Retinal small vessel pathology is associated with disease burden in multiple sclerosis.

BACKGROUND: Alterations of the superficial retinal vasculature are commonly observed in multiple sclerosis (MS) and can be visualized through optical coherence tomography angiography (OCTA). OBJECTIVES: This study aimed to examine changes in the retinal vasculature during MS and to integrate findings into current concepts of the underlying pathology. METHODS: In this cross-sectional study, including 259 relapsing-remitting MS patients and 78 healthy controls, we analyzed OCTAs using deep-learning-based segmentation algorithm tools. RESULTS: We identified a loss of small-sized vessels (diameter < 10 µm) in the superficial vascular complex in all MS eyes, irrespective of their optic neuritis (ON) history. This alteration was associated with MS disease burden and appears independent of retinal ganglion cell loss. In contrast, an observed reduction of medium-sized vessels (diameter 10-20 µm) was specific to eyes with a history of ON and was closely linked to ganglion cell atrophy. CONCLUSION: These findings suggest distinct atrophy patterns in retinal vessels in patients with MS. Further studies are necessary to investigate retinal vessel alterations and their underlying pathology in MS.

Quantitative assessment of retinochoroidal microvasculature in patients with carotid artery stenosis using OCT angiography.

PURPOSE: To investigate the alterations in retinochoroidal parameters measured by optical coherence tomography (OCT) and OCT angiography (OCTA) in patients with carotid artery stenosis (CAS) and assess their associations with digital subtraction angiography (DSA) data. METHOD: This study enrolled patients diagnosed with CAS and age-matched healthy controls. Both groups underwent OCT and OCTA examinations. DSA and assessment of carotid artery stenosis were performed only in the CAS group. The study evaluated various retinochoroidal parameters from OCT and OCTA, including linear vessel density (LVD), foveal avascular zone (FAZ), choroidal thickness (ChT), and retinal nerve fiber layer (RNFL) thickness. DSA-derived measures included cervical segment (C1) diameter, cavernous segment (C4) diameter, stenosis percentage, ophthalmic artery (OA) filling time, C1-OA filling time, and residual stenosis. RESULTS: A total of 42 eyes from 30 CAS patients and 60 eyes from 30 healthy controls were included. Patients with CAS displayed significantly decreased LVD compared to controls (p < 0.001). Additionally, the CAS group had thinner choroid and RNFL (p = 0.047 and p < 0.001, respectively). Macular LVD negatively correlated with both stenosis percentage and C1-OA filling time (p = 0.010 and p = 0.014, respectively). In patients who underwent carotid artery stenting, preoperative ChT significantly correlated with residual stenosis (Pearson r = -0.480, p = 0.020). CONCLUSION: OCT and OCTA provide a quantitative assessment of retinochoroidal microstructural changes associated with CAS, suggesting potential for noninvasive evaluation of the disease. This might contribute to the prevention of irreversible ocular complications and early detection of CAS. Furthermore, ChT may not only aid in diagnosing CAS more reliably but also offer prognostic information.

Imaging Assessment of Peripapillary Vessel Diameters in Postmortem Eyes.

PURPOSE: Proof of concept of ex vivo retinal vessel diameter measurements in human postmortem eyes. METHODS: En face near-infrared (IR) images and optical coherence tomography (OCT) of the optic nerve head (ONH) were captured ex vivo with a Heidelberg Engineering Spectralis (Spectralis, version 7.0.4, Image Capture Module, version 1.2.4, Heidelberg Heidelberg, Germany) device, using a custom-made eye chamber holding and positioning the eyes during the image process. Thirty-two formaldehyde-fixated eyes of 16 patients were imaged. In the IR images, two independent graders measured retinal vessel diameters at the intersection of a drawn circle centered on the ONH with diameters of 2.0 mm and 3.4 mm, respectively. The anatomically corresponding measurements between both graders were statistically analyzed using a Wilcoxon signed-rank test. RESULTS: A total of 246 matched measurements of both graders were analyzed across all 32 imaged eyes. Statistically significant differences between the graders were found for arterioles at 2 mm from the ONH. The other measurements did not show statistically significant intergrader differences. The mean values for arteriole diameters were 72.2 µm at 2.0 mm and 61.5 µm at 3.4 mm for grader 1, and 66.4 µm at 2.0 mm and 63.2 µm at 3.4 mm for grader 2. The mean diameter for venules were 75.5 µm at 2.0 mm and 79.3 µm at 3.4 mm for grader 1, and 67.4 µm at 2 mm and 79.1 µm at 3.4 mm for grader 2. CONCLUSION: To the best of our knowledge, this is the first study to present IR image-based retinal vessel diameters in ex vivo postmortem eyes. Retinal IR/OCT imaging is possible, and measurements are reproducible in formaldehyde-fixated human eyes. Fixation artefacts result in lower image quality, and this can impose challenges in correctly detecting, classifying, and measuring retinal vessels.

Retinal imaging for the assessment of stroke risk: a systematic review.

BACKGROUND: Stroke is a leading cause of morbidity and mortality. Retinal imaging allows non-invasive assessment of the microvasculature. Consequently, retinal imaging is a technology which is garnering increasing attention as a means of assessing cardiovascular health and stroke risk. METHODS: A biomedical literature search was performed to identify prospective studies that assess the role of retinal imaging derived biomarkers as indicators of stroke risk. RESULTS: Twenty-four studies were included in this systematic review. The available evidence suggests that wider retinal venules, lower fractal dimension, increased arteriolar tortuosity, presence of retinopathy, and presence of retinal emboli are associated with increased likelihood of stroke. There is weaker evidence to suggest that narrower arterioles and the presence of individual retinopathy traits such as microaneurysms and arteriovenous nicking indicate increased stroke risk. Our review identified three models utilizing artificial intelligence algorithms for the analysis of retinal images to predict stroke. Two of these focused on fundus photographs, whilst one also utilized optical coherence tomography (OCT) technology images. The constructed models performed similarly to conventional risk scores but did not significantly exceed their performance. Only two studies identified in this review used OCT imaging, despite the higher dimensionality of this data. CONCLUSION: Whilst there is strong evidence that retinal imaging features can be used to indicate stroke risk, there is currently no predictive model which significantly outperforms conventional risk scores. To develop clinically useful tools, future research should focus on utilization of deep learning algorithms, validation in external cohorts, and analysis of OCT images.

Quantitative assessment of retinal vasculature changes in systemic lupus erythematosus using wide-field OCTA and the correlation with disease activity.

Purpose: To assess the retinal vasculature changes quantitatively using wide-field optical coherence tomography angiography (OCTA) in systemic lupus erythematosus (SLE), and explore its correlation with systemic clinical features. Design: Prospective, cross-sectional, observational study. Participants and controls: Patients with SLE who presented to the Ophthalmology Department of Peking Union Medical College Hospital from November 2022 to April 2023 were collected. The subjects were divided into retinopathy and without retinopathy groups. Age and gender-matched healthy subjects were selected as controls. Methods: Patients with SLE and control subjects were imaged with 24×20 mm OCTA scans centered on the fovea and 6×6 mm OCTA scans centered on the optic disc. The sub-layers of OCTA images were stratified by the built-in software of the device and then the retinal thickness and vessel density were measured automatically. The characteristics of retinal OCTA parameters of SLE and its correlation with systemic clinical indicators of patients without retinopathy were analyzed. Main outcome measures: OCTA parameters, visual acuity, intraocular pressure, and systemic clinical indicators of patients such as disease activity index, autoimmune antibodies, and inflammatory marker levels were collected. Results: A total of 102 SLE patients were included, 24 of which had retinopathy, and 78 had unaffected retina. Wide-field OCTA could effectively detect retinal vascular obstruction, non-perfusion area, and morphological abnormalities in patients with lupus retinopathy. SLE patients without retinopathy had significantly higher retinal superficial vessel density (SVD) in foveal (P=0.02), para-foveal temporal (P=0.01), nasal (P=0.01), peripheral foveal temporal (P=0.02), and inferior areas (P=0.02), as well as subregion temporal (P=0.01) and inferior areas (P=0.03) when compared with healthy controls (n=65 eyes from 65 participants). The area under curve (AUC) value of subregion inferior SVD combined parafoveal temporal SVD was up to 0.70. There was a significantly positive correlation between SVD and disease activity in SLE without retinopathy group. Patients with severe activity had the most significant increase in SVD. Conclusion: Wide-field OCTA can provide a relatively comprehensive assessment of the retinal vasculature in SLE. In the absence of pathological changes of the retina, the SVD was significantly increased and was positively correlated with the disease activity of SLE.

The Assessment of Radial Peripapillary Capillary Vessel Density in Adult Children of Patients With Primary Open Angle Glaucoma.

PRCIS: The observed decrease in radial peripapillary capillary vessel density among adult children of individuals with primary open angle glaucoma, in comparison to controls, suggests the possibility of early microvascular alterations in the eyes of these at-risk individuals. PURPOSE: To compare the radial peripapillary capillary vessel density (RPCVD) and peripapillary retinal nerve fiber layer (RNFL) thickness values of eyes between healthy adults with a maternal or paternal history of primary open angle glaucoma (POAG) and age-matched healthy controls without a family history of POAG. MATERIALS AND METHODS: RPCVD values and RNFL thicknesses in the peripapillary region and 4 quadrants (superior, inferior, nasal, and temporal) were evaluated using optical coherence tomography angiography among 30 adult children of patients with POAG and 30 age-matched healthy controls without a family history of POAG. RESULTS: The mean whole image RPCVD (51.6±1.7% vs. 49.8±1.7%, P =0.0006) and average RPCVD (54.7±1.7% vs. 53.2±2.1%, P =0.006) values were significantly lower in the adult children of patients with POAG compared with age-matched healthy controls without a family history of POAG. There was no difference in terms of RNFL thickness values in any region. CONCLUSION: Despite having similar RNFL thickness values to the control group, the observation of lower RPCVD in the eyes of adult children of POAG patients may indicate potential early vascular alterations. The result of the present study encourages further longitudinal studies to determine the potential importance of the underlying vascular alterations in these high-risk individuals.

Wide-field swept-source optical coherence tomography angiography in the assessment of retinal microvasculature and choroidal thickness in patients with myopia.

BACKGROUND/AIMS: Pathological myopia (PM) is a leading cause of blindness worldwide. We aimed to evaluate microvascular and chorioretinal changes in different stages of myopia with wide-field (WF) swept-source (SS) optical coherence tomography angiography (OCTA). METHODS: This prospective cross-sectional observational study included 186 eyes of 122 patients who had undergone imaging between November 2018 and October 2020. Vessel density (VD) and vessel skeletonised density (VSD) of superficial capillary plexus, deep capillary plexus and whole retina, as well as foveal avascular zone parameters, retinal thickness (RT) and choroidal thickness (CT), were calculated. RESULTS: This study evaluated 75 eyes of 48 patients with high myopia (HM), 43 eyes of 31 patients with mild to moderate myopia and 68 eyes of 53 age-matched controls. Controlling for age and the presence of systemic hypertension, we found that HM was associated with decrease in VD and VSD in all layers on 12×12 mm² scans. Furthermore, HM was associated with a VD and VSD decrease in every Early Treatment Diabetic Retinopathy Study grid, with a larger decrease temporally (ßVD=-0.39, ßVSD=-10.25, p<0.01). HM was associated with decreased RT and CT. Reduction in RT was outside the macular region, while reduction in CT was in the macular region. CONCLUSION: Using WF SS-OCTA, we identified reduction in microvasculature and structural changes associated with myopia. Decrease in VD and VSD was greater in the temporal quadrant, and reductions in RT and CT were uneven across the retina. Further work may help identify risk factors for the progression of PM and associated vision-threatening complications.

Assessment of microvascular involvement in lupus nephritis patients by retinal OCT-angiography and kidney biopsies.

OBJECTIVES: Ocular and renal microvascular damage in lupus nephritis (LN) share similar physiopathological pathways that have investigated using traditional fundus examination and high-resolution colour electroretinography. Optical coherence tomography angiography (OCTA) is a recent, non-invasive technique for imaging the microvasculature of retina and choroid. Aim of the study was to investigate through OCTA analysis the relationship between retinal microvascular alterations and renal functional and histologic features. METHODS: Systemic lupus erythematosus (SLE) patients with LN, SLE without renal involvement and healthy controls were recruited and accomplished an ophthalmological evaluation, including OCTA. SLE-LN patients underwent a rheumatological evaluation, including disease-related clinical and laboratory features collection and kidney biopsy examination. RESULTS: This cross-sectional study enrolled forty-six eyes of 23 LN patients, thirty-two eyes of 16 SLE patients and forty-two eyes of 21 controls. Thirteen SLE-LN patients (56.5%) displayed lupus retinopathy, 10 at moderate (77%) and 3 at severe stage (23%) by fundus oculi examination. Analysis of OCTA data showed with high/moderate accuracy a reduction of retinal capillary vessel density in both SLE and SLE-LN patients compared to controls in superficial and deep plexi. A reduction in fovea thickness and an increase in foveal avascular zone were also detected. OCTA data of LN patients correlated with LN duration, disease activity, kidney function and the presence of LN-vascular lesions at kidney biopsy. CONCLUSIONS: Our results suggest the role of OCTA in early detection of systemic vascular involvement in SLE-LN patients and related kidney functional-histological impairment.

Assessment of changes in macular structural retinal layers in patients with pathological myopia.

Background/aim: This study aimed to examine changes in the thickness of individual macular retinal layers in eyes with pathological myopia (PM) and to compare the thickness of each retinal layer between the PM and control groups to gain insights into retinal perfusion. Materials and methods: The study included 51 eyes in the PM group and 51 eyes in the control group. Optical coherence tomography (OCT) was used to measure the thickness of each retinal layer in the central fovea, parafoveal, and perifoveal regions. Optical coherence tomography angiography (OCT-A) was used to evaluate the retinal capillary density. Results: In the PM group, the retinal nerve fiber layer (RNFL), ganglion cell layer (GCL), inner plexiform layer (IPL), and inner nuclear layer (INL) were thicker than in the control group (p = 0.004, p = 0.027, p = 0.020, and p < 0.001, respectively), whereas the outer nuclear layer (ONL) and photoreceptor layer (PRL) were thinner (p = 0.001 and p = 0.003, respectively). In other regions, the RNFL was thicker in the myopic group, whereas the GCL, IPL, INL, and ONL were thinner. OCT-A did not reveal any significant difference between the groups in terms of radial capillary plexus density (p = 0.381); however, the densities of the other plexuses were lower in the PM group. Conclusions: The results showed alterations in the thickness of retinal layers and capillary plexus density in PM. Thus, assessment of the thickness of individual retinal layers may serve as an indicator of vascular diseases that affect the circulation of the retina and choroid.

[Use of optical coherence tomography angiography in assessment in conjunctival vascular architecture in health and pathology]. / Vozmozhnosti opticheskoi kogerentnoi tomografii v angiorezhime v otsenke angioarkhitektoniki kon"yunktivy v norme i pri patologii.

PURPOSE: Investigation of the capabilities of anterior segment (AS) optical coherence tomography angiography (OCTA) in evaluation of conjunctival vascular architecture in healthy individuals and in various pathological conditions. MATERIAL AND METHODS: The study included 17 healthy volunteers (34 eyes; the control group) and 62 patients (68 eyes) with conjunctival lesions of various nature. All participants underwent AS-OCT and AS-OCTA with assessment of qualitative (vessels pattern, lumen, pathologic tortuosity) and quantitative parameters (vessel density (VD, %) in the lesion area). Mean VD (MVD) and local VD (LVD) were determined, as well as VD in perifocal tissues (PVD). RESULTS: OCTA scans in 8 conjunctival sectors showed mostly radial pattern of the vascular architecture, with vessel lumen remaining the same over their entire visible length. Larger-sized vessels in deeper conjunctival layers were discovered in most cases. The lowest VD value (33.3%) was registered in the superotemporal quadrant, and the highest (38.9%) - in the nasal. Tortuosity of the vessels with course disruption, uneven lumen over the length of the vessels and increase in VD were observed in the area of conjunctival lesions in all cases excluding congenital abnormalities, pingueculae and conjunctival melanocytic intraepithelial neoplasia. The malignant nature of the tumors was indicated by dense vessel distribution and difficulties for visualization of intravascular space, and confirmed by pathohistological analysis. An increase in the number of areas with a lace-like pattern was characteristic for melanomas, with mean VD of more than 50% in the most vascularized areas. CONCLUSION: AS-OCTA is an informative method for the visualization of vessels in healthy conjunctiva and in conjunctival pathology. Local VD in the lesion area should be measured when the vessels are unevenly distributed.

[The role of optical coherence tomography angiography in the assessment of retinal microcirculation in thrombotic microangiopathy associated with malignant arterial hypertension]. / Rol' opticheskoi kogerentnoi tomografii s funktsiei angiografii v otsenke retinal'noi mikrotsirkulyatsii pri tromboticheskoi mikroangiopatii, assotsiirovannoi so zlokachestvennoi arterial'noi gipertenziei.

Optical coherence tomography angiography (OCT-A) allows detailed assessment of the state of local blood flow in various systemic ischemic diseases, which include thrombotic microangiopathy (TMA) associated with malignant arterial hypertension (MAH). PURPOSE: To evaluate retinal microcirculation using OCT-A imaging data in the group of patients with TMA associated with MAH. MATERIAL AND METHODS: The study consisted of a qualitative and quantitative analysis of OCT-A data from 7 patients (14 eyes) with TMA associated with MAH and verified by renal biopsy. The control group included 7 healthy individuals (14 eyes). The following parameters were analyzed: area size of the foveal avascular zone FAZ, mm, vessel density (VD, %) and vessel skeleton density (VSD, %). The indicators were measured separately in the deep and superficial vascular plexuses and divided by localization into: the total density of the entire measured area, central density, density by quadrants (superior, inferior, nasal and temporal). All quadrants were subdivided into inner (corresponding to parafovea) and outer (corresponding to perifovea). RESULTS: Local foci of vascular attenuation of the deep retinal capillary plexus, pathological tortuosity of blood vessels in the deep and superficial retinal capillary plexuses were found in 100% of study group patients. Per-quadrant analysis of OCT-A finding in the macular zone revealed a statistically significant decrease in VD of the deep retinal capillary plexus (p<0.05). A direct correlation was found between glomerular filtration rate and the VD index in the outer inferior (r=0.567; p=0.034) and inner temporal quadrants (r=0.613; p=0.020) of the deep retinal capillary plexus, as well as the level of hemoglobin in blood serum and VD in inner temporal quadrant of the deep vascular plexus (r=0.596; p=0.025). CONCLUSION: Changes revealed with OCT-A are the symptoms of TMA in MAH patients spreading to the retinal microvasculature, mainly at the level of the deep retinal capillary plexus.

ASSESSMENT OF FLUORESCEIN ANGIOGRAPHY NONPERFUSION IN EYES WITH DIABETIC RETINOPATHY USING ULTRAWIDE FIELD RETINAL IMAGING.

PURPOSE: Evaluate association of retinal nonperfusion (NP) on ultrawide field (UWF) fluorescein angiography (FA) with diabetic retinopathy (DR) severity and predominantly peripheral lesions (PPL). METHODS: Multicenter observational study, 652 eyes (361 participants) having nonproliferative DR (NPDR) without center-involved diabetic macular edema in at least one eye. Baseline 200° UWF-color and UWF-FA images were graded by a central reading center for color-PPL and FA-PPL, respectively. UWF-FA was graded for NP index within concentric zones: posterior pole (<10 mm from fovea), midperiphery (10-15 mm), and far periphery (>15 mm). RESULTS: Baseline Early Treatment Diabetic Retinopathy Study DR severity was 31.7% no DR/mild NPDR, 24.1% moderate NPDR, 14.0% moderately severe NPDR, 25.6% severe/very severe NPDR, and 4.6% proliferative DR. Worse DR severity was associated with increased NP index overall (P = 0.002), in the posterior pole (P < 0.001), midperiphery (P < 0.001), and far periphery (P = 0.03). On average, 29.6% of imaged retinal NP was in the posterior pole, 33.7% in midperiphery, and 36.7% in far periphery. Increased NP index was associated with FA-PPL (P < 0.001) but not with color-PPL (P = 0.65). CONCLUSION: Approximately, 70% of NP in diabetic eyes is located outside the posterior pole. Increased NP is associated with the presence of FA-PPL, suggesting UWF-FA may better predict future DR worsening than UWF-color alone.

Expression of Long Non-Coding RNA (lncRNA) SNHG5 in Patients with Refractory Diabetic Macular Edema and Its Regulatory Mechanism.

BACKGROUND The aim of this study was to assess use of lncRNAs as biomarkers in serum and aqueous humor of patients with diabetic macular edema (DME). MATERIAL AND METHODS Optical coherence tomography and fundus photography were used to analyze the retinal features of the patients. RT-qPCR was used to analyze the differential expression of lncRNA snhg5 in patients who have idiopathic macular hole (MH), DME, or refractory DME. The relationship between SNHG5 and the clinical characteristics of the patients was analyzed. The effect of SNHG5 on the hyperplasia and apoptosis of human retino-microvascular endothelial cells (HRMECs) and its mechanism were analyzed in vitro. RESULTS Patients with idiopathic MH developed retinal nerve epithelium rupture and retinal fundus thickening, and patients with DME or refractory DME showed significant macular edema with hemorrhaging. The refractory DME patients improved after treatment but still showed significant macular edema and multiple laser scarring. SNHG5 expression was not only low in the atrial fluid and plasma in DME patients, but also lower in the refractory DME group compared to the idiopathic MH patients. SNHG5 expression in the aqueous humor and plasma was negatively correlated with disease duration, body mass index, and levels of fasting blood glucose, glycated hemoglobin, proteinuria, and glycosuria. In the in vitro experiments, SNHG5 expression was significantly downregulated in high glucose-induced HMECs. After SNHG5 overexpression, cell proliferation, angiogenesis, and VEGF-A protein levels were distinctly downregulated. CONCLUSIONS SNHG5 correlates with the development of DME and is a potential target for therapy.

Normative data assessment of age-related changes in macular and optic nerve head vessel density using optical coherence tomography angiography.

OBJECTIVE: To investigate macular and optic nerve head vessel density in healthy individuals using optical coherence tomography angiography (OCTA), and determine their relationship with age. METHOD: This retrospective study included 153 eyes of 153 individuals aged between 20 and 80 years, who had no systemic diseases, optic disk, or retinal pathologies. The retinal (6 × 6 mm) and optic disk (4.5 × 4.5 mm) OCTA images were evaluated for superficial capillary plexus (SCP), deep capillary plexus (DCP) and radial peripapillary capillary plexus (RPCP) vessel density, foveal avascular zone (FAZ) area, and choriocapillaris flow area and compared among 5 age groups. RESULTS: The SCP vessel density was significantly associated with age for the whole image (P = 0.001), parafovea (P = 0.038), and perifovea (P/ce:italic>= 0.001). The DCP vessel density significantly varied with age in the whole image (P = 0.004), parafovea (P = 0.001), and perifovea (P = 0.002). The SCP and DCP vessel densities were significantly lower in the older age groups, and more prominently so after 50 years of age. The FAZ area increased with age; however, this finding was not statistically significant (P = 0.660). The choriocapillaris flow area decreased with age (P = 0.002). The RPCP vessel density in the inside disk significantly decreased with age (P = 0.038). CONCLUSION: Age should be taken into consideration when using OCTA in the diagnosis and follow-up of retinal and optic nerve diseases. It is believed that the results here in can be used as a reference baseline for future studies.

Assessment of the microvasculature in poppers maculopathy.

PURPOSE: To investigate a possible microvascular component of poppers maculopathy (PMP) using optical coherence tomography angiography (OCTA). METHODS: Twelve patients suffering from poppers maculopathy were included. Health records, optical coherence tomography (OCT), and OCTA data was gathered and compared to a healthy control group (HC). PMP lesion type was determined by manifestation in OCT. OCTA-based evaluation of retinal vascular plexus and choriocapillaris (CC) was executed. Vessel density (VD) and vessel length density (VLD) in superficial and deep capillary plexus (SCP, DCP), as well as flow deficits (FD), within the foveal avascular zone (FAZ) in CC were assessed. RESULTS: Median age of PMP patients was 40 (min 24; max 64) years, all male. Eleven patients presented with ellipsoid zone-type lesions; one patient showed a vitelliform-type lesion. No qualitative microvascular changes between PMP patients and HC were identified. Quantitative values for VD and VLD of SCP and DCP did not differ in between the two groups. The analysis of FDs in CC showed no deviation from PMP patients to HC. CONCLUSIONS: No vascular anomalies in qualitative and quantitative analysis in OCTA were detected in PMP patients. The constitution of the CC within FAZ of PMP patients does not differ from HC when assessed as FD.

A novel multiple subdivision-based algorithm for quantitative assessment of retinal vascular tortuosity.

Vascular tortuosity as an indicator of retinal vascular morphological changes can be quantitatively analyzed and used as a biomarker for the early diagnosis of relevant disease such as diabetes. While various methods have been proposed to evaluate retinal vascular tortuosity, the main obstacle limiting their clinical application is the poor consistency compared with the experts' evaluation. In this research, we proposed to apply a multiple subdivision-based algorithm for the vessel segment vascular tortuosity analysis combining with a learning curve function of vessel curvature inflection point number, emphasizing the human assessment nature focusing not only global but also on local vascular features. Our algorithm achieved high correlation coefficients of 0.931 for arteries and 0.925 for veins compared with clinical grading of extracted retinal vessels. For the prognostic performance against experts' prediction in retinal fundus images from diabetic patients, the area under the receiver operating characteristic curve reached 0.968, indicating a good consistency with experts' predication in full retinal vascular network evaluation.

Quantitative assessment of retinal thickness and vessel density using optical coherence tomography angiography in patients with Alzheimer's disease and glaucoma.

PURPOSE: Assessment and a direct comparison of retinal vessel density with the thickness of inner retinal layer (IRL) and outer retinal layer (ORL) in the same regions of the macula in subjects with Alzheimer's disease (AD) and primary open-angle glaucoma (POAG). METHODS: We analyzed data from 48 eyes of healthy control (HC) participants, 71 eyes with POAG, and 49 eyes of AD patients. Ophthalmic examination included optical coherence tomography (OCT) imaging to measure IRL and ORL thickness and OCT angiography (OCTA) in the same region for the imaging of vessel density in the superficial vascular plexus (SVP) and deep vascular plexus (DVP) of the retina. A direct comparison of vessel density and retinal layers thickness, which different dynamic ranges, was obtained by normalizing values as percentage losses. RESULTS: Patients with AD presented significantly greater losses of vascular density in the DVP and ORL thickness compared to POAG (p <0.001), but percentage losses of vessel density in SVP and IRL thickness were considerable in POAG compared to AD eyes (p<0.001). Positive associations among presence of AD were observed primarily in outer retina where a 1% decrease of ORL thickness was associated with about 24-29% increase in odds of the presence of AD. According to OCTA measurements, a 1% decrease of vessel density in DVP was positively associated with a 4-9% increase in odds of the presence of AD. In POAG positive associations among presence of disease were observed only in inner retina where 1% loss of IRL thickness and a 1% loss of vessel density in the SVP were positively associated with a 13-23% increase in risk of presence of the disease. CONCLUSIONS: Analysis of ORL thickness and vessel density in DVP could potentially improve diagnostic capabilities and may provide a valuable approach for predicting of AD.

QUANTITATIVE ASSESSMENT OF THE FOVEAL AVASCULAR ZONE USING OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY BEFORE AND AFTER SURGERY FOR IDIOPATHIC EPIRETINAL MEMBRANE.

PURPOSE: To investigate, using optical coherence tomography angiography, the foveal avascular zone (FAZar), the FAZ perimeter (FAZp), the acircularity index of the FAZ (FAZai), and the density of vessels surrounding the FAZ (FAZvd) before and after idiopathic epiretinal membrane surgery, and associations of these parameters with postoperative best-corrected visual acuity, letter score gain, and central foveal thickness. METHODS: We retrospectively reviewed preoperative and postoperative (sixth month) medical records of 28 eyes of 28 patients who undergone epiretinal membrane surgery and had an intact ellipsoid zone. RESULTS: There were significant increases in best-corrected visual acuity, FAZar, and FAZp and decreases in central foveal thickness and FAZai (all P < 0.05). Postoperative best-corrected visual acuity was not significantly correlated with any preoperative parameters. Postoperative letter score gain and central foveal thickness correlated negatively with preoperative FAZar and preoperative FAZp (all P < 0.05). Multivariable linear regression analysis revealed that preoperative FAZp was independently associated with postoperative letter score gain (P < 0.05). CONCLUSION: The FAZ enlarges and becomes more circular after epiretinal membrane surgery. Postoperative best-corrected visual acuity is not associated with any FAZ parameters. In eyes with an intact foveal ellipsoid zone, especially a smaller preoperative FAZp is associated with more postoperative letter score gain.

A deep-learning system for the assessment of cardiovascular disease risk via the measurement of retinal-vessel calibre.

Retinal blood vessels provide information on the risk of cardiovascular disease (CVD). Here, we report the development and validation of deep-learning models for the automated measurement of retinal-vessel calibre in retinal photographs, using diverse multiethnic multicountry datasets that comprise more than 70,000 images. Retinal-vessel calibre measured by the models and by expert human graders showed high agreement, with overall intraclass correlation coefficients of between 0.82 and 0.95. The models performed comparably to or better than expert graders in associations between measurements of retinal-vessel calibre and CVD risk factors, including blood pressure, body-mass index, total cholesterol and glycated-haemoglobin levels. In retrospectively measured prospective datasets from a population-based study, baseline measurements performed by the deep-learning system were associated with incident CVD. Our findings motivate the development of clinically applicable explainable end-to-end deep-learning systems for the prediction of CVD on the basis of the features of retinal vessels in retinal photographs.

Radiomics-based assessment of ultra-widefield leakage patterns and vessel network architecture in the PERMEATE study: insights into treatment durability.

AIM: To evaluate the potential of radiomics-based ultra-widefield fluorescein angiography (UWFA)-derived imaging biomarkers in retinal vascular disease for predicting therapeutic durability of intravitreal aflibercept injection (IAI). METHODS: The Peripheral and Macular Retinal Vascular Perfusion and Leakage Dynamics in Diabetic Macular Edema and Retinal Venous Occlusions During Intravitreal Aflibercept Injection (IAI) Treatment for Retinal Edema (PERMEATE) study prospectively evaluated quantitative UWFA dynamics in diabetic macular oedema or macular oedema secondary to retinal vascular occlusion. 27 treatment-naïve eyes were treated with 2 mg IAI q4 weeks for the first 6 months, and then administered q8 weeks. Morphological and graph-based attributes were used to model the spatial distribution of leakage areas, while tortuosity measures were used to model the vessel network disorder. Eyes were grouped based on functional tolerance of the first 8-week treatment interval challenge. 'Non-rebounders' (N=15) maintained/improved best-corrected visual acuity (BCVA) following the 8-week challenge. 'Rebounders' (N=12) exhibited worsened BVCA. The image biomarkers were used with a machine learning classifier to preliminarily evaluate their ability to predict BCVA stability. RESULTS: Two new UWFA image-derived biomarkers were identified and extracted. The cross-validated area under the receiver operating characteristic curve (AUC) was 0.77±0.14 using baseline leakage distribution features and 0.73±0.10 for the UWFA baseline tortuosity measures. Additionally, the change in vascular tortuosity between month 4 and baseline yielded an AUC of 0.73±0.08. Three baseline clinical features of letter score, macular volume and central subfield thickness yielded a corresponding AUC of 0.42±0.09. CONCLUSIONS: Two computer-extracted UWFA radiomics-based descriptors were identified as potential biomarkers for predicting treatment durability and tolerance of longer treatment intervals. Conventional treatment parameters were not significantly different between these same groups.