human vitreous: low impact of very different formulations

et al. 2017

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Background The aim of the study was to measure pH changes of the human vitreous caused by the intravitreal drugs bevacizumab, ranibizumab, aflibercept, and ziv-aflibercept.MethodsFresh human vitreous samples were obtained during core vitrectomy (23-gauge) from patients with epiretinal gliosis. Aliquots of bevacizumab, ranibizumab, aflibercept or ziv-aflibercept (2 µl) were added consecutively to 200 µl of vitreous samples or 0.9% NaCl saline. The pH was measured using a pH-sensitive microelectrode. Rituximab, in off-label use against intraocular lymphoma, was tested as an IgG1 antibody.ResultsThe pH of the administered drugs was 5.91 for bevacizumab (95% CI 5.63–6.19), 5.32 for ranibizumab (95% CI 5.0–5.63), 6.05 for aflibercept (95% CI 5.78–6.31), ziv-aflibercept 6.1 (95% CI 6.05–6.15), and 6.29 for rituximab (95% CI 5.97–6.61). While the fresh and undiluted vitreous fluid showed pH values of 7.0–7.4, pH values increased if saline or rituximab were added. In contrast, the pH decreased slightly if aflibercept, bevacizumab, ranibizumab or ziv-aflibercept were supplemented. The observed pH decreases were not significant after ranibizumab was added. Significant changes were only notable with higher-than-normal amounts of bevacizumab (26–40 µl). The vitreous showed the most robust buffering capacity towards ranibizumab and rituximab.ConclusionsThe pH changes in vitreous samples elicited by the usual intravitreal anti-VEGF drugs differed clearly, but only by much higher concentrations than used in the clinical routine. Although the ingredient solution of ranibizumab showed the lowest pH, it caused only moderate changes of vitreal pH compared to bevacizumab, aflibercept or ziv-aflibercept.

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Section: Introductionmentioning

confidence: 99%

pH of anti-VEGF agents in the human vitreous: low impact of very different formulations

et al. 2017

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“…The combination of rituximab with high-dose methotrexate may improve the complete remission rates as well as the overall and progression-free survivals in immunocompetent patients with newly diagnosed PCNSL (78). Rituximab-based intravitreal chemotherapy has been reported to be safe and effective to induce remission in a majority of eyes with vitreoretinal lymphoma (79–81). Larkin et al treated 48 eyes of 34 vitreoretinal lymphoma patients with a median of 3.5 intravitreal injections of rituximab for new diagnosis (68.8%), progressive disease (29.9%) and maintenance therapy (2.1%).…”

Section: Pvrl Treatmentmentioning

confidence: 99%

“…Although rituximab-associated complications reported in 25% of the eyes, a 2-line loss of Snellen visual acuity occurred in only 2 eyes (4. 2%) (81). This result is encouraging.…”

Section: Pvrl Treatmentmentioning

confidence: 99%

Case 01-2017—Primary vitreoretinal lymphoma (PVRL): report of a case and update of literature from 1942 to 2016

2018

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Primary vitreoretinal lymphoma (PVRL), as a subset of primary central nervous system lymphoma (PCNSL), is a rare and fatal ocular malignancy. Most PVRL masquerades as chronic posterior uveitis, which makes the clinical diagnosis challenging. Vitreous cells, subretinal lesions and imaging techniques are essential for clinical diagnosis. Importantly, cytopathology/histopathology identification of malignant cells is the gold standard for the diagnosis of PVRL. In addition, molecular detection of immunoglobulin heavy chain (IgH) or T cell receptor (TCR) gene rearrangements, immunophenotyping for cell markers, and cytokine analysis of interleukine-10 elevation are often used as adjunct procedures. Current management of PVRL involves local radiation, intravitreal chemotherapy (methotrexate and rituximab), with or without systemic chemotherapy depending on the involvement of non-ocular tissues. In cases with concomitant PCNSL, systemic high-dose methotrexate/rituximab based therapy in conjunction with local therapy, whole brain radiotherapy and/or autologous stem cell transplantation is considered. Although PVRL normally responds well to initial treatment, high rates of relapse and CNS involvement usually lead to poor prognosis and limited survival. A professional team of medical experts in ophthalmologists, ocular pathologists, neuro-oncologists and hemato-oncologists is essential for optimizing patient management.

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“…Seven of the 31 eyes that had complete remission developed recurrent disease. Complications related to the injections included cataract, elevated intraocular pressure, granulomatous anterior uveitis, vitreous hemorrhage, and rhegmatogenous retinal detachment [58]. Another group studied intravitreal rituximab in patients who discontinued intravitreal methotrexate secondary to severe corneal epithelial toxicity.…”

Section: Therapeutic Optionsmentioning

confidence: 99%

Diagnostic Vitrectomy for Primary Intraocular Lymphoma

Hwang¹,

Yeh²,

Bergstrom³

2014

International Ophthalmology Clinics

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Primary intraocular lymphoma (PIOL) can present with uveitis, vitritis, or chorioretinal lesions. While fluorescein angiography, fundus autofluorescence, and optical coherence tomography may aid in the diagnosis of PIOL, a definitive diagnosis can only be achieved with tissue analysis. The specimen may be obtained with a vitreous or aqueous tap, however, a diagnostic pars plana vitrectomy with acquisition of diluted and undilated vitreous fluid or a chorioretinal biopsy is preferable. Once a specimen is obtained, cytopathology, flow cytometry, immunohistochemistry, gene rearrangement studies with polymerase chain reaction, and cytokine analysis can be performed to confirm the diagnosis of PIOL. Treatment is dependent on the presentation of PIOL and may include systemic chemotherapy, local intravitreal chemotherapy, radiation or a combination of therapies.

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Use of intravitreal rituximab for treatment of vitreoretinal lymphoma

Abstract: Approaches in rituximab-based intravitreal chemotherapy vary widely, but our findings suggest that this treatment may be safe and effective in inducing remission in a majority of eyes with vitreoretinal lymphoma.

Cited by 68 publications

References 30 publications

pH of anti-VEGF agents in the human vitreous: low impact of very different formulations

pH of anti-VEGF agents in the human vitreous: low impact of very different formulations

Case 01-2017—Primary vitreoretinal lymphoma (PVRL): report of a case and update of literature from 1942 to 2016

Diagnostic Vitrectomy for Primary Intraocular Lymphoma

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