Retinal Vascular Architecture Research Articles

Comparative evaluation of trypsin and elastase digestion techniques for isolation of murine retinal vasculature

Dysfunctional pericytes and disruption of adherens or tight junctions are related to many microvascular diseases, including diabetic retinopathy. In this context, visualizing retinal vascular architecture becomes essential for understanding retinal vascular disease pathophysiology. Although flat mounts provide a demonstration of the retinal blood vasculature, they often lack a clear view of microaneurysms and capillary architecture. Trypsin and elastase digestion are the two techniques for isolating retinal vasculatures in rats, mice, and other animal models. Our observations in the present study reveal that trypsin digestion impacts the association between pericytes and endothelial cells. In contrast, elastase digestion effectively preserves these features in the blood vessels. Furthermore, trypsin digestion disrupts endothelial adherens and tight junctions that elastase digestion does not. Therefore, elastase digestion emerges as a superior technique for isolating retinal vessels, which can be utilized to collect reliable and consistent data to comprehend the pathophysiology of disorders involving microvascular structures.

Analysis of the morphology of retinal vascular cells in zebrafish (Danio rerio).

Background: Zebrafish (Danio rerio) have been established in recent years as a model organism to study Diabetic Retinopathy (DR). Loss of endothelial cells and pericytes is an early hallmark sign of developing DR in the mammalian retina. However, morphology, numbers, ratios, and distributions of different vascular cells in the retinal compartment in zebrafish have not yet been analyzed and compared with the mammalian retina. Methods: The retinal trypsin digest protocol was established on the zebrafish retina. Cell types were identified using the Tg(nflk:EGFP)-reporter line. Cells were quantified using quantitative morphometry. Results: Vascular cells in the zebrafish retina have distinct morphologies and locations. Nuclei of vascular mural cells appear as long and flat nuclei located near the vessel wall. Round nuclei within the vessel walls can be identified as endothelial cells. The vessel diameter decreases from central to peripheral parts of the retina. Additionally, the numbers of vascular cells decrease from central to peripheral parts of the retina. Discussion: The retinal trypsin digest protocol, which can be applied to the zebrafish retina, provides novel insights into the zebrafish retinal vascular architecture. Quantification of the different cell types shows that, in comparison to the mammalian retina, zebrafish have higher numbers of mural cells and an increased mural cell to endothelial cell ratio. This protocol enables to quantify mural cell and endothelial cell numbers, is easily adaptable to different transgenic and mutant zebrafish lines and will enable investigators to compare novel models on a single cell level.

Retinal laminar and vascular characteristics in patients with incontinentia pigmenti

Incontinentia pigmenti (IP) is a rare systemic disease of x-linked dominant inheritance associated with abnormalities of the retina microvasculature. The recent development of optical coherence tomography angiography (OCT-A) permits non-invasive, quantitative analysis of the retinal vascular architecture. We aimed to characterise the retinal vasculature and structure at the macular region in patients with IP.

Noninvasive temporal detection of early retinal vascular changes during diabetes

Diabetes associated complications, including diabetic retinopathy and loss of vision, are major health concerns. Detecting early retinal vascular changes during diabetes is not well documented, and only few studies have addressed this domain. The purpose of this study was to noninvasively evaluate temporal changes in retinal vasculature at very early stages of diabetes using fundus images from preclinical models of diabetes.Non-diabetic and Akita/+ male mice with different duration of diabetes were subjected to fundus imaging using a Micron III imaging system. The images were obtained from 4 weeks- (onset of diabetes), 8 weeks-, 16 weeks-, and 24 weeks-old male Akita/+ and non-diabetic mice. In total 104 fundus images were subjected to analysis for various feature extractions. A combination of Canny Edge Detector and Angiogenesis Analyzer plug-ins in ImageJ were utilized to quantify various retinal vascular changes in fundus images. Statistical analyses were conducted to determine significant differences in the various extracted features from fundus images of diabetic and non-diabetic animals. Our novel image analysis method led to extraction of over 20 features. These results indicated that some of these features were significantly changed with a short duration of diabetes, and others remained the same but changed after longer duration of diabetes. These patterns likely distinguish acute (protective) and chronic (damaging) associated changes with diabetes. We show that with a combination of various plugging one can extract over 20 features from retinal vasculature fundus images. These features change during diabetes, thus allowing the quantification of quality of retinal vascular architecture as biomarkers for disease progression. In addition, our method was able to identify unique differences among diabetic mice with different duration of diabetes. The ability to noninvasively detect temporal retinal vascular changes during diabetes could lead to identification of specific markers important in the development and progression of diabetes mediated-microvascular changes, evaluation of therapeutic interventions, and eventual reversal of these changes in order to stop or delay disease progression.

Papillary Trunk Bifurcation Angles as Major Determinants of Ocular Perfusion: A Cross-Sectional Study

Background: Notable work has been done by Cecile and Murray in as early as 1926, on the structural and topological aspects of vasculature based on the concept that blood vessel size and arrangement is such that it provides blood flow with minimum energy loss. In the theoretical analysis of arterial networks, the existence of geometric optimisation for enabling functional adequacy has long been suggested, but observational studies have not yet fully corroborated these theories. Data on branching or bifurcation angles of retinal microvasculature is not only insufficient but also inconclusive. Aim: Attending to this gap in information, we compared the central retinal artery (CRA) branching angles of known diabetics with healthy subjects and explored their possible role in determining the circulatory adequacy of human retina. Methods: This study was done on North Indian subjects attending retina clinics of prominent tertiary centers of north India during 2019 through 2020. Fundus images were acquired through convenience sampling from 860 consecutive eyes of 430 subjects. Fluorescein fundus angiography was followed up for diabetics. CRA branching angles from digitalized fundus photographs of known diabetics and healthy subjects was analyzed through semi-automated digital image management tool and the readings were clinically correlated to note the occurrence and severity of retinopathic perfusion defects was Results: We found marked differences between CRA branching angles among diabetics and healthy subjects and a significant correlation between branching anless and the occurrence and severity of retinopathic perfusion defects. Discussion and Conclusion: The orientation of retinal blood vessels on the fundus plane is not merely ‘a matter of chance’ in the anatomic chronicle of the human body; rather, it has biological heralds and functional consequences. Direction, branching, angles; all determine the efficacy and abundance of blood flow in the human retina that hold indispensible relevance for optimal vision and might be subtle indicators of micro vascular damage in disease states. This study has elucidated retinal vascular geometrics of healthy and diseased Indians, a knowledge that can improve our understanding of ‘abnormal features’ and ‘natural variants’ in retinal vascular architecture. In this study, we quantified the ‘structural factors’ behind perfusion defects of the Diabetic retina.

2242-PUB: Retinal Biomarkers Indicative of Diabetic Peripheral Neuropathy

The purpose of this study was to identify biomarkers that are indicative of diabetic peripheral neuropathy (DPN). From a cohort of 21 DPN and 18 controls, optic disc- and macula-centered images were taken. Sixty vascular parameters were measured using computer-assisted software. Statistically significant differences in vascular parameters between subjects with DPN and controls showed that DPN subjects could be differentiated from controls using retinal biomarkers. Statistical significance (p < 0.05) was obtained for 13 retinal features, including fractal dimension, vein width, number of 1st branching vessels, and vessel tortuosity. The reduced fractal dimensions in DPN patients indicate a deterioration of the retinal vascular architecture. The reduced total number of vessels, as well as the total number of venules, contribute to the lower fractals in the DPN patients and supports the findings of a sparser retinal vascular network for DPN subjects. A difference in standard deviation for vessel width may suggest a greater loss of vascular tone and regulation in DPN subjects. A difference in the number of 1st branching vessels in venules was observed, which may indicate that the DPN subjects had fewer numbers of these first bifurcations. This feature would also contribute to the lower fractal dimension as well as a sparser retinal vascular network. Similarly, the statistical difference in the angle of the first daughter vessel suggests that the retinal vascular architecture has deviated from its optimal flow and/or function due to the disease process. The increased difference in curvature tortuosity in the arterioles in DPN correlates with chronic hypertensive retinopathy. We found statistically significant differences in 13 out of 60 retinal vascular features (22%) between control and DPN subjects. As such, the retina reflects the widespread vascular structural abnormalities occurring in diabetic patients with DPN. Disclosure S.C. Nemeth: None. M.R. Burge: None. J. Wigdahl: None. J.C. Carmichael: None. X. Guo: None. V. Joshi: None. P. Soliz: Stock/Shareholder; Self; VisionQuest Biomedical LLC. Funding National Institutes of Health (R43DK104578-01)

A Revised View on Growth and Remodeling in the Retinal Vasculature

The mouse retina provides an excellent model for studying angiogenesis. Recent advancements in high-throughput microscopy and image analysis provide great tools to visualize and describe the complexity of the retinal vascular architecture in a detailed and comprehensive way. Most developmental studies have focused on only a few parameters mostly in the inner-most layers that do not describe the entirety of the three-dimensional vascular network. Here, we analyzed the entire three-dimensional retinal vascular architecture and its growth and remodeling starting from the age of postnatal day 3 to 4 months in mice. We show plexus specific characteristics of the vasculature in terms of vascular tissue fraction, branching and length of the blood vessels, and distance and distribution between single capillaries. Such detailed knowledge is of particular interest, as it has become apparent that disease-specific mechanisms and treatments affect the retinal vasculature often in a plexus specific way.

Peripheral Retinal Nonperfusion in Pediatric Patients With Morning Glory Syndrome.

To report the association of morning glory syndrome (MGS) with peripheral retinal nonperfusion in pediatric patients with MGS. The authors retrospectively analyzed the records of pediatric patients with MGS using fundus fluorescein angiography. The peripheral retinal vascular architecture was recorded and graded according to the severity of peripheral retinal nonperfusion. Eighty-six eyes of 74 patients were enrolled. Seventy-three of 86 eyes (84.88%) had peripheral retinal nonperfusion, in which mild severity was found in 31 of 86 eyes (36.05%), moderate in 17 of 86 eyes (19.77%), severe in 18 of 86 eyes (20.93%), and extreme in seven of 86 eyes (8.14%). Secondary complications of nonperfusion included leakage in six of 73 eyes (8.22%), fibrovascular proliferation in two of 73 eyes (2.74%), and tractional retinal detachment in one of 73 eyes (1.34%). There is a high prevalence of peripheral retinal nonperfusion in pediatric MGS eyes, with secondary complications in some, suggesting that more attention should be paid to the peripheral retina in MGS. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:674-679.].

Sweet Stress: Coping With Vascular Dysfunction in Diabetic Retinopathy.

Oxidative stress plays key roles in the pathogenesis of retinal diseases, such as diabetic retinopathy. Reactive oxygen species (ROS) are increased in the retina in diabetes and the antioxidant defense system is also compromised. Increased ROS stimulate the release of pro-inflammatory cytokines, promoting a chronic low-grade inflammation involving various signaling pathways. An excessive production of ROS can lead to retinal endothelial cell injury, increased microvascular permeability, and recruitment of inflammatory cells at the site of inflammation. Recent studies have started unraveling the complex crosstalk between retinal endothelial cells and neuroglial cells or leukocytes, via both cell-to-cell contact and secretion of cytokines. This crosstalk is essential for the maintenance of the integrity of retinal vascular structure. Under diabetic conditions, an aberrant interaction between endothelial cells and other resident cells of the retina or invading inflammatory cells takes place in the retina. Impairment in the secretion and flow of molecular signals between different cells can compromise the retinal vascular architecture and trigger angiogenesis. In this review, the synergistic contributions of redox-inflammatory processes for endothelial dysfunction in diabetic retinopathy will be examined, with particular attention paid to endothelial cell communication with other retinal cells.

Retinal Vascular Degeneration in the Transgenic P23H Rat Model of Retinitis Pigmentosa.

Retinitis pigmentosa (RP) is a group of inherited retinal degenerative diseases involving a progressive degeneration of photoreceptor cells. Following the loss of photoreceptors, retinal vascularization tends to decrease, which seems to play a role in the degenerative process of retinal cells. This study reports changes in retinal vascular network architecture in the P23H rat model of RP at different stages of retinal degeneration. Homozygous P23H line-3 rats of ages ranging from 18 days to 16 months were used in this study. Age-matched Sprague-Dawley (SD) rats were used as control animals. Vertical sections and wholemount retinas were immunolabeled for type IV collagen or stained using NADPH diaphorase histochemistry, and retinal vascular networks were drawn using a camera lucida. The superficial and deep capillary plexus (DCP) were fully developed at P18 in P23H rat retinas and showed no differences from the control animals. In 4-month-old P23H rat retinas, the superficial and intermediate capillary plexus were similar to those observed in age-matched SD rats, but a reduction in the DCP could be observed in these animals, with a significant decrease in both capillary density and capillary loops. At 16 months, the DCP was completely lost, and only vessels exhibiting an abnormal, tortuous dead-end could be observed. The middle capillary plexus had virtually disappeared at this age. Only perpendicular vessels connecting the superficial and DCP were found. The superficial plexus showed no changes in the vascular surface with age. In RP, photoreceptor loss is accompanied by degenerative changes in the retinal vascular network. The disruption of the capillary plexus, with loss of capillary density and capillary loops, can hamper the normal supply of oxygen and nutrients to retinal cells, thus accelerating retinal degeneration. Therefore, changes in retinal vascularization must be taken into account in the design of therapies targeting retinal degenerative diseases.

Analysis of normal human retinal vascular network architecture using multifractal geometry.

To apply the multifractal analysis method as a quantitative approach to a comprehensive description of the microvascular network architecture of the normal human retina. Fifty volunteers were enrolled in this study in the Ophthalmological Clinic of Cluj-Napoca, Romania, between January 2012 and January 2014. A set of 100 segmented and skeletonised human retinal images, corresponding to normal states of the retina were studied. An automatic unsupervised method for retinal vessel segmentation was applied before multifractal analysis. The multifractal analysis of digital retinal images was made with computer algorithms, applying the standard box-counting method. Statistical analyses were performed using the GraphPad InStat software. The architecture of normal human retinal microvascular network was able to be described using the multifractal geometry. The average of generalized dimensions (Dq ) for q=0, 1, 2, the width of the multifractal spectrum (Δα=αmax - αmin ) and the spectrum arms' heights difference (|Δf|) of the normal images were expressed as mean±standard deviation (SD): for segmented versions, D0 =1.7014±0.0057; D1 =1.6507±0.0058; D2 =1.5772±0.0059; Δα=0.92441±0.0085; |Δf|= 0.1453±0.0051; for skeletonised versions, D0 =1.6303±0.0051; D1 =1.6012±0.0059; D2 =1.5531±0.0058; Δα=0.65032±0.0162; |Δf|= 0.0238±0.0161. The average of generalized dimensions (Dq ) for q=0, 1, 2, the width of the multifractal spectrum (Δα) and the spectrum arms' heights difference (|Δf|) of the segmented versions was slightly greater than the skeletonised versions. The multifractal analysis of fundus photographs may be used as a quantitative parameter for the evaluation of the complex three-dimensional structure of the retinal microvasculature as a potential marker for early detection of topological changes associated with retinal diseases.

The Association of Type 2 Diabetes Mellitus with Cerebral Gray Matter Volume Is Independent of Retinal Vascular Architecture and Retinopathy.

It is uncertain whether small vessel disease underlies the relationship between Type 2 Diabetes Mellitus (T2DM) and brain atrophy. We aimed to study whether retinal vascular architecture, as a proxy for cerebral small vessel disease, may modify or mediate the associations of T2DM with brain volumes. In this cross-sectional study using Magnetic Resonance Imaging (MRI) scans and retinal photographs in 451 people with and without T2DM, we measured brain volumes, geometric measures of retinal vascular architecture, clinical retinopathy, and MRI cerebrovascular lesions. There were 270 people with (mean age 67.3 years) and 181 without T2DM (mean age 72.9 years). T2DM was associated with lower gray matter volume (p = 0.008). T2DM was associated with greater arteriolar diameter (p = 0.03) and optimality ratio (p = 0.04), but these associations were attenuated by adjustments for age and sex. Only optimality ratio was associated with lower gray matter volume (p = 0.03). The inclusion of retinal measures in regression models did not attenuate the association of T2DM with gray matter volume. The association of T2DM with lower gray matter volume was independent of retinal vascular architecture and clinical retinopathy. Retinal vascular measures or retinopathy may not be sufficiently sensitive to confirm a microvascular basis for T2DM-related brain atrophy.

Real Time, In Vivo Analysis of the Onset of Retinogenesis: Assessment of the Retinal Vascular Plexus, Electrophysiological Response and Architecture in Neonatal Mice

PurposeTo evaluate the retinal vascular network in P0 and P1 neonates in vivo in real time.MethodsC57Bl/6J neonates were dark‐adapted overnight. Animals were subjected to clinical investigation by using electroretinography (ERG) and spectral domain optical coherence tomography (SD‐OCT) coupled to fluorescein angiography (FA).ResultsFA in P0 neonates revealed that vascularization starts as ring‐shaped vascular sprouts growing radially from the optic nerve head, becoming progressively interconnected by a capillary plexus between them. OCT data indicated that neonatal retina consisted of three layers; ganglion cell, inner plexiform and neuroblastic. The retinal thickness in P0 and P1 pups were 45 ± 7 μm, 50.2 ± 2 μm, respectively. ERG recordings were observed as early as day 0; however they exhibited a nearly abolished b‐waves and relatively preserved a‐waves. This suggests that synaptic functionality develops at the onset of postnatal retinogenesis.ConclusionsWe report here for the first time the imaging of the developing retina in real time as early as P0, which was coupled to focal‐ERG and OCT measurements. Our data indicated that despite the nearly abolished b‐wave, the retina was responsive to light stimuli. Our data also suggest that the positive‐going b‐wave of the dark‐adapted ERG response is generated by the precursor neuronal cells within the developing NBL and the response to light stimulation occurs long before the appearance of the rods and cones in the developing photoreceptor layer.

Mapping the 3D Connectivity of the Rat Inner Retinal Vascular Network Using OCT Angiography.

The purpose of this study is to demonstrate three-dimensional (3D) graphing based on optical coherence tomography (OCT) angiography for characterization of the inner retinal vascular architecture and determination of its topologic principles. Rat eyes (N = 3) were imaged with a 1300-nm spectral/Fourier domain OCT microscope. A topologic model of the inner retinal vascular network was obtained from OCT angiography data using a combination of automated and manually-guided image processing techniques. Using a resistive network model, with experimentally-quantified flow in major retinal vessels near the optic nerve head as boundary conditions, theoretical changes in the distribution of flow induced by vessel dilations were inferred. A topologically-representative 3D vectorized graph of the inner retinal vasculature, derived from OCT angiography data, is presented. The laminar and compartmental connectivity of the vasculature are characterized. In contrast to sparse connectivity between the superficial vitreal vasculature and capillary plexuses of the inner retina, connectivity between the two capillary plexus layers is dense. Simulated dilation of single arterioles is shown to produce both localized and lamina-specific changes in blood flow, while dilation of capillaries in a given retinal vascular layer is shown to lead to increased total flow in that layer. Our graphing and modeling data suggest that vascular architecture enables both local and lamina-specific control of blood flow in the inner retina. The imaging, graph analysis, and modeling approach presented here will help provide a detailed characterization of vascular changes in a variety of retinal diseases, both in experimental preclinical models and human subjects.

Digital Image Processing for Ophthalmology: Detection and Modeling of Retinal Vascular Architecture

The monitoring of the effects of retinopathy on the visual system can be assisted by analyzing the vascular architecture of the retina. This book presents methods based on Gabor filters to detect blood vessels in fundus images of the retina. Forty images of the retina from the Digital Retinal Images for Vessel Extraction (DRIVE) database were used to evaluate the performance of the methods. The results demonstrate high efficiency in the detection of blood vessels with an area under the receiver operating characteristic curve of 0.96. Monitoring the openness of the major temporal arcade (MTA) could facilitate improved diagnosis and optimized treatment of retinopathy. This book presents methods for the detection and modeling of the MTA, including the generalized Hough transform to detect parabolic forms. Results obtained with 40 images of the DRIVE database, compared with hand-drawn traces of the MTA, indicate a mean distance to the closest point of about 0.24mm. This book illustrates a plications of the methods mentioned above for the analysis of the effects of proliferative diabetic retinopathy and retinopathy of prematurity on retinal vascular architecture.

The fractal properties of the retinal vascular architecture

AbstractPurpose The human retinal vasculature has been demonstrated to exhibit fractal, or statistically self similar properties. Fractal analysis offers a simple quantitative method to characterise the complexity of the branching vessel network in the retina. Several methods have been proposed to quantify the fractal properties of the retina.Methods Twenty five healthy volunteers underwent retinal photography, retinal oximetry and ocular biometry. A robust method to evaluate the fractal properties of the retinal vessels is proposed; it consists of manual vessel segmentation and box counting of 50 degree retinal photographs centred on the fovea.Results Data is presented on the associations between the fractal properties of the retinal vessels and various functional properties of the retina.Conclusion Fractal properties of the retina could offer a promising tool to assess the risk and prognostic factors that define retinal disease. Outstanding efforts surround the need to adopt a standardised protocol for assessing the fractal properties of the retina, and further demonstrate its association with disease processes.

Multifractal Geometry in Analysis and Processing of Digital Retinal Photographs for Early Diagnosis of Human Diabetic Macular Edema

Objective: The purpose of this paper is to determine a quantitative assessment of the human retinal vascular network architecture for patients with diabetic macular edema (DME). Multifractal geometry and lacunarity parameters are used in this study.Materials and methods: A set of 10 segmented and skeletonized human retinal images, corresponding to both normal (five images) and DME states of the retina (five images), from the DRIVE database was analyzed using the Image J software. Statistical analyses were performed using Microsoft Office Excel 2003 and GraphPad InStat software.Results: The human retinal vascular network architecture has a multifractal geometry. The average of generalized dimensions (Dq) for q = 0, 1, 2 of the normal images (segmented versions), is similar to the DME cases (segmented versions). The average of generalized dimensions (Dq) for q = 0, 1 of the normal images (skeletonized versions), is slightly greater than the DME cases (skeletonized versions). However, the average of D2 for the normal images (skeletonized versions) is similar to the DME images. The average of lacunarity parameter, Λ, for the normal images (segmented and skeletonized versions) is slightly lower than the corresponding values for DME images (segmented and skeletonized versions).Conclusion: The multifractal and lacunarity analysis provides a non-invasive predictive complementary tool for an early diagnosis of patients with DME.

Retinal Vascular Geometry in Asian Persons with Diabetes and Retinopathy

Our purpose was to examine the relationship of retinal vascular parameters with diabetes and retinopathy in an older Asian population. Retinal photographs from participants of a population-based survey of Asian Malay persons aged 40-80 years were analyzed. Specific retinal vascular parameters (tortuosity, branching angle, fractal dimension, and caliber) were measured using a semiautomated computer-based program. Diabetes was defined as random plasma glucose ≥ 11.1 mmol/liter, the use of diabetes medication, or physician-diagnosed diabetes. Retinopathy signs were graded from photographs using the modified Airlie House classification system. A total of 2735 persons were included in the study. Persons with diabetes (n = 594) were more likely to have straighter (less tortuous) arterioles and wider arteriolar and venular caliber than those without diabetes (n = 2141). Among subjects with diabetes, those with retinopathy had wider venular caliber than those without retinopathy (211.3 versus 204.9 mm, p = .001). Among nondiabetic subjects, however, those with retinopathy had more tortuous venules than those without retinopathy [5.19(×10(4)) versus 4.27(×10(4)), p < .001]. Retinal vascular parameters varied by diabetes and retinopathy status in this older Asian cohort. Our findings suggest that subtle alterations in retinal vascular architecture are influenced by diabetes.

Retinal Vascular Changes in Pre-Diabetes and Prehypertension

The retinal vasculature can be viewed directly and noninvasively, offering a unique and easily accessible “window” to study the health and disease of the human microcirculation in vivo. In the last decade, advances in digital retinal photography and imaging techniques have allowed precise characterization of subtle retinal vascular changes in large populations. These retinal changes can be broadly divided into four groups: 1 ) classic retinal vascular changes in diabetes and hypertension (i.e., diabetic and hypertensive retinopathy), 2 ) isolated retinopathy signs in individuals with diabetes or hypertension (e.g., microaneurysm, retinal hemorrhage, or cotton wool spot), 3 ) changes in retinal vascular caliber, and 4 ) changes in retinal vascular architecture (e.g., retinal tortuosity). New studies in large populations now show that retinal vascular changes are common in the general population and may precede the subsequent development of overt diabetes and hypertension. A consistent pattern of associations is also emerging, showing that specific retinal vascular changes may be related differently to hyperglycemia and blood pressure. In this review, we summarize recent studies on the retinal vascular changes seen in diabetes and hypertension and speculate on potential research and clinical implications. ### Diabetic retinopathy In individuals with diabetes, the classic primary retinal vascular complication—diabetic retinopathy—is well described (1). Diabetic retinopathy signs are broadly divided into nonproliferative and proliferative retinopathy. The prevalence of diabetic retinopathy increases with duration of diabetes. The Australian Diabetes, Obesity and Lifestyle Study (AusDiab) showed that the prevalence of diabetic retinopathy is less than 10% in those with diabetes duration of less than 5 years but more than 50% in those with 20 years or longer diabetes (2). The two major risk factors of diabetic retinopathy are hyperglycemia and hypertension, with hyperlipidemia as a possible third major risk factor. The importance of hyperglycemia has been confirmed in epidemiological studies (3), as well as two pivotal …

Quantification of topological changes in retinal vascular architecture in essential and malignant hypertension

Grading of hypertension severity by fundoscopic appearance is difficult and inaccurate. We investigated whether essential hypertension (EHT) and malignant phase hypertension (MHT) were associated with quantifiable abnormalities of the topology and architecture of the retinal circulation. The topology and architecture of the retinal microvasculature were compared in images from 20 normotensive subjects, 20 patients with EHT and 20 patients with MHT. Digitized retinal photographs were analysed by a novel multiscale image analysis method using a semi-automated program to quantify geometrical and topological properties of arteriolar and venular trees. EHT was associated with an increase in the arteriolar length-to-diameter ratio (P < 0.01). There were also alterations in arteriolar topology indicative of rarefaction, including a marked reduction in the number of terminal branches in EHT (P < 0.01). These changes in the arteriolar network were exaggerated in MHT and there was also increased venular tortuosity and venular rarefaction in MHT compared with normotensive subjects. Hypertension is associated with marked topological alterations in the retinal vasculature, and quantification of these changes may be a useful novel approach to the assessment of target organ damage in hypertension.