ResearchPad - retinal-vessels https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Automatic analysis of normative retinal oximetry images]]> https://www.researchpad.co/article/elastic_article_15756 Retinal oximetry is an important screening tool for early detection of retinal pathologies due to changes in the vasculature and also serves as a useful indicator of human-body-wide vascular abnormalities. We present an automatic technique for the measurement of oxygen saturation in retinal arterioles and venules using dual-wavelength retinal oximetry images. The technique is based on segmenting an optic-disc-centered ring-shaped region of interest and subsequent analysis of the oxygen saturation levels. We show that the two dominant peaks in the histogram of the oxygen saturation levels correspond to arteriolar and venular oxygen saturations from which the arterio-venous saturation difference (AVSD) can be calculated. For evaluation, we use a normative database of Asian Indian eyes containing 44 dual-wavelength retinal oximetry images. Validations against expert manual annotations of arterioles and venules show that the proposed technique results in an average arteriolar oxygen saturation (SatO2) of 87.48%, venular SatO2 of 57.41%, and AVSD of 30.07% in comparison with the expert ground-truth average arteriolar SatO2 of 89.41%, venular SatO2 of 56.32%, and AVSD of 33.09%, respectively. The results exhibit high consistency across the dataset indicating that the automated technique is an accurate alternative to the manual procedure.

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<![CDATA[Quantity and quality of image artifacts in optical coherence tomography angiography]]> https://www.researchpad.co/article/5c6448bed5eed0c484c2ed28

Objective

To analyze quality and frequency of OCTA artifacts and to evaluate their impact on the interpretability of OCTA images.

Design

75 patients with diabetic retinopathy (DR), retinal artery occlusion (RAO), retinal vein occlusion (RVO), or neovascular age-related macular degeneration (nAMD) and healthy controls were enrolled in this cross-sectional study in the outpatient department of a tertiary eye care center.

Methods

All participants underwent an OCTA examination (spectral domain OCT Cirrus 5000 equipped with the AngioPlex module). OCTA scans were analyzed independently by two experienced ophthalmologists. Frequency of various artifacts for the entire OCTA scan and for different segmentation layers and the grading of OCTA interpretability were investigated.

Results

The analysis of 75 eyes of 38 women and 37 men between 24 and 94 years were included. Six eyes had no retinal disease, 19 eyes had nAMD, 16 had DR, 19 eyes had RVO, and 15 eyes showed RAO. A macular edema (ME) was present in 40 of the diseased eyes. Projection artifacts occurred in all eyes in any structure below the superficial retinal vessel layer, segmentation and motion artifacts were found in 55% (41/75) and 49% (37/75) of eyes, respectively. Other artifacts occurred less frequently. Segmentation artifacts were significantly more frequent in diseased than in healthy eyes (p<0.01). Qualitative assessment of OCTA images was graded as excellent in 65% and sufficient in 25% of cases, adding up to 91% images deemed acceptable for examination. Presence of ME was associated with a significantly poorer interpretability (p<0.01).

Conclusion and Relevance

Various artifacts appear at different frequencies in OCTA images. Nevertheless, a qualitative assessment of the OCTA images is almost always possible. Good knowledge of possible artifacts and critical analysis of the complete OCTA dataset are essential for correct clinical interpretation and determining a precise clinical diagnosis.

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<![CDATA[Spectral domain optical coherence tomography as an adjunctive tool for screening Behçet uveitis]]> https://www.researchpad.co/article/5c1966d1d5eed0c484b52faa

Background

This study investigated the association of central macular thickness (CMT) and macular volume (MV) with severity of Behçet uveitis in the absence of macular edema (ME).

Methods

This retrospective, interventional study included a total 131 treatment-naïve Behçet patients with varying degree of uveitis in the absence of ME. The mean CMT and MV were obtained by spectral domain optical coherence tomography (SD ODT). The patients were classified according to the anatomical classification of Behçet uveitis. The main outcome measure was comparison of mean CMT and MV with the types of Behçet uveitis.

Results

Sixty patients (45.8%) with no uveitis, 41 patients (31.3%) with anterior uveitis, 18 patients (13.7%) with posterior uveitis, and 12 patients (9.2%) with panuveitis. The mean CMT were 261.6±22.2 μm in no uveitis, 268.1±17.8 μm in anterior uveitis, 306.4±32.9 μm in posterior uveitis, and 300.4±44.0 μm in panuveitis (P < 0.001). The mean MV was 8.7±0.3 mm3 in those without uveitis, 8.8±0.3 mm3 in anterior uveitis, 9.9±1.1 mm3 in those with posterior uveitis, and 9.7±0.4 mm3 in panuveitis (P < 0.001). Types of Behçet uveitis was the only significant factor correlated with the mean CMT (B = 18.170, β = 0.408, P < 0.001) and the mean MV (B = 0.328, β = 0.652, P < 0.001).

Conclusions

The mean CMT and MV were significantly thicker in the Behçet uveitis with posterior involvement. SD OCT can be used for an adjunctive tool for screening Behçet uveitis, especially for the presence of posterior involvement.

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<![CDATA[Analysis of Potential Ischemic Effect of Intravitreal Bevacizumab on Unaffected Retina in Treatment-Naïve Macular Edema Due to Branch Retinal Vein Occlusion: A Prospective, Interventional Case-Series]]> https://www.researchpad.co/article/5989db34ab0ee8fa60bd2701

Background

To study potential ischemic effects of intravitreal Bevacizumab (IVB) on unaffected retina in treatment-naive eyes with macular edema secondary to branch retinal vein occlusion (BRVO) and contralateral eyes secondary to systemic absorption.

Methods and Findings

Prospective, interventional series included 27 treatment-naive eyes with BRVO and macular edema. Exclusion criteria: Eyes with diabetic retinopathy, glaucoma, vasculitides, papilledema or systemic neurologic condition. Subjects underwent complete ophthalmological examination including fluoroscein angiography (FA), optical coherence tomography (OCT) and multifocal electroretinogram (mf-ERG). All subjects received single 1.25 mg/0.05ml IVB injection. Two observers measured all parameters; inter-observer agreements were expressed as kappa values. Paired t-test was used to compare values at baseline and follow-up. The statistical analysis was done using SPSS for Windows, Version 14.0. (Chicago, SPSS Inc.) Presenting mean CFT (central foveal thickness) was 499.5(+/-229.7) μm, mean BCVA (best corrected visual acuity) was 0.64(+/-0.41) logMAR. At last follow-up, mean CFT was 267.9(+/-159.3) μm (P<0.001), 95% CI [127.18, 422.32]; mean BCVA was 0.28(+/-0.24) logMAR. Respectively, mean N1 and P1 amplitudes of mfERG in 'unaffected quadrant' at presentation were -6.10(+/-4.00) nV/deg2 and 17.17(+/-11.54)nV/deg2; and -5.33(+/-1.30)nV/deg2 and 15.29(+/-4.69)nV/deg2 at final follow-up (P = 0.631 and 0.197, respectively), (95% CIs [-0.93, 1.42] and [-4.22, 1.08] respectively). In fundus quadrant of fellow eyes corresponding to unaffected quadrant in treated eyes, mean N1 and P1 amplitudes at presentation were -5.39(+/-1.56)nV/deg2 and 15.89(+/-3.89)nV/deg2; and -5.39(+/-1.90)nV/deg2 and 15.9(+/-5.52)nV/deg2 (P = 0.380 and 0.208), (95% CIs [-0.57, 1.28] and [-4.1, 1.1]) at last follow-up, respectively. Limitations: This study analysed the effects with a single injection of bevacizumab. However, whether ischemic adverse effects will emerge with repeated IVB injections as a consequence of cumulative dosing needs further investigation. The setting of our study being a tertiary care centre, the numbers of fresh BRVO cases without prior intervention were limited. Thus, the limitations of our study include a small sample size with a small follow-up period. No major ocular/systemic adverse event was observed in the study period.

Conclusion

No evidence of progressive ischaemia attributable to single bevacizumab treatment was observed in this study. However, a larger prospective study involving subjects with cumulative dosing of bevacizumab and a longer follow-up could provide a better understanding of the potential ischaemic effects of bevacizumab or other anti-VEGF agents.

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<![CDATA[Unsupervised Retinal Vessel Segmentation Using Combined Filters]]> https://www.researchpad.co/article/5989dacfab0ee8fa60bb5a61

Image segmentation of retinal blood vessels is a process that can help to predict and diagnose cardiovascular related diseases, such as hypertension and diabetes, which are known to affect the retinal blood vessels’ appearance. This work proposes an unsupervised method for the segmentation of retinal vessels images using a combined matched filter, Frangi’s filter and Gabor Wavelet filter to enhance the images. The combination of these three filters in order to improve the segmentation is the main motivation of this work. We investigate two approaches to perform the filter combination: weighted mean and median ranking. Segmentation methods are tested after the vessel enhancement. Enhanced images with median ranking are segmented using a simple threshold criterion. Two segmentation procedures are applied when considering enhanced retinal images using the weighted mean approach. The first method is based on deformable models and the second uses fuzzy C-means for the image segmentation. The procedure is evaluated using two public image databases, Drive and Stare. The experimental results demonstrate that the proposed methods perform well for vessel segmentation in comparison with state-of-the-art methods.

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<![CDATA[Retinal oximetry measures systemic hypoxia in central nervous system vessels in chronic obstructive pulmonary disease]]> https://www.researchpad.co/article/5989db50ab0ee8fa60bdbf96

Background

Determination of the blood oxyhemoglobin saturation in the retinal vessels of the eye can be achieved through spectrophotometric retinal oximetry which provides access to the state of oxyhemoglobin saturation in the central nervous system circulation. The purpose of this study was to test the capability of the Oxymap T1 oximeter to detect systemic hypoxemia and the effect of supplemental oxygen on retinal vessel oxyhemoglobin saturation.

Methods

Oxygen saturation of hemoglobin in retinal arterioles and venules was measured in 11 subjects with severe chronic obstructive pulmonary disease (COPD) on long term oxygen therapy. Measurements were made with and without their daily supplemental oxygen. Eleven healthy age and gender matched subjects were measured during ambient air breathing for comparison of oxyhemoglobin saturation in retinal arterioles and venules. Retinal arteriolar oxyhemoglobin saturation in COPD subjects inspiring ambient air was compared with finger pulse oximetry and blood samples from radial artery.

Results

COPD subjects had significantly lower oxyhemoglobin saturation during ambient air breathing than healthy controls in both retinal arterioles (87.2%±4.9% vs. 93.4%±4.3%, p = 0.02; n = 11) and venules (45.0%±10.3% vs. 55.2%±5.5%, p = 0.01). Administration of their prescribed supplemental oxygen increased oxyhemoglobin saturation in retinal arterioles (87.2%±4.9% to 89.5%±6.0%, p = 0.02) but not in venules (45.0%±10.3% to 46.7%±12.8%, p = 0.3). Retinal oximetry values were slightly lower than radial artery blood values (mean percentage points difference = -5.0±5.4, 95% CI: -15.68 to 5.67) and finger pulse oximetry values (-3.1±5.5, 95% CI: -14.05 to 7.84).

Conclusions

The noninvasive Oxymap T1 retinal oximetry detects hypoxemia in central nervous system vessels in patients with severe COPD compared with healthy controls. The instrument is sensitive to changes in oxygen breathing but displays slightly lower measures than finger pulse oximetry or radial artery measures. With further technological improvement, retinal oximetry may offer noninvasive “on-line” measurement of oxygen levels in central circulation in general anesthesia and critically ill patients.

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<![CDATA[Critical Endothelial Regulation by LRP5 during Retinal Vascular Development]]> https://www.researchpad.co/article/5989d9d5ab0ee8fa60b65bad

Vascular abnormalities in the eye are the leading cause of many forms of inherited and acquired human blindness. Loss-of-function mutations in the Wnt-binding co-receptor LRP5 leads to aberrant ocular vascularization and loss of vision in genetic disorders such as osteoporosis-pseudoglioma syndrome. The canonical Wnt-β-catenin pathway is known to regulate retinal vascular development. However, it is unclear what precise role LPR5 plays in this process. Here, we show that loss of LRP5 function in mice causes retinal hypovascularization during development as well as retinal neovascularization in adulthood with disorganized and leaky vessels. Using a highly specific Flk1-CreBreier line for vascular endothelial cells, together with several genetic models, we demonstrate that loss of endothelium-derived LRP5 recapitulates the retinal vascular defects in Lrp5-/- mice. In addition, restoring LRP5 function only in endothelial cells in Lrp5-/- mice rescues their retinal vascular abnormalities. Furthermore, we show that retinal vascularization is regulated by LRP5 in a dosage dependent manner and does not depend on LRP6. Our study provides the first direct evidence that endothelium-derived LRP5 is both necessary and sufficient to mediate its critical role in the development and maintenance of retinal vasculature.

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<![CDATA[Quantitative Spatial and Temporal Analysis of Fluorescein Angiography Dynamics in the Eye]]> https://www.researchpad.co/article/5989da07ab0ee8fa60b7618a

Purpose

We describe a novel approach to analyze fluorescein angiography to investigate fluorescein flow dynamics in the rat posterior retina as well as identify abnormal areas following laser photocoagulation.

Methods

Experiments were undertaken in adult Long Evans rats. Using a rodent retinal camera, videos were acquired at 30 frames per second for 30 seconds following intravenous introduction of sodium fluorescein in a group of control animals (n = 14). Videos were image registered and analyzed using principle components analysis across all pixels in the field. This returns fluorescence intensity profiles from which, the half-rise (time to 50% brightness), half-fall (time for 50% decay) back to an offset (plateau level of fluorescence). We applied this analysis to video fluorescein angiography data collected 30 minutes following laser photocoagulation in a separate group of rats (n = 7).

Results

Pixel-by-pixel analysis of video angiography clearly delineates differences in the temporal profiles of arteries, veins and capillaries in the posterior retina. We find no difference in half-rise, half-fall or offset amongst the four quadrants (inferior, nasal, superior, temporal). We also found little difference with eccentricity. By expressing the parameters at each pixel as a function of the number of standard deviation from the average of the entire field, we could clearly identify the spatial extent of the laser injury.

Conclusions

This simple registration and analysis provides a way to monitor the size of vascular injury, to highlight areas of subtle vascular leakage and to quantify vascular dynamics not possible using current fluorescein angiography approaches. This can be applied in both laboratory and clinical settings for in vivo dynamic fluorescent imaging of vasculature.

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<![CDATA[Regulation of C3 Activation by the Alternative Complement Pathway in the Mouse Retina]]> https://www.researchpad.co/article/5989da29ab0ee8fa60b81b7b

The purpose of this study was to examine the retinas of mice carrying hemizygous and null double deletions of Cfb-/- and Cfh-/-, and to compare these with the single knockouts of Cfb, Cfh and Cfd. Retinas were isolated from wild type (WT), Cfb-/-/Cfh-/-, Cfb-/-/Cfh+/-, Cfh-/-/Cfb+/-, Cfb-/-, Cfh-/- Cfd-/-, and Cfd+/- mice. Complement proteins were evaluated by western blotting, ELISA and immunocytochemistry, and retinal morphology was assessed using toluidine blue stained semi-thin sections. WT mice showed staining for C3 and its breakdown products in the retinal vasculature and the basal surface of the retinal pigment epithelium (RPE). Cfb-/- mice exhibited a similar C3 staining pattern to WT in the retinal vessels but a decrease in C3 and its breakdown products at the basal surface of the RPE. Deletion of both Cfb and Cfh restored C3 to levels similar to those observed in WT mice, however this reversal of phenotype was not observed in Cfh-/-/Cfb+/- or Cfb-/-/Cfh+/- mice. Loss of CFD caused an increase in C3 and a decrease in C3 breakdown products along the basal surface of the RPE. Overall the retinal morphology and retinal vasculature did not appear different across the various genotypes. We observed that C3 accumulates at the basal RPE in Cfb-/-, Cfb-/-/Cfh-/-, Cfb-/-/Cfh+/-, Cfd-/- and WT mice, but is absent in Cfh-/- and Cfh-/-/Cfb+/- mice, consistent with its consumption in the serum of mice lacking CFH when CFB is present. C3 breakdown products along the surface of the RPE were either decreased or absent when CFB, CFH or CFD was deleted or partially deleted.

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<![CDATA[Evaluation of Fundus Blood Flow in Normal Individuals and Patients with Internal Carotid Artery Obstruction Using Laser Speckle Flowgraphy]]> https://www.researchpad.co/article/5989dac7ab0ee8fa60bb2f85

Purpose

We investigated whether laser speckle flowgraphy (LSFG) results are comparable in both eyes and whether it is useful in the diagnosis of disparity in ocular ischemic syndrome (OIS) patients.

Methods

We compared the mean blur rate (MBR) value for various fundus regions in both eyes of 41 healthy subjects and 15 internal carotid artery occlusion (ICAO) cases. We calculated the standard value of the Laterality Index (LI), which was the MBR comparison of both eyes in each of the regions, in the control subjects. We then investigated the correlation between both eyes for the LIs in the entire fundus, the degree of ICAO and visual function.

Results

The disparity of the LIs in both eyes was least in the entire area of the fundus in control subjects and there was a significant correlation between both eyes of the 41 healthy individuals (P = 0.019). Significant correlations were found for the LI, visual acuity and degree of ICAO. The specificity and sensitivity of LI in the entire area was 93.8% and 100%, respectively.

Conclusions

LSFG revealed normal individuals have symmetrical fundus blood flow. LSFG could detect OIS and might be a useful tool for detecting disparities in fundus blood flow.

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<![CDATA[Retinal Microaneurysms Detection Using Gradient Vector Analysis and Class Imbalance Classification]]> https://www.researchpad.co/article/5989db38ab0ee8fa60bd3da9

Retinal microaneurysms (MAs) are the earliest clinically observable lesions of diabetic retinopathy. Reliable automated MAs detection is thus critical for early diagnosis of diabetic retinopathy. This paper proposes a novel method for the automated MAs detection in color fundus images based on gradient vector analysis and class imbalance classification, which is composed of two stages, i.e. candidate MAs extraction and classification. In the first stage, a candidate MAs extraction algorithm is devised by analyzing the gradient field of the image, in which a multi-scale log condition number map is computed based on the gradient vectors for vessel removal, and then the candidate MAs are localized according to the second order directional derivatives computed in different directions. Due to the complexity of fundus image, besides a small number of true MAs, there are also a large amount of non-MAs in the extracted candidates. Classifying the true MAs and the non-MAs is an extremely class imbalanced classification problem. Therefore, in the second stage, several types of features including geometry, contrast, intensity, edge, texture, region descriptors and other features are extracted from the candidate MAs and a class imbalance classifier, i.e., RUSBoost, is trained for the MAs classification. With the Retinopathy Online Challenge (ROC) criterion, the proposed method achieves an average sensitivity of 0.433 at 1/8, 1/4, 1/2, 1, 2, 4 and 8 false positives per image on the ROC database, which is comparable with the state-of-the-art approaches, and 0.321 on the DiaRetDB1 V2.1 database, which outperforms the state-of-the-art approaches.

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<![CDATA[Evaluation of Retinal Vessel Morphology in Patients with Parkinson's Disease Using Optical Coherence Tomography]]> https://www.researchpad.co/article/5989dadbab0ee8fa60bb9cf0

Purpose

The retina has been found affected in Parkinson’s disease (PD). It is unclear if this is due to neurodegeneration of local dopamine-dependent retinal cells, a result of central nervous degeneration including the optic nerve or retinal small vessel disease. This study aimed to detect changes of the retinal vasculature in PD patients compared to controls.

Methods

We examined 49 PD patients and 49 age- and sex-matched healthy controls by spectral domain optical coherence tomography (SD-OCT) with a circular scan centred at the optic disc. Vessels within the retinal nerve fibre layer were identified by an automated algorithm and thereafter manually labelled as artery or vein. Layer segmentation, vessel lumen and direct surrounding tissue were marked automatically with a grey value and the contrast between both values in relation to the surrounding tissue was calculated. The differences in these grey value ratios among subjects were determined and used as an indicator for differences in vessel morphology. Furthermore, the diameters of the veins and arteries were measured and then compared between the groups.

Results

The contrast of retinal veins was significantly lower in PD patients compared to controls, which indicates changes in vessel morphology in PD. The contrast of arteries was not significantly different. Disease duration, disease stage according to Hoehn and Yahr or age did not influence the grey value ratios in PD patients. Vessel diameter in either veins or arteries did not differ between subject groups. The contrast of retinal veins contralateral to the clinically predominant and first affected side was significantly lower compared to the ipsilateral side.

Conclusion

Our data show a potential difference of the retinal vasculature in PD patients compared to controls. Vascular changes in the retina of PD patients might contribute to vision-related complaints in PD.

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<![CDATA[Metamorphopsia Associated with Branch Retinal Vein Occlusion]]> https://www.researchpad.co/article/5989dae7ab0ee8fa60bbdd44

Purpose

To apply M-CHARTS for quantitative measurements of metamorphopsia in eyes with acute branch retinal vein occlusion (BRVO) and to elucidate the pathomorphology that causes metamorphopsia.

Methods

This prospective study consisted of 42 consecutive patients (42 eyes) with acute BRVO. Both at baseline and one month after treatment with ranibizumab, metamorphopsia was measured with M-CHARTS, and the retinal morphological changes were examined with optical coherence tomography.

Results

At baseline, metamorphopsia was detected in the vertical and/or horizontal directions in 29 (69.0%) eyes; the mean vertical and horizontal scores were 0.59 ± 0.57 and 0.52 ± 0.67, respectively. The maximum inner retinal thickness showed no association with the M-CHARTS score, but the M-CHARTS score was correlated with the total foveal thickness (r = 0.43, p = 0.004), the height of serous retinal detachment (r = 0.31, p = 0.047), and the maximum outer retinal thickness (r = 0.36, p = 0.020). One month after treatment, both the inner and outer retinal thickness substantially decreased. However, metamorphopsia persisted in 26 (89.7%) of 29 eyes. The posttreatment M-CHARTS score was not correlated with any posttreatment morphological parameters. However, the posttreatment M-CHARTS score was weakly correlated with the baseline total foveal thickness (r = 0.35. p = 0.024) and closely correlated with the baseline M-CHARTS score (r = 0.78, p < 0.001).

Conclusions

Metamorphopsia associated with acute BRVO was quantified using M-CHARTS. Initial microstructural changes in the outer retina from acute BRVO may primarily account for the metamorphopsia.

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<![CDATA[Interruption of Wnt Signaling in Müller Cells Ameliorates Ischemia-Induced Retinal Neovascularization]]> https://www.researchpad.co/article/5989daffab0ee8fa60bc600c

Retinal Müller cells are major producers of inflammatory and angiogenic cytokines which contribute to diabetic retinopathy (DR). Over-activation of the Wnt/β-catenin pathway has been shown to play an important pathogenic role in DR. However, the roles of Müller cell-derived Wnt/β-catenin signaling in retinal neovascularization (NV) and DR remain undefined. In the present study, mice with conditional β-catenin knockout (KO) in Müller cells were generated and subjected to oxygen-induced retinopathy (OIR) and streptozotocin (STZ)-induced diabetes. Wnt signaling was evaluated by measuring levels of β-catenin and expression of its target genes using immunoblotting. Retinal vascular permeability was measured using Evans blue as a tracer. Retinal NV was visualized by angiography and quantified by counting pre-retinal nuclei. Retinal pericyte loss was evaluated using retinal trypsin digestion. Electroretinography was performed to examine visual function. No abnormalities were detected in the β-catenin KO mice under normal conditions. In OIR, retinal levels of β-catenin and VEGF were significantly lower in the β-catenin KO mice than in littermate controls. The KO mice also had decreased retinal NV and vascular leakage in the OIR model. In the STZ-induced diabetic model, disruption of β-catenin in Müller cells attenuated over-expression of inflammatory cytokines and ameliorated pericyte dropout in the retina. These findings suggest that Wnt signaling activation in Müller cells contributes to retinal NV, vascular leakage and inflammation and represents a potential therapeutic target for DR.

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<![CDATA[Long-term consequences of developmental vascular defects on retinal vessel homeostasis and function in a mouse model of Norrie disease]]> https://www.researchpad.co/article/5989db5cab0ee8fa60be0268

Loss of Norrin signalling due to mutations in the Norrie disease pseudoglioma gene causes severe vascular defects in the retina, leading to visual impairment and ultimately blindness. While the emphasis of experimental work so far was on the developmental period, we focus here on disease mechanisms that induce progression into severe adult disease. The goal of this study was the comprehensive analysis of the long-term effects of the absence of Norrin on vascular homeostasis and retinal function. In a mouse model of Norrie disease retinal vascular morphology and integrity were studied by means of in vivo angiography; the vascular constituents were assessed in detailed histological analyses using quantitative retinal morphometry. Finally, electroretinographic analyses were performed to assess the retinal function in adult Norrin deficient animals. We could show that the primary developmental defects not only persisted but developed into further vascular abnormalities and microangiopathies. In particular, the overall vessel homeostasis, the vascular integrity, and also the cellular constituents of the vascular wall were affected in the adult Norrin deficient retina. Moreover, functional analyses indicated to persistent hypoxia in the neural retina which was suggested as one of the major driving forces of disease progression. In summary, our data provide evidence that the key to adult Norrie disease are ongoing vascular modifications, driven by the persistent hypoxic conditions, which are ineffective to compensate for the primary Norrin-dependent defects.

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<![CDATA[Quantitative microvascular analysis of retinal venous occlusions by spectral domain optical coherence tomography angiography]]> https://www.researchpad.co/article/5989db54ab0ee8fa60bdd165

Purpose

To quantitatively evaluate the retinal microvasculature in human subjects with retinal venous occlusions (RVO) using optical coherence tomography angiography (OCTA).

Design

Retrospective, cross-sectional, observational case series.

Participants

Sixty subjects (84 eyes) were included (20 BRVO, 14 CRVO, 24 unaffected fellow eyes, and 26 controls).

Methods

OCTA was performed on a prototype, spectral domain-OCTA system in the 3x3mm central macular region. Custom software was used to quantify morphology and density of retinal capillaries using four quantitative parameters. The vasculature of the segmented retinal layers and nonsegmented whole retina were analyzed.

Main outcome measures

Fractal dimension (FD), vessel density (VD), skeletal density (SD), and vessel diameter index (VDI) within the segmented retinal layers and nonsegmented whole retina vasculature.

Results

Nonsegmented analysis of RVO eyes demonstrated significantly lower FD (1.64±0.01 vs 1.715±0.002; p<0.001), VD (0.32±0.01 vs 0.432±0.002; p<0.001), and SD (0.073±0.004 vs 0.099±0.001; p<0.001) compared to controls. Compared to the fellow eye, FD, VD and SD were lower (p<0.001), and VDI was higher (p<0.001). FD, VD, and SD progressively decreased as the extent (or type) of RVO increased (control vs BRVO vs CRVO; p<0.001). In the unaffected fellow eye FD, VD and SD showed significant differences when compared to control eyes or affected RVO eyes (p<0.001).

Conclusions

Quantitative OCTA of the central 3x3mm macular region demonstrates significant differences in capillary density and morphology among subjects with BRVO and CRVO compared to controls or unaffected fellow eyes in all vascular layers. The unaffected fellow eyes also demonstrate significant differences when compared to controls. OCTA allows for noninvasive, layer-specific, quantitative evaluation of RVO-associated microvascular changes.

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<![CDATA[Retinal Oximetry with Scanning Laser Ophthalmoscope in Infants]]> https://www.researchpad.co/article/5989d9f0ab0ee8fa60b6e4eb

Purpose

Dual wavelength retinal oximetry has been developed for adults, but is not available for infants. Retinal oximetry may provide insight into the pathophysiology of oxygen-mediated diseases like retinopathy of prematurity. More insight in the oxygen metabolism of the retina in infants may provide valuable clues for better understanding and subsequent prevention or treatment of the disease. The measurements of oxygen saturation are obtained with two fundus images simultaneously captured in two different wavelengths of light. The comparison in light absorption of oxygenated and deoxygenated hemoglobin can be used to estimate the oxygen saturation within the retinal vessels by means of a software algorithm. This study aims to make retinal oximetry available for neonates. The first step towards estimating retinal oxygen saturation is determining the optical density ratio. Therefore, the purpose of this study is to image healthy newborn infants with a scanning laser ophthalmoscope and determine the optical density ratio for retinal oximetry analysis.

Methods

Images of the retina of full-term healthy infants were obtained with an SLO, Optomap 200Tx (Optos), with two laser wavelengths (532nm and 633nm). The infant lay face down on the lower arm of the parent, while the parent supported the chest and chin with one hand, and stabilized the back with the other hand. No mydriatics or eyelid specula were used during this study. The images were analyzed with modified Oxymap Analyzer software for calculation of the Optical Density Ratio (ODR) and vessel width. The ODR is inversely and approximately linearly related to the oxygen saturation. Measurements were included from the superotemporal vessel pair. A paired t-test was used for statistical analysis.

Results

Fifty-nine infants, (58% female), were included with mean gestational age of 40 ± 1.3 weeks (mean ± SD) and mean post-natal age of 16 ± 4.8 days. A total of 28 images were selected for retinal oximetry analysis. The ODR was 0.256 ± 0.041 for the arterioles and 0.421 ± 0.089 for the venules (n = 28, p < 0.001). The measured vessel-width for the arterioles was 14.1 ± 2.7 pixels and for the venules 19.7 ± 3.7 pixels (n = 28, p < 0.001).

Conclusions

Retinal oximetry can be performed in newborn infants by combining an SLO and a dual-wavelength algorithm software. Sensitivity of the approach is indicated by the fact that the ODR measurements are significantly different between the arterioles and the venules. However, more variability in ODR is seen with the SLO approach in babies than is seen with conventional oximetry in adults. This approach is completely non-invasive, non-contact and even avoids the use of mydriatics or eyelid specula.

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<![CDATA[Etiology and Features of Eyes with Rubeosis Iridis among Korean Patients: A Population-Based Single Center Study]]> https://www.researchpad.co/article/5989daf2ab0ee8fa60bc1781

Purpose

To estimate the etiology and features of the eyes with rubeosis iridis among Korean patients.

Materials and Methods

This study is a retrospective review of 533 Korean patients with rubeosis iridis who visited an eye hospital in Seoul, Korea. We defined rubeosis iridis as visible blood vessels on the iris surface detected during a slit-lamp examination. All cases were reviewed for age at the time of diagnosis, medical history, the most likely cause of rubeosis iridis, visual acuity, and intraocular pressure.

Results

The most commonly observed cause of rubeosis iridis was diabetic retinopathy (DR; n = 337, 63.2%), followed by retinal vein occlusion (RVO; n = 101, 18.9%), ocular ischemic syndrome (OIS; n = 24, 4.5%), retinal detachment (n = 17, 3.2%), and uveitis (n = 15, 2.8%). The cause was classified as miscellaneous in 18 cases (3.4%); in 21 eyes (3.9%), the cause was not clear. Age at the time of rubeosis iridis diagnosis was lower in patients with DR (56.5 years) than in those with RVO (61.0 years) and OIS (64.8 years; P < 0.01). Intraocular pressure of the eyes with DR (37.3 mmHg) and RVO (39.5 mmHg) was higher than that of the eyes with OIS (25.8 mmHg; P < 0.01).

Conclusion

In our population-based single center study, DR was the leading cause of rubeosis iridis followed by RVO and OIS among Korean patients. The clinical characteristics of the eyes with rubeosis iridis differed according to etiology. This finding may be useful when assessing eyes with rubeosis iridis.

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<![CDATA[Fzd4 Haploinsufficiency Delays Retinal Revascularization in the Mouse Model of Oxygen Induced Retinopathy]]> https://www.researchpad.co/article/5989dafcab0ee8fa60bc51e4

Mutations in genes that code for components of the Norrin-FZD4 ligand-receptor complex cause the inherited childhood blinding disorder familial exudative vitreoretinopathy (FEVR). Statistical evidence from studies of patients at risk for the acquired disease retinopathy of prematurity (ROP) suggest that rare polymorphisms in these same genes increase the risk of developing severe ROP, implying that decreased Norrin-FZD4 activity predisposes patients to more severe ROP. To test this hypothesis, we measured the development and recovery of retinopathy in wild type and Fzd4 heterozygous mice in the absence or presence of ocular ischemic retinopathy (OIR) treatment. Avascular and total retinal vascular areas and patterning were determined, and vessel number and caliber were quantified. In room air, there was a small delay in retinal vascularization in Fzd4 heterozygous mice that resolved as mice reached maturity suggestive of a slight defect in retinal vascular development. Subsequent to OIR treatment there was no difference between wild type and Fzd4 heterozygous mice in the vaso-obliterated area following exposure to high oxygen. Importantly, after return of Fzd4 heterozygous mice to room air subsequent to OIR treatment, there was a substantial delay in retinal revascularization of the avascular area surrounding the optic nerve, as well as delayed vascularization toward the periphery of the retina. Our study demonstrates that a small decrease in Norrin-Fzd4 dependent retinal vascular development lengthens the period during which complications from OIR could occur.

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<![CDATA[Optical Coherence Tomography Angiography Findings in Stargardt Disease]]> https://www.researchpad.co/article/5989db51ab0ee8fa60bdc225

Background

to assess vessel density of superficial capillary plexus (SCP), deep capillary plexus (DCP) and choriocapillaris (CC) in advanced Stargardt disease (STGD) using optical coherence tomography angiography (OCTA) and correlate these findings with macular function using pattern electroretinogram (PERG) and multifocal electroretinogram (mfERG).

Methods

Twelve patients (24 eyes) with advanced STGD underwent vessel densities and macular thickness measurements using OCTA. A control group of 24 healthy controls (24 eyes) was chosen for comparison. In the STGD group correlation between vessel density and macular thickness and between macular function and morphologic parameters were evaluated.

Results

Whole parafoveal vessel density (VD) of SCP was significantly lower in STGD group compared to the control group (p<0.05). Foveal VD and whole parafoveal VD of the DCP were significantly lower in STGD group compared to the controls (p<0.05). CC was significantly decreased in STGD compared to controls (p<0.05). Foveal macular thickness (MT), full parafoveal MT, and inner limiting membrane (ILM)-inner plexiform layer (IPL) parafoveal MT thickness were decreased in STGD eyes compared to controls (p<0.001). PERG and mfERG were both significantly reduced in STGD compared to controls (p<0.001). A direct correlation was found between full parafoveal MT and vessel density in the STGD group.

Conclusions

Patients with advanced STGD showed a reduction of SCP, DCP and CC compared to healthy eyes related to a reduction of total and ILM-IPL macular thickness. These results suggest that both retinal capillaris plexuses and choriocapillaris reduction occur in STDG along with inner and outer retinal thinning.

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