Trimethylamine-N-oxide (TMAO), a microbiota-dependent metabolite derived from trimethylamine (TMA)-containing nutrients that are abundant in a Western diet, enhances both platelet responsiveness and in vivo thrombosis potential in animal models and predicts incident atherothrombotic event risks in clinical studies. Here, utilizing a mechanism-based inhibitor approach targeting a major microbial TMA-generating enzyme (CutC/D), we developed potent, time-dependent and irreversible inhibitors that do not affect commensal viability. In animal models, a single oral dose of a CutC/D inhibitor significantly reduced plasma TMAO levels for up to 3 days and rescued diet-induced enhanced platelet responsiveness and thrombus formation, without observable toxicity or increased bleeding risk. The inhibitor selectively accumulated within intestinal microbes to millimolar levels, a concentration over a million-fold higher than needed for a therapeutic effect. These studies reveal that mechanism-based inhibition of gut microbial TMA/TMAO production reduces thrombosis potential, a critical adverse complication in heart disease. They also offer a generalizable approach for the selective non-lethal targeting of gut microbial enzymes linked to host disease, while limiting systemic exposure of the inhibitor in the host.

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The overall risk for RRD after cataract surgery by phacoemulsification was small. However, in the younger patient, the risk for pseudophakic detachment was higher. In light of this finding, the requirement for cataract surgery in this group should be reassessed.

This study shows that the Inject and Extend protocol is safe and efficacious for the treatment of age-related macular degeneration. Head-to-head studies are needed to compare directly with other regimens currently in use, as well as economic analysis to investigate the financial implications.

The Ang/Tie2 pathway complements VEGF-mediated activity in retinal vascular diseases such as DME, AMD, and RVO by decreasing vascular integrity, increasing neovascularization, and increasing inflammatory signaling. Faricimab is a bispecific antibody that has been developed as an inhibitor of both VEGF and Ang2 that has shown positive results in phase I, II and III trials. Recent Year 1 data from phase III clinical trials YOSEMITE, RHINE, TENAYA, and LUCERNE have confirmed the efficacy, safety, durability, and superiority of faricimab in patients with DME and nAMD. Faricimab, if approved, may significantly decrease treatment burden in patients with retinal vascular diseases to a greater extent than would current standard of care anti-VEGF injections.

Purpose Photobiomodulation therapy (PBT) has emerged as a possible treatment for age-related macular degeneration (AMD) and diabetic retinopathy (DR). This review seeks to summarize the application of PBT in AMD and DR. Methods The National Clinical Trial (NCT) database and PubMed were queried using a literature search strategy and reviewed by the authors. Results Fourteen studies examining the application of PBT for AMD and nine studies examining the application of PBT for diabetic macular edema (DME) were extracted from 60 candidate publications. Discussion Despite notable methodological differences between studies, PBT has been reported to treat certain DR and AMD patients. DR patients with center involving DME and VA ≥ 20/25 have demonstrated response to treatment. AMD patients at Age-Related Eye Disease Study Stages 2–4 with VA ≥20/200 have also shown response to treatment. Results of major clinical trials are pending. Conclusion PBT remains an emergent therapy with possible applications in DR and AMD. Further, high powered studies monitored by a neutral party with standard devices, treatment delivery and treatment timing are needed.

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