Rituximab for refractory manifestations of the antiphospholipid syndrome: a multicentre Israeli experience.

OBJECTIVES: The clinical manifestations of the antiphospholipid syndrome (APS) are heterogeneous and related to anti-phospholipid antibodies (aPL). There is some evidence that B cells are involved in the pathogenesis of this condition. Thus the ability of rituximab (RTX) to deplete B cells makes it an appealing potential therapy for refractory antiphospholipid syndrome (APS). Real world data on RTX treatment of APS are still lacking. This study was conducted to report outcomes of RTX administration in the treatment of different aspects of APS. METHODS: This is a retrospective case series study on APS patients from 3 medical centres in Israel who were treated with RTX during 2010-2019 for refractory manifestations of APS including diffuse alveolar haemorrhage, recurrent thrombosis, cytopenia, neurological and skin manifestations. Medical records were reviewed regarding the clinical indication for RTX treatment, concomitant medications, RTX protocol, aPL status and response to treatment. Outcomes were defined as complete response if full resolution of the "indicated manifestation" was achieved and maintained for at least 12 months, partial response or no response. RESULTS: We identified 40 APS patients who were treated with RTX for refractory manifestations of this condition, of whom, 24 patients (60%) were female with a mean age of 40 years, and 31 patients (78%) were diagnosed with primary APS. A favourable response to RTX was documented in 32 patients (80%) including a complete response in 22 patients (55%). Response to RTX treatment was associated with a rituximab protocol of 375mg/m2 x 4 compared to a fixed dose of 1000 mg x2 (100% vs. 65%; p=0.01). Complete response was associated with a decrease in aPL titres within 4-6 months post treatment, whereas no significant change in aPL titres was observed in patients with partial or no response. CONCLUSIONS: Consistent with previous small case series, we report a good therapeutic response to RTX in patients with difficult to treat manifestations of APS. In this cohort, treatment protocols were associated with outcomes. Although further studies are required to verify our observations, our data support a plausible role for B cell depletion in refractory APS.

Chromatic Multifocal Pupillometer for Objective Perimetry and Diagnosis of Patients with Retinitis Pigmentosa.

PURPOSE: To assess visual field (VF) defects and retinal function objectively in healthy participants and patients with retinitis pigmentosa (RP) using a chromatic multifocal pupillometer. DESIGN: Cross-sectional study. PARTICIPANTS: The right eyes of 16 healthy participants and 13 RP patients. METHODS: Pupil responses to red and blue light (peak, 485 and 625 nm, respectively) presented by 76 light-emitting diodes, 1.8-mm spot size at different locations of a 16.2° VF were recorded. Subjective VFs of RP patients were determined using chromatic dark-adapted Goldmann VFs (CDA-GVFs). Six healthy participants underwent 2 pupillometer examinations to determine test-retest reliability. MAIN OUTCOME MEASURES: Three parameters of pupil contraction were determined automatically: percentage of change of pupil size (PPC), maximum contraction velocity (MCV; in pixels per second), and latency of MCV (LMCV; in seconds). The fraction of functional VF was determined by CDA-GVF. RESULTS: In healthy participants, higher PPC and MCV were measured in response to blue compared with red light. The LMCV in response to blue light was relatively constant throughout the VF. Healthy participants demonstrated higher PPC and MCV and shorter LMCV in central compared with peripheral test points in response to red light. Test-retest correlation coefficients were 0.7 for PPC and 0.5 for MCV. In RP patients, test point in which the PPC and MCV were lower than 4 standard errors from the mean of healthy participants correlated with areas that were indicated as nonseeing by CDA-GVF. The mean absolute deviation in LMCV parameter in response to the red light between different test point was significantly higher in RP patients (range, 0.16-0.47) than in healthy participants (range, 0.02-0.16; P < 0.0001) and indicated its usefulness as a diagnostic tool with high sensitivity and specificity (area under the receiver operating characteristic curve (AUC), 0.97, Mann-Whitney-Wilcoxon analysis). Randomly reducing the number of test points to a total of 15 points did not significantly reduce the AUC in RP diagnosis based on this parameter. CONCLUSIONS: This study demonstrates the feasibility of using a chromatic multifocal pupillometer for objective diagnosis of RP and assessment of VF defects.

Ethnicity and Antiphospholipid Syndrome in Israel.

OBJECTIVE: Antiphospholipid syndrome (APS) is an acquired coagulopathy associated with the presence of antiphospholipid antibodies. Whether ethnicity modulates APS clinical course is not known. The aim of our study was to assess the interplay of ethnicity and APS in Israel. METHODS: We retrospectively evaluated the ethnic distribution of APS patients from 3 medical centers in Israel compared to the general population. Ethnic groups were defined according to the Israeli Bureau of Statistics as Ashkenazi (European), former Union of Soviet Socialist Republics (USSR), North African, Asian (West Asia, Greece, and Turkey), Israeli Arab individuals, and others. RESULTS: Our cohort included 382 patients. The prevalence of Ashkenazi and Asian ethnicities was more pronounced (33% versus 12.8% and 15.4% versus 7.7%, respectively; P < 0.001), while Israeli Arabs were less represented (5.2% versus 31.1%; P < 0.001) relative to their part in the general population. Arab patients were younger at presentation (mean ± SD 28 ± 10 years versus 34 ± 13 years; P < 0.001) and were more likely to present with venous thrombosis (50% versus 35%; P = 0.037) and to suffer from venous thrombotic recurrence (45% versus 16%; P < 0.001) compared to other ethnicities. Mortality was higher among patients of Asian ethnic origin (8.8% versus 1.1%; P = 0.005); intriguingly, this group experienced cardiovascular risk factors more often (i.e., dyslipidemia and hypertension). CONCLUSION: Ethnicity may affect the prevalence and/or natural course of APS, which is less prevalent and differs clinically in Israeli Arab patients, while mortality was linked with Asian ethnicity.