Vavrek Sarah R, Nalbant Elif Kayaalp, Konopek Nicholas, Decker Nicole L, Fawzi Amani A, Mieler William F, Tichauer Kenneth M, Kang-Mieler Jennifer J
Department of Biomedical Engineering, Illinois Institute of Technology, Chicago, Illinois.
Department of Ophthalmology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.
Ophthalmol Sci. 2024 Oct 26;5(2):100636. doi: 10.1016/j.xops.2024.100636. eCollection 2025 Mar-Apr.
To investigate retinal vascular permeability mapping as a potential biomarker for diabetic retinopathy in subjects with diabetes with no signs of retinopathy and with mild nonproliferative retinopathy.
This is a case-control study.
Participants included 7 healthy controls, 22 subjects with diabetes mellitus and no clinical signs of retinopathy (DMnoDR), and 7 subjects with mild nonproliferative diabetic retinopathy (NPDR).
All participants underwent routine retinal fluorescein videoangiography (FVA). Each FVA dataset was analyzed with the dynamic tracer kinetic model (DTKM) method to estimate 5 parameters: extraction fraction (), blood flow, arrival time, transit time, and rate constant defined via adiabatic solution. The DTKM method was based on indicator dilution theory, including sequential use of 2 prominent kinetic models: the plug flow model and the adiabatic approximation to the tissue homogeneity model.
Extraction fraction, i.e., the fluorescein dye leakage measured during 1 pass through surrounding retinal tissue, is extracted via DTKM method and directly relates to retinal vascular permeability. Thus, represents the preclinical biomarker, retinal vascular permeability.
The 3 diagnostic groups were found to have significantly different permeability ( = 0.003). Despite having no clinical signs of retinopathy, the mean rank of average vascular was significantly higher in DMnoDR subjects compared with healthy controls ( = 0.04), as was the mean rank of for mild NPDR subjects ( = 0.002). The average for mild NPDR, DMnoDR, and control subjects was 0.10 ± 0.04, 0.07 ± 0.04, and 0.04 ± 0.01, respectively.
The vascular permeability extracted from FVA datasets using the DTKM method is a promising biomarker for detecting preclinical retinal pathology in patients with diabetes. Longitudinal studies are ongoing to explore the ability of this biomarker to distinguish those subjects with diabetes who will progress to clinically apparent retinopathy from those who will not.
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
研究视网膜血管通透性图谱作为无视网膜病变体征和轻度非增殖性视网膜病变的糖尿病患者糖尿病视网膜病变潜在生物标志物的情况。
这是一项病例对照研究。
参与者包括7名健康对照者、22名无视网膜病变临床体征的糖尿病患者（糖尿病无视网膜病变组）以及7名轻度非增殖性糖尿病视网膜病变患者（轻度非增殖性糖尿病视网膜病变组）。
所有参与者均接受常规视网膜荧光血管造影（FVA）。每个FVA数据集采用动态示踪剂动力学模型（DTKM）方法进行分析，以估计5个参数：提取分数（）、血流量、到达时间、通过时间以及通过绝热解定义的速率常数。DTKM方法基于指示剂稀释理论，包括依次使用2个著名的动力学模型：平推流模型和组织均匀性模型的绝热近似。
提取分数，即在一次通过周围视网膜组织期间测量的荧光素染料渗漏，通过DTKM方法提取，与视网膜血管通透性直接相关。因此，代表临床前生物标志物——视网膜血管通透性。
发现3个诊断组的通透性有显著差异（=0.003）。尽管糖尿病无视网膜病变组患者无视网膜病变的临床体征，但其平均血管的平均秩次与健康对照者相比显著更高（=0.04），轻度非增殖性糖尿病视网膜病变组患者的平均秩次也是如此（=0.002）。轻度非增殖性糖尿病视网膜病变组、糖尿病无视网膜病变组和对照组患者的平均分别为0.10±0.04、0.07±0.04和0.04±0.01。
采用DTKM方法从FVA数据集中提取的血管通透性是检测糖尿病患者临床前视网膜病变的一种有前景的生物标志物。正在进行纵向研究，以探索该生物标志物区分糖尿病患者中哪些会进展为临床明显视网膜病变以及哪些不会的能力。
专有或商业披露信息可在本文末尾的脚注和披露中找到。
