Studies of the retinal microcirculation using human donor eyes and high-resolution clinical imaging: Insights gained to guide future research in diabetic retinopathy

Balaratnasingam, Chandrakumar; An, Dong; Hein, Martin; Yu, Paula K.; Yu, Dao‐Yi

doi:10.1016/j.preteyeres.2022.101134

Cited by 16 publications

(48 citation statements)

References 347 publications

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“… 64 – 66 Key retinal elements that control retinal perfusion include these pericytes, smooth muscle cells, and glia. 17 , 67 , 68 Smooth muscle α-actin is a key protein that confers contractile properties to some of these cells in response to regional changes in glutamate, lactate, and nitric oxide concentrations. 69 , 70 Tomasek and colleagues 71 utilized knockout mice to demonstrate that the lack of smooth muscle α-actin in pericytes and smooth muscle cells altered the properties of the blood–retina barrier, including vascular permeability.…”

Section: Discussionmentioning

confidence: 99%

“… 16 Vasoactive factors are released by retinal neurons, glial cells, and vascular endothelial cells during neurovascular coupling, but production of these factors may be altered during retinal ischemia. 1 , 17 Ischemic retinopathies are a major cause of severe vison loss in adults and children. 18 – 20 The relationship between retinal ischemia and capillary perfusion is difficult to investigate because a myriad of physiologic and disease variables can modulate retinal blood flow.…”

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confidence: 99%

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Variability in Capillary Perfusion Is Increased in Regions of Retinal Ischemia Due to Branch Retinal Vein Occlusion

Hein,

Mehnert,

Freund

et al. 2023

Invest. Ophthalmol. Vis. Sci.

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Purpose To investigate alterations in macular perfusion variability due to branch retinal vein occlusion (BRVO) using a novel approach based on optical coherence tomography angiography (OCTA) coefficient of variation (CoV) analysis. Methods Thirteen eyes of 13 patients with macular ischemia due to BRVO were studied. Multiple consecutive en face OCTA images were acquired. Bias field correction, spatial alignment, and normalization of intensities across the images were performed followed by pixelwise computation of standard deviation divided by the mean to generate a CoV map. Region of interest–based CoV values, derived from this map, for arterioles, venules, and the microvasculature were compared between regions with macular ischemia and control areas of the same eye. Control areas were regions of the same macula that were not affected by the BRVO and had normal retinal vascular structure as seen on multimodal imaging and normal retinal vascular density measurements as quantified using OCTA. Results CoV increased by a mean value of 17.6% within the microvasculature of ischemic regions compared to the control microvasculature ( P < 0.0001). CoV measurements of microvasculature were consistently greater in the ischemic area of all 13 eyes compared to control. There were no differences in CoV measurements between ischemic and control areas for arterioles ( P = 0.13) and venules ( P = 1.0). Conclusions Greater variability in microvasculature perfusion occurs at sites of macular ischemia due to BRVO. We report a novel way for quantifying macular perfusion variability using OCTA. This technique may have applicability for studying the pathophysiology of other retinal vascular diseases.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Variability in Capillary Perfusion Is Increased in Regions of Retinal Ischemia Due to Branch Retinal Vein Occlusion

Hein,

Mehnert,

Freund

et al. 2023

Invest. Ophthalmol. Vis. Sci.

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“…[13][14][15][16] The compensatory proliferation of retinal vessels stimulated by DM leads to protein and blood leakage, which may ultimately result in blindness. [17,18] Diabetic nephropathy is diagnosed when urinary albumin excretion increases without other renal conditions. Insulin-independent glucose uptake by kidney cells promotes glucose metabolism through non-glycolytic pathways, causing mitochondrial dysfunction, oxidative stress, and inflammation.…”

Section: Influence Of Long-term Complicationsmentioning

confidence: 99%

Role and molecular mechanism of Salvia miltiorrhiza associated with chemical compounds in the treatment of diabetes mellitus and its complications: A review

Li,

Liu,

Shi

et al. 2024

Medicine

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Diabetes mellitus (DM) is one of the most prevalent diseases worldwide, greatly impacting patients’ quality of life. This article reviews the progress in Salvia miltiorrhiza, an ancient Chinese plant, for the treatment of DM and its associated complications. Extensive studies have been conducted on the chemical composition and pharmacological effects of S miltiorrhiza, including its anti-inflammatory and antioxidant activities. It has demonstrated potential in preventing and treating diabetes and its consequences by improving peripheral nerve function and increasing retinal thickness in diabetic individuals. Moreover, S miltiorrhiza has shown effectiveness when used in conjunction with angiotensin-converting enzyme inhibitors, angiotensin receptor blockers (ARBs), and statins. The safety and tolerability of S miltiorrhiza have also been thoroughly investigated. Despite the established benefits of managing DM and its complications, further research is needed to determine appropriate usage, dosage, long-term health benefits, and safety.

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“…Vascular morphology has been established as a biomarker for the development, progression and prognosis of several retinal diseases 10 ;61 , including diabetic retinopathy 26 ;30 and age-related macular degeneration 44 ;55 . Changes in these metrics may indicate impairment to retinal or macular blood flow, which could contribute to the development of the disease.…”

Section: Introductionmentioning

confidence: 99%

Linking Structure and Function: Image-Based Virtual Populations of the Retinal Vasculature

Hernandez,

Madhusudhan,

Zheng

et al. 2023

Preprint

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PurposeThis study explores the relationship between microvascular parameters as delineated by optical coherence tomography angiography (OCTA) and retinal perfusion. We introduce a versatile framework to examine the interplay between the retinal vasculature structure and function, generating virtual vasculatures from central retinal vessels to macular capillaries. Alongside this, we develop a haemodynamics model which tests the associations between vascular morphology and retinal perfusion.MethodsThe generation of the vasculature is based on the distribution of four clinical parameters pertaining to the dimension and blood pressure of the central retinal vessels, constructive constrained optimisation and Voronoi diagram. Arterial and venous trees are generated in the temporal retina and connected through three layers of capillaries at different depths in the macula. The correlations between total retinal blood flow and macular flow fraction and vascular morphology are derived as Spearman rank coefficients and uncertainty from input parameters is quantified.ResultsA virtual cohort of 200 healthy vasculatures were generated. Mean and standard deviation for retinal blood flow and macular flow ratio were 19.15±7.34 μL/min and 4.52±1.19 %. Retinal blood flow was correlated with vessel area density, vessel diameter index, fractal dimension and vessel calibre index. The macular flow fraction was not correlated with any morphological metrics.ConclusionsThe proposed framework is able to reproduce vascular networks in the macula that are morphologically and functionally similar to real vasculature. The framework provides quantitative insights into how macular perfusion can be affected by changes in vascular morphology delineated on OCTA.

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Studies of the retinal microcirculation using human donor eyes and high-resolution clinical imaging: Insights gained to guide future research in diabetic retinopathy

Cited by 16 publications

References 347 publications

Variability in Capillary Perfusion Is Increased in Regions of Retinal Ischemia Due to Branch Retinal Vein Occlusion

Variability in Capillary Perfusion Is Increased in Regions of Retinal Ischemia Due to Branch Retinal Vein Occlusion

Role and molecular mechanism of Salvia miltiorrhiza associated with chemical compounds in the treatment of diabetes mellitus and its complications: A review

Linking Structure and Function: Image-Based Virtual Populations of the Retinal Vasculature

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