Single-cell analysis of anti-BCMA CAR T cell therapy in patients with central nervous system autoimmunity.

Chimeric antigen receptor (CAR) T cell immunotherapy for the treatment of neurological autoimmune diseases is promising, but CAR T cell kinetics and immune alterations after treatment are poorly understood. Here, we performed single-cell multi-omics sequencing of paired cerebrospinal fluid (CSF) and blood samples from patients with neuromyelitis optica spectrum disorder (NMOSD) treated with anti-B cell maturation antigen (BCMA) CAR T cells. Proliferating cytotoxic-like CD8+ CAR T cell clones were identified as the main effectors in autoimmunity. Anti-BCMA CAR T cells with enhanced features of chemotaxis efficiently crossed the blood-CSF barrier, eliminated plasmablasts and plasma cells in the CSF, and suppressed neuroinflammation. The CD44-expressing early memory phenotype in infusion products was potentially associated with CAR T cell persistence in autoimmunity. Moreover, CAR T cells from patients with NMOSD displayed distinctive features of suppressed cytotoxicity compared with those from hematological malignancies. Thus, we provide mechanistic insights into CAR T cell function in patients with neurological autoimmune disease.

Progression rate to primary angle closure following laser peripheral iridotomy in primary angle-closure suspects: a randomised study.

AIM: To report the progression rate (PR) to primary angle closure (PAC) following laser peripheral iridotomy (LPI) in PAC suspects (PACS). METHODS: Prospective, randomized controlled interventional clinical trial conducted at the Handan Eye Hospital, China. Totally 134 bilateral PACS, defined as non-visibility of the posterior trabecular meshwork for ≥180 degrees on gonioscopy were randomly assigned to undergo LPI in one eye. Gonioscopy and Goldmann applanation tonometry were performed prior to, on day 7 and 12mo post LPI. RESULTS: Eighty of 134 patients (59.7%) could be followed up at one year. The mean intraocular pressure (IOP) in treated eyes was 15.9±2.6 mm Hg at baseline, 15.4±3.0 mm Hg on day 7; 16.5±2.9 mm Hg at one month, and 15.5±2.9 mm Hg at 12mo; the IOP in untreated eyes was similar (P=0.834). One or more quadrants of the angle opened in 93.7% of the LPI treated eyes, but 67.0% (53/79) remained closed in two or more quadrants. The PR to PAC in untreated eyes was 3.75% and one developed acute angle-closure glaucoma (AACG); the PR to PAC in treated eyes was 2.5% and none had developed peripheral anterior synechia (PAS) or AACG. CONCLUSION: LPI can open some of the occludable angle in the majority of eyes with PACS, but 67% continue to have non-visibility of the trabecular meshwork for over 180 degrees.

Long-term Efficacy of Trabeculectomy on Chinese Patients with Pigmentary Glaucoma: A Prospective Case Series Observational Study.

BACKGROUND: Though trabeculectomy is often performed on patients with medically refractive pigmentary glaucoma (PG), the clinical outcomes of surgical treatment on PG remain unknown. The aim of this study was to summarize the long-term efficacy and safety of trabeculectomy on PG. METHODS: This was a prospective case series observational study. Eighteen consecutive PG patients were followed up for 8 years after trabeculectomy from May 2006 to April 2007. Visual acuity (VA), best-corrected visual acuity (BCVA), slit lamp biomicroscopy, intraocular pressure (IOP) measurement, Humphrey visual field analysis (VFA), and stereoscopic funduscopy were performed on admission and every 6 months after the surgery. Postoperative IOP, VA, BCVA, VFA, adjunctive anti-glaucoma medication, treatment-related side-effects, changes in blebs, and main clinical findings in the anterior segment of PG were recorded and compared with the baseline. RESULTS: Eighteen PG eyes from 18 patients, with average preoperative IOP of 34.5 ± 4.7 mmHg (range: 21-47 mmHg, 1 mmHg=0.133 kPa) were enrolled in this study. All enrolled patients completed the follow-up visits and required examinations. Eight years after trabeculectomy, all surgical eyes (18/18) had satisfactory IOP control with an average of 13.7 ± 2.5 mmHg (range: 9-19 mmHg), which was significantly lower than baseline (P = 0.001). Majority (15/18) of the PG eyes had stable VA, BCVA, VFA, and optic disc cupping parameters. Functional blebs still existed in 12/18 of the PG eyes at the last follow-up visit. Unanimously, pigmentation in the anterior segment attenuated with time after surgical treatment. No severe side-effects were recorded in any of the surgical eyes. CONCLUSIONS: All surgical PG eyes in this study had satisfactory IOP control 8 years after the surgery with well-preserved visual function. The long-term efficacy and safety of trabeculectomy are promising in PG patients.