Citations

The iStent series constitutes a range of trabecular bypass minimally invasive glaucoma surgery (MIGS) devices, which offers intraocular pressure (IOP) reduction with favourable safety profiles, in patients with open-angle glaucoma (OAG). Having undergone significant evolution since its initial US FDA-approval in 2012, successive generations address previous limitations, while enhancing IOP-lowering efficacy through device and delivery system design iterations. Longer-term and real-world iStent data demonstrate the durability of IOP- and medication-lowering outcomes with minimal complications, while preliminary studies across a wider spectrum of glaucoma subtypes and severities provide limited evidence of successful outcomes beyond mild-to-moderate OAG, both with and without concomitant cataract surgery. Aqueous humour outflow assessment and novel intra-operative techniques may further facilitate more accurate and effective iStent positioning. Despite typically higher upfront costs, results from both cost-effectiveness and patient-reported outcome studies are encouraging. Combination MIGS with the iStent, leveraging on the multiple mechanisms of actions of various procedures, may provide greater IOP-lowering efficacy without compromising safety. With expanding clinical data and progressive enhancements, iStent technology is likely to remain a key component of the evolving MIGS landscape.

ABSTRACT Neurodegenerative diseases are characterised by the assembly of a limited number of disease-specific proteins into amyloid filaments, which form intracellular inclusions or extracellular deposits in the central nervous system (CNS) 1,2 . We previously found that amyloid filaments of TATA-binding protein-associated factor 15 (TAF15) characterise a subtype of frontotemporal lobar degeneration with FET protein-immunoreactive inclusions (FTLD-FET) 3 , termed atypical FTLD with ubiquitin-positive inclusions (aFTLD-U) 4 , which causes early-onset, rapidly progressive behavioural variant frontotemporal dementia (FTD). However, it was not clear if TAF15 proteinopathy was more widespread in neurodegenerative diseases. Two additional FTLD-FET subtypes have been proposed, neuronal intermediate filament inclusion body disease (NIFID) and basophilic inclusion body disease (BIBD) 5,6 , which have more heterogenous clinical presentations including FTD, motor neuron diseases (MND) and movement disorders. Here, we used electron cryo-microscopy (cryo-EM) to determine a total of 32 amyloid filament structures from the brains of 17 individuals encompassing all three proposed subtypes of FTLD-FET and their diverse clinical presentations. All cases were characterised by TAF15 filaments, in the absence of filaments of the other FET proteins, fused in sarcoma (FUS) and Ewing’s sarcoma (EWS). All three aFTLD-U cases had the previously-reported TAF15 fold 3 . Unexpectedly, we found four distinct TAF15 folds among 11 NIFID cases. Eight of these cases shared a common fold, while the remaining three were each distinct. Furthermore, we found distinct TAF15 folds for each of the three BIBD cases. Neuropathological reassessment of the neocortical TAF15 inclusion pathology of these cases distinguished the NIFID cases with the common fold from the others. Thus, TAF15 filament structures form the basis of a new, expanded classification of FTLD-FET subtypes. Moreover, we discovered a TAF15 Y38C variant in the filament fold of one of the individuals with BIBD. The structure is unable to incorporate wild-type TAF15, despite the individual being heterozygous, suggesting that this variant drives TAF15 filament assembly. This study provides structural and genetic evidence that TAF15 amyloid filaments underlie the diverse group of neurodegenerative diseases currently termed FTLD-FET, which we therefore rename FTLD-TAF15.

Précis: Glaucoma patients with significant visual field defects show poorer driving performance, higher collision risks, and a greater likelihood of driving cessation. They face difficulties with lane maintenance, slower hazard responses, and self-regulation while driving. Purpose: Glaucoma is a chronic, progressive optic neuropathy associated with visual field (VF) defects, which in advanced disease has been shown to affect patients’ activities of daily living. This systematic review qualitatively analyzes existing literature that explores the impact of glaucomatous VF loss on the driving performance of glaucoma patients, the extent of driving limitation and cessation, as well as the risk of motor vehicle collisions (MVCs). Methods: A literature search of MEDLINE and Embase (via Ovid), PubMed, Cochrane Library, and Web of Science databases was performed for studies published from 2003 to 2023, with the terms “glaucoma,” “visual field defect/disorder,” and “driving,” followed by selective vetting based on inclusion criteria. Within studies, data pertaining to study design, subject demographics, VF defect characteristics, driving performance and related outcomes were extracted. Results: Initial search yielded 835 studies, with 20 studies selected. Three more studies were included through hand-searching, with a total of 23 studies included for final review. Moderate to severe VF defects resulted in poorer driving performance, with slower response times to road hazards, decreased ability for lane maintenance, and increased difficulty driving at night. Patients with more severe VF defects and with bilateral glaucoma were more likely to limit or cease driving compared with those with milder and unilateral glaucoma. A greater severity of VF loss was associated with a higher risk of MVCs. Conclusion: More severe glaucomatous VF and bilateral glaucoma is associated with worse driving performances and a higher risk of MVCs, in both simulator and real-world settings.

A systematic review was conducted of studies published up to 30 August 2024. Studies comparing conventional visual field (VF) indices, ability to detect central visual field defects (CVFDs), structure–function (S-F) concordance, and test characteristics across the HVF 24-2C SITA-Faster, 24-2 SITA-Standard/Faster, and 10-2 SITA-Standard/Fast tests were included. Eight studies with 1239 subjects (49.1% male; mean age, 54.8–66.9 years) were analyzed. The 24-2C produced similar global VF indices compared to the 10-2 and 24-2 (Standard/Faster) (ICC = 0.95 and 0.80, p < 0.001), detected more VF defects and CVFD clusters, and demonstrated greater S-F concordance than the 24-2 (Standard/Faster). Although the 10-2 (Standard/Fast) detected significantly more CVFDs and had a greater S-F concordance, the agreement between the 24-2C and 10-2 grids was substantial (ĸ = 0.488 to 0.708). The 24-2C was also faster compared to the 24-2 Standard and 10-2 (Standard/Fast), with comparable false positives, higher false negatives, and fewer fixation losses than the 24-2 Standard. In conclusion, the HVF 24-2C is quicker and identifies more CVFDs than the 24-2 grid, demonstrates high agreement with the 10-2 grid, and aids in CVFD screening.

Précis: ASOCT features of greater bleb height, thicker bleb walls, and lower reflectivity are associated with trabeculectomy success, supporting the ASOCT’s utility in monitoring and predicting outcomes postsurgery through standardized imaging protocols. Purpose: To evaluate and quantify the relationship between bleb characteristics on ASOCT with surgical outcomes. Methods: A literature search was conducted across Medline, Embase, Cochrane, and Scopus for studies from the past 20 years, until 16 September 2024, on “glaucoma,” “trabeculectomy,” and “ASOCT.” Data collected included patient characteristics, each study’s definition of bleb success, clinical outcomes, as well as bleb characteristics. A literature review was conducted on studies that could not be used for meta-analysis. Results: Eleven studies, with a pooled total of 528 eyes in 517 patients, were included in the final meta-analysis. Successful blebs had significantly higher mean bleb height [mean difference (MD) 0.38 mm, 95% CI: 0.20-0.56 mm, P=0.002], greater maximum bleb wall thickness (MD: 0.21 mm, 95% CI: 0.07-0.35 mm, P=0.009), and decreased reflectivity (MD: −48.9%, 95% CI: −78.3 to −19.4%, P=0.010), compared with failed blebs. No significant differences were found in bleb fluid cavity height and bleb area. Narrative synthesis revealed that wider blebs, increased fluid-filled cavity height, increased number of microcysts, larger filtration opening widths, and multiform bleb walls were also associated with higher rates of bleb success. Early bleb parameters were statistically significant predictors of bleb success up to 12 months postoperatively. Conclusions: Greater bleb height, thicker bleb walls, and lower reflectivity on ASOCT are consistently associated with successful trabeculectomy outcomes. The ASOCT may be useful in predicting bleb success and in supplementing postoperative monitoring, hence guiding timely medical or procedural interventions, to ensure long-term bleb success.

Objective To evaluate the safety and efficacy of MicroPulse Transscleral Laser Therapy (MicroPulse TLT) with the Revised P3 ® Delivery Device. Design Prospective, single-surgeon, interventional study in a tertiary hospital setting. Participants Sixty-two eyes of 40 patients with refractory glaucoma. Methods All subjects received 360-degree MicroPulse TLT treatment (2500 mW, 31.33% duty cycle) over a total of 240 s (8 sweeps; n = 20), 300 s (10 sweeps; n = 22), or 200 s (10 sweeps; n = 20). Participants were followed up for 6 months to assess changes in intraocular pressure (IOP), glaucoma medication burden, and best-corrected visual acuity (BCVA). Surgical success was defined as a reduction of IOP ≥ 30% from baseline and between 6–18 mmHg at last follow-up with no additional anti-glaucoma medications or secondary reinterventions. Results Surgical success was achieved in 72.7% (300 s group), 75.0% (240 s group), and 80.0% (200 s group) of eyes. Mean IOP was significantly reduced ( p < 0.001) by 49.0% (300 s group), 45.66% (240 s group), and 39.8% (200 s group) at 6 months. With all groups combined, the mean number of glaucoma medications was significantly reduced by 17.8% ( p = 0.005), and no significant changes in BCVA were observed at 6 months. Complications were minimal, including four eyes with IOP spikes, one eye with hyphema, and one eye with cystoid macular edema (CME), all of which resolved. Two eyes of the total sample (3.2%) required secondary glaucoma surgery before 6 months. Conclusions Second-generation MicroPulse TLT at fluence values of 154–229 J/cm 2 appears to be a safe and effective option for IOP reduction in refractory glaucoma.

Non-ST-segment elevation myocardial infarction (NSTEMI) can be managed by ischemia guide strategies or early invasive strategies. Here, we present the findings of an updated contemporary analysis regarding the use of intracoronary imaging (ICI)-guided PCI versus angiography-guided PCI and in-hospital mortality in patients with NSTEMI in the United States using the NIS database from 2016 to 2021. ICI use increased by nearly threefold between 2016 and 2021, without a significant difference in in-hospital mortality, though interestingly, mortality rates compared with angiography guidance were similar and relatively low. In this study, the use of ICI was associated with lower adjusted odds of in-hospital mortality, cardiogenic shock, and cardiac arrest, but with a longer length of stay and cost of hospitalization.