The aim of the study was to compare, in a randomized prospective study, the efficacy and safety of intraorbital administration of low doses of RTX versus intravenous glucocorticoids (GCs) to treat patients affected by moderately severe thyroid-associated active orbitopathy. Twenty patients with active, moderately severe TAO, whose mean age was 56.7 years±10.2 SD participated in the study. Patients were randomly selected and treated with intraorbital injections of RTX or with i.v. GCs. Disease activity and severity were assessed by the Clinical Activity Score (CAS) and the NOSPECS. Computed tomography or magnetic resonance scans were performed in all patients. In the RTX group, full blood cell count and flow cytometric analysis on peripheral blood lymphocytes were done. The patients were followed for 20 months. In both groups, CAS and NOSPECS indexes were significantly reduced (p<0.005). In particular, CAS reduction was evident since the first follow-up with both treatments. Proptosis decreased significantly only in group B and diplopia showed no significant changes during follow-up times in both groups. Neither of the treatments affected the peripheral TRab. In group A, 5 weeks after the first injection, the CD20+ peripheral lymphocytes value was nearly zero. One patient treated with rituximab progressed to severe TAO (optic neuropathy) following the second injection so the treatment was discontinued. The data confirm the therapeutic efficacy of RTX in active TAO, even in low doses and locally administered. The efficacy on the inflammatory component of the disease is comparable to that of steroids and seems to be related with the reduction of peripheral CD20+ lymphocytes. Caution should be given to an accurate patient selection.

This study suggests that intralesional administration of rituximab for treating localized ocular adnexal CD20+ lymphomas could be an effective front-line therapeutic option with negligible side effects and a good response rate and duration.

Background: The aim of this study was to analyze patients diagnosed, staged and treated for orbital and eyelid B-cell lymphoma (OEL). Methods: One hundred and forty-one cases of OEL were included in this study. Primary endpoints were to analyze the histopathologic findings, the main risk factors and the type of treatment and to correlate them with recurrence of OEL. The secondary endpoint was to determine the progression-free survival (PFS) time. Results: Extranodal marginal zone B-cell lymphoma was the most frequent subtype (66%), followed by small lymphocytic lymphoma (12.7%), diffuse large B-cell lymphoma (DLBCL) (9.2%), follicular lymphoma (6.6%), mantle cell lymphoma (4.3%) and Burkitt lymphoma (1.2%). The probability of relapse was influenced by the histopathologic subtype DLBCL (OR = 7.7, 95% CI 1.8–32.3) and treatment with chemotherapy (OR = 14.9, 95% CI 2.6–83.7). Multivariate analysis showed that the histopathologic subtype DLBCL and chemotherapy treatment retained statistical significance for a poorer PFS, with hazard ratios of 8.581 (p = 0.0112) and 9.239 (p = 0.0094), respectively. Conclusions: Five lymphoma subtypes were found in patients with OEL. The histopathologic subtype and the type of treatment were found to be the main factors influencing treatment outcome.

To analyze the clinical and histopathological effects of low doses of intraorbital and intralesional Rituximab (RTX) in three patients affected by idiopathic orbital inflammatory syndrome (IOIS). Three patients with IOIS were enrolled, all of whom underwent lesion biopsy to confirm the diagnosis, complete blood examinations (thyroid function tests, complete blood cell count, fasting blood glucose, liver and renal function tests, erythrocyte sedimentation rate, serum ACE, C-reactive protein, rheumatoid factor, antinuclear antibody, antineutrophil cytoplasmic antibody, serum IGg4 level tests) and magnetic resonance imaging (MRI). Patients received the planned treatment schedule, consisting of a complete cycle of intraorbital injections of RTX (MabThera(®); Roche, Basel, Switzerland, 100 mg/10 ml): 10 mg, once a week for 1 month (four injections/month), in two patients repeated. The clinical and imaging follow-ups were at an average of 17.6 months (range 14-24 months) after treatment. A post-treatment bioptic procedure was performed in one patient. All patients showed a significant MRI reduction of the orbital lesion and a stable clinical improvement for the follow-up time of observation. The post-treatment histopathological specimen showed a disappearance of inflammatory cells. Low doses of intralesional RTX, which are safe, efficacious and used in other B cell-mediated disorders, are a useful treatment in IOIS, with decreased risks of generalized immunosuppression and fewer side effects than are afforded by systemic high doses of glucocorticoids and RTX. The result is very quick, effective and prolonged on the inflammatory component of the disease and seems to be related to the histologic reduction of infiltrating CD20+ lymphocytes.

An interventional pilot study to assess the tolerability and activity of the intralesional injection of rituximab, a chimeric mAb that targets the CD20 antigen, in patients with orbital B-cell lymphoma. Five patients received four intralesional injections (one injection a week) of rituximab together with ropivicaine 2%. Side-effects and tumor response were assessed after each injection and during the follow-up (20 months). Two patients obtained complete remission of the intraorbital lesion. Two patients showed incomplete response after induction therapy and received planned escalating rituximab doses, obtaining regression of subjective symptoms. One patient did not achieve tumor regression after the first injection and underwent systemic treatment. This small exploratory study suggests that intralesional rituximab is a well-tolerated treatment for patients with primary ocular adnexal lymphoma. These preliminary findings suggest that intralesional rituximab is a well-tolerated strategy in anterior intraorbital lesion localization of lymphoma. (Cancer Sci 2011; 102: 1565-1567 S everal studies suggest that extranodal marginal zone lymphoma (1,2) of mucosa-associated lymphoid tissue (MALT) is the most common type of primary ocular adnexal lymphoma (OAL). Mucosa-associated lymphoid tissue lymphoma is an indolent B-cell non-Hodgkin's lymphoma (NHL) characterized by mitotic division of the marginal zone cells within the reactive follicles.(3) It is most commonly seen in the elderly, most frequently affects the stomach, and normally follows an indolent course. It usually arises at sites of chronic inflammation secondary to persistent infections or autoimmune disorders.(4) Ocular MALT lymphoma has been shown to be related to the Chlamydia psittaci infection (5) but results from several studies are conflicting. (3,6) The accepted criteria for the diagnosis of MALT are strong staining for CD20, with CD10, CD23, and BCL6 negativity. In order to assess the disease and to define the optimal treatment the following criteria should be considered: (i) histopathological subtype; (ii) extent of the disease (in the ocular region and systemically); and (iii) impact of the lymphoma on the eye and visual function. Thus, the treatment decision varies from patient to patient and uniform guidelines for the treatment of ophthalmic lymphoma have yet to be established.It is now well accepted that localized proliferation of primary OAL can be controlled using radiotherapy. (7,8) Chemotherapy alone or in combination with radiotherapy is considered to be standard therapy for patients with extraorbital involvement. (9) However, there are significant adverse effects of the current treatment strategy.Recent evidence shows that systemic treatment using the monoclonal anti-CD20 antibody rituximab seems to be an effective, safe alternative for localized CD20 + OAL and for intraocular diffuse large B-cell lymphoma.(10) However, systemic treatment with rituximab is expensive and not without sideeffects. Intralesional injection of rituximab has also be...