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使用微通道辅助离子电渗法增强核黄素基质递送用于角膜交联

Enhanced Riboflavin Stromal Delivery Using Microchannel-Assisted Iontophoresis for Corneal Crosslinking.

作者信息

Joshi Rohan, Bradford Samantha, Luo Shangbang, Farrah Emily, Xie Yilu, Brown Donald J, Juhasz Tibor, Jester James V

机构信息

Department of Ophthalmology, Gavin Herbert Eye Institute, University of California - Irvine, Irvine, CA, USA.

Department of Biomedical Engineering, University of California - Irvine, Irvine, CA, USA.

出版信息

Transl Vis Sci Technol. 2025 Mar 3;14(3):18. doi: 10.1167/tvst.14.3.18.

DOI:10.1167/tvst.14.3.18
PMID:40100211
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11927301/
Abstract

PURPOSE

The purpose of this study was to determine if iontophoresis of riboflavin (Rf) combined with femtosecond generated epithelial microchannels (MCs) could shorten the time required for Rf stromal delivery and subsequent crosslinking (CXL).

METHODS

Eighty-four ex vivo rabbit eyes were divided into three groups: group 1 = iontophoresis alone; group 2 = iontophoresis with MC; and group 3 = MC alone. Iontophoresis was performed using a small electric current with varying current and time. MCs were generated using a 1030 nm femtosecond (FS) laser to machine the corneal epithelial surface in a 6 mm diameter region. Ex vivo eyes were treated with topical iso-osmolar Rf solution, and stromal Rf concentration was determined spectrophotometrically by eluting Rf from trephined stromal buttons. In vivo, six rabbits underwent iontophoresis or iontophoresis + MC followed by ultraviolet-A crosslinking (UVA CXL) and imaged for collagen autofluorescence (CAF) signal to determine CXL efficacy.

RESULTS

Ex vivo iontophoresis achieved a threefold increase in stromal Rf concentration when combined with MC for 5 to 10 minutes (equivalent to MC alone for 30 minutes compared to iontophoresis alone). In vivo, iontophoresis + MC resulted in a significantly higher (4-fold) CAF intensity than iontophoresis alone.

CONCLUSIONS

MCs and low current iontophoresis produce a significantly higher stromal Rf concentration than iontophoresis alone and equivalent to MC alone at greatly reduced Rf treatment time. Additionally, the combined treatment results in a four-fold increase in CAF intensity over iontophoresis alone.

TRANSLATIONAL RELEVANCE

A combined treatment of iontophoresis and MC significantly enhances stromal Rf concentration resulting in increased CXL while significantly reducing procedure time.

摘要

目的

本研究的目的是确定核黄素(Rf)离子导入联合飞秒激光产生的上皮微通道(MCs)是否能缩短Rf基质递送及后续交联(CXL)所需的时间。

方法

84只离体兔眼分为三组:第1组 = 单纯离子导入;第2组 = 离子导入联合MC;第3组 = 单纯MC。使用不同电流和时间的小电流进行离子导入。使用1030纳米飞秒(FS)激光在直径6毫米的区域对角膜上皮表面进行加工以产生MCs。用局部等渗Rf溶液处理离体眼,并通过从环钻取下的基质纽扣中洗脱Rf,用分光光度法测定基质Rf浓度。在体内,6只兔子接受离子导入或离子导入 + MC,随后进行紫外线A交联(UVA CXL),并对胶原自发荧光(CAF)信号进行成像以确定CXL疗效。

结果

离体实验中,当离子导入与MC联合5至10分钟时,基质Rf浓度增加了三倍(与单纯离子导入相比,相当于单纯MC 30分钟的效果)。在体内,离子导入 + MC产生的CAF强度比单纯离子导入显著更高(4倍)。

结论

MCs和低电流离子导入产生的基质Rf浓度比单纯离子导入显著更高,且在大大缩短Rf治疗时间的情况下与单纯MC相当。此外,联合治疗导致CAF强度比单纯离子导入增加了四倍。

转化相关性

离子导入和MC的联合治疗显著提高了基质Rf浓度,从而增加了CXL效果,同时显著缩短了手术时间。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9723/11927301/cb9b9fbe7297/tvst-14-3-18-f005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9723/11927301/2b41dcef259b/tvst-14-3-18-f001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9723/11927301/d2afa0e8e80c/tvst-14-3-18-f002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9723/11927301/ebd8db4f4598/tvst-14-3-18-f003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9723/11927301/a890f1915a6f/tvst-14-3-18-f004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9723/11927301/cb9b9fbe7297/tvst-14-3-18-f005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9723/11927301/2b41dcef259b/tvst-14-3-18-f001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9723/11927301/d2afa0e8e80c/tvst-14-3-18-f002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9723/11927301/ebd8db4f4598/tvst-14-3-18-f003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9723/11927301/a890f1915a6f/tvst-14-3-18-f004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9723/11927301/cb9b9fbe7297/tvst-14-3-18-f005.jpg

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本文引用的文献

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2
Bowman Layer Transplantation With Stromal Inclusion Using Femtosecond Laser: 3-Year Results.使用飞秒激光进行含基质植入的Bowman层移植:3年结果
Cornea. 2025 Mar 1;44(3):332-336. doi: 10.1097/ICO.0000000000003620. Epub 2024 Jul 10.
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Criteria for patient selection and indication for intracorneal ring segments in keratoconus.
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Eye Vis (Lond). 2024 Mar 26;11(1):13. doi: 10.1186/s40662-024-00379-0.
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Keratoconus: exploring fundamentals and future perspectives - a comprehensive systematic review.圆锥角膜:探索基础与未来展望——一项全面的系统综述
Ther Adv Ophthalmol. 2024 Mar 20;16:25158414241232258. doi: 10.1177/25158414241232258. eCollection 2024 Jan-Dec.
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Intrastromal corneal ring segments for keratoconus patients: up to 12 years follow up.圆锥角膜患者的基质内角膜环植入术:长达12年的随访
Int Ophthalmol. 2024 Feb 9;44(1):50. doi: 10.1007/s10792-024-02912-5.
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Customized corneal allogenic intrastromal ring segments (CAIRS) for keratoconus with decentered asymmetric cone.用于偏心不对称圆锥角膜的定制角膜同种异体基质环段(CAIRS)
Indian J Ophthalmol. 2023 Dec 1;71(12):3723-3729. doi: 10.4103/IJO.IJO_1988_23. Epub 2023 Nov 20.
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Short- and long-term safety and efficacy of corneal collagen cross-linking in progressive keratoconus: A systematic review and meta-analysis of randomized controlled trials.角膜交联术治疗进行性圆锥角膜的短期和长期安全性及有效性:一项随机对照试验的系统评价和荟萃分析
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