Intraorbital injection of Rituximab in idiopathic orbital inflammatory syndrome: case reports.

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 epidemiologic analysis of the association between eyelid disorders and ocular motility disorders in pediatric age.

Aim of the study was to assess: (a) the prevalence and type of strabismus, ptosis and eyelid dynamic disorders features, (b) the prevalence of refractive errors, amblyopia and, (c) their association with ocular/systemic syndromes in a cohort of patients. This is a retrospective observational multicenter cohort study. Patients with coexisting ocular motility disorders, comitant and incomitant strabismus, ptosis and dynamic eyelid disorders who have never undergone surgery were enrolled throughout a 3-years a study period. 137 out of 19,089 patients were enrolled, of which 97 with uniocular and 40 with binocular disease. Isolated congenital ptosis was observed in 84 patients. A polymalformative syndrome was present in almost one third of cases, whilst among strabismus type, esotropia was slightly more prevalent. Most patients were hypermetropic. In monocular disease, myopia mainly affected older patients, who were characterized by a worse ptosis margin reflex distance and levator function, and significantly higher astigmatism. Amblyopia occurred in 67.4% of the study sub-population. Of note, in monocular disease this was mild in 25.8%, moderate in 24.2% and severe in 11.3% of cases, whilst in binocular disease it was mild in 25%, moderate in 41.7% and severe in 16.7%. All patients with coexisting eyelid and ocular motility dysfunctions in pediatric age need ophthalmologic and systemic evaluation to accurately assess amblyopia, refractive errors and systemic/ocular disorders.

Evaluation of intraorbital injection of rituximab for treatment of primary ocular adnexal lymphoma: a pilot study.

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.

Relation of the eighth edition of the American Joint Committee on Cancer staging system with histological risk classification for primary eyelid basal cell carcinoma.

PURPOSE: To investigate the relation between the eighth edition of the American Joint Committee on Cancer staging system and histological risk classification for primary eyelid basal cell carcinoma. METHODS: Retrospective, observational case series of patients undergoing excisional biopsy for primary eyelid basal cell carcinoma in two tertiary centres between 2008 and 2018. Patients with <6 months of follow-up were excluded. Outcomes measured included histological subtype, American Joint Committee on Cancer 7 and 8 staging. RESULTS: A total of 222 cases were included over a 10-year period, with a mean (range) follow-up of 25.74 (6-120) months and a median (range) age of 70 (28-93) years. According to American Joint Committee on Cancer 8, the most common T category was T1a (64%), followed by T1b (18%) and T2a (8%). Of the 222 specimens, 183 (82.43%), 17 (7.66%), 19 (8.56%) and 3 (1.35%) were staged as IA, IB, IIA and IIB, respectively. The most common histological subtype was nodular in IA category and infiltrative in categories IB and IIA. Histologically, low-risk basal cell carcinomas were related to lower American Joint Committee on Cancer staging (IA), whereas high-risk basal cell carcinomas were related to American Joint Committee on Cancer stages IB and IIA (p < 0.001). No significant relation was found between T categorisation and risk stratification when adopting American Joint Committee on Cancer 7. CONCLUSION: American Joint Committee on Cancer 8 staging system is strongly related to primary eyelid basal cell carcinoma histological risk classification.

Orbital and Eyelid B-Cell Lymphoma: A Multicenter Retrospective Study.

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.

Corneal Topographic Changes After Eyelid Ptosis Surgery.

PURPOSE: To evaluate the corneal topography and the topographic changes after ptosis surgery on patients affected by congenital and acquired blepharoptosis. METHODS: Twenty eyes of 17 patients affected by acquired and congenital ptosis underwent surgical correction through anterior levator complex tightening. Computerized tomography (Syrius Sistem; CSO) was used to analyze any change in corneal astigmatism (CYL), simulated keratometry, anterior corneal symmetry index front, apical keratometry front, and central corneal thickness. Visual acuity, margin reflex distance, and levator function were also measured. RESULTS: After surgical ptosis repair, corneal topography demonstrated a reduction in average keratometry of 0.15 ± 0.47 diopters (D) and in corneal astigmatism of 0.26 ± 1.12 D. Significant differences were found in apical keratometry front (-1.84 ± 1.76 D) and in best-corrected visual acuity (-0.18 ± 0.06 logMAR) in the postoperative examinations. Central corneal thickness did not show significant differences between preoperative and postoperative examinations. Postoperative topographic maps showed a reduction of symmetry index front (0.10 ± 0.64 D). CONCLUSIONS: Eyelid ptosis modifies anterior corneal surface inducing refractive errors and modifying corneal astigmatism in patients, thus affecting the quality of vision. The surgical correction of blepharoptosis induces anterior corneal surface modification, restoring corneal symmetry and regular corneal astigmatism. Postoperative corneal topography showed normal corneal contours.

Intraorbital injection of rituximab versus high dose of systemic glucocorticoids in the treatment of thyroid-associated orbitopathy.

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.

Long-term outcomes of primary ocular adnexal lymphoma treatment with intraorbital rituximab injections.

PURPOSE: We recently reported on the efficacy of intralesional rituximab for treating primary ocular adnexal lymphoma in a pilot study. After treatment, a complete response was observed in two of five patients, a partial response in one patient, and lesion recurrence in two patients. In this study, we evaluate the long-term follow-up of the five previously treated patients as well as the response of two new patients to an augmented dose of rituximab. METHODS: We followed up the five patients who were treated with rituximab during the initial pilot study. Two additional patients were also enrolled and treated with four intraorbital injections of 10 mg rituximab once a week for 1 month (total dose of 40 mg). Median follow-up period was 4 years for the first five patients and 1 year for the last two patients. RESULTS: Lymphoma did not relapse in the two patients who originally responded immediately to treatment. Of the initial partial responders, one became disease-free after additional rituximab treatment, and one experienced a standardized uptake value reduction, as measured with positron emission tomography-CT. One patient who experienced abdominal and pulmonary localization 7 months later showed no local recurrence. The two newly enrolled patients had complete remission after the first cycle of treatment and no disease recurrence eight and 11 months later, respectively. CONCLUSIONS: 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.

Secondary orbital and intraocular lymphoma treated with immunochemotherapy.

PURPOSE: To assess ocular and orbital structure by ocular echography and magnetic resonance imaging, fluoroangiography, indocyanine green angiography, and optical coherence tomography before and after therapy with rituximab (Mabthera) and chlorambucil in a patient with concurrent intraorbital and intraocular lymphoma and diplopia. METHODS: A 69-year-old man referred blurred vision and proptosis in his left eye associated with diplopia. Best-corrected visual acuity was 0.3 logarithm of the minimum angle of resolution in the left eye and 0.02 logarithm of the minimum angle of resolution in the right eye. Ocular echography and magnetic resonance imaging revealed the presence of concurrent orbital and intraocular tumor, and a B-cell lymphocytic lymphoma was diagnosed by incisional biopsy. The patient was treated with the oral alkylating agent chlorambucil and with intravenous infusions of the monoclonal anti-CD20 antibody rituximab (Mabthera) and evaluated with visual acuity, echography, fluoroangiography, indocyanine green angiography, and magnetic resonance imaging. RESULTS: After combined immunochemotherapy with rituximab/chlorambucil, the patient showed in the left eye a significant improvement of visual acuity (0.1 logarithm of the minimum angle of resolution) and a disappearance of diplopia at the end of follow-up. CONCLUSION: In this case report, combined systemic therapy with chlorambucil and rituximab was effective to reduce and control orbital and intraocular lymphoma.

Effect of vertical transposition of the medial rectus muscle on primary position alignment in infantile esotropia with A- or V-pattern strabismus.

PURPOSE: To determine the effect of vertical displacement of muscle insertions on the surgical dose-response relationship in patients undergoing bilateral medial rectus recessions. METHODS: Retrospective chart review of patients undergoing bilateral medial rectus recessions for correction of congenital esotropia with or without vertical displacement for A or V patterns. Patients were clustered into A pattern, V pattern, and "simple" (no pattern) groups. Strabismus angle at distance and near before and after surgery was recorded. Surgical dose-response relationships (in prism diopters/mm) were determined at the 6-month follow-up visit and compared. RESULTS: A total of 55 patients (28 male and 27 female patients; mean age, 6.9 years; range, 2-17 years) were included. Of these, 28 had either A pattern (18) or V pattern (10), and 27 were in the simple group. Mean preoperative angle of deviation was 34Δ at distance and 40Δ at near. The surgical dose-response relationship was significantly greater (at both distance and near) in the A pattern group (2.43Δ/mm, distance [p=0.005]; 2.76Δ/mm, near [p=0.04]) than in the simple group (1.56Δ/mm, distance; 2.03Δ/mm, near). The surgical response in the V pattern group (1.96Δ/mm, distance [p=0.34]; 2.03Δ/mm, near [p=0.94]) was not significantly different from the simple group. CONCLUSIONS: Upward displacement of the medial rectus muscles increased the surgical dose/response relationship in patients with A-pattern esotropia. A similar effect was not observed with downward displacement in patients with V-pattern strabismus. Surgeons should be aware of this enhanced response when planning surgery for A-pattern esotropia.

Intralesional administration of rituximab for treatment of CD20 positive orbital lymphoma: safety and efficacy evaluation.

B-cell lymphomas constitute the most frequent malignant neoplasm of the ocular adnexal, often presenting with localized disease. Five patients with primary localized CD20 positive B cell non Hodgkin ocular adnexal lymphomas received intralesional rituximab at the dose of 5mg once a week for one month, followed by 10mg weekly in case of incomplete response. Four of five patients obtained regression of symptoms and 2 of them showed complete response. No patients experienced side effects besides pain on the site of the injection. Local treatment with Rituximab for OAL is a safe and useful first-line therapeutic option.