ReCLAIM-2: A Randomized Phase II Clinical Trial Evaluating Elamipretide in Age-related Macular Degeneration, Geographic Atrophy Growth, Visual Function, and Ellipsoid Zone Preservation.

Objective: This study evaluated the safety and efficacy of elamipretide in dry age-related macular degeneration (AMD) with noncentral geographic atrophy (GA).

Design: ReCLAIM-2 was a prospective, phase II, randomized, placebo-controlled, double-masked, multicenter trial (NCT03891875).

Subjects: Patients aged ≥55 years with ≥1 eye with dry AMD with GA were enrolled.

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.

Imaging-Guided Classification of Neovascularization in Neovascular Age-Related Macular Degeneration: Progress to Date.

To review the evolution of terminology describing the classification of lesions in neovascular age-related macular degeneration (nAMD) based on retinal imaging technologies. A review of the current and historical literature on imaging-guided classification of neovascularization in nAMD was performed. Imaging-guided classification of neovascularization in nAMD facilitates understanding of the pathological mechanisms and disease progression.

MACULAR CHANGES IN ADULTS WITH HISTORY OF PREMATURE BIRTH.

Purpose: To characterize changes in the macular structure and vascularity seen in premature-birth adults.

Methods: Retrospective review of adult patients seen in the clinic from July 2018 to November 2020 with history of premature birth not requiring treatment for retinopathy of prematurity, as well as healthy controls. Swept-source ocular coherence tomography-angiography scans were analyzed for various parameters related to the macular structure and vascularity.

Update on Retinal Drug Safety: Proceedings of the ASRS ReST Committee Webinar Part 1.

To review the first Research and Safety in Therapeutics (ReST) Committee webinar and summarize the most current recommendations regarding diagnosis and management. The ReST Committee is comprised of members of the American Society of Retina Surgeons (ASRS). At regular internal meetings, safety issue reports from the website are reviewed.

EFFICACY AND SAFETY OF THE PROPOSED BIOSIMILAR AFLIBERCEPT, SDZ-AFL, IN PATIENTS WITH NEOVASCULAR AGE-RELATED MACULAR DEGENERATION: 52-Week Results From the Phase 3 Mylight Study.

Purpose: The Phase 3 Mylight study was designed to confirm clinical equivalence of proposed biosimilar aflibercept (SOK583A1; Sandoz [proposed biosimilar aflibercept, SDZ-AFL]) to its reference biologic (Eylea; Regeneron Pharmaceuticals, Inc; Bayer AG [reference aflibercept, Ref-AFL]).

Method: Mylight was a prospective, double-masked, 2-arm, parallel Phase 3 study. Participants with neovascular age-related macular degeneration were randomized 1:1 to receive eight injections of SDZ-AFL (n = 244) or Ref-AFL (n = 240) over 48 weeks.

Vascular smooth muscle BK channels limit ouabain-induced vasocontraction: Dual role of the Na/K-ATPase as a hub for Src-kinase and the Na/Ca-exchanger.

Large-conductance, calcium-activated potassium channels (BK channels) and the Na/K-ATPase are expressed universally in vascular smooth muscle. The Na/K-ATPase may act via changes in the intracellular Ca concentration mediated by the Na/Ca exchanger (NCX) and via Src kinase. Both pathways are known to regulate BK channels.

Pyrimidine Triones as Potential Activators of p53 Mutants.

p53 is a crucial tumor suppressor in vertebrates that is frequently mutated in human cancers. Most mutations are missense mutations that render p53 inactive in suppressing tumor initiation and progression. Developing small-molecule drugs to convert mutant p53 into an active, wild-type-like conformation is a significant focus for personalized cancer therapy.

β-TrCP-Mediated Proteolysis of Mis18β Prevents Mislocalization of CENP-A and Chromosomal Instability.

Restricting the localization of evolutionarily conserved histone H3 variant CENP-A to the centromere is essential to prevent chromosomal instability (CIN), an important hallmark of cancers. Overexpressed CENP-A mislocalizes to non-centromeric regions and contributes to CIN in yeast, flies, and human cells. Centromeric localization of CENP-A is facilitated by the interaction of Mis18β with CENP-A specific chaperone HJURP.

Huntingtin contains an ubiquitin-binding domain and regulates lysosomal targeting of mitochondrial and RNA-binding proteins.

Understanding the normal function of the Huntingtin (HTT) protein is of significance in the design and implementation of therapeutic strategies for Huntington's disease (HD). Expansion of the CAG repeat in the gene, encoding an expanded polyglutamine (polyQ) repeat within the HTT protein, causes HD and may compromise HTT's normal activity contributing to HD pathology. Here, we investigated the previously defined role of HTT in autophagy specifically through studying HTT's association with ubiquitin.

Exploring the fragility of meta-analyses in ophthalmology: a systematic review.

Objective: The fragility index (FI) of a meta-analysis evaluates the extent that the statistical significance can be changed by modifying the event status of individuals from included trials. Understanding the FI improves the interpretation of the results of meta-analyses and can help to inform changes to clinical practice. This review determined the fragility of ophthalmology-related meta-analyses.

Mck1-mediated proteolysis of CENP-A prevents mislocalization of CENP-A for chromosomal stability in Saccharomyces cerevisiae.

Centromeric localization of evolutionarily conserved CENP-A (Cse4 in Saccharomyces cerevisiae) is essential for chromosomal stability. Mislocalization of overexpressed CENP-A to noncentromeric regions contributes to chromosomal instability in yeasts, flies, and humans. Overexpression and mislocalization of CENP-A observed in many cancers are associated with poor prognosis.

International Classification System for Ocular Complications of Anti-VEGF Agents in Clinical Trials.

Purpose: Complications associated with intravitreal anti-VEGF therapies are reported inconsistently in the literature, thus limiting an accurate evaluation and comparison of safety between studies. This study aimed to develop a standardized classification system for anti-VEGF ocular complications using the Delphi consensus process.

Design: Systematic review and Delphi consensus process.

Mother, child and adolescent health outcomes in two long-term refugee camp settings at the Thai-Myanmar border 2000-2018: a retrospective analysis.

Aim: The study assessed mothers, children and adolescents' health (MCAH) outcomes in the context of a Primary Health Care (PHC) project and associated costs in two protracted long-term refugee camps, along the Thai-Myanmar border.

Background: Myanmar refugees settled in Thailand nearly 40 years ago, in a string of camps along the border, where they fully depend on external support for health and social services. Between 2000 and 2018, a single international NGO has been implementing an integrated PHC project.

Cadmium binding by the F-box domain induces p97-mediated SCF complex disassembly to activate stress response programs.

The F-box domain is a highly conserved structural motif that defines the largest class of ubiquitin ligases, Skp1/Cullin1/F-box protein (SCF) complexes. The only known function of the F-box motif is to form the protein interaction surface with Skp1. Here we show that the F-box domain can function as an environmental sensor.

Imaging Characteristics and Clinical Utility of Half-Dose versus Full-Dose Ultrawidefield Fundus Fluorescein Angiography.

Purpose: In early 2022, a fluorescein shortage occurred in the United States. To meet the standard of care for patients who required ultrawidefield fundus fluorescein angiography (UWFFA), a regimen of half-dose (250 mg) sodium fluorescein (10%) was adopted instead of the full dose (500 mg) at the Cole Eye Institute (CEI). In this paper, we compare the image quality, clinical utility, and the side-effect profile of half-dose versus full-dose fluorescein in UWFFA for a cohort of stable patients.

Bispecific VEGF-A and Angiopoietin-2 Antagonist RO-101 Preclinical Efficacy in Model of Neovascular Eye Disease.

Objective: To investigate preclinical data regarding the efficacy and biocompatibility of a bispecific protein, RO-101, with effects on VEGF-A and angiopoietin-2 (Ang-2) for use in retinal diseases.

Design: Experimental study.

Subjects: Brown Norway rats and New Zealand White Cross rabbits.

SUPRACHOROIDAL SPACE INJECTION TECHNIQUE: Expert Panel Guidance.

Purpose: To develop professional guidelines for best practices for suprachoroidal space (SCS) injection, an innovative technique for retinal therapeutic delivery, based on current published evidence and clinical experience.

Methods: A panel of expert ophthalmologists reviewed current published evidence and clinical experience during a live working group meeting to define points of consensus and key clinical considerations to inform the development of guidelines for in-office SCS injection.

Results: Core consensus guidelines for in-office SCS injection were reached and reported by the expert panel.

Compartmental Exudative Dynamics in Neovascular Age-Related Macular Degeneration: Volumetric Outcomes and Impact of Volatility in a Phase III Clinical Trial.

Purpose: To examine retinal feature dynamics in eyes with neovascular age-related macular degeneration (nAMD) treated with anti-VEGF therapy and the relationship of these features with visual acuity.

Design: Post hoc analysis of the phase III, randomized, HAWK nAMD clinical trial.

Participants: Participants randomized to the brolucizumab 6 mg or aflibercept 2 mg arms of the trial.

Considerations for the Identification and Management of Geographic Atrophy: Recommendations from an Expert Panel.

Newly approved treatments for patients with geographic atrophy are changing the treatment paradigm, highlighting the need for eye care providers (ECPs) to have a set of recommendations on how to best manage GA patients. Here, we outline how to identify various stages of age-related macular degeneration including geographic atrophy (GA) by examining optimal management scenarios implicating various ECPs and reviewing treatment considerations for patients with GA. Early identification of GA will lead to optimal patient outcomes, while a standardized management scenario will reduce clinical burden among ECPs treating patients with GA.