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OBJECTIVE: Giant Cell arteritis (GCA) is a large vessel vasculitis, typically involving the aorta and its branches with predilection for the scalp arteries. Intracranial involvement is still part of ongoing research. We assess inflammation of the intracranial arteries on 3D-black-blood magnetic resonance imaging (3D-CS-BB-MRI) in patients with GCA and age-matched controls. METHODS: 105 patients with 3D-CS-BB-MRI of the brain were included in this retrospective dual-center case-control study; 55 with diagnosed GCA and 50 age-matched controls. High-resolution 3D-CS-BB-MRI was performed on a 3 Tesla MR scanner with a post-contrast 3D-compressed-sensing (CS) MR pulse sequence, specifically a T1-weighted sampling perfection, application-optimized contrasts using different flip angle evolution (SPACE) pulse sequence with whole-brain coverage and isotropic resolution of 0.55 mm3. Two neuroradiologists blinded to clinical data independently scored the cerebral arteries qualitatively for inflammation; circumferential vessel wall thickening and contrast enhancement were scored positive for vasculitis. RESULTS: 8 of 55 GCA patients (14.5%) showed inflammation of at least one intracranial artery. The internal carotid artery (ICA) was affected in 6/55 (10.9%), the vertebral artery in 4/55 (7.3%) and the basilar artery and posterior cerebral artery in 1/55 (1.8%). All patients with inflammatory changes reported headaches and none showed any focal neurological deficit. Besides headache and general weakness, there was no significant correlation between inflammation of the intracranial arteries and clinical symptoms. No age-matched control patient showed inflammatory changes of the intracranial arteries. CONCLUSION: High-resolution 3D-CS-BB-MRI revealed inflammatory changes of intracranial arteries in 14.5% of GCA patients with the intradural ICA as the most frequently affected vessel.
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Belantamab mafodotin (belantamab) is a first-in-class anti-BCMA antibody-drug conjugate approved for the treatment of triple-class refractory multiple myeloma. It provides a unique therapeutic option for patients ineligible for CAR-T and bispecific antibody therapy, and/or patients progressing on anti-CD38 treatment where CAR-T and bispecifics might be kept in reserve. Wider use of the drug can be challenged by its distinct ocular side effect profile, including corneal microcysts and keratopathy. While dose reduction has been the most effective way to reduce these toxicities, the underlying mechanism of this BCMA off-target effect remains to be characterized. In this study, we provide the first evidence for soluble BCMA (sBCMA) in lacrimal fluid and report on its correlation with tumor burden in myeloma patients. We confirm that corneal cells do not express BCMA, and show that sBCMA-belantamab complexes may rather be internalized by corneal epithelial cells through receptor-ligand independent pinocytosis. Using an hTcEpi corneal cell-line model, we show that the pinocytosis inhibitor EIPA significantly reduces belantamab-specific cell killing. As a proof of concept, we provide detailed patient profiles demonstrating that, after belantamab-induced cell killing, sBCMA is released into circulation, followed by a delayed increase of sBCMA in the tear fluid and subsequent onset of keratopathy. Based on the proposed mechanism, pinocytosis-induced keratopathy can be prevented by lowering the entry of sBCMA into the lacrimal fluid. Future therapeutic concepts may therefore consist of belantamab-free debulking therapy prior to belantamab consolidation and/or concomitant use of gamma-secretase inhibition as currently evaluated for belantamab and nirogacestat in ongoing studies.
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PURPOSE: Postoperative hypotony following PRESERFLO MicroShunt (PMS) implantation is a frequent cause of complications such as choroidal detachment and hypotony maculopathy. This study aims at evaluating the impact of intraluminal stenting of the PMS during the early postoperative period. METHODS: We retrospectively analyzed the data of 97 patients who underwent PMS implantation with intraoperative placement of a Nylon 10-0 suture as intraluminal stent (PStent) and compared the outcomes to those of an existing database of the traditional MicroShunt implantation technique (PTrad, n = 120). The primary outcome measure was the intraocular pressure (IOP) at one week postoperatively. As a secondary outcome measure, adverse hypotony, defined as an IOP ≤ 5 mmHg with significant choroidal effusion and/or anterior chamber shallowing or the presence of macular folds was also assessed. Additionally, the time to stent removal and the IOP one week after stent removal were reported. RESULTS: Preoperative median IOP was 25.0 (20.5-30.3) mmHg in PStent and 25.0 (19.3-32.0) mmHg in PTrad (p = 0.62). One week after surgery, the median IOP dropped to 10.0 (8.0-13.0) mmHg in PStent and 7.0 (5.0-9.0) in PTrad (p < 0.01). At one month, the IOP was 12.0 (10.0-14.0) mmHg in PStent and 10.0 (8.0-11.0) mmHg in PTrad (p < 0.01). After 3 months, both groups showed similar median IOP levels of 11.0 (8.0-13.5) mmHg and 10.0 (9.75-13.0) mmHg in PStent and PTrad, respectively (p = 0.66). The presence of adverse hypotony was significantly lower in PStent compared to PTrad (6.2% vs 15.8%, p < 0.05). In PStent the stent was removed after 30.0 (21.0-42.5) days. One week after stent removal the mean IOP drop was 6.1 ± 0.5 mmHg (p < 0.01). CONCLUSION: In the early follow-up period, intraluminal stenting of the PMS appears to be safe and effective in controlling the IOP while reducing early postoperative hypotony. Surgical success is not compromised by stent placement. Based on our data, it is recommended to remove the suture two to six weeks after surgery for most patients with uncomplicated postoperative clinical findings.