The University of Queensland, School of Pharmacy, Brisbane, Queensland, Australia.
The University of Queensland, Faculty of Medicine, Brisbane, Queensland, Australia.
Theranostics. 2023 Jun 19;13(11):3582-3638. doi: 10.7150/thno.82884. eCollection 2023.
Ultrasound has long been identified as a promising, non-invasive modality for improving ocular drug delivery across a range of indications. Yet, with 20 years of learnings behind us, clinical translation remains limited. To help address this, and in accordance with PRISMA guidelines, the various mechanisms of ultrasound-mediated ocular drug delivery have been appraised, ranging from first principles to emergent applications spanning both and models. The heterogeneity of study methods precluded meta-analysis, however an extensive characterisation of the included studies allowed for semi-quantitative and qualitative assessments. In this review, we reflected on study quality of reporting, and risk of bias (RoB) using the latest Animal Research: Reporting of Experiments (ARRIVE 2.0) guidelines, alongside the Systematic Review Centre for Laboratory animal Experimentation (SYRCLE) RoB tools. Literature studies from 2002 to 2022 were initially characterised according to methods of ultrasound application, ultrasound parameters applied, animal models employed, as well as safety and efficacy assessments. This exercise contributed to developing a comprehensive understanding of the current state of play within ultrasound-mediated ocular drug delivery. The results were then synthesised and processed into a guide to aid future study design, with the goal of improving the reliability of data, and to support efficient and timely translation to the clinic. Key attributes identified as hindering translation included: poor reporting quality and high RoB, skewed use of animals unrepresentative of the human eye, and the over reliance of reductionist safety assessments. E modelling studies were often unable to have comprehensive safety assessments performed on them, which are imperative to determining treatment safety, and represent a pre-requisite for clinical translation. With the use of our synthesised guide, and a thorough understanding of the underlying physicochemical interactions between ultrasound and ocular biology provided herein, this review offers a firm foundation on which future studies should ideally be built, such that ultrasound-mediated ocular drug delivery can be translated from concept to the coalface where it can provide immense clinical benefit.
超声长期以来被认为是一种有前途的、非侵入性的方法，可改善多种适应症的眼部药物传递。然而，尽管我们已经有 20 年的经验，但临床转化仍然有限。为了解决这个问题，并根据 PRISMA 指南，评估了超声介导的眼部药物传递的各种机制，从第一性原理到新兴应用，涵盖了 和 模型。研究方法的异质性使得无法进行荟萃分析，然而，对纳入研究的广泛描述允许进行半定量和定性评估。在本综述中，我们根据最新的动物实验报告实验原则（ARRIVE 2.0）指南，以及系统评价实验室动物实验中心（SYRCLE）的偏倚工具，对报告质量和偏倚风险（RoB）进行了反思。2002 年至 2022 年的文献研究最初根据超声应用方法、应用的超声参数、所采用的动物模型以及安全性和疗效评估进行了描述。这项工作有助于全面了解超声介导的眼部药物传递的当前状态。然后对结果进行综合处理，形成一个指南，以帮助未来的研究设计，目标是提高数据的可靠性，并支持向临床的高效和及时转化。被确定为阻碍转化的关键因素包括：报告质量差和 RoB 高、动物使用不平衡，不能代表人眼，以及对简化安全性评估的过度依赖。在 E 模型研究中，通常无法对其进行全面的安全性评估，这对于确定治疗安全性至关重要，也是临床转化的前提。使用我们综合的指南，以及对超声和眼部生物学之间的潜在物理化学相互作用的深入理解，本综述为未来的研究提供了坚实的基础，理想情况下，未来的研究应该在此基础上进行，以便将超声介导的眼部药物传递从概念转化为能够提供巨大临床益处的前沿。
