Article

Correlation between the radial peripapillary capillaries and the retinal nerve fibre layer in the normal human retina

December 2014
Experimental Eye Research 129:83-92

December 2014
129:83-92

DOI:10.1016/j.exer.2014.10.020

Source
PubMed

Authors:

Paula Yu

University of Western Australia

Stephen John Cringle

University of Western Australia

Dao-Yi Yu

University of Western Australia

This study aims to provide evidence of the importance of radial peripapillary capillaries (RPCs) by quantitative study of the relationship between the RPCs and retinal nerve fibre layer (RNFL) in normal human donor eyes. The retinal microvasculature in eleven normal human donor eyes was perfused, fixed and labelled after cannulation of the central retinal artery. The retinas were dissected and whole-mounted for confocal microscopy. Six study regions were taken radially from the edge of the optic disc. RPCs from the optic disc edge to a radial distance up to 2.5 mm were imaged and their diameters, inter-capillary distance and volume occupation measured. These were correlated with the study region as well as thickness of the RNFL. It was found that the pooled average diameter of the RPCs in the first 2.5 mm from the optic disk was 8.9 μm. Significant differences in capillary diameter were present in the six regions, with larger diameter RPCs in the superior, inferior and nasal regions, and significantly smaller diameter in the temporal region. RPCs in the arcuate fibre regions extend the furthest from the optic disc, maintained a close inter-capillary distance for a longer distance than other regions, and have the highest RPCs volume occupancy. The RPCs volume was generally correlated with RNFL thickness. In conclusion, a close correlation between RNFL and RPCs presence has been demonstrated which is supportive of their functional reliance/co-dependence. The significantly smaller temporal RPCs may be a result of the greater presence of RPCs in the two bordering arcuate fibre regions and therefore a richer availability of nutrients diffusing from these two regions. Copyright © 2014 Elsevier Ltd. All rights reserved.

Effect of axial length on peripapillary microvasculature: An optical coherence tomography angiography study

Article

Full-text available

Oct 2021
PLOS ONE

Objective To investigate the effects of axial length (AL) on the peripapillary microvascular density acquired from optical coherence tomography angiography (OCTA). Methods Retrospective observational study. A total of 111 eyes from 111 normal healthy subjects were examined. The subjects were divided into three groups according to the AL: Group 1 (AL: < 24.0 mm; 35 eyes), Group 2 (AL: 24.0–25.99 mm; 37 eyes), and Group 3 (AL: ≥ 26 mm; 39 eyes). Peripapillary OCTA images were acquired using 6× 6 mm angiography scans, and vessel density (VD) and perfusion density (PD) of the superficial capillary plexus were calculated automatically. VD and PD were compared among the three groups according to the distance from the optic disc (inner and outer rings). Linear regression analyses were also performed to identify clinical factors associated with average VD. Results The average ALs of Groups 1–3 were 23.33± 0.57, 25.05± 0.60, and 27.42± 0.82, respectively. Average VD (P = 0.009) and PD (P = 0.029) in the inner ring increased with increasing AL. However, average VD (P < 0.001) and PD (P < 0.001) in the outer ring decreased with AL increased; the same trends were found for the full areas (VD, p<0.001; PD, p = 0.001). Average VDs in the inner and outer rings were not associated (P = 0.938). Conclusions Peripapillary VD and PD were significantly associated with AL. Depending on the distance from the disc, peripapillary VDs and PDs of the inner and outer rings were differentially affected by AL. Physicians should therefore consider the effects of AL in the analyses of peripapillary microvasculature.

Distributions of Radial Peripapillary Capillary Density and Correlations with Retinal Nerve Fiber Layer Thickness in Normal Subjects

Article

Full-text available

Aug 2021
MED SCI MONITOR

Background The aim of this study was to investigate distribution rules of radial peripapillary capillaries (RPCs) density and correlations with retinal nerve fiber layers (RNFL) thickness in normal subjects. Material/Methods We included 78 eyes of 78 healthy subjects examined by optical coherence tomography angiography (OCTA). RPCs density and RNFL thickness were measured automatically. Distributions of RPCs density and RNFL thickness were analyzed at different locations. Correlations of these 2 parameters and relationship with large vessels were evaluated by Spearman test. Results Average density for overall, peripapillary, and inside disc RCPs was 56.12±2.51%, 58.56±2.84%, and 60.16±4.01%, respectively. Overall and peripapillary RCPs density were positively correlated with RNFL thickness (r=0.595, P<0.0001; r=0.578, P<0.0001). The highest RCPs density was found in the temporal quadrant and was lowest nasally, whereas the RNFL thickness was found to be lowest temporally and higher in the nasal region. However, a positive correlation was found in each sector, which was highest in the temporal inferior (r=0.550, P<0.0001). Large vessels were insignificantly correlated with both RCPs density and RNFL thickness in sector analysis. Conclusions Although the distributions of RPCs density and RNFL thickness were different, a positive correlation was found in each sector. Distribution rules of RPCs density and RNFL thickness were related to both vascular-structure and activity-vascular.

Quantitative Analysis of the RPC Vessel Density and the RNFL Thickness in Patients with Type 2 Diabetes Mellitus by Using OCT Angiography

Article

Full-text available

Jul 2021
OPHTHAL RES

Introduction: This study aims to compare the structural differences in the optic disc blood perfusion and the peripapillary retinal nerve fibre layer (pRNFL) thickness in age-matched healthy subjects and patients with type 2 diabetes mellitus (DM) by using quantitative analysis with optical coherence tomography angiography (OCTA). Methods: A cross-sectional cohort study on patients with type 2 DM with or without diabetic retinopathy (DR) and healthy subjects was conducted. The 4.5-mm scanning angio-disc pattern of the OCTA system was used to assess the optic disc. The analysed indices included radial peripapillary capillary (RPC) vessel density and pRNFL thickness. Results: A total of 78 eyes from 78 patients with type 2 DM, including 27 without clinical DR (NDR), 26 with non-proliferative DR (NPDR), and 25 with proliferative DR (PDR), and 28 age-matched healthy subjects were enrolled. The average RPC vessel density of the whole (p < 0.001) and the peripapillary (p < 0.001) regions was significantly different in different groups, whereas the pRNFL was not statistically significant (p = 0.764). Compared with that in healthy subjects, the RPC vessel densities in 4, 5, and 8 peripapillary sectors in NDR (all p < 0.05), NPDR (all p < 0.05), and PDR (all p < 0.05) groups, respectively, were reduced. Compared with that in healthy subjects, the pRNFL thickness significantly decreased in the inferior nasal sector (p = 0.001) in NDR but significantly increased in the 2 sectors (all p < 0.01) in PDR. The DR severity was negatively correlated with the peripapillary RPC vessel density (r = -0.583, p < 0.001) but had no correlation with the pRNFL thickness (r = -0.045, p = 0.648). The positive correlation between the peripapillary RPC vessel density and the pRNFL thickness was statistically significant in the control (r = 0.531, p = 0.004), NDR (r = 0.528, p = 0.004), and NPDR (r = 0.405, p = 0.040) groups but not in the PDR group (r = 0.394, p = 0.05). Conclusions: The peripapillary RPC perfusion decreased with DR aggravation, which may be considered as a useful indicator of DR severity. However, the pRNFL thickness had little diagnostic power in differentiating healthy and DM eyes.

Changes of Peripapillary Region Perfusion in Patients with Chiasmal Compression Caused by Sellar Region Mass

Article

Full-text available

Jun 2021

Purpose: To evaluate the peripapillary vessel density (pVD) and the peripapillary nerve fiber layer (pRNFL) thickness in patients with chiasmal compression caused by sellar region mass using optical coherence tomography angiography (OCTA). Methods: This is an observational, cross-sectional study of 31 patients (31 eyes) with chiasmal compression caused by sellar region mass and 34 healthy controls (34 eyes). Automated perimetry and OCTA were performed. The pVD and pRNFL thickness were compared between the two groups. The impact of tumor diameter, duration of symptoms, and cavernous sinus (CS) invasion on visual dysfunction, pVD, and pRNFL thickness was also analyzed. Furthermore, we divided the patients into two subgroups according to whether there was an absolute defect in the central visual field and evaluated their pVD and pRNFL thickness, respectively. Results: Compared to the healthy control group, there was a statistically significant decrease in pVD and pRNFL thickness in patients with chiasmal compression (p < 0.05), especially in patients with substantial absolute defects in the central visual field. Tumor diameter, duration of symptoms, and CS invasion did not appear to be associated with pVD and pRNFL thickness. There was a significant positive correlation between the pVD and pRNFL thickness in patients with chiasmal compression (p < 0.001). Conclusion: pVD and pRNFL thickness are significantly decreased in patients with chiasmal compression revealed by OCTA, especially in patients with more severe visual field defects. A significant correlation between pVD and pRNFL thickness was demonstrated, which provides a clue for the study of the mechanism of changes in retinal perfusion in compressive optic neuropathy. It requires considerable attention that OCTA may play an important role in disease monitoring of sellar region mass. Hence, further studies are needed to verify whether OCTA is helpful to predict the prognosis of visual function after decompression surgery.

The Evaluation of Giant-Cell Arteritis (Temporal Arteritis) Cases with Optical Coherence Tomography Angiography (OCT-A)

Preprint

Full-text available

Aug 2023

AIM: This study aimed tomeasureinactive giant cell arteritis (GCA) using optical coherence tomography angiography (OCT-A) in patients previously affected by GCAand treated (patient group), and to compare these measures with those of healthy volunteers (control group). METHODS: In this observational case-control study, 18 eyes of 18 GCA cases previously diagnosed, treated with anterior arteritic ischemic optic neuropathy (AAION) were examined. 22 eyes of 22 ophthalmically healthy volunteers were included in the study. After external ophthalmic examinations of all participants were performed, their measurements were made with serial OCT-A. Superficial capillary plexus (SCP), deep capillary plexus (DCP), foveal avascular zone (FAZ), area covering 300 degrees around the fovea (FD-300), choriocapillaris (CC), retinal nerve fiber layer (RNFL), cup/disc (C/D) ratio and optic disc vessel densities (OD-VD) were evaluated. A value of p<0.05 was considered significant for statistical analyses. RESULTS: There was no difference between the two groups in terms of age, gender and shooting quality. Whole-SCP, SCP-foveal, SCP-parafoveal and SCP-perifoveal VD values were lower in the patient group. Whole-DCP, DCP-parafoveal and DCP-perifoveal VD values were also lower in the patient group than control group. FAZ areas were similar between groups, but the FD-300 VD was different. Whole-OD VD and inside-OD VD were significantly lower in the patient group. Peripapillary-OD VD and RNFL values were similar. The C/D ratio was higher in the patient group.The effect on the microvascular process was significant in OCT-A. CONCLUSION: The results suggested that even if the ischemic process still continues and there is no active inflammation, microvascular structures may continue to be affected.

OCT angiography, RNFL and the visual field at different values of intraocular pressure

Article

Full-text available

Mar 2022

The aim of the present study was to investigate the relationship between intraocular pressure (IOP), vessel density (VD), retinal nerve fiber layer (RNFL) parameters and overall defect (OD) of the visual field in eyes where antiglaucoma treatment had not yet been initiated. A total of 61 subjects (122 eyes) who had an IOP of >20 mmHg on several occasions, in at least one eye, in routine outpatient care were included. These were subjects who had never been treated for hypertension glaucoma. The cohort was divided into four subgroups. In the first group, there were 18 eyes with an IOP value of <20 mmHg. In the second group, there were 39 eyes with IOP values of 20-22 mmHg. The third group consisted of 32 eyes with IOP values of 22-24 mmHg and the final group consisted of 33 eyes with IOP values of >24 mmHg. The IOP results were compared with VD, RNFL and OD using Pearson's correlation coefficient to assess the relationship between the selected parameters. RNFL and OD were moderately correlated only in the group of eyes with an IOP value >24 (r=0.48); in the other groups the correlation was very weak. However, changes in visual field were already observed in eyes with IOP 20-22 mmHg (r=-0.27). There was a moderate correlation in eyes with an IOP value >24 mmHg (r=-0.53). The most significant result observed was the relationship between VD and RNFL. In eyes with an IOP value ≤20, a moderate to strong correlation between these parameters was observed. This relationship increased with increasing IOP values up to a very strong correlation in the group with an IOP value >24 mmHg. A moderate to strong dependence between VD and RNFL in eyes with an IOP value ≤20 mmHg was observed, and this dependence was very strongly correlated in the eyes with an IOP value >24 mmHg.

Association of Neuroretinal Thinning and Microvascular Changes with Hypertension in an Older Population in Southern Italy

Article

Full-text available

Feb 2022

Background: Retinal microvasculature assessment at capillary level may potentially aid the evaluation of early microvascular changes due to hypertension. We aimed to investigate associations between the measures obtained using optical coherence tomography (OCT) and OCT-angiography (OCT-A) and hypertension, in a southern Italian older population. Methods: We performed a cross-sectional analysis from a population-based study on 731 participants aged 65 years+ subdivided into two groups according to the presence or absence of blood hypertension without hypertensive retinopathy. The average thickness of the ganglion cell complex (GCC) and the retinal nerve fiber layer (RNFL) were measured. The foveal avascular zone area, vascular density (VD) at the macular site and of the optic nerve head (ONH) and radial peripapillary capillary (RPC) plexi were evaluated. Logistic regression was applied to assess the association of ocular measurements with hypertension. Results: GCC thickness was inversely associated with hypertension (odds ratio (OR): 0.98, 95% confidence interval (CI): 0.97-1). A rarefaction of VD of the ONH plexus at the inferior temporal sector (OR: 0.95, 95% CI: 0.91-0.99) and, conversely, a higher VD of the ONH and RPC plexi inside optic disc (OR: 1.07, 95% CI: 1.04-1.10; OR: 1.04, 95% CI: 1.02-1.06, respectively) were significantly associated with hypertension. Conclusion: A neuroretinal thinning involving GCC and a change in capillary density at the peripapillary network were related to the hypertension in older patients without hypertensive retinopathy. Assessing peripapillary retinal microvasculature using OCT-A may be a useful non-invasive approach to detect early microvascular changes due to hypertension.

Does the ISNT rule apply to the radial peripapillary capillary vessel density in OCT angiography?

Article

Full-text available

Jan 2022
GRAEF ARCH CLIN EXP

PurposeTo investigate the applicability of ISNT (inferior ≥ superior ≥ nasal ≥ temporal), IST (inferior ≥ superior ≥ temporal), and T min (temporal quadrant with the minimum value) rules to the peripapillary nerve fiber layer (NFL) thickness and radial peripapillary capillary (RPC) vessel density (VD) using Optical Coherence Tomography (OCT) and OCT angiography (OCT-A).Materials and methodsThis cross-sectional study included 134 eyes of 74 healthy individuals. NFL thickness and RPC VD were measured in all four quadrants using OCT and OCT-A in order to determine the number of eyes that obey the ISNT, IST, and T min rules.ResultsMean age was 48.8 ± 15.5 (range 25–82) years. The ISNT rule was valid in 52 eyes (38.81%) on OCT and only 12 eyes (8.95%) on OCT-A scans. The IST rule was followed by 83 (61.94%) and 37 (27.61%) eyes on OCT and OCT-A scans respectively. The T min rule was valid in 86 eyes (64.18%) in OCT scans and in 26 eyes (19.4%) in OCT-A scans.Conclusion The topography of the RPC network does not obey the ISNT rule in healthy eyes. The ISNT rule and its variants were found to be more relevant in OCT NFL thickness measurements compared to OCT-A RPC VD measurements.

Early vascular modifications after endoscopic endonasal pituitary surgery: The role of OCT-angiography

Article

Full-text available

Oct 2020
PLOS ONE

PurposeThe aim of the present study is to analyze the changes in retinal vessel density (VD), using Optical Coherence Tomography Angiography (OCT-A), in patients that received endoscopic endonasal approach for the removal of an intra-suprasellar pituitary adenoma compressing optic chiasm.Methods We evaluated the VD in Superficial Capillary Plexus (SCP), Deep Capillary Plexus (DCP), Radial Peripapillary Capillary (RPC) and the Foveal Avascular Zone (FAZ) area in a series of fourteen patients (7 males, 7 females, mean age 56 ± 13 years), as compared to healthy controls. We also detected the structural Spectral Domain (SD)-OCT parameters: Ganglion Cell Complex (GCC), Retinal Nerve Fiber Layer (RNFL), visual field parameters (Mean Deviation, Pattern Standard Deviation) and Best Corrected Visual Acuity (BCVA). These measurements were performed prior than surgery and 48 hours after.ResultsThe patients showed a significant decrease in VD of the macular and papillary regions, a significant increase in FAZ area, a significant impairment in SD-OCT, VF parameters and BCVA respect to 14 eyes of 14 healthy controls (p

Multifunctional adaptive optics optical coherence tomography allows cellular scale reflectometry, polarimetry, and angiography in the living human eye

Article

Full-text available

Jan 2024

Clinicians are unable to detect glaucoma until substantial loss or dysfunction of retinal ganglion cells occurs. To this end, novel measures are needed. We have developed an optical imaging solution based on adaptive optics optical coherence tomography (AO-OCT) to discern key clinical features of glaucoma and other neurodegenerative diseases at the cellular scale in the living eye. Here, we test the feasibility of measuring AO-OCT-based reflectance, retardance, optic axis orientation, and angiogram at specifically targeted locations in the living human retina and optic nerve head. Multifunctional imaging, combined with focus stacking and global image registration algorithms, allows us to visualize cellular details of retinal nerve fiber bundles, ganglion cell layer somas, glial septa, superior vascular complex capillaries, and connective tissues. These are key histologic features of neurodegenerative diseases, including glaucoma, that are now measurable in vivo with excellent repeatability and reproducibility. Incorporating this noninvasive cellular-scale imaging with objective measurements will significantly enhance existing clinical assessments, which is pivotal in facilitating the early detection of eye disease and understanding the mechanisms of neurodegeneration.

Retinal Microvascular Changes in Internal Carotid Artery Stenosis

Article

Full-text available

Sep 2023

Purpose: We aimed to analyze retinal microvascular parameters, measured by optical coherence tomography angiography in patients with internal carotid artery stenosis compared to healthy individuals. Materials and Methods: A total of 41 eyes from 30 patients who had varying degrees of carotid stenosis, and 42 eyes from 42 healthy controls, were enrolled in this study. Depending on the degree of stenosis evaluated by Doppler ultrasonographic imaging, the patient group was further subclassified into mild, moderate, and severe carotid artery stenosis. Superficial and deep capillary plexus vessel densities, radial peripapillary capillary vessel density, foveal avascular zone, and flow densities in the choriocapillaris and outer retina were evaluated by optical coherence tomography angiography. Results: The superficial and deep capillary plexus vessel densities were significantly reduced among the groups, only sparing the foveal region. The mean superficial plexus vessel density was 45.67 ± 4.65 and 50.09 ± 4.05 for the patient and control group, respectively (p = 0.000). The mean deep capillary plexus density was 46.33% ± 7.31% and 53.27% ± 6.31% for the patient and control group, respectively (p = 0.000). The mean superficial and deep capillary vessel densities in the foveal region did not show any statistical difference between the patient and control groups (p = 0.333 for the superficial and p = 0.195 for the deep plexus vessel density). Radial peripapillary capillary vessel density was decreased in the patient group (p = 0.004). The foveal avascular zone area was wider in the patient group but this difference did not show a significant difference (p = 0.385). Conclusions: Retinal microvascular changes are a prominent outcome of internal carotid disease, and even mild stenosis can lead to alterations in the retinal microvascular bed which could be detected by OCTA. By early detection of microvascular changes in the retina in this patient group, we might speculate the overall vascular condition.

Assessment of Retinal Vessels Density and Blood Flow Density in Patients with Primary Open Angle Glaucoma Using Ocular Coherence Tomography Angiography

Article

Apr 2023

Discrepancy between peripapillary retinal and choroidal microvasculature and the rate of localized retinal nerve fiber layer thinning in glaucoma

Article

Full-text available

Apr 2023

This observational case series study is conducted to compare the extent of microvasculature impairment in the peripapillary retina and choroid in eyes with primary open-angle glaucoma (POAG), and to investigate the association of the discrepancy between the microvasculature impairments of each layer with the rate of progressive retinal nerve fiber layer (RNFL) thinning. A total of 88 POAG eyes with a localized RNFL defect were enrolled, including 67 eyes with and 21 eyes without choroidal microvasculature dropout (CMvD). Circumferential widths of retinal microvascular impairment (RMvI) and CMvD were measured, and eyes were classified based on the relative width of CMvD to RMvI (CMvD/RMvI ratio). The rate of RNFL thinning was determined by linear regression based on ≥ 5 serial OCT examinations. Thinner global RNFL and worse visual field mean deviation at baseline were associated with a larger circumferential width of the RMvI, whereas the presence of cold extremities, lower mean arterial pressure and thinner juxtapapillary choroid were associated with a larger circumferential width of the CMvD. The rate of global RNFL thinning was faster in eyes with larger relative CMvD width than in eyes with equal CMvD and RMvI widths and in eyes without CMvD (P = 0.001). Lower mean arterial pressure (P = 0.041), larger CMvD width (P = 0.046), larger CMvD/RMvI ratio (P = 0.041), and detection of disc hemorrhage during the follow-up (P = 0.013) were significant factors associated with faster global RNFL thinning. Larger CMvD width relative to RMvI width may be indicative of an increased risk of faster RNFL thinning in POAG with localized RNFL defect. Comparing the microvasculature impairment in individual layers may help predict more rapid glaucoma progression.

A Deep Learning System Using Optical Coherence Tomography Angiography to Detect Glaucoma and Anterior Ischemic Optic Neuropathy

Article

Full-text available

Jan 2023

Introduction: Glaucoma and non-arteritic anterior ischemic optic neuropathy (NAION) are optic neuropathies that can both lead to irreversible blindness. Several studies have compared optical coherence tomography angiography (OCTA) findings in glaucoma and NAION in the presence of similar functional and structural damages with contradictory results. The goal of this study was to use a deep learning system to differentiate OCTA in glaucoma and NAION. Material and methods: Sixty eyes with glaucoma (including primary open angle glaucoma, angle-closure glaucoma, normal tension glaucoma, pigmentary glaucoma, pseudoexfoliative glaucoma and juvenile glaucoma), thirty eyes with atrophic NAION and forty control eyes (NC) were included. All patients underwent OCTA imaging and automatic segmentation was used to analyze the macular superficial capillary plexus (SCP) and the radial peripapillary capillary (RPC) plexus. We used the classic convolutional neural network (CNN) architecture of ResNet50. Attribution maps were obtained using the "Integrated Gradients" method. Results: The best performances were obtained with the SCP + RPC model achieving a mean area under the receiver operating characteristics curve (ROC AUC) of 0.94 (95% CI 0.92-0.96) for glaucoma, 0.90 (95% CI 0.86-0.94) for NAION and 0.96 (95% CI 0.96-0.97) for NC. Conclusion: This study shows that deep learning architecture can classify NAION, glaucoma and normal OCTA images with a good diagnostic performance and may outperform the specialist assessment.

Diabetogenic Effects of Antihypertensive Drugs and Statins

Chapter

Full-text available

Jan 2023

Data obtained from observational studies have shown that patients with untreated hypertension display an increased incidence of type 2 diabetes mellitus compared with the normotensive state. They have also shown that this phenomenon is made worse when thiazide diuretics or beta-blockers are administered chronically. Pathophysiological mechanisms recognize in inflammation and impaired insulin sensitivity the principal factors responsible for the new-onset diabetes in hypertensive subjects in particular when affected by concomitant presence of obesity, metabolic syndrome, and heart failure. Patients at high cardiovascular risk needing far a primary and/or secondary prevention with statins have also shown that the use of these drugs are associated with development of new-onset diabetes or worsening of glycemic profile. This could be attributed to the pathophysiological mechanisms of statins that induce an impaired insulin sensitivity and an inflammatory status. This paper will review the above data and discuss their clinical implications for protection of patients from hypertension or dyslipidemia based on current treatment of these conditions.

Molecular Mechanisms Underlying Vascular Disease in Diabetes

Chapter

Jan 2023

The major cause of morbidity and mortality in diabetes is cardiovascular disease due to microvascular and macrovascular disease. Macrovascular disease in diabetes is typically associated with atherosclerosis and calcification leading to heart disease and stroke. Microvascular disease leads to retinopathy, nephropathy and neuropathy. Clinically this manifests as reduced vision and blindness, kidney dysfunction and peripheral neuropathy—major complications of diabetes. Vascular effects in diabetes are exacerbated by hypertension and other comorbidities, such as obesity and dyslipidaemia. Accordingly, diabetes and hypertension are closely interlinked due to similar risk factors such as endothelial dysfunction, vascular inflammation, arterial remodelling, atherosclerosis, dyslipidaemia and obesity. Pathophysiological processes that cause diabetes-associated vasculopathy include hyperglycaemia and insulin resistance. Molecular mechanisms that underlie microvascular and macrovascular disease include oxidative stress, inflammation, activation of the immune system, miRNAs and advanced glycation end products (AGEs). This chapter discusses the vasculopathy in diabetes and discusses the pathophysiology and molecular mechanisms of vascular complications associated with diabetes.

Densidad vascular macular y peripapilar medida con angiografía por tomografía de coherencia óptica en glaucoma preperimétrico, hipertensos oculares y ojos normales

Article

Full-text available

Sep 2022

Introducción: El objetivo del estudio fue comparar la densidad vascular (DV) peripapilar y macular medidos con la angiografía por tomografía óptica (OCTA) entre pacientes con glaucoma preperimétrico (GP), hipertensión ocular (HTO) y sanos. Material y métodos: Estudio transversal, de cohorte, observacional y prospectivo. Se incluyeron 90 ojos de 90 pacientes divididos en: 30 con GP, 30 con HTO y 30 sanos; durante octubre del 2020 hasta enero 2021. Se usó la OCTA de fuente de barrido (SS-DRI OCT; Triton, Topcon, Japón). Resultados: Encontramos diferencia estadísticamente significativa en la DV macular entre los 3 grupos (ANOVA p < 0.001), pero no en la DV peripapilar (ANOVA p = 0.081). En el análisis por cuadrantes de la DV macular y peripapilar, hallamos diferencias estadísticamente significativas en todos, excepto en el cuadrante temporal (ANOVA p = 0.449) y nasal (ANOVA p = 0.532) respectivamente. Todos los espesores de la capa de bras nerviosas retinales (CFNR), se redujeron significativamente en los cuadrantes temporal (ANOVA, p = 0.001) e inferior (ANOVA p = 0.011). Al correlacionar la CFNR y su correspondiente DV macular y peripapilar, no fue significativa en ninguno de los cuadrantes del grupo GP. Conclusiones: La OCTA es una tecnología prometedora que permite la visualización no invasiva de los vasos capilares peripapilares y retinianos. Existe una diferencia significativa en la densidad vascular promedio y por sectores entre los pacientes con GP, HTO y sanos. Aún no es claro si el daño estructural antecede al daño vascular.

Reduced choroidal peripapillary capillaries in thyroid-associated ophthalmopathy with early stage of dysthyroid optic neuropathy

Article

Full-text available

Jul 2022

Aim: To investigate whether the subtle change of choroidal/retinal vessel densities and volumes in thyroid-associated ophthalmopathy (TAO) could be an early sign to detect dysthyroid optic neuropathy (DON). Methods: This was a retrospective cross-sectional study, and a total of 98 eyes from 50 subjects were enrolled under certain criteria. Thirty-four eyes of normal controls and 64 eyes of TAO, including 39 eyes of DON and 25 eyes of TAO without DON, underwent optical coherence tomography angiography (OCTA) scanning. All the tested parameters of OCTA scanning including choroid radial peripapillary capillaries (RPC), retinal nerve fiber layer (RNFL), and macular ganglion cell complex (GCC) were compared among groups, and the correlation between OCTA parameters and visual function parameters was also investigated. Results: Whole choroidal RPC was significantly reduced in DON (48.24%±0.4978%) compared to normal (50.33%±0.3173%) and TAO without DON (49.16%±0.5463%; P=0.0041). The reduction of whole choroidal RPC was also correlated with visual field (VF) defect in DON (r=0.5422, n=39). Although vision acuity and VF were improved in all the patients with DON after being treated with medical and surgical decompression, the reduction of RPC density were not reversed. Conclusion: There is a notable reduction in choroidal RPC in DON, which is correlated with VF defect. The reduction of RPC density could not be reversed immediately by medical and surgical decompression even when vision and VF were improved. These findings suggest that choroidal RPC could be a useful parameter to diagnose and monitor early stage of DON.

Evaluation of the radial peripapillary capillary density in unilateral branch retinal vein occlusion and the unaffected fellow eyes

Article

Full-text available

Apr 2022

Background Given that unilateral branch retinal vein occlusion (BRVO) and glaucoma share common systemic vascular risk factors, the fellow eyes of patients with BRVO may be at increased risk of glaucoma. Objectives To analyze the radial peripapillary capillary density (RPCD) in eyes with unilateral BRVO and their unaffected fellow eyes using optical coherence tomography angiography (OCTA). Design Cross-sectional, prospective study. Methods The study included 120 eyes of 80 patients: 40 affected eyes of BRVO, 40 fellow eyes of BRVO, and 40 control eyes. The RPCD, retinal nerve fiber layer thickness (RNFLT) were analyzed using OCTA. Results RPCDs in the whole image, peripapillary region, all the hemispheres, and quadrants were statistically lower in the affected eyes than in both the fellow and control eyes ( p < 0.05 for all). RPCD values in the whole image and the peripapillary region were significantly lower in the fellow eyes than in the control eyes ( p = 0.013, and p = 0.021, respectively). RNFLTs in the peripapillary region, inferior hemisphere and inferior quadrant were significantly lower in the affected eyes than in the control eyes ( p < 0.05 for all). No significant differences were detected between the fellow eyes and the control eyes in term of RNFLT values in any regions ( p > 0.05 for all). Conclusion Lower RPCD values despite similar RNFLT values were observed in the fellow eyes of patients with unilateral BRVO compared with healthy controls. These results may indicate the shared vascular mechanisms and risk factors that account for the development of BRVO and glaucoma.

Patients with unilateral retinal vein occlusion show reduced radial peripapillary capillary density in their fellow eyes

Article

Full-text available

Dec 2021
BMC Ophthalmol

Background To evaluate the radial peripapillary capillary (RPC) density in the fellow eyes of unilateral retinal vein occlusion (RVO) patients using optical coherence tomography angiography (OCTA), and further analyze the correlation between RPC density and peripapillary retinal nerve fiber layer (RNFL) thickness. Methods Seventy-eight unilateral RVO patients and 70 normal controls were included in the study. OCTA was conducted with the 4.5 × 4.5-mm scan pattern centered on the optic nerve head, and the RPC density and peripapillary RNFL thickness were quantified. Results The peripapillary RNFL in the RVO fellow eyes was significantly thinner than in normal controls in the average, inferior-hemisphere, inferior quadrant, and temporal quadrant ( P < 0.05, respectively). The RPC density in the fellow eyes was also significantly lower in the average, inferior-hemisphere, nasal quadrant, and temporal quadrant (( P < 0.05, respectively). There were no significant differences in RNFL thickness and RPC density between branch RVO fellow eyes and central RVO fellow eyes. Pearson’s correlation analysis showed significant positive correlations between the RPC density and RNFL thickness in all measurements ( P < 0.001, respectively). Conclusions The regional RPC density was reduced in the RVO fellow eyes, which might contribute to peripapillary RNFL thinning in the corresponding region, suggesting the influence of systemic risk factors on RVO. OCTA may offer new insights into the pathophysiology of RVO.

Assessment of the retinal vasculature in healthy Chinese preschool children aged 4–6 years old using optical coherence tomography angiography

Article

Full-text available

Dec 2021
BMC Ophthalmol

Purpose To establish normal parameters of macular and optic disc vasculature by optical coherence tomography angiography (OCTA) in healthy preschool children aged 4–6 years old in China. OCTA reflects retinal metabolism and development in children at these ages and could be used clinically and in future studies to aid diagnosis and prediction of retinal abnormalities and developmental stagnation. Methods In this cross-sectional study, we measured foveal, parafoveal, and perifoveal vessel density in the superficial capillary plexus (SCP); the deep capillary plexus (DCP), the foveal avascular zone (FAZ), and the radial capillary peripapillary (RPC) in the optic disc using investigational spectral-domain OCTA. The magnification effect of the FAZ area and microvasculature measurements was corrected by Littman and the modified Bennett formula. Results A total of 242 eyes (116 males and 126 females, 5.31 ± 0.73 years) were recruited for the analysis. The mean macular vessel density was 48.10 ± 2.92% and 48.74 ± 6.51% in the SCP and the DCP, respectively. The RPC vessel density was 47.17 ± 2.52%, 47.99 ± 4.48%, and 48.41 ± 3.07% in the whole image, inside disc, and peripapillary, respectively; and the mean FAZ area was 0.28 ± 0.11 mm ² . A significant difference between male and female participants was found in the retinal vasculature (DCP, SCP, and RPC). None of these parameters were significantly different in age ( P > 0.05), except that DCP slightly increased with aging. The right and left eyes had good consistency in the parameters of the macula and optic disc. Conclusions Our study establishes the macular and optic disc OCTA reference values in 4- to 6-year-old healthy preschool children. They may be used in longitudinal OCTA studies and clinical applications.

Carotid disease and retinal optical coherence tomography angiography parameters in patients with non-arteritic anterior ischemic optic neuropathy

Article

Full-text available

Jan 2022
Int Ophthalmol

Fatma Selin Kaya

PurposeIn order to analyze the data and retinal microvasculature for non-arteritic anterior ischemic optic neuropathy (NAION), patients were referred to have carotid Doppler ultrasound (CDU) from 2016 to 2020.Methods In this case–control observational study, 30 NAION patients were evaluated with CDU. Twenty-two NAION patients (at least 3 months after the onset of symptoms) and 9 normal subjects underwent a complete ophthalmic examination including optical coherence tomography (OCT) and optical coherence tomography angiography (OCT-A). NAION eyes and fellow eyes were further divided into two groups based on the presence of carotid stenosis (CS). NAION patients with CS were termed “CS-NAION”; and those without CS were termed “NCS-NAION.” Measurements of radial peripapillary capillary vessel density (RPC VD), ganglion cell complex (GCC), retinal nerve fiber layer (RNFL) thicknesses were compared among groups.ResultsFourteen of 30 NAION patients referred to have carotid Doppler were positive for CS with each one of such referrals having less than 50% stenosis. RNLF, GCC and RPC VDs were reduced in NAION patients’ eyes, when compared to controls and the fellow eyes. RPC VD was significantly lower in the temporal-superior (P = 0.037) and the superior-temporal (P = 0.012) sectors of the NCS-NAION patients than in the CS-NAION patients. No significant differences were found between CS-fellow eyes and NCS-fellow eyes in terms of RPC VDs, RNLF or GCC.Conclusion Results of the study highlight the effect of the carotid artery stenosis on ocular perfusion pressure in the pathogenesis of NAION. More extensive studies are necessary.

Peripapillary Vascular Density and Retinal Nerve Fiber Layer Changes in Patients with Chronic Obstructive Pulmonary Disease

Article

Full-text available

Mar 2021
CLIN RESPIR J

Introduction Chronic obstructive pulmonary disease (COPD) is a systemic disease which may cause end organ damage. Objectives In this study, we aimed to investigate the radial peripapillary capillary (RPC) density and retinal nerve fiber layer (RNFL) thickness changes in patients with COPD. Methods The right eyes of 35 patients with COPD and 35 healthy controls were evaluated with optical coherence tomography angiography (OCTA). RPC density values and RNFL thicknesses were measured and compared. Results The mean inside disc vascular density and the mean peripapillary vascular density values were lower in the COPD group (p=0.002, p <0.001, respectively). When the peripapillary area was evaluated independently as eight different quadrants, the RPC density values were lower in the COPD group in all of the quadrants except superotemporal and temporal superior quadrants. RNFL was thinner in all quadrants in the COPD group compared to the control group. But this difference was significant only in the nasal superior and inferonasal quadrants (p=0.03, p=0.04, respectively). Although, there was no correlation between the mean RPC density and the mean peripapillary RNFL thickness of the patients, FEV1 values for all patients were found to be correlated with the mean peripapillary RPC density (r=0.406, p=0.015). Conclusion OCTA may have a potential to be used in the follow‐up of COPD patients.

Carotid Disease and Retinal Optical Coherence Tomography Angiography Parameters in Patients with Non-arteritic Anterior İschemic Optic Neuropathy

Preprint

Full-text available

Feb 2021

Fatma Selin Kaya

Purpose: To analyze the data and retinal microvasculature for nonarteritic anterior ischemic optic neuropathy (NAİON) patients referred to have carotid Doppler ultrasound from 2016 to 2020. Methods: In this case-control observational study, 30 NAİON patients evaulated with carotid doppler sonography. 22 NAION patients (at least 3 months after onset of symptoms) and 9 normal subjects underwent a complete ophthalmic examination including optical coherence tomography (OCT), optical coherence tomography angiography (OCT-A). NAİON eyes and fellow eyes were further divided into the groups according to presence of carotid stenosis (CS). NAION patients with CS were termed "CS-NAION"; those without were termed "NCS-NAION". Measurements of radial peripapillary capillary vessel density (RPC VD) and ganglion cell complex (GCC), disk retinal nerve fiber layer (RNFL) thickness were compared among groups. Results: Fourteen of 30 NAİON patients referred for carotid Doppler were positive for CS with all of such referrals having less than 50% stenosis. RNLF, GCC and RPC VDs were reduced in NAION eyes, when compared to controls and the fellow eyes. RPC VD was significantly lower in the temporal-superior (P=0.037) and the superior-temporal (P=0.012) sectors of the NCS-NAION patients than in the CS-NAION patients. No significant differences were found between CS-fellow eyes and NCS-fellow eyes in terms of RPC VDs, RNLF or GCC. Conclusion: Results of the study highlight the effect of carotid artery stenosis on ocular perfusion pressure in the pathogenesis of NAİON. More extensive studies are necessary.

Macula Structure and Microvascular Changes in Recent Small Subcortical Infarct Patients

Article

Full-text available

Jan 2021

Purpose: This study aimed to assess the macula structure and capillaries in the macula and optic nerve head in recent small subcortical infarct (RSSI) patients. Methods: This observational cross-sectional study included 40 RSSI patients and 46 healthy controls. Optical coherence tomography angiography was used to image the capillaries in the macula and optic nerve head. An inbuilt algorithm was used to measure the densities in the microvasculature of the macula [superficial retinal capillary plexus (SRCP) and deep retinal capillary plexus (DRCP)] and optic nerve head [radial peripapillary capillary (RPC)] and thickness around the optic nerve head, peripapillary retinal nerve fiber layer (pRNFL). Results: Densities in RPC (P < 0.001), SRCP (P = 0.001), and DRCP (P = 0.003) were reduced in RSSI patients when compared with healthy controls. The pRNFL thickness was thinner (P < 0.001) in RSSI patients than healthy controls. In the RSSI group, the SRCP density significantly correlated with the DRCP density (rho = 0.381, P = 0.042). The pRNFL thickness displayed a significant relationship with the RPC density (rho = 0.482, P = 0.003) in the RSSI group. Conclusions: RSSI patients showed interrupted capillary plexuses leading to its significant impairment and neurodegeneration. Our report provides insight into the macula capillary microcirculation changes in RSSI.

Correlation Analysis between Nerve Fiber Layer Thickness and Peripapillary Vessel Density and Influencing Factors of Peripapillary Vessel Density in Preclinical Diabetic Retinopathy

Article

Full-text available

Dec 2020

Purpose. To observe the changes of the retinal nerve fiber layer (RNFL) thickness and the optic disc vessel density (VD) in preclinical diabetic retinopathy (DR) and the relationship between RNFL changes and VD, as well as to investigate the influencing factors on peripapillary vessel density. Methods. This was a cross-sectional study. Thirty-four eyes of 34 type 2 diabetes mellitus (T2DM) patients diagnosed with preclinical diabetic retinopathy (DR) were included in our study, with twenty-three eyes of 23 healthy subjects set up as normal controls. History of diabetes, hypertension, and dyslipidemia was recorded in detail. All participants underwent color fundus photography (CFP), RNFL around the optic disc, and OCT angiography (OCTA) over the optic disc. The 4.5 mm × 4.5 mm Angio Disc scan mode was performed with all participants by using the OCTA instrument. The relationship between changes of RNFL in the four quadrants (superior, inferior, temporal, and nasal) and VD changes was analyzed. Results. Vessel density was significantly lower in the superior (t = −2.27) and temporal (t = −2.02) peripapillary sectors of diabetic eyes compared to normal eyes (P

Evaluation of radial peripapillary capillary density in patients with newly diagnosed iron deficiency anemia

Article

Full-text available

Feb 2021
Int Ophthalmol

Purpose: To investigate the effects of iron deficiency anemia (IDA) on radial peripapillary capillary vessel density (RPCvd) and retinal nerve fiber layer (RNFL) thickness. Methods: Forty patients with IDA, and 46 healthy participants, were enrolled in this study. Optical coherence tomography angiography was used to determine RNFL thickness and RPCvd measurements. In addition, hemoglobin (Hb), hematocrit (HCT), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), and ferritin laboratory values were evaluated. Results: Analysis of retinal regions (whole images, peripapillary, superior-hemi, inferior-hemi, inferior-nasal, inferior-temporal, temporal-inferior, temporal-superior, superior-nasal) showed that RPCvd values were significantly lower in patients with IDA compared to the control group values (p < 0.05 for all). However, there were no significant differences in RNFL thickness values between the IDA patient group and the control group (p > 0.05 for all). In addition, there were significant positive correlations between RPCvd values and hematological values for Hb, HCT, MCV, MCH, MCHC, and ferritin. Conclusion: It is important to identify changes in retinal vascularity to prevent possible ocular problems in patients with IDA. Specifically, the significant positive correlations between RPCvd values and hematological values suggest that anemia treatment is important for optic nerve perfusion.

Peripapillary Optical Coherence Tomography Angiography in Alzheimer's Disease, Mild Cognitive Impairment, and Normal Cognition

Article

Feb 2024

Objective This study aimed to identify peripapillary microvascular changes in Alzheimer's disease (AD) and mild cognitive impairment (MCI). Patients and Methods In this prospective study, 66 eyes of 36 subjects with AD, 119 eyes of 63 with MCI, and 513 eyes of 265 controls with normal cognition were enrolled. Peripapillary capillary perfusion density (CPD), capillary flux index (CFI), and retinal nerve fiber layer (RNFL) thickness were determined. Results Average CPD differed significantly between all three groups ( P = 0.001), being significantly greater in AD vs controls (0.446 ± 0.015 vs 0.439 ± 0.017, P = 0.001) and MCI vs controls (0.443 ± 0.020 vs 0.439 ± 0.017, P = 0.007) but not AD vs MCI ( P = 0.69). CFI and average RNFL thickness did not significantly differ among groups (all P > 0.05). Conclusion Peripapillary CPD is increased in eyes with AD or MCI compared to controls despite similar RNFL thickness. [ Ophthalmic Surg Lasers Imaging Retina 2024;55:78–84.]

Parapapillary choroidal microvasculature in retrobulbar optic neuritis: An optical coherence tomography angiography study

Article

Dec 2023

Differences in Retinal and Choroidal Microvasculature and Structure in Dementia With Lewy Bodies Compared With Normal Cognition

Article

Nov 2023

Purpose: To evaluate the retinal and choroidal microvasculature and structure in individuals with dementia with Lewy bodies (DLB) compared with controls with normal cognition using optical coherence tomography (OCT) and OCT angiography (OCTA). Methods: An institutional review board–approved cross-sectional comparison of patients with DLB and cognitively normal controls was performed. The Cirrus HD-OCT 5000 with AngioPlex (Carl Zeiss Meditec) was used to obtain OCT and OCTA images. Results: Thirty-four eyes of 18 patients with DLB and 85 eyes of 48 cognitively normal patients were analyzed. The average capillary perfusion density (CPD) was higher in the DLB group than in the control group ( P = .005). The average capillary flux index (CFI) and ganglion cell inner-plexiform layer (GC-IPL) thickness were lower in the DLB group than in the control group ( P = .016 and P = .040, respectively). Conclusions: Patients with DLB had an increased peripapillary CPD, decreased peripapillary CFI, and attenuated GC-IPL thickness compared with those with normal cognition.

Research Progress of OCTA in Diabetic Retinopathy

Article

Full-text available

Jan 2023

景馨张

Evaluation of Ocular Microvascular Characteristics in Smokers and Patients with Chronic Obstructive Pulmonary Disease Using an Optical Coherence Tomography Angiography

Article

Apr 2023

Purpose: To investigate retinal microvascular changes in patients with chronic obstructive pulmonary disease (COPD) using optical coherence tomography angiography (OCTA) and to compare these values with those of smokers and healthy non-smokers. Methods: This study was performed on 38 eyes of 38 patients with COPD, 30 eyes of 30 smokers, and 31 eyes of 31 healthy non-smokers. Foveal avascular zone (FAZ) area, superficial (SCP) and deep (DCP) capillary plexus (whole image, fovea, parafovea, and perifovea) and radial peripapillary capillary (RPC) vessel densities (whole image, peripapillary, and inside disc) were evaluated via OCTA device (Optovue, Fremont, CA, USA). The forced expiratory volume in the first second (FEV1)/forced vital capacity (FVC) ratio and FEV1 values of patients with COPD were recorded. Results: There were statistically similar values in smoking pack-years between the smoker and COPD groups (p = 0.059). Entire SCP and DCP vessel densities were significantly different among the all groups (p < 0.05); for these parameters, the control group had the highest and the COPD group had the lowest vessel density values. Significantly decreased RPC vessel densities in all regions were detected in the COPD group compared with the other groups. Multiple regression analysis showed significant positive correlations between the FEV1 and the SCP, DCP, and RPC vessel densities (for all, p < 0.05). Conclusions: This study detected lower vessel densities in patients with COPD than in smokers and healthy controls and reported decreased vessel density measurements with increasing COPD severity. COPD patients with or without a history of smoking may benefit from higher prioritization in terms of ophthalmic screening to prevent ocular complications.

Évaluation de la rétine par angiographie par tomographie à cohérence optique (OCTA) chez les patients atteints d'une infection à coronavirus (COVID-19)

Article

Apr 2023

Peripapillary and macular microvasculature features of non-arteritic anterior ischemic optic neuropathy

Article

Full-text available

Jan 2023

Purpose: The hallmark of non-arteritic anterior ischemic optic neuropathy (NAION) is vascular compromise to the anterior optic nerve and thinning of the retinal nerve fiber layer (RNFL) and secondary degeneration of the retinal ganglion cell body or thinning of the ganglion cell complex (GCC). This study investigates optical coherence tomography (OCT) and OCT Angiography (OCTA) changes in chronic NAION and identifies imaging biomarkers that best predict disease. Methods: We performed a retrospective case-control study of 24 chronic NAION eyes (18 patients) and 70 control eyes (45 patients) to compare both whole-eye and regional OCT, OCTA, static perimetry measurements. OCT measurements were quantified automatically using commercial software, and OCTA was analyzed using custom MATLAB script with large vessel removal to measure 154 total parameters per eye. Results: We confirmed that static perimetry mean deviation (MD) was significantly worse in chronic NAION (-13.53 ± 2.36) than control (-0.47 ± 0.72; P < 0.001) eyes, and NAION eyes had 31 μm thinner RNFL (control: 95.9 ± 25.8 μm; NAION: 64.5 ± 18.0, P < 0.001), and 21.8 μm thinner GCC compared with controls (control: 81.5 ± 4.4 μm; NAION: 59.7 ± 10.5, P < 0.001). Spearman correlation analysis of OCTA parameters reveal that vessel area density (VAD) and flux are highly correlated with visual field MD and OCT measurements. Hierarchical clustering two distinct groups (NAION and control), where standardized measurements of NAION eyes were generally lower than controls. Two-way mixed ANOVAs showed significant interaction between patient status (control and chronic NAION) and structure (optic disk and macula) for annulus VAD and flux values and mean RNFL and GCC thickness. Post-hoc tests showed this effect stems from lower peripapillary values in NAION compared to controls. Separate logistic regression models with LASSO regularization identified VAD and flux are one of the best OCTA parameters for predicting NAION. Conclusion: Ischemic insult to the optic disk is more severe likely from primary degeneration of the affected peripapillary region while macula is affected by secondary retrograde degeneration and loss of retinal ganglion cells. In addition to OCT measurements, peripapillary and macular vascular parameters such as VAD and flux are good predictors of optic nerve and retinal changes in NAION.

Diabetic Retinopathy

Chapter

Jan 2023

Andrea Grosso

Diabetes mellitus (DM) is a global epidemic [1], and diabetic retinopathy (DR) is one of the major causes of visual impairment in working middle-aged adults [2–5]. As outlined by Prof. Tien Yin Wong during the Euretina Lecture “Improving awareness and knowledge about the natural history of diabetes and the risk of complications, including diabetic retinopathy, is recognized as an important public health strategy. However, awareness of DR in diabetes patients continues to be suboptimal [3].

Longitudinal change of peripapillary vessel density and retinal nerve fibre layer thickness in normal tension and primary angle closure glaucoma

Article

Dec 2022

Purpose To compare the rates of peripapillary vessel density (pVD) loss and retinal nerve fibre layer (RNFL) thinning in normal tension glaucoma (NTG) and primary angle closure glaucoma (PACG). Methods Baseline age and severity-matched NTG and PACG eyes (75 eyes of 60 patients for each subtype) were observed longitudinally. All participants’ RNFL thickness were measured by optical coherence tomography (OCT); pVD were measured by swept-source OCT-angiography (OCT-A) and quantified by a customised MATLAB program. The rate of pVD loss and RNFL thinning were estimated by linear mixed-effects models. Results NTG eyes had significant pVD loss in all sectors (p≤0.05) while PACG eyes’ pVD loss was borderline significant in the global region (p=0.05). Significant RNFL thinning was detected in the inferotemporal and superonasal regions of both groups, and the superotemporal region in the NTG group (all p≤0.02). NTG had faster rate of pVD loss in the global (difference (95% CI) −1.08 (−1.90 to –0.27) %/year), temporal (−1.57 (−2.91 to –0.23) %/year) and superotemporal (−1.46 (−2.65 to –0.26) %/year) regions than PACG (all p ≤ 0.02), without significant difference of the rate of RNFL thinning. A lower baseline mean deviation (MD) was associated with a faster rate of global pVD loss, while a lower baseline pVD was associated with a slower rate of global pVD loss in multivariable analyses (both p≤0.04). Conclusions NTG had more extensive and faster rate of pVD loss than PACG. Baseline global pVD and MD were independently associated with the rate of pVD loss in NTG.

Effects of Exercise on Optic Nerve and Macular Perfusion in Glaucoma and Normal Subjects

Article

Jul 2022
J GLAUCOMA

Prcis: Using optical coherence tomography angiography, we found an increase in the blood flow in regional macular without significant changes in the optic disk in patients with glaucoma after a moderate exercise regime. Purpose: To investigate the effect of moderate exercise on optic nerve and macular perfusion in glaucoma patients. Methods: Overall, 25 eyes of 25 patients with primary open angle glaucoma and 22 eyes of 22 normal subjects were included in the glaucoma and control groups, respectively. Foveal avascular zone parameters, whole and regional vessel density (VD) in the superficial layer of macula, VDs in the radial peripapillary capillary layer of the optic nerve head, intraocular pressure, and cardiovascular parameters were measured using optical coherence tomography angiography before, immediately after, and 30 minutes after a 20-minute run at moderate speed. Results: In the glaucoma group, macular superficial VD of the whole image, parafovea, and superior and nasal regions were higher after 30 minutes of rest (44.049±5.704, 47.238±5.741, 48.692±6.648, and 47.852±5.078) than immediately after exercise (43.229±5.867, 46.334±5.984, 47.840±6.895, 46.793±5.238, P <0.05). The VD in the temporal and nasal regions was higher 30 minutes after exercise (45.105±5.512 and 47.852±5.078) than before exercise (44.265±5.803 and 46.750±5.639, P <0.05). The intraocular pressure decreased immediately after exercise (14.20±2.51 and 14.51±2.96 mmHg for glaucoma and controls, respectively) but was restored after 30 minutes of rest (15.84±3.57 mmHg for glaucoma and 16.50±2.25 mmHg for controls) in both groups ( P <0.001). Cardiovascular parameters were similar in both groups. Conclusion: Moderate physical exercise for 20 minutes increased blood flow in the macula region without significant change to the optic nerve and lowered intraocular pressure in glaucoma and normal subjects. The benefit of these findings to glaucoma patients needs further study.

Effect of Optic Disc Tilt on the Measurement of Peripapillary Vessel Density Using Optical Coherence Tomography Angiography

Article

Jun 2022
J GLAUCOMA

Precis: Eyes with tilted disc had significantly lower peripapillary vessel density (pVD) and lower long-term measurement reproducibility in OCTA. After adjusting for confounding factors, disc tilt still contributed to the reduction of pVD in most sectors. Purpose: To investigate the effect of optic disc tilt on the measurement of sectoral peripapillary vessel density (pVD) by optical coherence tomography angiography (OCTA) and on the long-term measurement reproducibility. Methods: This retrospective observational case control study included 70 healthy eyes. Average and eight-sector pVDs and peripapillary retinal nerve fiber layer (pRNFL) thicknesses were obtained from OCTA at two visits at 1-year intervals. The disc tilt was quantified by ovality ratio (the longest/shortest disc diameter) on fundus photography, with a tilted disc (TD) defined as an ovality ratio ≥1.3. pVD and pRNFL thickness of each sector were compared in the TD and non-tilted disc (NTD) groups. Long-term reproducibility was assessed by the intraclass correlation coefficients (ICC) for both groups. Factors associated with pVD were evaluated by uni- and multivariable linear regression analyses. Results: Thirty-five eyes each had TD and NTD. Average pVD was lower in the TD than in the NTD group (47.0±3.5% vs. 51.7±2.8%, P<0.001), as were pVDs in all eight sectors. The long-term reproducibilities of average and sectoral pVD measurements were lower in the TD (ICC 0.46-0.83) than in the NTD (ICC 0.67-0.96) group. Disc tilt was significantly associated with pVD in average and all sectors except for nasal inferior sector after adjusting for axial length, pRNFL thickness, and signal strength index of OCTA image. Conclusion: OCTA measured pVD and the long-term reproducibility were lower in eyes with TD than NTD. These findings should be considered when interpreting OCTA measured pVD.

The use of optical coherence tomography angiography in patients with chiasmal compression (literature review)

Article

Full-text available

Jun 2022

Optical coherence tomography (OCT) is currently the leading method for the observation and evaluation of microstructural changes in the retina in vivo. In recent years, OCT has been used in clinical practice to monitor the progression of compressive optic neuropathy in patients with chiasmal-sellar region neoplasms. The results obtained in the course of the studies opened up new opportunities for studying the pathogenesis of the development of compressive optic neuropathy in patients of this group. The advent of OCT-angiography (OCTA), developed on the basis of OCT, made it possible to study changes in the blood flow of the radial peripapillary capillary network, superficial and deep capillary plexuses, which opens up many opportunities for further research into the pathogenesis of visual impairment in this group of patients, prognosis of the development of the disease, and selection optimal terms of treatment. The literature review presents and analyzes the currently available results of the use of OCTA in patients with chiasmal compression.

Early Retinal Microcirculation in Nonfunctioning Pituitary Adenomas Without Visual Field Defects Using Optical Coherence Tomography Angiography

Article

Apr 2022

Background: For patients with nonfunctioning pituitary adenoma (NFPA) without manifesting visual acuity impairment or visual field defect (VFD), more sensitive and objective assessment methods will allow earlier detection before irreversible damage to the visual system. This study aimed to evaluate retinal vessel densities (VDs) alterations in these patients using optical coherence tomography angiography and to determine its diagnostic abilities. Methods: Between patients with NFPA without VFDs and age-matched, sex-matched healthy control individuals, comparisons of visual field metrics, retinal structural thickness, and microcirculation were conducted after adjusting for axial length (AL) and signal index of scans. Receiver operating characteristic (ROC) curves were further depicted to assess the diagnostic performance of significant parameters. To explore the impact of symptom duration, tumor size, and axial length on the significant parameters, multivariate regression analysis was conducted. Results: This cross-sectional study reviewed 107 patients with NFPA. Twenty-seven eyes of patients with NFPA without VFDs and 27 eyes of healthy controls were enrolled. Compared with healthy controls, patients with NFPA without VFDs had similar foveal avascular zone areas and perimeters, macular ganglion cell complex (mGCC) and peripapillary retinal nerve fiber layer thicknesses, and macular VDs. Only the VD in the radial peripapillary capillary (RPC) segment of the inferior temporal (IT) sector was much lower in the patient group. The 2 largest area under the ROC curves were the focal loss volume (FLV) of the mGCC and the VD in the RPC of the IT sector, both of which were significantly related to symptom duration and tumor size. Conclusions: At the early stage of NFPA before VFD and retinal thickness thinning, fundus microcirculation impairments may occur initially in the microvascular density of the RPC segment of the IT sector. The FLV and the VD of RPC at the IT sector may provide a basis for the early diagnosis of NFPA without VFD in clinical practice.

Baseline Vessel Density Parameters for Predicting Visual Field Progression in Open-Angle Glaucoma Eyes With Central Visual Field Damage

Article

Dec 2021
AM J OPHTHALMOL

PURPOSE To identify the baseline vessel density (VD) parameters that predict visual field (VF) progression in open-angle glaucoma (OAG) patients with central visual field (CVF) damage. DESIGN Retrospective cohort study METHODS This study enrolled 208 eyes from 208 consecutive OAG patients with CVF damage at baseline and with a minimum 2 years follow-up. Optical coherence tomography (OCT) angiography was used to measure circumpapillary and macular VDs in the retina and parapapillary VD in the choroid (pCVD) at the baseline. The circumpapillary retinal nerve fiber layer (cpRNFL) and macular ganglion cell-inner plexiform layer (mGCIPL) thicknesses were also measured as reference standards. Cox proportional hazard analysis was performed to identify the baseline clinical factors associated with VF progression according to the glaucoma stage. The relationships between the CVF mean sensitivity (MS) reduction rate during follow-up and the baseline clinical factors were evaluated. RESULTS VF progression was detected in 54 eyes (26.0%) during 2.78 years of mean follow-up. A lower pCVD (hazard ratio [HR] = 0.916; P = 0.014) at baseline in early-stage OAG eyes, and a reduced baseline average mGCIPL thickness (mGCIPLT) (HR = 0.896; P = 0.001) in eyes with moderate to advanced glaucoma, were independent predictors of VF progression. The baseline pCVD (β = 0.018; P = 0.028) in eyes with early-stage glaucoma, and the baseline average mGCIPLT (β = 0.035; P = 0.013) in eyes with moderate to advanced glaucoma, were significantly correlated with the rate (dB/year) of CVF MS reduction. CONCLUSION In OAG eyes with CVF damage, a lower baseline pCVD in early-stage glaucoma and a reduced mGCIPLT at baseline in moderate to advanced glaucoma are significantly associated with subsequent VF progression.

OCT and OCT-angiography parameters of intraocular blood flow in healthy adults

Article

Jul 2021

PURPOSE. To identify the relationship between the parameters of choroidal and retinal blood flow by optical coherence tomography (OCT) and OCT angiography (OCT-A), and the structural, hydrodynamic and systemic hemodynamic parameters in healthy adults. METHODS. The study included 42 male subjects aged 54.43±4.1 years without signs of local or systemic pathologies. The following parameters were evaluated on the RTVue-XR tomograph (USA): structural and microcirculatory parameters of the optic disc (OD) — peripapillary retinal nerve fiber layer (pRLNF) and radial peripapillary capillary plexus (RPCP); the macula — thickness, superficial capillary plexus (SCP), deep vascular complex (DVC), foveolar avascular zone (FAZ); the choroid — thickness, structure. Blood pressure was determined using the Riva–Rocci method; tonometry — by the Maklakov method. The parameters of bidirectional corneal applanation were evaluated, and perfusion and tolerance pressure were calculated. RESULTS. Negative correlations were revealed between intraocular pressure, pRNFL and capillary density of RCP (R= −0.58… −0.73); between choroid thickness, systemic blood flow, and tolerant pressure (R= −0.56… −0.72); between the thickness of the choroid and the volume of focal losses (FLV, %), as well as the OCT-A parameters of FAZ (area, perimeter, and density of foveolar vessels) (R= −0.45… −0.58). Positive correlations were found between perifoveal thickness (including ganglion complex) with the pRNFL (R=0.58–0.71), as well as with the thickness of the choroid (R=0.41–0.65). The confidence level was p≤0.001. CONCLUSION. The relationship of retinal, choroidal, micro hemodynamics parameters by OCT (choroid thickness) and OCT-A (RCC) (HD Angio Disc 4.5 protocol); area, perimeter, and vascular density of FAZ (Angio Retina 3.0 protocol) with the parameters of systemic blood flow in healthy subjects can likely be considered as hemodynamic biomarkers in the diagnosis, monitoring, and evaluation of treatment effectiveness of any intraocular vascular process (including glaucoma).

Quantitative Analysis of Radial Peripapillary Capillary Network in Patients With Papilledema Compared with Healthy Subjects Using Optical Coherence Tomography Angiography

Article

Oct 2021
J NEURO-OPHTHALMOL

Background: To quantitatively compare the peripapillary microvascular network between patients with papilledema and healthy subjects using swept source optical coherence tomography angiography. Methods: In this retrospective observational study, patients with papilledema secondary to idiopathic intracranial hypertension and healthy controls were imaged with swept source optical coherence tomography angiography (PLEX Elite 9000; Carl Zeiss Meditec, Dublin, CA) using a 6 × 6 mm scan pattern centered on the optic disc. The capillary perfusion density (CPD) and capillary flux index (CFI) of the radial peripapillary capillaries in the retinal nerve fiber layer (RNFL) were calculated using Zeiss algorithm. Results: Thirty-nine eyes of 20 patients with papilledema and 66 eyes of 33 healthy subjects were imaged. The mean (P < 0.01), superior (P < 0.01), inferior (P < 0.01), and temporal (P = 0.02) CPD significantly differed between both groups. No significant difference was found between both groups for the CFI. The mean (P < 0.01), superior (P < 0.01), inferior (P = 0.01), temporal (P < 0.01), and nasal (P < 0.01) quadrants of the RNFL were positively associated with the CFI. The mean (P < 0.01), superior (P = 0.01), inferior (P = 0.01), temporal (P < 0.01), and nasal (P = 0.01) quadrants of the RNFL were negatively associated with the CPD. Conclusion: Our study showed a decreased peripapillary capillary density without changes in flux intensity in eyes with papilledema. There were a positive association between the CFI and the RNFL and a negative association between the CPD and the RNFL. It confirmed the discriminatory ability of OCTA in differentiating a papilledema secondary to IIH from a normal optic disc, while providing complementary information for understanding papilledema pathophysiology.

Evaluation of the Effect of Religious Fasting on Retinal Vessel Density and Retinal Thickness Using Optical Coherence Tomography Angiography

Article

Nov 2021

We conducted this study to assess the effect of religious fasting on intraocular pressure (IOP) as well as retinal parameters and retinal thickness during Ramadan using optical coherence tomography angiography (OCTA) performed on a spectral domain device. All the participants ate a pre-dawn meal and drink, and then fasted for at least 15 hours. We assessed a total of 61 eyes from 31 healthy volunteers with a mean age of 32.87 ± 8.07. A significant decrease was found in the median IOP after fasting at 10.00 mmHg in comparison with the pre-fasting value of 12.00 mmHg (p < .0001). Retinal peri-papillary capillary (RPC) whole image, RPC inside disk, and RPC mean values showed significant decreases after fasting (p = .011, .012, and .032 respectively). RPC whole vessel density (VD), RPC inside VD, and RPC VD mean values also showed significant decreases after fasting period (p = .025, <.0001, and .003, respectively). Religious fasting during the warm season could decrease IOP. It could also reduce the blood flow of the retina, specifically the macula, and the retinal peri-papillary VD.

Microvascular alterations detected by optical coherence tomography angiography in non‐arteritic anterior ischaemic optic neuropathy: a meta‐analysis

Article

Jun 2021

Purpose To evaluate microvascular alterations with optical coherence tomography angiography (OCTA) in eyes with non-arteritic anterior ischaemic optic neuropathy (NAION) and the unaffected fellow eyes. Design Systematic review and meta-analysis. Methods A comprehensive literature search was conducted in the PubMed and Embase databases through 6 September 2020, to identify the studies on NAION and the unaffected fellow eyes using OCTA. Eligible studies and data of interest were extracted and analysed by RevMan Software v. 5.4 and Stata Software v.14.0. The weighted mean differences and 95% confidence intervals were used to assess the strength of the association. Results Seventeen observational comparative studies, including 379 eyes with NAION, 175 unaffected contralateral eyes and 470 eyes of healthy controls, were identified. Compared to those of the healthy controls, the perfusion density (PD) of radial peripapillary capillary (RPC) and peripapillary superficial capillary plexus (ppSCP) of NAION were significantly lower. Moreover, the PD of the macular SCP (mSCP) in NAION was significantly reduced in the whole image, superior quadrant and temporal quadrant, while the macular deep capillary plexus (mDCP) showed a decreasing PD only within the whole image. Between unaffected fellow eyes and healthy eyes, significant differences of PD were demonstrated in the whole image and some peripapillary regions of the RPC and ppSCP. Conclusion Our results suggested that compared to those of healthy controls, the eyes affected by NAION and unaffected fellow eyes demonstrated significant microvascular impairments in different regions. Between acute and non-acute NAION, macular OCTA parameters showed different characteristic patterns.

Identifying peripapillary radial capillary plexus alterations in Parkinson’s disease using optical coherence tomography angiography

Article

Mar 2021

Purpose To compare radial peripapillary capillary plexus vascular parameters and retinal nerve fiber layer (RNFL) thickness between Parkinson’s disease (PD) and controls. Design Prospective cross-sectional study. Participants One hundred and fifty-one eyes of 81 PD participants and 514 eyes of 314 controls. Methods Participants underwent optical coherence tomography (OCTA) imaging using the Zeiss Cirrus HD-5000 AngioPlex. Capillary perfusion density (CPD) and capillary flux index (CFI) were assessed using a 4.5x4.5 mm peripapillary scan, and RNFL thickness was assessed using a 200x200 μm optic nerve cube OCT scan. Hoehn and Yahr clinical staging for PD was determined by an experienced movement disorders specialist. Generalized estimating equations adjusted for age and sex were used for analysis. Main Outcome Measures Differences in RNFL thickness, CPD, and CFI as assessed using multivariable generalized estimating equations between individuals with PD and controls. Results After adjustment for age and sex, average CPD (0.446% ± 0.018% vs 0.439% ± 0.017%, p < 0.001) and CFI (0.434 ± 0.031 vs 0.426 ± 0.036, p = 0.008) were significantly higher in PD eyes. Average RNFL thickness was similar between groups (PD 89.71 ± 10.45 μm vs control 88.20 ± 10.33 μm, p = 0.19). Significant correlations between Hoehn and Yahr stage and OCTA parameters were not observed. OCTA parameters were not significantly different between eyes of the same patient. Conclusions Increased peripapillary microvascular density and flux were detected in a large cohort of individuals with PD compared to controls after adjusting for age and sex; however, RNFL thickness was similar between groups. Peripapillary OCTA parameters may not correlate with the severity of Parkinson’s disease. OCTA may serve as a non-invasive method to identify novel biomarkers for the early diagnosis of Parkinson’s disease; as such, this methodology deserves further investigation.

Associations Between Capillary Diameter, Capillary Density, and Microaneurysms in Diabetic Retinopathy: A High-Resolution Confocal Microscopy Study

Article

Full-text available

Feb 2021

Purpose: To use high-resolution histology to define the associations between microaneurysms, capillary diameter and capillary density alterations in diabetic retinopathy (DR). Methods: Quantitative comparisons of microaneurysm number, capillary density and capillary diameter were performed between eight human donor eyes with nonproliferative DR and six age- and eccentricity-matched normal donor eyes after retinal vascular perfusion labelling. The parafovea, 3-mm, 6-mm, and 9-mm retinal eccentricities were analyzed and associations between microvascular alterations defined. Results: Mean capillary density was reduced in all retina regions in the DR group (P = 0.013). Microaneurysms occurred in all retina regions in the DR group, but the association between decreased capillary density and microaneurysm number was only significant in the 3-mm (P = 0.040) and 6-mm (P = 0.007) eccentricities. The mean capillary diameter of the DR group (8.9 ± 0.53 µm) was greater than the control group (7.60 ± 0.40 µm; P = 0.033). There was no association between capillary diameter increase and capillary density decrease (P = 0.257) and capillary diameter increase and microaneurysm number (P = 0.147) in the DR group. Within the parafovea of the DR group, capillary density was significantly reduced, and capillary diameter was significantly increased in the deep capillary plexus compared with the superficial and intermediate plexuses (all P < 0.05). Conclusions: In DR, capillary density reduction occurs across multiple retina eccentricities with a predilection for the deep capillary plexus. The association between microaneurysm number and capillary density is specific to retina eccentricity. Capillary diameter increase may be an early biomarker of DR. These findings may refine the application of optical coherence tomography angiography techniques for the management of DR.

Peripapillary and Macular Vessel Density Measurement with Optical Coherence Angiography in Exfoliation Syndrome

Article

Sep 2020

Precis: Although peripapillary retinal nerve fiber layer thickness (RNFLTs) and vessel density (VD) values were similar to healthy group, eyes with exfoliation syndrome had significantly lower superficial macular VDs and minimum ganglion cell analysis values. Purpose: To compare peripapillary and macular perfused capillary densities with optical coherence tomography angiography (OCT-A) between patients with eyes having exfoliation syndrome (XFS) and normal age-matched healthy controls. Patients and methods: This cross-sectional study included patients diagnosed with XFS from December 2017 to January 2020 at the Glaucoma Department. Peripapillary and parafoveal superficial VDs were obtained using OCT-A. The RNFLTs and ganglion cell analysis values were compared. Results: Thirty-nine eyes of 39 XFS patients (26 women; mean age, 69.0±8.1 y) and 39 eyes of 39 healthy patients (25 women; mean age, 68.0±8.6 y) were enrolled. There were no statistically significant differences in sex or age distribution, central corneal thickness measurements, refractive errors, or intraocular pressures between both groups (all P>0.05). There were no statistically significant differences in the peripapillary VD or peripapillary RNFLT between XFS eyes and healthy eyes (P>0.05 for all). In the macular region, most superficial VD parameters were significantly reduced in the XFS group (P=0.02 for parafoveal VD, P=0.04 for both hemifields). While the average ganglion cell and internal plexiform layer (GCL+IPL) values were similar between groups (P=0.19), the minimum GCL+IPL value was lower in the XFS group than in the healthy group (P=0.03). Conclusion: Although structural test results, especially peripapillary RNFLT and mean GCL+IPL, were similar between the healthy and XFS groups, macular VD values were lower in XFS eyes. Our findings implicate microvascular damage can be the mechanism underlying XFS-related changes and indicate that it precedes significant structural damage.

The correlation of radial peripapillary capillary density measurements with optic nerve head morphology and retinal nerve fiber layer thickness in healthy eyes

Article

Sep 2020

Background: To investigate the association between radial peripapillary capillary (RPC) density and optic nerve head morphology in healthy eyes METHODS: One hundred twenty-seven eyes of 64 volunteers were included in the study. The RNFL thickness and ONH parameters were measured with Cirrus 5000 HD OCT. Angioplex OCT angiography with a 4.5 x 4.5 mm scan pattern was used to evaluate for RPC density and flux index (FI). SPSS 25.0 version for Windows was used for statistical analysis. Results: There was a significant positively correlation between the mean overall RPC perfusion and FI the mean average RNFL thickness (r = 0.417, p < 0.001 and r = 0.239, p = 0.007, respectively). The mean rim area was significantly positively correlated with the mean overall RPC perfusion and FI (r = 0.308 p < 0.001 and r = 0.233 p = 0.008, respectively). There was a significant negatively correlation between cup volume and the mean overall FI (r = - 0.218 p = 0.01). Conclusion: Our study shows that not only RNFL thickness, but the density of RPCs network may also be associated with ONH parameters. OCTA analysis may be a useful method to clarify these associations quantitatively.

Quantification of vascular and neuronal changes in the peripapillary retinal area secondary to diabetic retinopathy

Article

Sep 2020
BRIT J OPHTHALMOL

Purpose: To investigate and quantify peripapillary vascular and neuronal changes secondary to diabetic retinopathy, using spectral-domain optical coherence tomography (OCT) and OCT angiography (OCTA). Design: This was a cross-sectional study. Methods: 51 eyes of 51 patients affected by non-proliferative diabetic retinopathy (NPDR) and 19 age-matched healthy control eyes underwent full ophthalmic examination, including OCT and OCTA in the peripapillary area. Vessel area density (VAD), vessel length fraction (VLF) and vessel diameter index (VDI) were quantified in a ring-shaped region of interest of each OCTA image. Capillaries and larger vessels were separately analysed. The thickness of the peripapillary retinal nerve fibre layer (pRNFL) and macular ganglion cell complex (GCC) was also analysed. Results: VAD and VLF of peripapillary capillaries were significantly reduced in NPDR eyes, along with the progression of NPDR (p<0.05). VDI was significantly reduced in mild (p=0.0093) and moderate (p=0.0190) NPDR eyes, but not in severe NPDR (p=0.0841). Larger peripapillary vessels showed a significant increase of both VAD and VDI in NPDR eyes. pRNFL and GCC thickness decreased in NPDR eyes, reaching statistical significance only for GCC. No statistically significant correlation was found between perfusion parameters and pRNFL and GCC thickness. Conclusions: Retinal capillary remodelling in NPDR involves the peripapillary vascularisation too, as confirmed by OCTA quantitative parameters. The peripapillary macrovasculature and microvasculature need to be separately evaluated. The lack of direct correlation between peripapillary capillaries changes and the loss of retinal nerve fibres suggests that neuronal damage cannot be simply considered secondary to the microvascular one.

Quantitative Confocal Imaging of the Retinal Microvasculature in the Human Retina

Article

Full-text available

Jul 2012

We investigated quantitatively the distribution of blood vessels in different neural layers of the human retina. A total of 16 human donor eyes was perfusion-fixed and labeled for endothelial f-actin. Retinal eccentricity located 3 mm superior to the optic disk was studied using confocal scanning laser microscopy. Immunohistochemical methods applied to whole-mount and transverse sections were used to colocalize capillary networks with neuronal elements. Capillary morphometry, diameter, and density measurements were compared among networks. Four different capillary networks were identified and quantified in the following regions: Nerve fiber layer (NFL), retinal ganglion cell (RGC) layer, border of the inner plexiform layer (IPL) and superficial boundary of the inner nuclear layer (INL), and boundary of the deep INL and outer plexiform layer. The innermost and outermost capillary networks demonstrated a laminar configuration, while IPL and deep INL networks displayed a complex three-dimensional configuration. Capillary diameter in RGC and IPL networks were significantly less than in other networks. Capillary density was greatest in the RGC network (26.74%), and was significantly greater than in the NFL (13.69%), IPL (11.28%), and deep INL (16.12%) networks. The unique metabolic demands of neuronal sub-compartments may influence the morphometric features of regional capillary networks. Differences in capillary diameter and density between networks may have important correlations with neuronal function in the human retina. These findings may be important for understanding pathogenic mechanisms in retinal vascular disease.

Age and Retinal Nerve Fiber Layer Thickness Measured by Spectral Domain Optical Coherence Tomography

Article

Full-text available

Jun 2012

To evaluate the association between age and peripapillary retinal nerve fiber layer (RNFL) thickness measured by Cirrus high-definition (HD) spectral domain optical coherence tomography (OCT) in healthy Korean subjects. A total of 302 eyes from 155 healthy Korean subjects (age range, 20 to 79 years) underwent RNFL thickness measurements using the Cirrus HD-OCT. Average, quadrant, and clock-hour RNFL thickness parameters were analyzed in terms of age using linear mixed effect models. Average RNFL demonstrated a slope of -2.1 µm per decade of age (p < 0.001). In quadrant analysis, superior (-3.4 µm/decade, p < 0.001) and inferior (-2.9 µm/decade, p < 0.001) quadrants showed steeper slopes, whereas temporal (-1.1 µm/decade, p < 0.001) and nasal (-1.0 µm/decade, p < 0.001) quadrants revealed shallower slopes. Among the 12 clock-hour sectors, clock hours 6 (-4.5 µm/decade, p < 0.001) and 1 (-4.1 µm/decade, p < 0.001) showed the greatest tendency to decline with age; RNFLs of the 3 (-0.2 µm/decade, p = 0.391) and 4 (-0.6 µm/decade, p = 0.052) o'clock hour sectors did not show significant decay. RNFL thickness was associated with age, especially in superior and inferior areas. The topographic distribution of correlation between age and RNFL thickness was not uniform.

In-vivo imaging of retinal nerve fiber layer vasculature: Imaging histology comparison

Article

Full-text available

Sep 2009
BMC Ophthalmol

Although it has been suggested that alterations of nerve fiber layer vasculature may be involved in the etiology of eye diseases, including glaucoma, it has not been possible to examine this vasculature in-vivo. This report describes a novel imaging method, fluorescence adaptive optics (FAO) scanning laser ophthalmoscopy (SLO), that makes possible for the first time in-vivo imaging of this vasculature in the living macaque, comparing in-vivo and ex-vivo imaging of this vascular bed. We injected sodium fluorescein intravenously in two macaque monkeys while imaging the retina with an FAO-SLO. An argon laser provided the 488 nm excitation source for fluorescence imaging. Reflectance images, obtained simultaneously with near infrared light, permitted precise surface registration of individual frames of the fluorescence imaging. In-vivo imaging was then compared to ex-vivo confocal microscopy of the same tissue. Superficial focus (innermost retina) at all depths within the NFL revealed a vasculature with extremely long capillaries, thin walls, little variation in caliber and parallel-linked structure oriented parallel to the NFL axons, typical of the radial peripapillary capillaries (RPCs). However, at a deeper focus beneath the NFL, (toward outer retina) the polygonal pattern typical of the ganglion cell layer (inner) and outer retinal vasculature was seen. These distinguishing patterns were also seen on histological examination of the same retinas. Furthermore, the thickness of the RPC beds and the caliber of individual RPCs determined by imaging closely matched that measured in histological sections. This robust method demonstrates in-vivo, high-resolution, confocal imaging of the vasculature through the full thickness of the NFL in the living macaque, in precise agreement with histology. FAO provides a new tool to examine possible primary or secondary role of the nerve fiber layer vasculature in retinal vascular disorders and other eye diseases, such as glaucoma.

Relationship of Retinal Vascular Caliber with Retinal Nerve Fiber Layer Thickness: The Singapore Malay Eye Study

Article

Full-text available

Jun 2009

To describe the relationship of retinal arteriolar and venular caliber with retinal nerve fiber layer (RNFL) thickness. A population-based, cross-sectional study of Malay persons aged 40 to 80 years residing in Singapore was conducted from 2004 to 2006. Retinal arteriolar and venular calibers were measured with a computer-based technique according to a validated, standardized protocol. RNFL was assessed with retinal tomography. There were 2706 persons with gradable retinal photographs and HRT images of acceptable quality available for analysis. In linear regression models that adjusted for age, sex, diabetes, body mass index, intraocular pressure, and other factors, each standard deviation decrease in arteriolar and venular caliber was associated with a 5.81- and 8.37-microm decrease, respectively, in mean global RNFL thickness (both P < 0.001). These associations remained similar after persons with glaucoma were excluded. In persons with glaucoma, retinal venular caliber was independently associated with the temporal and temporal-to-inferior region of mean RNFL thickness in multivariate analysis; each SD decrease in retinal venular diameter was associated with an 8.54-microm decrease in the temporal region (P = 0.022), and a 38.32-microm decrease in the temporal-to-inferior region (P = 0.006) of mean RNFL thickness. Narrower retinal vessel caliber was associated with reduced RNFL thickness in this Asian population.

Cellular energy utilization and molecular origin of standard metabolic rate in mammals

Article

Full-text available

Aug 1997

The molecular origin of standard metabolic rate and thermogenesis in mammals is examined. It is pointed out that there are important differences and distinctions between the cellular reactions that 1) couple to oxygen consumption, 2) uncouple metabolism, 3) hydrolyze ATP, 4) control metabolic rate, 5) regulate metabolic rate, 6) produce heat, and 7) dissipate free energy. The quantitative contribution of different cellular reactions to these processes is assessed in mammals. We estimate that approximately 90% of mammalian oxygen consumption in the standard state is mitochondrial, of which approximately 20% is uncoupled by the mitochondrial proton leak and 80% is coupled to ATP synthesis. The consequences of the significant contribution of proton leak to standard metabolic rate for tissue P-to-O ratio, heat production, and free energy dissipation by oxidative phosphorylation and the estimated contribution of ATP-consuming processes to tissue oxygen consumption rate are discussed. Of the 80% of oxygen consumption coupled to ATP synthesis, approximately 25-30% is used by protein synthesis, 19-28% by the Na(+)-K(+)-ATPase, 4-8% by the Ca2(+)-ATPase, 2-8% by the actinomyosin ATPase, 7-10% by gluconeogenesis, and 3% by ureagenesis, with mRNA synthesis and substrate cycling also making significant contributions. The main cellular reactions that uncouple standard energy metabolism are the Na+, K+, H+, and Ca2+ channels and leaks of cell membranes and protein breakdown. Cellular metabolic rate is controlled by a number of processes including metabolic demand and substrate supply. The differences in standard metabolic rate between animals of different body mass and phylogeny appear to be due to proportionate changes in the whole of energy metabolism. Heat is produced by some reactions and taken up by others but is mainly produced by the reactions of mitochondrial respiration, oxidative phosphorylation, and proton leak on the inner mitochondrial membrane. Free energy is dissipated by all cellular reactions, but the major contributions are by the ATP-utilizing reactions and the uncoupling reactions. The functions and evolutionary significance of standard metabolic rate are discussed.

Histochemical localisation of mitochondrial enzyme activity in human optic nerve and retina

Article

Full-text available

Mar 1999

To demonstrate the quantitative distribution of mitochondrial enzymes within the human optic nerve and retina in relation to the pathogenesis of ophthalmic disease. Enucleations were performed at the time of multiple organ donation and the optic nerve and peripapillary retina immediately excised en bloc and frozen. Reactivities of the mitochondrial enzymes cytochrome c oxidase and succinate dehydrogenase were demonstrated in serial cryostat sections using specific histochemical assays. In the optic nerve the unmyelinated prelaminar and laminar regions were rich in both cytochrome c oxidase and succinate dehydrogenase. Myelination of fibres as they exited the lamina cribrosa was associated with an abrupt reduction in enzyme activity. Within the retina, high levels of enzyme activity were found localised within the retinal ganglion cells and nerve fibre layer, the outer plexiform layer, inner segments of photoreceptors, and the retinal pigment epithelium. Mitochondrial enzyme activity is preserved in human optic nerve and retina retrieved at the time of multiple organ donation. The distribution of enzyme activity within the eye has implications for the understanding of the pattern of ophthalmic involvement seen in mitochondrial diseases and the site of ganglion cell dysfunction in those patients with optic nerve involvement.

Regional variation in brain capillary density and vascular response to ischemia

Article

Full-text available

Sep 2001
BRAIN RES

Differences in brain neuroarchitecture have been extensively studied and recent results demonstrated that regional differences in the physiological properties of glial cells are equally common. Relatively little is known on the topographic differences in vascular supply, distribution and density of brain capillaries in different CNS regions. We developed a simple method consisting of intravascular injection of fluorescent dyes coupled to immunocytochemical techniques that allows for simultaneous observation of glia-neuronal-vascular interactions in immersion-fixed brain specimens from small rodents. This technique permits quantitative evaluation of regional differences in glial/neuronal distribution and the study of their relationship to vascular densities. Variations of this technique also allow the detection of abnormal microvasculature (i.e. 'leaky' vessels), a useful feature for studies of blood-brain barrier function in health and disease. By use of quantitative confocal microscopy, the three-dimensional geometry of cortical and hippocampal structures revealed remarkable differences in vascularization between cortical gray/white matter junction, and hippocampal formation (CA1 and CA3 regions). Significant differences were also observed within the same investigative region: CA1 was characterized by low capillary density compared to neighboring CA3. Following an ischemic insult, CA1 vessels had more extensive blood-brain barrier leakage than CA3 vessels. We conclude that in addition to neuronal and glial heterogeneity, cortical structures are also endowed with region-specific vascular patterns characterized by distinct pathophysiological responses.

Histological measurement of retinal nerve fibre layer thickness

Article

Full-text available

Jun 2005

Accurate assessment of the retinal nerve fibre layer (RNFL) is central to the diagnosis and follow-up of glaucoma. The in vivo measurement of RNFL thickness by a variety of digital imaging technologies is becoming an important measure for early detection, as well as for follow-up, of glaucomatous damage. However, when drawing clinical inference concerning the state of the RNFL, it is important to have valid reference data on RNFL thickness in both healthy and diseased eyes. In this review, we summarize the knowledge currently available about RNFL thickness in human and primate eyes. A review of the literature on histological analysis of RNFL thickness in the context of glaucomatous damage. Six studies have so far analysed RNFL thickness. Despite the diverse study methodology taken, a consistent feature of all the data is that the superior and inferior quadrants of the peripapillary retina are thicker than the nasal and temporal quadrants; that the RNFL thickness rapidly diminishes with increasing distance from the disc margin; and that apparently at different locations the ratio of axons to supportive tissue varies significantly. We conclude that limited data are available to describe the normal variation in RNFL thickness in the normal human eye. Further studies may help better characterize the RNFL thickness in health and disease and to facilitate the correlation with clinical methods for nerve fibre layer assessment.

Peripapillary Nerve Fiber Layer Thickness Profile Determined with High Speed, Ultrahigh Resolution Optical Coherence Tomography High-Density Scanning

Article

Full-text available

Aug 2007
INVEST OPHTH VIS SCI

To determine the retinal nerve fiber layer (RNFL) thickness profile in the peripapillary region of healthy eyes. Three-dimensional, Fourier/spectral domain optical coherence tomography (OCT) data were obtained as raster scan data (512 x 180 axial scans in a 6 x 6-mm region centered on the optic nerve head [ONH]) with high-speed, ultrahigh-resolution OCT (hsUHR-OCT) from 12 healthy subjects. RNFL thickness was measured on this three-dimensional data set with an in-house software program. The disc margin was defined subjectively in each image and RNFL thickness profiles relative to distance from the disc center were computed for quadrants and clock hours. A mixed-effects model was used to characterize the slope of the profiles. Thickness profiles in the superior, inferior, and temporal quadrants showed an initial increase in RNFL thickness, an area of peak thickness, and a linear decrease as radial distance from the disc center increased. The nasal quadrant showed a constant linear decay without the initial RNFL thickening. A mixed-effects model showed that the slopes of the inferior, superior, and nasal quadrants differed significantly from the temporal slope (P = 0.0012, P = 0.0003, and P = 0.0004, respectively). RNFL thickness is generally inversely related to the distance from the ONH center in the peripapillary region of healthy subjects, as determined by hsUHR-OCT. However, several areas showed an initial increase in RNFL, followed by a peak and a gradual decrease.

Varicosities of intraretinal ganglion cell axons in human and nonhuman primates

Article

Full-text available

Feb 2003
INVEST OPHTH VIS SCI

To describe varicosities of intraretinal ganglion cell axons in the nerve fiber layer of human and nonhuman primate retinas. Intraretinal ganglion cell axons of seven human donors (1-85 years old) and two nonhuman primates (Macaca mulatta, 15 and 17 years old) were immunohistochemically stained with an antibody of neurofilament on flatmounted retinas and examined with light microscopy. In addition, the axons within the retinal nerve fiber layer were examined with transmission electron microscopy in one human and one nonhuman retina. The variations of diameters of single axons were measured on transverse- and parallel-cut sections, and the frequency distributions of the diameters were statistically evaluated. Varicosities of the intraretinal ganglion cell axons were found throughout the retinas in both nonhuman primate and human eyes of all ages examined. The varicosities were rich in mitochondria and had desmosome- and hemidesmosome-like junctions with other axons and retinal glial cells. Measured on parallel-cut axons, the mean diameter (+/-SD) of varicosities was 2.7 +/- 0.9 micro m, whereas the mean diameter of intervaricosity regions was 0.7 +/- 0.3 micro m. The diameter distribution for transverse-cut axons was also bimodal, but the two peaks were much closer because the peak of the larger-diameter group decreased. The results demonstrated that intraretinal ganglion cell axons are predominantly varicose fibers in both human and nonhuman primates. Size variations exist within a single axon's diameter and thereby affect the patterns of diameter distribution seen in transverse-cut preparations. The mitochondria-rich varicosities and the presence of intercellular junctions suggest that the varicosities may be functional sites that serve local high-energy demands of unmyelinated fibers and signal transmission.

Varicosities of Intraretinal Ganglion Cell Axons in Human and Nonhuman Primates

Article

Jan 2003
INVEST OPHTH VIS SCI

Lin Wang

purpose. To describe varicosities of intraretinal ganglion cell axons in the nerve fiber layer of human and nonhuman primate retinas. methods. Intraretinal ganglion cell axons of seven human donors (1–85 years old) and two nonhuman primates (Macaca mulatta, 15 and 17 years old) were immunohistochemically stained with an antibody of neurofilament on flatmounted retinas and examined with light microscopy. In addition, the axons within the retinal nerve fiber layer were examined with transmission electron microscopy in one human and one nonhuman retina. The variations of diameters of single axons were measured on transverse- and parallel-cut sections, and the frequency distributions of the diameters were statistically evaluated. results. Varicosities of the intraretinal ganglion cell axons were found throughout the retinas in both nonhuman primate and human eyes of all ages examined. The varicosities were rich in mitochondria and had desmosome- and hemidesmosome-like junctions with other axons and retinal glial cells. Measured on parallel-cut axons, the mean diameter (±SD) of varicosities was 2.7 ± 0.9 μm, whereas the mean diameter of intervaricosity regions was 0.7 ± 0.3 μm. The diameter distribution for transverse-cut axons was also bimodal, but the two peaks were much closer because the peak of the larger-diameter group decreased. conclusions. The results demonstrated that intraretinal ganglion cell axons are predominantly varicose fibers in both human and nonhuman primates. Size variations exist within a single axon’s diameter and thereby affect the patterns of diameter distribution seen in transverse-cut preparations. The mitochondria-rich varicosities and the presence of intercellular junctions suggest that the varicosities may be functional sites that serve local high-energy demands of unmyelinated fibers and signal transmission.

Retinal ganglion cells: Energetics, compartmentation, axonal transport, cytoskeletons and vulnerability

Article

Jul 2013

Retinal ganglion cells (RGCs) are specialized projection neurons that relay an immense amount of visual information from the retina to the brain. RGC signal inputs are collected by dendrites and output is distributed from the cell body via very thin (0.5-1 μm) and long (∼50 mm) axons. The RGC cell body is larger than other retinal neurons, but is still only a very small fraction (one ten thousandths) of the length and total surface area of the axon. The total distance traversed by RGCs extends from the retina, starting from synapses with bipolar and amacrine cells, to the brain, to synapses with neurons in the lateral geniculate nucleus.

Structural and Hemodynamic Analysis of the Mouse Retinal Microcirculation

Article

Nov 2003
INVEST OPHTH VIS SCI

In the holangiotic retina, little is known about the connections between and the circulation within microvessel layers. The goal of the present study was to explore the three-dimensional arrangement and hemodynamics of mouse retinal microvessels. Confocal microscopy was performed on fluorescein dextran-filled retinal flatmounts. Capillary velocity in the deep layer was measured by epifluorescence intravital microscopy. The changes in the studied parameters after branch retinal vein occlusion were evaluated. The superficial and intermediate layers are both asymmetric crossroads for capillary blood flow, with approximately 70% of the capillary connections directing the flow from the arterioles into the deep layer. The venous flow from the deep layer joins the major veins in the superficial layer through transverse venules, indicating that major veins are directly connected to the deep layer. Red and white blood cell velocities +/- SD in the deep layer were 1.26 +/- 0.34 and 0.8 +/- 0.32 mm/sec respectively. After branch vein occlusion, venule dilation and decreased velocity were observed in the deep layer. In the mouse retina, a tridimensional model of retinal microcirculation was established, showing that most microvessel connections on the arteriolar side direct the flow from the superficial to the deep layer, and vice versa on the venular side. However, the presence of direct arteriovenous connections in the superficial layer and the longer vessel length in the deep layer offer the possibility of actively modulating intraretinal flow. Compared with other capillary beds, both the capillary velocity and microhematocrit are high, a situation that favors nutrient delivery to the inner retina.

Quantitative Morphometry of Perifoveal Capillary Networks in the Human Retina

Article

Jul 2012

To quantify the distribution and morphometric characteristics of capillary networks in the human perifovea. To determine correlations between the location of neuronal subcellular compartments and the morphometric features of regional capillary networks in the layered retina. The perifoveal region, located 2 mm nasal to the fovea, was studied in 17 human donor eyes. Novel micropipette technology was used to cannulate the central retinal artery and label the retinal microcirculation using a phalloidin perfusate. γ-synuclein, Goα, and parvalbumin antibodies were also used to co-localize the nerve fiber layer (NFL), retinal ganglion cell layer (RGCL), inner plexiform layer (IPL), and inner nuclear layer (INL). Confocal scanning laser microscopy was used for capillary imaging. Capillary diameter, capillary density, and capillary loop area measurements were compared between networks. Four capillary networks were identified in the following retinal layers: (1) NFL, (2) RGCL and superficial portion of IPL, (3) deep portion of IPL and superficial portion of INL, and (4) deep portion of INL. Laminar configurations were present in NFL and deep INL networks. Remaining networks demonstrated three-dimensional configurations. Capillary density was greatest in the networks serving the IPL. Capillary loop area was smallest in the two innermost networks. There was no difference in capillary diameter between networks. Capillary networks in the human perifovea are morphometrically heterogeneous. Morphometric features of regional capillary networks in the layered retina may serve a critical role in supporting neuronal homeostasis. Improved knowledge of these features may be important for understanding pathogenic mechanisms underlying retinal vascular diseases.

Selektive Atrophie der radialen peripapill??ren Netzhautcapillaren und glaukomat??se Gesichtsfelddefekte

Article

Apr 1975

B Daicker

Der Autor vergleicht Vorkommen und Verteilung selektiv atropher radialer peripapillärer Capillaren in 33 Autopsieaugen von Patienten mit Glaucoma simplex oder Opticusatrophien anderer Urasche mit deren Gesichtsfelddefekten und Stärke der Opticusatrophie. Es konnte keine Korrelation zwischen atrophen RPC und Gesichtsfelddefekten gefunden werden. Die selektive Atrophie von radialen peripapillären Capillaren scheint vielmehr als Folge pathogenetisch differenter Papillenatrophien entstehen zu können. The existence and distribution of atrophic radial peripapillary capillaries in33 autopsy eyes of patients with chronic glaucoma or different optic nerve atrophies are compared with their visual field defects and stage of atrophy or excavation of the disc. No correlation of defective RPC and visual field defects was found. The selective atrophy of RPC is therefore supposed to be secondary to different atrophies of the disc.

Microstructure and Network Organization of the Microvasculature in the Human Macula

Article

Dec 2010

To characterize the topography and cellular structure of the macular microvasculature using a recently developed technique of arterial cannulation, perfusion, fixation, and staining of human donor eyes. Sixteen human donor eyes were used. The central retinal artery was cannulated and perfused with Ringer's, then fixative, membrane permeabilizing, and selected labeling solutions. The eyes were immersion fixed, and the retina was flat mounted for confocal microscopy. The macular area, including the foveola, fovea, and parafovea, was sampled. The intracellular cytoskeleton of vascular endothelial and smooth muscle cells was studied in different orders of arterioles and venules and in the capillaries. To evaluate the degree of asymmetry within vascular networks, the distribution of generation numbers and the Horton-Strahler approach to vessel naming were compared. The distribution of the microvascular network in the macular region was complex but followed a general theme. The parafoveal region was supplied by dense vasculature with approximately nine closely arranged pairs of arterioles and venules. Each arteriole had abundant branches and a high degree of asymmetry (∼10 generations and 3.5 orders within 1.2-mm length). Only a few arterioles (average ∼2.9) supplied the terminal capillary ring. Very long spindle endothelial cells were seen in the superficial and deep capillaries. Significant heterogeneity of distribution and shape of the endothelial and smooth muscle cells was evident in different orders of the macular vasculature. The authors have demonstrated for the first time the cellular structure and topographic features of the macular microvasculature in human donor eyes.

The Structural Relationship between the Microvasculature, Neurons, and Glia in the Human Retina

Article

Aug 2009

To develop a new technique for detailed study of the spatial distribution of retinal and choroidal microvasculature and their relationship to neurons and glial cells at the cellular level in human cadaveric eyes. Twenty-six human donor eyes were used. Wherever possible, the central retinal artery and a branch of the posterior ciliary artery were individually cannulated and perfused with oxygenated Ringer's solution with 0.5% bovine serum albumin. The perfusion pressure was continuously monitored. Once residual blood was washed out, the perfusate solutions were switched to fixative, membrane-permeabilizing solution and selected labeling solutions. The eyes were then immersion fixed and the retina and choroid flat-mounted for immunolabeling and confocal imaging before cryosectioning. The microstructures of vascular, glial, and neuronal cells in the retina and the stroma in the choroid were studied. The retinal microvasculature was fully perfused and stained by cannulation of the central retinal artery. Regional distribution of choroidal vasculature perfusion was dependent on the specific feeder artery cannulated. The detailed spatial relationship between endothelial cells, glial cells, and neurons at the cellular and subcellular levels was identified with confocal microscopy and immunohistochemical labeling of retinal sections. In the choroid, endothelial cells were clearly identifiable down to the level of the intracellular cytoarchitecture of the choriocapillaris, along with their relationship to Bruch's membrane and the feeding and drainage vessels. A microperfusion fixation and staining technique has been developed that allows studies of the structural relationships of vascular, glial, and neuronal elements at the cellular level in human donor eyes.

Studies on the radial peripapillary capillaries (RPCs). (1) Clinical features on fluorescein fundus angiography (Japanese)

Article

Jun 1976

H Ueno

The aim was to clarify the patho physiology of the radial peripapillary capillaries (RPCs) of the human retina by fluorescein fundus angiography. Highly resolved fluorescein fundus photos of the following diseases were evaluated: tortuositas vasorum retinae, fundus hypertonicus, renal retinopathy, systemic lupus erythematosus, obstruction of retinal artery, obstruction of retinal vein, choked disc, retrobulbar optic neuritis, pulseless disease, diabetic retinopathy and Behcet's disease. The following results were obtained. The RPCs were well demonstrated in the diseases with circulatory disturbance (ischemic or occlusive) in the retina. Generalized dilatation, microaneurysm formation, and hyperpermeability of vessel walls were recognized in the RPCs in the beginning stages of chronic ischemic angiopathies such as pulseless disease, but the RPCs were found conversely to survive strongly in the advanced stages of the disease. In severe ischemic angiopathies, such as obstruction of the retinal artery, the capillaries proper in the retina were more severely involved than the RPCs. The RPCs were well demonstrated in the early stages of occlusive retinal angiopathies such as fundus hypertonicus, but irregular dilatation, selective obstruction, and hyperpermeability of the vessel walls were found in the RPCs of the advanced stages of the disease. Intense engorgement, spiral and microaneurysm formation, and increased permeability of vessel walls secondary to venous stasis were recognized in the RPCs in retinal vein obstructions. Intense angiopathies were found in non RPC areas of the retina in diabetic retinopathy, but in exceptional cases, angiopathies were located only in the RPCs. Radial epipapillary capillaries (RECs) were well demonstrated with intense engorgement in cases of choked disc. Both RPCs and RECs, except on the temporal side of the disc, were well demonstrated in cases of retrobulbar optic neuritis with temporal atrophy. Various features in the RPCs were found in various fundus diseases and in variable degrees of disease. It was suggested that fluorographical features of the RPCs might yield important information in diagnosis and evaluating clinical course.

[Selective atrophy of the radial peripapillary capillaries and visual field defects in glaucoma (author's transl)]

Article

Feb 1975

B Daicker

The existence and distribution of atrophic radial peripapillary capillaries in 33 autopsy eyes of patients with chronic glaucoma or different optic nerve atrophies are compared with their visual field defects and stage of atrophy or excavation of the disc. No correlation of defective RPC and visual field defects was found. The selective atrophy of RPC is therefore supposed to be secondary to different atrophies of the disc.

Fundus diseases with greater visibility of fluorescein angiographic features of radial peripapillary capillaries (Japanese)

Article

May 1975

M Matsuyama

With high resolution fluorescein fundus angiography various patterns of radial peripapillary capillaries (RPC) were observed in fundus diseases with varying degrees of retinal circulatory disturbances. They included arteriosclerosis, hypertensive retinopathy, incomplete obstruction of retinal vein, diabetic retinopathy, uveitis, papilledema, disease of Takayasu, retinitis pigmentosa, tuberous sclerosis, and chorioretinitis juxtapapillaris. In these cases greater visibility of RPC with relation to generalized dilatation of the retinal vascular system and ischemic changes are discussed. Greater visibility of RPC depended upon the pathologic basis of circulatory disturbances in the innermost layer of the retina. Parallel relationship of visibility of RPC to ischemic changes was suggested. However, the features of RPC could not be demonstrated in cases with the most severe obstructive changes of retinal circulation. Follow up examination of RPC might have a diagnostic value and give a clue in the evaluation of the clinical course of fundus signs after medical and operative treatments.

Perfusion and superfusion fixation effects on rat mesentery microvascular beds. Intravital and electron microscope analyses

Article

Aug 1986
J Submicr Cytol

J.A.G. Rhodin

The effects of glutaraldehyde on dimensions and ultrastructure of microvascular beds in rat mesentery were studied in two kinds of experiment, administering the fixative by intra-arterial perfusion at a pressure of 80 mm Hg and by superfusion of the exteriorized mesenteric membrane. The microvascular segments were observed by means of intravital microscopy and recorded on videotape before, during, and after glutaraldehyde reached the microvascular segment being observed. Vascular outer diameters were measured at exactly the same points before and after fixation; in Epon embedded whole-mounts; and in sections analyzed by light and transmission electron microscopy, confirming positively the various segments of the microvascular bed and yielding information concerning the preservation of cellular components. Both experiments confirmed that neither perfusion nor superfusion of glutaraldehyde changes the outer diameter of any segment of the microvascular bed compared to the dimensions 5-10 sec before the blood vessels are reached by the fixative. They remain unaltered also after embedding in epoxy resin. During superfusion, there is a 20-50 sec delay until the blood flow comes to a complete stop. This delay is assumed to give rise to the recorded small undulations of luminal endothelial cell membranes and slight buckling of the entire endothelial layer, probably due to a gradual fall in intravascular pressure. Occasionally, the ultrastructure of some endothelial cells is less well preserved after superfusion fixation. This study demonstrates that intraarterial perfusion of glutaraldehyde renders an instantaneous fixation of mesenteric microvessels, preserving the prefixation dimensions of the various segments and the ultrastructure of the cells. Superfusion of glutaraldehyde is slower in reaching the microvessels and may change slightly the appearance of the vascular wall, and cause some impairment of microvascular functions, such as increased postcapillary leukocyte margination and extravasation.

Relation between superficial capillaries and foveal structures in the human retina

Article

Jan 1987
INVEST OPHTH VIS SCI

When examining semithin Epon sections of human retinas, it became evident that superficial capillaries showed four different positions, according to the thickness of the ganglion cell layer. For the clear view of the distribution of the position of superficial capillaries, the intrafoveal region was subdivided into four zones, based on the thickness of the ganglion cell layer; the foveola and the A-, B-, and C-zone. The foveola has no ganglion cell layer, and the A-zone has a ganglion cell layer thinner than 15 microns. These regions lack superficial capillaries. In the B-zone, the ganglion cell layer is 15-45 microns thick, and here the superficial capillaries lie in the outer boundary of the ganglion cell layer. The C-zone and parafovea have a ganglion cell layer thicker than 45 microns, and superficial capillaries are present within the ganglion cell layer. The perifovea has a ganglion cell layer 15-45 microns thick. In the temporal perifovea, where the nerve fiber layer is not so distinct, superficial capillaries are located on the outer boundary of the ganglion cell layer. In the other portion of the perifovea, superficial capillaries lie in the inner boundary of the ganglion cell layer. Out of the perifovea, where the ganglion cell layer is thinner than 15 microns, most of superficial capillaries touch both boundaries of the ganglion cell layer. Major retinal vessels touch the ganglion cell layer and lie in the similar position to that of superficial capillaries.

Selective Atrophy of the Radial Peripapillary Capillaries in Chronic Glaucoma

Article

Jan 1969
ARCH OPHTHALMOL-CHIC

The radial peripapillary capillaries of the retina are the most superficial of the capillary layers, They are limited to the area around the optic disc in the nerve fiber layer, especially along the upper and lower temporal vessels. They take a linear, more or less parallel course, are longer than the average capillary, and anastomose infrequently with each other and adjacent capillaries. All these factors combine to make them more vulnerable to increased intraocular pressure of a prolonged nature. Fifteen postmortem eyes in ten patients with chronic glaucoma are presented, showing varying degrees of atrophy in this layer of capillaries. The clinical implications of this type of selective capillary atrophy are discussed.

Radial peripapillary capillaries: III. Their development in the cat

Article

Sep 1973

Indian-inked retinal flat mounts from kittens aged less than i day to 8 weeks were studied regarding the development of the radial peripapillary capillaries. RPCswere noted only in retinae of kittens more than 2 I days old. They appeared to develop in a mature form in areas where the primitive vascular meshwork had already undergone maturation. A somewhat similar growth pattern of the deep retinal capillaries at the posterior pole was confirmed.

Pathophysiology of retinal cotton-wool spots

Article

Jun 1970

NORMAN ASHTON

Radial peripapillary capillaries of the retina. II. Possible role in Bjerrum scotoma

Article

Feb 1968

Symposium on glaucoma: joint meeting with the National Society for the Prevention of Blindness. New observations on the radial peripapillary capillaries

Article

May 1967
Investig Ophthalmol

P Henkind

Effects of formaldehyde fixation on basilar artery caliber

Article

Jan 1980

The external diameters of rat and rabbit basilar arteries were determined before and after formaldehyde fixation in relaxed and drug constricted vessels. Fixation usually resulted in an immediate vessel constriction followed by partial relaxation after several hours. However, the results were inconstant from vessel to vessel and from area to area of the same vessel. It is concluded that morphologic as well as morphometric assessment of formaldehyde-fixed basilar arteries is unreliable.

Energy as a Constraint on the Coding and Processing of Sensory Information

Article

Sep 2001
CURR OPIN NEUROBIOL

Simon B Laughlin

Neurons use significant amounts of energy to generate signals. Recent studies of retina and brain connect this energy usage to the ability to transmit information. The identification of energy-efficient neural circuits and codes suggests new ways of understanding the function, design and evolution of nervous systems.

Optic Nerve Tissue Shrinkage During Pathologic Processing After Enucleation for Retinoblastoma

Article

Feb 2003
ARCH OPHTHALMOL-CHIC

To quantify and analyze the differences between the length of the optic nerve as measured by the ophthalmologist in the operating room after enucleation and the length as measured by the pathologist after fixation. The authors performed a retrospective review of patients who underwent either primary or secondary enucleation for retinoblastoma at the Ophthalmic Oncology Center of the New York-Presbyterian Hospital-Cornell campus between November 1979 and August 2001. Intraoperative notes and pathologic reports were reviewed to determine the length of the resected optic nerve as recorded by both the surgeon and pathologist. Sufficient data for inclusion in the study were available from 100 enucleation specimens belonging to 96 patients. A significant degree of shrinkage of the optic nerve occurred after fixation, with a mean shrinkage of 30.3% from the time of enucleation to the time of measurement by the pathologist. Age at enucleation affected the degree of optic nerve shrinkage; nerves from younger children underwent more shrinkage than nerves from older patients. Sex of the patient and the laterality of disease did not significantly affect optic nerve shrinkage. A significant degree of shrinkage of the optic nerve occurs in retinoblastoma enucleation specimens after fixation prior to pathologic analysis. This finding must be taken into account when comparing different series and making recommendations for chemoprophylaxis based solely on histopathologic examination.

Regional variation in brain capillary density and vascular response to ischemia. Brain Res. 910, 81e93 Quantitative morphometry of perifoveal capillary networks in the human retina Selective atrophy of the radial peripapillary capillaries and visual field defects in glaucoma (author's transl)

Jan 1975
27-32

M Cavaglia
S M Dombrowski
J Drazba
A Vasanji
P M Bokesch
D Janigro
G Chan
C Balaratnasingam
P K Yu
W H Morgan
I L Mcallister
S J Cringle
D Y Yu

Cavaglia, M., Dombrowski, S.M., Drazba, J., Vasanji, A., Bokesch, P.M., Janigro, D., 2001. Regional variation in brain capillary density and vascular response to ischemia. Brain Res. 910, 81e93. Chan, G., Balaratnasingam, C., Yu, P.K., Morgan, W.H., McAllister, I.L., Cringle, S.J., Yu, D.Y., 2012. Quantitative morphometry of perifoveal capillary networks in the human retina. Invest. Ophthalmol. Vis. Sci. 53, 5502e5514. Daicker, B., 1975. Selective atrophy of the radial peripapillary capillaries and visual field defects in glaucoma (author's transl). Albrecht Von Graefes Arch. Klin. Exp. Ophthalmol. 195, 27e32.

Perfusion and superfusion fixation effects on rat mesentery microvascular beds. Intravital and electron microscope analyses Cellular energy utilization and molecular origin of standard metabolic rate in mammals

Jan 1986

J A Rhodin
D F S Rolfe
G C Brown
D Scoles
D C Gray
J J Hunter
R Wolfe
B P Gee
Y Geng
B D Masella
R T Libby

Rhodin, J.A., 1986. Perfusion and superfusion fixation effects on rat mesentery microvascular beds. Intravital and electron microscope analyses. J. Submicrosc. Cytol. 18, 453e470. Rolfe, D.F.S., Brown, G.C., 1997. Cellular energy utilization and molecular origin of standard metabolic rate in mammals. Physiol. Rev. 77, 731e758. Scoles, D., Gray, D.C., Hunter, J.J., Wolfe, R., Gee, B.P., Geng, Y., Masella, B.D., Libby, R.T., Russell, S., Williams, D.R., Merigan, W.H., 2009. In-vivo imaging of retinal nerve fiber layer vasculature: imaging histology comparison. BMC Ophthalmol. 9, 9.

Quantitative confocal imaging of the retinal microvasculature in the human retina Studies on the radial peripapillary capillaries (RPCs). (1) Clinical features on fluorescein fundus angiography (author's transl)

Jan 1976

P E Tan
P K Yu
C Balaratnasingam
S J Cringle
W H Morgan
I L Mcallister
D Y Yu

Tan, P.E., Yu, P.K., Balaratnasingam, C., Cringle, S.J., Morgan, W.H., McAllister, I.L., Yu, D.Y., 2012. Quantitative confocal imaging of the retinal microvasculature in the human retina. Invest. Ophthalmol. Vis. Sci. 53, 5728e5736. Ueno, H., 1976. Studies on the radial peripapillary capillaries (RPCs). (1) Clinical features on fluorescein fundus angiography (author's transl). Nihon Ganka Gakkai Zasshi 80, 267e280.

The structural relationship between the microvasculature, neurons, and glia in the human retina Relationship of retinal vascular caliber with retinal nerve fiber layer thickness: the Singapore Malay eye study

Jan 2009
4091-4096

P K Yu
C Balaratnasingam
W H Morgan
S J Cringle
I L Mcallister
D Y Yu

Yu, P.K., Balaratnasingam, C., Morgan, W.H., Cringle, S.J., McAllister, I.L., Yu, D.Y., 2010b. The structural relationship between the microvasculature, neurons, and glia in the human retina. Invest. Ophthalmol. Vis. Sci. 51, 447e458. Zheng, Y., Cheung, N., Aung, T., Mitchell, P., He, M., Wong, T.Y., 2009. Relationship of retinal vascular caliber with retinal nerve fiber layer thickness: the Singapore Malay eye study. Invest. Ophthalmol. Vis. Sci. 50, 4091e4096.

Correlation between the radial peripapillary capillaries and the retinal nerve fibre layer in the normal human retina

Abstract

No full-text available

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