Visual Loss in Geographic Atrophy: Learnings From the Lampalizumab Trials.

Purpose: To assess the correlation of lesion growth rate and baseline factors, including foveal involvement and focality, on visual loss as measured by best-corrected visual acuity (BCVA) in patients with geographic atrophy (GA) secondary to age-related macular degeneration (AMD).

Design: Retrospective analysis of the lampalizumab phase 3 (NCT02247479 and NCT02247531) and prospective observational (NCT02479386) trials.

Participants: Patients with bilateral GA.

Topographic Clinical Insights From Deep Learning-Based Geographic Atrophy Progression Prediction.

Purpose: To explore the contributions of fundus autofluorescence (FAF) topographic imaging features to the performance of convolutional neural network-based deep learning (DL) algorithms in predicting geographic atrophy (GA) growth rate.

Methods: Retrospective study with data from study eyes from three clinical trials (NCT02247479, NCT02247531, NCT02479386) in GA. The algorithm was initially trained with full FAF images, and its performance was considered benchmark.

Deep Learning Approaches for Detecting of Nascent Geographic Atrophy in Age-Related Macular Degeneration.

Purpose: Nascent geographic atrophy (nGA) refers to specific features seen on OCT B-scans, which are strongly associated with the future development of geographic atrophy (GA). This study sought to develop a deep learning model to screen OCT B-scans for nGA that warrant further manual review (an artificial intelligence [AI]-assisted approach), and to determine the extent of reduction in OCT B-scan load requiring manual review while maintaining near-perfect nGA detection performance.

Design: Development and evaluation of a deep learning model.

Macular Sensitivity Endpoints in Geographic Atrophy: Exploratory Analysis of Chroma and Spectri Clinical Trials.

Purpose: To assess different microperimetry (MP) macular sensitivity outcome measures capturing functional deterioration in eyes with geographic atrophy (GA) secondary to age-related macular degeneration (AMD).

Design: Patients were included from 2 identically designed, phase III, double-masked, randomized controlled clinical trials, Chroma (NCT02247479) and Spectri (NCT02247531).

Participants: Patients enrolled were aged ≥ 50 years with bilateral GA and no evidence of previous or active neovascular AMD.

Interreader Agreement and Longitudinal Progression of Incomplete/Complete Retinal Pigment Epithelium and Outer Retinal Atrophy in Age-Related Macular Degeneration.

Objective: To analyze the ability to evaluate changes over time of individual lesions of incomplete or complete retinal pigment epithelium (RPE) and outer retinal atrophy (iRORA and cRORA, respectively) in patients with intermediate age-related macular degeneration (iAMD).

Design: OCT images from patients enrolled in Proxima B clinical trial (NCT02399072) were utilized.

Participants: Patients enrolled in the Proxima B clinical trial, from the cohort with geographic atrophy (GA) in 1 eye and iAMD in the other eye at baseline, were included.

Geographic Atrophy Segmentation Using Multimodal Deep Learning.

Purpose: To examine deep learning (DL)-based methods for accurate segmentation of geographic atrophy (GA) lesions using fundus autofluorescence (FAF) and near-infrared (NIR) images.

Methods: This retrospective analysis utilized imaging data from study eyes of patients enrolled in Proxima A and B (NCT02479386; NCT02399072) natural history studies of GA. Two multimodal DL networks (UNet and YNet) were used to automatically segment GA lesions on FAF; segmentation accuracy was compared with annotations by experienced graders.

The Role of the Complement Pathway in Clinical Progression of Geographic Atrophy: Analysis of the Phase III Chroma and Spectri Trials.

Purpose: To investigate the relationship between complement pathway activities and progression of geographic atrophy (GA) secondary to age-related macular degeneration in samples collected from patients enrolled in the Chroma and Spectri trials.

Design: Chroma and Spectri were phase III, double-masked, and sham-controlled, 96-week trials.

Participants: Aqueous humor (AH) samples collected at baseline and week 24 visits from 81 patients with bilateral GA across all 3 treatment groups (intravitreal lampalizumab 10 mg every 6 weeks, every 4 weeks, or corresponding sham procedures) were tested, along with patient-matched plasma samples collected at baseline.

Alternative Complement Pathway Inhibition by Lampalizumab: Analysis of Data From Chroma and Spectri Phase III Clinical Trials.

Purpose: Lampalizumab, an antigen-binding fragment of a humanized monoclonal antibody directed against complement factor D (CFD), is designed to treat geographic atrophy (GA) secondary to age-related macular degeneration. Given the lack of clinical efficacy observed in patients with GA in the phase III Chroma/Spectri trials, we investigated the impact of lampalizumab on the complement system in vivo. We developed 6 novel assays to measure changes in complement pathway activities in aqueous humor samples collected from patients enrolled in these trials.

Deep Learning to Predict Geographic Atrophy Area and Growth Rate from Multimodal Imaging.

Objective: To develop deep learning models for annualized geographic atrophy (GA) growth rate prediction using fundus autofluorescence (FAF) images and spectral-domain OCT volumes from baseline visits, which can be used for prognostic covariate adjustment to increase power of clinical trials.

Design: This retrospective analysis estimated GA growth rate as the slope of a linear fit on all available measurements of lesion area over a 2-year period. Three multitask deep learning models-FAF-only, OCT-only, and multimodal (FAF and OCT)-were developed to predict concurrent GA area and annualized growth rate.

Dose-dependent inactivation of airway tryptase with a novel dissociating anti-tryptase antibody (MTPS9579A) in healthy participants: A randomized trial.

Tryptase is the most abundant secretory granule protein in human lung mast cells and plays an important role in asthma pathogenesis. MTPS9579A is a novel monoclonal antibody that selectively inhibits tryptase activity by dissociating active tetramers into inactive monomers. The safety, tolerability, pharmacokinetics (PKs), and systemic and airway pharmacodynamics (PDs) of MTPS9579A were assessed in healthy participants.

Conversion from Intermediate Age-Related Macular Degeneration to Geographic Atrophy in a Proxima B Subcohort Using a Multimodal Approach.

Introduction: This retrospective analysis assessed geographic atrophy (GA) progression in fellow eyes from the Proxima B trial intermediate age-related macular degeneration (iAMD) subcohort using high-resolution multimodal imaging anchored on optical coherence tomography (OCT).

Methods: Thirty-two patients from the Proxima B iAMD subcohort were assessed; all had GA with no macular neovascularization (MNV) in the contralateral eye. Imaging data, including color fundus photography, fluorescein angiography, near-infrared reflectance, fundus autofluorescence (FAF), and spectral-domain OCT, were obtained.

Survival forests under test: Impact of the proportional hazards assumption on prognostic and predictive forests for amyotrophic lateral sclerosis survival.

We investigate the effect of the proportional hazards assumption on prognostic and predictive models of the survival time of patients suffering from amyotrophic lateral sclerosis. We theoretically compare the underlying model formulations of several variants of survival forests and implementations thereof, including random forests for survival, conditional inference forests, Ranger, and survival forests with splitting, with two novel variants, namely distributional and transformation survival forests. Theoretical considerations explain the low power of log-rank-based splitting in detecting patterns in non-proportional hazards situations in survival trees and corresponding forests.

Target engagement in an alzheimer trial: Crenezumab lowers amyloid β oligomers in cerebrospinal fluid.

Objective: Oligomeric forms of amyloid β protein (oAβ) are believed to be principally responsible for neurotoxicity in Alzheimer disease (AD), but it is not known whether anti-Aβ antibodies are capable of lowering oAβ levels in humans.

Methods: We developed an ultrasensitive immunoassay and used it to measure oAβ in cerebrospinal fluid (CSF) from 104 AD subjects participating in the ABBY and BLAZE phase 2 trials of the anti-Aβ antibody crenezumab. Patients received subcutaneous (SC) crenezumab (300mg) or placebo every 2 weeks, or intravenous (IV) crenezumab (15mg/kg) or placebo every 4 weeks for 68 weeks.