Assessment of Conjunctival Microvascular Hemodynamics in Stages of Diabetic Microvasculopathy

Abstract

Diabetes impairs the microcirculation and function of various vital tissues throughout the body. The conjunctival microcirculation can be non-invasively imaged and thus enables assessment of microvascular hemodynamics. In this study, alterations in conjunctival microvascular hemodynamics were quantitatively assessed at stages of increasing diabetic microvasculopathy based on diabetic retinopathy (DR). Subjects were categorized into non-diabetic control (C, N = 34), no clinically visible DR (NDR, N = 47), non-proliferative DR (NPDR, N = 45), and proliferative DR (PDR, N = 35). Conjunctival hemodynamic descriptors, namely vessel diameter (D), blood velocity (V), blood flow (Q), wall shear rate (WSR), and wall shear stress (WSS) were measured in arterioles and venules, and compared between DR and C subjects using generalized linear mixed models. In arterioles, V, WSR, and WSS were lower in NDR (P ≤ 0.01). V was lower in NDR than NPDR and PDR subjects (P ≤ 0.02). In venules, D was higher in NDR and NPDR (P ≤ 0.03), while V was lower in PDR (P = 0.04). Venular V and Q were higher in NPDR than PDR subjects (P ≤ 0.04). WSR and WSS were lower in all stages of DR (P ≤ 0.05), suggestive of the potential of WSS as a marker of diabetic microvasculopathy. Quantitative assessment of conjunctival hemodynamics can potentially be useful for evaluation of diabetic microvasculopathy.

Eye care providers’ emerging roles in early detection of diabetes and management of diabetic changes to the ocular surface: a review

“…55 The increase in conjunctival microvasculopathy was identified even prior to the onset of clinical retinopathy. 56 Further testing is needed to understand the relationship between conjunctival and retinal microvasculopathy but, due to the non-invasive nature of the testing, conjunctival microvascular testing could be a useful screening tool for early diabetic retinal disease. 56 A detailed review of tear components modified by diabetes and other diseases has been published elsewhere and is beyond the scope of this paper.…”

“…56 Further testing is needed to understand the relationship between conjunctival and retinal microvasculopathy but, due to the non-invasive nature of the testing, conjunctival microvascular testing could be a useful screening tool for early diabetic retinal disease. 56 A detailed review of tear components modified by diabetes and other diseases has been published elsewhere and is beyond the scope of this paper. 57 But, in brief, many tear inflammatory mediators and neuropeptide (eg, substance P) are altered in diabetes but there are no significant changes in the main tear proteins, including lactoferrin, albumin, lipocalin, lysozyme and secretary IgA.…”

A Network Pharmacology Based Analysis of The Potential Mechanisms of Compound Danshen Dripping Pill for Treatment of Diabetic Retinopathy

“…[19][20][21][81][82][83][84][85][86][87] Except for the biochemical changes, physiological changes also play a role in the process of DR. Hemodynamic dysfunction has been found in DR and may precede clinical DR. [88][89][90][91][92] Hemodynamic parameters, wall shear rate and wall shear stress are suggested reduced in the early stage of DR, as well as retinal blood velocity and ow, which could be markers of microvasculopathy. 88,93,94 Atherosclerosis has also been considered associated with the severity of DR, manifesting increased macrovascular artery intima-media wall thickness and accompanied by wider retinal vessel diameter in DR. [95][96][97] These studies emphasize the vital role of hemodynamic changes in the early stage of DR. CDDP in TCM theory is characterized by improving blood circulation (Pharmacopoeia of the People's Republic of China). The early application of CDDP in NPDR patients can signi cantly shorten the retinal circulation time and reduce capillary hemangioma, hard exudates, retinal hemorrhaging.…”

Inter-visit variability of conjunctival microvascular hemodynamic measurements in healthy and diabetic retinopathy subjects

“…Alterations in the conjunctival microvascular hemodynamics can be readily quantified due to microcirculation accessibility for direct imaging (Cheung et al, 2002a; Cheung et al, 2009; Devaraj et al, 2007; Khansari et al, 2016b; Khansari et al, 2017; Kord Valeshabad et al, 2015; Koutsiaris et al, 2013; Smith et al, 2009). Furthermore, conjunctival microcirculation can provide insight into pathophysiology of conditions that can alter systemic circulation (Ohtani, 1996; Schaser et al, 2003; Tamosuitis et al, 2016; Yin et al, 2016).…”

“…Furthermore, commercial devices such as retinal functional imager (Jiang et al, 2013) and Heidelberg retinal flowmeter (Duench et al, 2007) have been modified to measure conjunctival hemodynamics. Application of these imaging modalities has shown conjunctival microvasculopathy and hemodynamic alterations due to systemic diseases such as Alzheimer's disease (Smith et al, 2009), hypertension (To et al, 2013), hypotension (Gaynes et al, 2012), diabetes (Khansari et al, 2017; Cheung et al, 2009; Cheung et al, 2001; Owen et al, 2008; To et al, 2011), and sickle cell disease (Cheung et al, 2002a; Kord Valeshabad et al, 2015; Paton, 1962; Wanek et al, 2013). Furthermore, a recent study showed a significant decrease in conjunctival blood flow, vessel density and non-perfused areas in brain dead subjects as compared to normal controls (Tamosuitis et al, 2016).…”