Singapore "I" Vessel Assessment Research Articles

Automated Retinal Vessel Analysis Based on Fundus Photographs as a Predictor for Non-Ophthalmic Diseases-Evolution and Perspectives.

The study of retinal vessels in relation to cardiovascular risk has a long history. The advent of a dedicated tool based on digital imaging, i.e., the retinal vessel analyzer, and also other software such as Integrative Vessel Analysis (IVAN), Singapore I Vessel Assessment (SIVA), and Vascular Assessment and Measurement Platform for Images of the Retina (VAMPIRE), has led to the accumulation of a formidable body of evidence regarding the prognostic value of retinal vessel analysis (RVA) for cardiovascular and cerebrovascular disease (including arterial hypertension in children). There is also the potential to monitor the response of retinal vessels to therapies such as physical activity or bariatric surgery. The dynamic vessel analyzer (DVA) remains a unique way of studying neurovascular coupling, helping to understand the pathogenesis of cerebrovascular and neurodegenerative conditions and also being complementary to techniques that measure macrovascular dysfunction. Beyond cardiovascular disease, retinal vessel analysis has shown associations with and prognostic value for neurological conditions, inflammation, kidney function, and respiratory disease. Artificial intelligence (AI) (represented by algorithms such as QUantitative Analysis of Retinal vessel Topology and siZe (QUARTZ), SIVA-DLS (SIVA-deep learning system), and many others) seems efficient in extracting information from fundus photographs, providing prognoses of various general conditions with unprecedented predictive value. The future challenges will be integrating RVA and other qualitative and quantitative risk factors in a unique, comprehensive prediction tool, certainly powered by AI, while building the much-needed acceptance for such an approach inside the medical community and reducing the "black box" effect, possibly by means of saliency maps.

Retinal vascular fractal dimension measurements in patients with obstructive sleep apnea syndrome: a retrospective case-control study.

We performed a case-control study to investigate the correlation between the apnea-hypopnea index (AHI) and the retinal vascular fractal dimension (FD). We selected 527 individuals who underwent polysomnography during health checkups at the Huadong Sanatorium from January to December 2021 as the study population, of whom 468 were included and 59 were excluded. All participants underwent a detailed health examination, including medical history assessment, physical examination, assessment of lifestyle factors, fundus photography, and laboratory examinations. The retinal vasculature was quantitatively assessed using Singapore I Vessel Assessment (SIVA) software. The relationship between the AHI and the retinal vessel quantitative was examined by multiple linear regression analyses and restricted cubic spline. Among the 468 studied individuals, the average age was 51.51 (43-58) years, with 369 (78.85%) men and 99 (21.15%) women. According to the AHI indicator, 355 individuals were diagnosed with obstructive sleep apnea (OSA) syndrome, with an average AHI of 17.00 (9.200-30.130) events/h; 113 individuals were classified as controls, with an average AHI of 2.13 (0.88-3.63) events/h. In multiple linear regression, following varying degrees of adjustment for confounding factors, FD was reduced by 0.013 (P = .012; 95% confidence interval [CI]: -0.024 to -0.003), FD arteriole (FDa) was reduced by 0.013 (P = .019; 95% CI: -0.024 to -0.002), and FD venule (FDv) was reduced by 0.014 (P = .08; 95% CI: -0.024 to -0.004) in the high-AHI group compared with the low-AHI group. All tests for trend P values were < .05. The restricted cubic spline in the overall OSA population and the individuals without diabetes revealed a U-shaped pattern of decreasing, then increasing, FD, FDa, and FDv with a rising AHI. In the OSA individual with diabetes, FD, FDa, and FDv gradually decreased with increasing AHI. The FD is associated with AHI in OSA individuals. The link between AHI and FD varied for OSA individuals with and without diabetes. Wang J, Chen T, Qi X, Li Y, Yang X, Meng X. Retinal vascular fractal dimension measurements in patients with obstructive sleep apnea syndrome: a retrospective case-control study. J Clin Sleep Med. 2023;19(3):479-490.

Prediction of Cardiovascular Parameters With Supervised Machine Learning From Singapore "I" Vessel Assessment and OCT-Angiography: A Pilot Study.

PurposeAssessment of cardiovascular risk is the keystone of prevention in cardiovascular disease. The objective of this pilot study was to estimate the cardiovascular risk score (American Hospital Association [AHA] risk score, Syntax risk, and SCORE risk score) with machine learning (ML) model based on retinal vascular quantitative parameters.MethodsWe proposed supervised ML algorithm to predict cardiovascular parameters in patients with cardiovascular diseases treated in Dijon University Hospital using quantitative retinal vascular characteristics measured with fundus photography and optical coherence tomography – angiography (OCT-A) scans (alone and combined). To describe retinal microvascular network, we used the Singapore “I” Vessel Assessment (SIVA), which extracts vessel parameters from fundus photography and quantitative OCT-A retinal metrics of superficial retinal capillary plexus.ResultsThe retinal and cardiovascular data of 144 patients were included. This paper presented a high prediction rate of the cardiovascular risk score. By means of the Naïve Bayes algorithm and SIVA + OCT-A data, the AHA risk score was predicted with 81.25% accuracy, the SCORE risk with 75.64% accuracy, and the Syntax score with 96.53% of accuracy.ConclusionsPerformance of these algorithms demonstrated in this preliminary study that ML algorithms applied to quantitative retinal vascular parameters with SIVA software and OCT-A were able to predict cardiovascular scores with a robust rate. Quantitative retinal vascular biomarkers with the ML strategy might provide valuable data to implement predictive model for cardiovascular parameters.Translational RelevanceSmall data set of quantitative retinal vascular parameters with fundus and with OCT-A can be used with ML learning to predict cardiovascular parameters.

Association between the retinal vascular network and retinal nerve fiber layer in the elderly: The Montrachet study.

To investigate the association between the characteristics of the retinal vascular network in the elderly and retinal nerve fiber layer (RNFL) thickness in a population-based study. We conducted a population-based study, the Montrachet study (Maculopathy Optic Nerve, nuTRition neurovAsCular, and HEarT disease), in participants aged ≥ 75 years. RNFL thickness was assessed with spectral-domain optical coherence tomography (SD-OCT). Analysis of the retinal vascular network was performed by means of the Singapore "I" Vessel Assessment (SIVA) software based on fundus photography. Data from 970 participants were suitable for analysis. Patients with optic neuropathy were excluded. In multivariable analysis, each standard deviation (SD) decrease in the caliber of the six largest arterioles and veins in zone B and the six largest arterioles and veins in zone C was associated with a decrease in global RNFL thickness (β = -1.62 μm, P = 0.001; β = -2.39 μm, P < 0.001; β = -1.56 μm, P = 0.002; and β = -2.64 μm, P < 0.001, respectively). Our study found that decreased retinal vessels caliber were associated with a decreased RNFL thickness in the elderly without optic neuropathy.

Retinal Arteriolar Narrowing in Young Adults With Glaucomatous Optic Disc.

Glaucomatous optic disc (GOD) might represent various subclinical processes. However, whether the presence of GOD is related to vascular processes is less clear. This study aimed to assess the retinal vessel diameter, as surrogate markers of vascular regulation, in healthy young adults with GOD compared with normal. This was a clinic-based case-control study of 54 participants, aged between 18 and 30 years. We included patients with GOD (confirmed with slit-lamp and optical coherence tomography examination having cup-to-disc ratio ≥0.5), intraocular pressure ≤21 mm Hg, no history of hypertension, cardiovascular and kidney disease, anemia, diabetes mellitus, and spherical correction of ≤-1.5 D. Controls were healthy subjects with similar criteria but no sign of GOD. Retinal vessel diameters were measured using semiautomated program [Singapore I Vessel Assessment (SIVA) version 4.0] and expressed as central retinal arteriolar equivalent (CRAE) and central retinal venular equivalent. The mean CRAE was significantly narrower in patients with GOD than controls (110.6±12.16 vs. 118.6±12.17; P=0.019). Central retinal venular equivalent was not significantly different. A CRAE narrower than 107.1 μm was significantly associated with GOD (odds ratio, 8.59; 95% confidence interval, 1.68-43.9; P<0.001) compared with controls. Retinal arterioles were narrower in young adults with GOD compared with normal, suggesting that the presence of GOD might be associated with subclinical changes in retinal vascularization even in the absence of increased intraocular pressure. However, the clinical significance of these findings deserves further studies.

Association between the retinal vascular network with Singapore "I" Vessel Assessment (SIVA) software, cardiovascular history and risk factors in the elderly: The Montrachet study, population-based study.

PurposeTo identify patterns summarizing the retinal vascular network in the elderly and to investigate the relationship of these vascular patterns with cardiovascular history.MethodsWe conducted a population-based study, the Montrachet study (Maculopathy Optic Nerve nuTRition neurovAsCular and HEarT diseases), in participants older than 75 years. The history of cardiovascular disease and a score-based estimation of their 10-year risk of cardiovascular mortality (Heart SCORE) were collected. Retinal vascular network analysis was performed by means of Singapore “I” Vessel Assessment (SIVA) software. Principal component analysis was used to condense the information contained in the high number of variables provided and to identify independent retinal vascular patterns.ResultsOverall, 1069 photographs (1069 participants) were reviewed with SIVA software. The mean age was 80.0 ± 3.8 years. We extracted three vascular patterns summarizing 41.3% of the vascular information. The most clinically relevant pattern, Sparse vascular network, accounted for 17.4% of the total variance. It corresponded to a lower density in the vascular network and higher variability in vessel width. Diabetic participants with hypoglycemic treatment had a sparser vascular network pattern than subjects without such treatment (odds ratio, [OR], 1.68; 95% CI, 1.04–2.72; P = 0.04). Participants with no history of cardiovascular disease who had a sparser vascular network were associated with a higher Heart SCORE (OR, 1.76; 95% CI, 1.08–2.25; P = 0.02).ConclusionsThree vascular patterns were identified. The Sparse vascular network pattern was associated with having a higher risk profile for cardiovascular mortality risk at 10 years.

Towards Standardization of Quantitative Retinal Vascular Parameters: Comparison of SIVA and VAMPIRE Measurements in the Lothian Birth Cohort 1936.

PurposeSemiautomated software applications derive quantitative retinal vascular parameters from fundus camera images. However, the extent of agreement between measurements from different applications is unclear. We evaluate the agreement between retinal measures from two software applications, the Singapore “I” Vessel Assessment (SIVA) and the Vessel Assessment and Measurement Platform for Images of the Retina (VAMPIRE), and examine respective associations between retinal and systemic outcomes.MethodFundus camera images from 665 Lothian Birth Cohort 1936 participants were analyzed with SIVA and VAMPIRE. Intraclass correlation coefficients (ICC) and Bland-Altman plots assessed agreement between retinal parameters: measurements of vessel width, fractal dimension, and tortuosity. Retinal–systemic variable associations were assessed with Pearson's correlation, and intersoftware correlation magnitude differences were examined with Williams's test.ResultsICC values indicated poor to limited agreement for all retinal parameters (0.159–0.410). Bland-Altman plots revealed proportional bias in the majority, and systematic bias in all measurements. SIVA and VAMPIRE measurements were associated most consistently with systemic variables relating to blood pressure (SIVA r's from −0.122 to −0.183; VAMPIRE r's from −0.078 to −0.177). Williams's tests indicated significant differences in the magnitude of association between retinal and systemic variables for 7 of 77 comparisons (P < 0.05).ConclusionsAgreement between two common software applications was poor. Further studies are required to determine whether associations with systemic variables are software-dependent.Translational RelevanceStandardization of the measurement of retinal vascular parameters is warranted to ensure that they are reliable and application-independent. This would be an important step towards realizing the potential of the retina as a source of imaging-derived biomarkers that are clinically useful.

A spectrum of retinal vasculature measures and coronary artery disease

Background and aimsWe aimed to comprehensively describe a spectrum of retinal vessel measures including fractal dimension (Df) and their associations with indices of coronary artery disease (CAD) extent and severity, as well as hypertension and diabetes. MethodsThe Australian Heart Eye Study (AHES) is an observational study that surveyed 1680 participants presenting to a tertiary referral hospital for the evaluation of potential CAD by coronary angiography. A range of newer retinal vessel geometric measures (Df, curvature tortuosity, and branching angle) were quantified from retinal photographs using semi-automated software, the Singapore ‘I’ Vessel Assessment (SIVA) tool. A combined retinal score was constructed, aiming to assess the joint effect of multiple retinal vessel parameters on CAD, comprising of those variables that were most strongly significant in multivariate analysis - Df, arteriolar curvature tortuosity, and retinal arteriolar calibre. CAD was objectively quantified using a range of measures obtained from coronary angiography. ResultsA total of 1187 participants had complete data on retinal vessel measurements and coronary vessel evaluation. Retinal vascular Df and curvature tortuosity decreased with increasing age; women had significantly lower Df than men (p<0.003). Straighter retinal vessels were associated with CAD extent and Gensini scores in multivariable analysis (p<0.02). Accounting for media opacity by sub-group analysis in pseudophakic patients, the combined retinal score was associated with stenosis greater than 50% in any coronary artery segment (vessel score) and obstructive coronary stenosis in all three main coronary arteries (segment score) (p = 0.01). Lower Df and narrower arteriolar branching angle were associated with CAD vessel score (p<0.03). In sex-stratified multivariate analyses, straighter arterioles were associated with greater odds of CAD in men, and narrower venular branching angle was associated with CAD in women. ConclusionsA range of retinal vessel measures were associated with CAD extent and severity. A sparser retinal microvascular network (smaller Df) was associated with older age and female gender. After accounting for the impact of media opacity, retinal vessel measures were associated with more diffuse and severe CAD.

Association between the retinal vascular network, cardiovascular history and risk factors in the elderly

PurposeTo identify patterns summarizing the retinal vascular network in the elderly and to investigate the relationship of these vascular patterns with cardiovascular history.MethodsWe conducted a population‐based study, the Montrachet study (Maculopathy Optic Nerve nuTRition neurovAsCular and HEarT diseases), in participants older than 75 years. History of cardiovascular disease and a score‐based estimation of their 10‐year risk of cardiovascular mortality (Heart SCORE) were collected. Retinal vascular network analysis was performed by means of Singapore “I” Vessel Assessment (SIVA) software. Principal component analysis was used to condense the information contained in the high number of variables provided and to identify independent retinal vascular patterns.ResultsOverall, 1069 photographs (1069 participants) were reviewed with SIVA software. The mean age was 80.0 ± 3.8 years. We extracted three vascular patterns summarizing 41.3% of the vascular information. The most clinically relevant pattern, Sparse vascular network, accounted for 17.4% of the total variance. It corresponded to a lower density in the vascular network and higher variability in vessel width. Diabetic participants with hypoglycemic treatment had a sparser vascular network pattern than subjects without such treatment (Odds ratio, [OR], 1.68; 95% CI, 1.04–2.72; P = 0.04). Participants without history of cardiovascular disease who had a sparser vascular network were associated with a higher Heart SCORE (OR, 1.76; 95% CI, 1.08–2.25; P = 0.02).ConclusionsThree vascular patterns were identified. The Sparse vascular network pattern was associated with being a higher risk profile for cardiovascular mortality risk at 10 years.

Retinal microvascular network geometry and cognitive abilities in community-dwelling older people: The Lothian Birth Cohort 1936 study

AimTo examine the relationship between retinal vascular morphology and cognitive abilities in a narrow-age cohort of community-dwelling older people.MethodsDigital retinal images taken at age ∼73 years from 683 participants of...

Retinal microvascular diameter, a hypertension-related trait, in ECG-gated vs. non-gated images analyzed by IVAN and SIVA.

The diameters of the retinal microvasculature reflect intermediate target organ damage and predict adverse health outcomes. In view of the pulsatility of the cerebral blood flow and refinement of software used for off-line analysis, we assessed the repeatability of retinal microvascular diameters in ECG-gated vs. non-gated images using nonmydriatic retinal photographs (Canon Cr-DGi visualization system) postprocessed by IVAN (Vasculomatic ala Nicola, version 1.1) or SIVA (Singapore I Vessel Assessment, version 3.6). Using these algorithms, we determined the central retinal arteriolar (CRAE) and venular (CRVE) equivalents and their ratio (arteriole-to-venule ratio (AVR)). The estimates of CRAE (mean, 158.5 μm), CRVE (222.5 μm) and AVR (0.71) in 10 volunteers were unaffected (P⩾0.059) by ECG gating. We assessed intragrader repeatability by the Bland and Altman approach in 30 participants with non-gated images and 30 with ECG-gated photographs. Repeatability, which was expressed as the percentage of near maximal variability (4-s.d. range), did not improve with ECG gating. Using SIVA, CRAE and CRVE were systematically larger (P⩽0.031), and the AVR estimates were similar (P⩾0.15) compared with IVAN. The differences (IVAN-SIVA) averaged -5.4 μm for CRAE, -3.9 μm for CRVE and -0.012 for AVR in the non-gated images and -3.3 μm, -6.9 μm and 0.006, respectively, in the ECG-gated photographs. In conclusion, ECG gating does not affect estimates of the retinal microvascular diameters or improve intragrader repeatability. SIVA yields slightly but significantly larger estimates of the retinal arteriolar and venular diameters. Combining historical readings analyzed by IVAN with more recent readings by SIVA is possible only for AVR and is not recommended for either CRAE or CRVE.

Characterization of Fatty Acid Binding Protein 7 (FABP7) in the Murine Retina

To characterize the mouse retina lacking fatty acid binding protein (FABP7-/-). Immunohistochemistry (IHC) was performed in 8-week-old mice to localize FABP7 in the retina. Retinal thickness was measured using image-guided spectral-domain optical coherence topography images. Electroretinography was carried out to assess retinal function. Fundus photography and fundus fluorescein angiography were performed on FABP7-/- and littermate wild-type (WT) mice, and retinal vascular changes were calculated using Singapore I Vessel Assessment (SIVA) analysis. Blood glucose levels were measured in the 8-week-old WT and FABP7-/- mice. In addition, retina was processed for trypsin digestion and retinal flat mounts for isolectin staining. Transcript levels of FABP7, VEGF, GFAP, and Na+K+ATPase were quantified using real-time PCR, and protein expression was analyzed by IHC and Western blot. Fatty acid binding protein 7 is expressed in the inner nuclear layer, outer plexiform layer, and photoreceptor inner segments. No significant difference in retinal thickness and ERG responses was observed between FABP7-deficient and WT retinas. FABP7-/- mice have significantly decreased retinal venular caliber retinal arteriolar fractal dimension compared with WT littermates. FABP7-/- mice showed significant increased areas of fluorescein leakage in the retina. FABP7-/- mice exhibited elevated high blood glucose levels compared with WT mice. Trypsin digested FABP7-/- mice retina showed increased acellular strands and endothelial cell drop outs, and reduced microvasculature branching compared with WT retina. FABP7-/- mice retina also have increased GFAP and VEGF expression. Fatty acid binding protein 7 is expressed in the retina and might play an important role in maintaining retinal vasculature.