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航天相关神经-眼部综合征卧床模拟实验中的视神经血管系统及对策评估

Optic Nerve Vasculature and Countermeasure Assessment in a Bedrest Analogue of Spaceflight-Associated Neuro-Ocular Syndrome.

作者信息

He Ye, Karanjia Rustum, Zhang Xiaowei, Wanderer Daniel, Walker Evan, Lee Seung Hyen, Poczatek Matthew J, O'Grady Cambria S, Marion Kenneth M, Young Millennia, Moestl Stefan, Mulder Edwin, Stern Claudia, Sadda Srinivas R, Laurie Steven S, Macias Brandon R, Huang Alex S

机构信息

From the Doheny Eye Institute and University of California (Y.H., R.K., K.M.M., and S.R.S.), Los Angeles, California, USA.

From the Doheny Eye Institute and University of California (Y.H., R.K., K.M.M., and S.R.S.), Los Angeles, California, USA; Department of Ophthalmology (R.K.), Ottawa Eye Institute, University of Ottawa, Ottawa, Canada.

出版信息

Am J Ophthalmol. 2025 Jun 20;278:317-327. doi: 10.1016/j.ajo.2025.06.032.

Abstract

PURPOSE

To evaluate cephalad fluid shift countermeasures (CMs) as well as optic nerve structure and vasculature in a strict and chronic head-down tilt bedrest (HDTBR) model of Spaceflight-Associated Neuro-ocular Syndrome (SANS).

DESIGN

A prospective randomized interventional study.

PARTICIPANTS

Forty-seven subjects.

METHODS

An HDTBR study was performed with 4 groups. One group underwent 30 days of strict HDTBR. The remaining groups did the same with one of three fluid shift CMs: lower body negative pressure, exercise with veno-constrictive thigh cuffs (EX + CUFF), or intermittent upright posture (all groups, n = 11-12). All subjects underwent testing pre-BR, in HDTBR, and after returning to an upright posture. Ocular tests included optical coherence tomography (OCT), OCT-angiography, multicolor imaging, and intravenous fluorescein angiography. Total retinal thickness 250 microns away from Bruch's membrane opening (TRT250) was measured using a National Aeronautics and Space Administration-defined convention of ∆TRT250 > 20 μm as OCT-determined disc edema in SANS.

RESULTS

Only the upright posture (which intermittently reverses headward fluid shifts) resulted in a ∆TRT250 of <20 microns (18.6 ± 5.5 μm; mean ± 95% CI). The remaining three groups (including two CMs) showed a ∆TRT250 of > 20 microns with no differences between groups. As a result, all subjects were then combined. Pre-HDTBR cup width, depth, and volume were associated with increasing ∆TRT250 (P = .001-.002). Increasing ∆TRT250 was associated with both increasing optic nerve hyperfluorescence on intravenous fluorescein angiography (P < .001-.002) and decreasing peripapillary perfusion density on OCT-angiography (P = .04).

DISCUSSION

Upright posture is the first SANS CM to show a ∆TRT250 less than the National Aeronautics and Space Administration threshold for optic disc change in this HDTBR Earth-bound analogue of SANS, supporting the headward fluid-shift hypothesis in SANS. The inability to distinguish between the other conditions may have been due to risk factors that are not fully understood. This includes the risk factor of a smaller baseline optic nerve cup, which is associated with SANS-like changes in this study, and as previously shown in astronauts. Finally, the presence of optic disc vascular alterations (increased hyperfluorescence and decreased peripapillary perfusion density), which are also observed in Earth-bound disc edemas, highlights that optic nerve vascular damage is occurring.

摘要

目的

在模拟太空飞行相关神经-眼部综合征(SANS)的严格慢性头低位卧床休息(HDTBR)模型中,评估头向体液转移对策(CMs)以及视神经结构和脉管系统。

设计

一项前瞻性随机干预研究。

参与者

47名受试者。

方法

进行了一项HDTBR研究,分为4组。一组接受30天的严格HDTBR。其余组采用三种体液转移CMs之一进行相同操作:下体负压、使用静脉收缩性大腿袖带进行锻炼(EX + CUFF)或间歇性直立姿势(所有组,n = 11 - 12)。所有受试者在卧床休息前、HDTBR期间以及恢复直立姿势后均接受测试。眼部测试包括光学相干断层扫描(OCT)、OCT血管造影、多色成像和静脉注射荧光素血管造影。使用美国国家航空航天局定义的 convention of ∆TRT250 > 20 μm作为SANS中OCT确定的视盘水肿,测量距布鲁赫膜开口250微米处的总视网膜厚度(TRT250)。

结果

只有直立姿势(间歇性逆转头向体液转移)导致∆TRT250 < 20微米(18.6 ± 5.5微米;平均值 ± 95% CI)。其余三组(包括两种CMs)显示∆TRT250 > 20微米,组间无差异。因此,所有受试者随后合并。HDTBR前视杯宽度、深度和体积与∆TRT250增加相关(P = 0.001 - 0.002)。∆TRT250增加与静脉注射荧光素血管造影上视神经高荧光增加(P < 0.001 - 0.002)以及OCT血管造影上视乳头周围灌注密度降低(P = 0.04)均相关。

讨论

在这个模拟SANS的地球HDTBR模型中,直立姿势是首个显示∆TRT250低于美国国家航空航天局视盘变化阈值的SANS CM,支持了SANS中的头向体液转移假说。无法区分其他情况可能是由于尚未完全理解的风险因素。这包括基线视神经杯较小的风险因素,在本研究中其与类似SANS的变化相关,并且如先前在宇航员中所示。最后,视盘血管改变(高荧光增加和视乳头周围灌注密度降低)的存在,这在地面视盘水肿中也有观察到,突出表明正在发生视神经血管损伤。

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