Retinal Microvascular Parameters Research Articles

Retinal Vascular Changes in Heart Failure with Preserved Ejection Fraction Using Optical Coherence Tomography Angiography.

Background: Systemic microvascular regression and dysfunction are considered important underlying mechanisms in heart failure with preserved ejection fraction (HFpEF), but retinal changes are unknown. Methods: This prospective study aimed to investigate whether retinal microvascular and structural parameters assessed using optical coherence tomography angiography (OCT-A) differ between patients with HFpEF and control individuals (i.e., capillary vessel density, thickness of retina layers). We also aimed to assess the associations of retinal parameters with clinical and echocardiographic parameters in HFpEF. HFpEF patients, but not controls, underwent echocardiography. Macula-centered 6 × 6 mm volume scans were computed of both eyes. Results: Twenty-two HFpEF patients and 24 controls without known HFpEF were evaluated, with an age of 74 [68-80] vs. 68 [58-77] years (p = 0.027), and 73% vs. 42% females (p = 0.034), respectively. HFpEF patients showed vascular degeneration compared to controls, depicted by lower macular vessel density (p < 0.001) and macular ganglion cell-inner plexiform layer thickness (p = 0.025), and a trend towards lower total retinal volume (p = 0.050) on OCT-A. In HFpEF, a lower total retinal volume was associated with markers of diastolic dysfunction (septal e', septal and average E/e': R2 = 0.38, 0.36, 0.25, respectively; all p < 0.05), even after adjustment for age, sex, diabetes mellitus, or atrial fibrillation. Conclusions: Patients with HFpEF showed clear levels of retinal vascular changes compared to control individuals, and retinal alterations appeared to be associated with markers of more severe diastolic dysfunction in HFpEF. OCT-A may therefore be a promising technique for monitoring systemic microvascular regression and cardiac diastolic dysfunction.

Association between albuminuria and retinal microvascular parameters measured with swept-source optical coherence tomography angiography in patients with diabetic retinopathy.

To evaluate the relationship between urine albumin excretion (UAE) and retinal microvascular parameters assessed using swept-source optical coherence tomography angiography (SS-OCTA) in patients with diabetic retinopathy (DR). This retrospective cross-sectional study included 180 patients with diabetes and 50 age-matched controls. Patients with diabetes were grouped according to the five-stage DR severity, combined with the presence of albuminuria. All subjects underwent 12×12mm2 field SS-OCTA. The foveal avascular zone metrics, vessel density, and capillary nonperfusion area (NPA) were quantified using a semi-automatic software algorithm on three different rectangular fields (3×3 mm2, 6×6 mm2, and 10×10 mm2). The correlations between albuminuria and the four OCTA parameters were analyzed. A total of 105 subjects had normal UAE, and 75 subjects had albuminuria. Of the 102 subjects whose DR severity was higher than mild non-proliferative DR (NPDR), capillary NPA on the 3×3 mm2, 6×6 mm2, and 10×10 mm2 fields was significantly larger in the albuminuria group. None of the OCTA parameters were significantly different between the two groups in subjects with mild NPDR or without DR. Multiple logistic regression analysis showed that an increase in NPA in the 6×6 mm2 and 10×10 mm2 fields was a significant risk factor for the presence of albuminuria (odds ratio = 1.92 and 1.35). An increase in capillary NPA was independently associated with albuminuria in patients with clinically significant DR levels. SS-OCTA imaging can be a useful marker for the early detection of diabetic nephropathy.

Correlations between Retinal Microvascular Parameters and Clinical Parameters in Young Patients with Type 1 Diabetes Mellitus: An Optical Coherence Tomography Angiography Study

Objectives: In the current study, we investigated the correlations between retinal microvascular parameters using optical coherence tomography angiography (OCTA) and clinical parameters for a group of 69 young patients with type 1 diabetes mellitus (T1DM). Materials and Methods: This retrospective, exploratory study enrolled 69 patients between 5 years old and 30 years old who met the inclusion criteria. All the study participants underwent a comprehensive ophthalmic examination and OCTA scans for the evaluation of the retinal microcirculation. The retinal OCTA parameters were correlated with the following clinical parameters: the patient’s age at the onset of the disease, the duration of T1DM, the BMI at the time of enrollment in the study, the HbA1C values at onset, the mean values of HbA1C over the period of monitoring the disease and the degree of DKA at onset. Results: For the study group, the foveal avascular zone (FAZ) area and perimeter correlated positively with the mean value of HbA1C (Pearson correlation, Sig.2-Tailed Area: 0.044; perimeter: 0.049). The total vessel density in the superficial capillary plexus (SCP) correlated negatively with the duration of T1DM, based on the superior and inferior analyzed areas (Spearman correlation, Sig.2-Tailed SCP in total region: 0.002; SCP in the superior region: 0.024; SCP in the inferior region: 0.050). The foveal thickness also correlated negatively with the levels of diabetic ketoacidosis (DKA) at onset (Spearman correlation, Sig.2-Tailed: 0.034) and the levels of HbA1C at onset (Spearman correlation, Sig.2-Tailed: 0.047). Further on, the study patients were distributed into two groups according to the duration of the disease: group 1 included 32 patients with a duration of T1DM of less than 5 years, and group 2 included 37 patients with a duration of T1DM of more than 5 years. Independent t-tests were used to compare the OCTA retinal parameters for the two subgroups. While the FAZ-related parameters did not show significant statistical differences between the two groups, the vessel densities in both the SCP and DCP were significantly lower in group 2. Conclusions: Our data suggest that specific alterations in OCTA imaging biomarkers correlate with various clinical parameters: the FAZ area and perimeter increase with higher mean values of HbA1C, leading to poor metabolic control. Moreover, the SCP total vessel density decreases as the duration of T1DM increases. Regarding the vessel densities in the SCP and the DCP, they decrease with a duration of the disease of more than 5 years.

Ocular biomarkers of cognitive decline based on deep-learning retinal vessel segmentation

BackgroundThe current literature shows a strong relationship between retinal neuronal and vascular alterations in dementia. The purpose of the study was to use NFN+ deep learning models to analyze retinal vessel characteristics for cognitive impairment (CI) recognition.MethodsWe included 908 participants from a community-based cohort followed for over 15 years (the prospective KaiLuan Study) who underwent brain magnetic resonance imaging (MRI) and fundus photography between 2021 and 2022. The cohort consisted of both cognitively healthy individuals (N = 417) and those with cognitive impairment (N = 491). We employed the NFN+ deep learning framework for retinal vessel segmentation and measurement. Associations between Retinal microvascular parameters (RMPs: central retinal arteriolar / venular equivalents, arteriole to venular ratio, fractal dimension) and CI were assessed by Pearson correlation. P < 0.05 was considered statistically significant. The correlation between the CI and RMPs were explored, then the correlation coefficients between CI and RMPs were analyzed. Random Forest nonlinear classification model was used to predict whether one having cognitive decline or not. The assessment criterion was the AUC value derived from the working characteristic curve.ResultsThe fractal dimension (FD) and global vein width were significantly correlated with the CI (P < 0.05). Age (0.193), BMI (0.154), global vein width (0.106), retinal vessel FD (0.099), and CRAE (0.098) were the variables in this model that were ranked in order of feature importance. The AUC values of the model were 0.799.ConclusionsEstablishment of a predictive model based on the extraction of vascular features from fundus images has a high recognizability and predictive power for cognitive function and can be used as a screening method for CI.

Retinal structural and microvascular deterioration independent of optic neuritis in aquaporin-4 antibody-positive neuromyelitis optica spectrum disorders: An optical coherence tomography angiography study

PurposeTo assess the retinal structural and microvascular change in aquaporin-4 antibody (AQP4) positive neuromyelitis optica spectrum disorder (NMOSD) patients and the correlation with clinical features. MethodsA cross-sectional study was performed with optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA) to measure retinal structure and microvascular parameters in AQP4 positive NMOSD patients. ResultsSixty-two NMOSD patients (44 eyes with ON, NMOSD+ON; 77 eyes without ON, NMOSD-ON) and 62 healthy controls (HC, 124 eyes) were included. BCVA was worse in NMOSD patients compared to HC (p<0.001). Peripapillary retinal nerve fiber layer (pRNFL, p<0.001) and ganglion cell complex (GCC, p<0.001) was thinner in NMOSD+ON eyes compared to NMOSD-ON eyes and HC. Compared to HC, pRNFL (p = 0.002) and GCC (p = 0.001) was thinner in NMOSD-ON eyes. The vessel density (VD) in superficial capillary plexus (SCP, NMOSD+ON vs HC p<0.001, NMOSD-ON vs HC p = 0.002) and radial peripapillary capillary (RPC, NMOSD+ON vs HC p<0.001, NMOSD-ON vs HC p = 0.001) were also lower in NMOSD patients than HC independent of the history of ON. ON frequency and BCVA were correlated with the thickness of pRNFL and GCC, and VD in SCP and RPC (all p<0.001). EDSS was correlated with thickness of GCC (p = 0.008), and VD in SCP (p = 0.013), DCP (p<0.001) and RPC (p = 0.009). ConclusionsSubclinical degradation of retinal structure and microvasculature was found in NMOSD patients before the occurrence of ON, and was correlated with clinical disability. Retinal parameter might be a tool to estimate the disease progression and investigate the pathogenesis of NMOSD.

The association of global vessel width with cognitive decline and cerebral small vessel disease burden in the KaiLuan study.

As the retinal microvasculature shares similarities with the cerebral microvasculature, numerous studies have shown that retinal vascular is associated with cognitive decline. In addition, several population-based studies have confirmed the association between retinal vascular and cerebral small vessel disease (CSVD) burden. However, the association of retinal vascular with CSVD burden as well as cognitive function has not been explored simultaneously. This study investigated the relations of retinal microvascular parameters (RMPs) with CSVD burden and cognitive function. We conducted a cross-sectional study of participants in the KaiLuan study. Data were collected from subjects aged ≥18 years old who could complete retinal photography and brain magnetic resonance imaging (MRI) between December 2020 to October 2021 in the Kailuan community of Tangshan. RMPs were evaluated using a deep learning system. The cognitive function was measured using the Montreal Cognitive Assessment (MoCA). We conducted logistic regression models, and mediation analysis to evaluate the associations of RMPs with CSVD burden and cognitive decline. Of the 905 subjects (mean age: 55.42±12.02 years, 54.5% female), 488 (53.9%) were classified with cognitive decline. The fractal dimension (FD) [odds ratio (OR), 0.098, 95% confidence interval (CI): 0.015-0.639, P=0.015] and global vein width (OR: 1.010, 95% CI: 1.005-1.015, P<0.001) were independent risk factors for cognitive decline after adjustment for potential confounding factors. The global artery width was significantly associated with severe CSVD burden (OR: 0.985, 95% CI: 0.974-0.997, P=0.013). The global vein width was sightly associated with severe CSVD burden (OR: 1.005, 95% CI: 1.000-1.010, P=0.050) after adjusting for potential confounders. The multivariable-adjusted odds ratios (95% CI) in highest tertile versus lowest tertile of global vein width were 1.290 (0.901-1.847) for cognitive decline and 1.546 (1.004-2.290) for severe CSVD burden, respectively. Moreover, CSVD burden played a partial mediating role in the association between global vein width and cognitive function (mediating effect 6.59%). RMPs are associated with cognitive decline and the development of CSVD. A proportion of the association between global vein width and cognitive decline may be attributed to the presence of CSVD burden.

Quantitative microvascular alterations in butterfly-shaped pattern dystrophy and adult-onset foveomacular vitelliform dystrophy

To study retinal microvascular parameters in patients with butterfly-shaped pattern dystrophy (BPD) and adult foveomacular vitelliform dystrophy (AFVD). This case-control study included BPD and AFVD patients in a tertiary university hospital. Eyes with known ocular disease and prior ocular surgery other than uncomplicated cataract surgery were excluded. Right eyes of healthy individuals without systemic or ocular disease were included as controls. En face 6×6mm angiograms were obtained with the RTVue XR Avanti (Optovue, USA). We used the Kruskal-Wallis test to compare vessel density (VD) values of the retina, optic disc and foveal avascular zone (FAZ) between groups. Dunn-Bonferroni correction was used for pairwise comparisons. Eighteen eyes of 10 BPD patients, 17 eyes of 9 AFVD patients, and 26 right eyes of 26 controls were included. Six patients in the BPD, 4 patients in the AFVD, and 16 patients in the control group were female. The groups did not differ by sex (P=0.650). AFVD patients were of higher mean age (64.3±7.8) than BPD patients (55.9±11.1) and controls (53.6±5.5) (P=0.008, p=0.009). In BPD (P=0.008, P=0.044) and AFVD (P=0.006, P=0.002), parafoveal and perifoveal vessel density (VD) of the superficial capillary plexus were lower than controls. Parafoveal VD of the deep capillary plexus in AFVD was lower than in controls (P=0.012). There was no difference in the foveal avascular area between groups (P=0.563). Optic discs parameters did not differ. A comparable loss in vascular density may indicate shared pathophysiology or represent a common sign of impairment in retinal homeostasis. Further research is needed to clarify underlying microvascular pathogenetic mechanisms in pattern dystrophies.

Retinal Microvascular Changes in Internal Carotid Artery Stenosis.

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

Longitudinal Analysis of Retinal Microvascular and Choroidal Imaging Parameters in Parkinson's Disease Compared with Controls

To quantify rate of change of retinal microvascular and choroidal structural parameters in subjects with Parkinson's disease (PD) compared with controls using OCT and OCT angiography (OCTA). Prospective longitudinal study. Seventy-four eyes of 40 participants with PD and 149 eyes of 78 control individuals from the Eye Multimodal Imaging in Neurodegenerative Disease database. Subjects underwent OCT and OCTA imaging at 2 time points approximately 12 months apart. Imaging parameters included central subfield thickness, ganglion cell-inner plexiform layer (GC-IPL) thickness, peripapillary retinal nerve fiber layer thickness, choroidal vascularity index, superficial capillary plexus perfusion density (PFD), vessel density (VD), and foveal avascular zone area. Participants with PD had greater rate of yearly decrease in GC-IPL (PD=-0.403μm, control=+ 0.128 μm; P= 0.01), greater yearly decline in PFD in the 3× 3 mm ETDRS circle (PD=-0.016, control=+ 0.002; P<0.001) and ring (PD=-0.016, control=+ 0.002; P < 0.001); 6× 6 mm ETDRS circle (PD=-0.021, control= 0.00; P= 0.001), and outer ring (PD=-0.022, control= 0.00; P= 0.001). Participants with PD had greater rate of yearly decline in VD in 3× 3 mm circle (PD=-0.939/mm, control=+ 0.006/mm; P < 0.001) and ring (PD=-0.942/mm, control=+ 0.013/mm; P < 0.001); 6× 6 mm circle (PD=-0.72/mm, control=-0.054/mm; P= 0.006), and outer ring (PD=-0.746/mm, control=-0.054/mm; P= 0.005). When stratified by PD severity based on Hoehn and Yahr stage, faster rates of decline were seen in Hoehn and Yahr stages 3 to 4 in the 3× 3 mm circle PFD and VD as well as 3× 3 mm ring VD. Individuals with PD experience more rapid loss of retinal microvasculature quantified on OCTA and more rapid thinning of the GC-IPL than controls. There may be more rapid loss in patients with greater disease severity. The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Association of retinal microvascular density and complexity with incident coronary heart disease

Background and aimsThe high mortality rate and huge disease burden of coronary heart disease (CHD) highlight the importance of its early detection and timely intervention. Given the non-invasive nature of fundus photography and recent development in the quantification of retinal microvascular parameters with deep learning techniques, our study aims to investigate the association between incident CHD and retinal microvascular parameters. MethodsUK Biobanks participants with gradable fundus images and without a history of diagnosed CHD at recruitment were included for analysis. A fully automated artificial intelligence system was used to extract quantitative measurements that represent the density and complexity of the retinal microvasculature, including fractal dimension (Df), number of vascular segments (NS), vascular skeleton density (VSD) and vascular area density (VAD). ResultsA total of 57,947 participants (mean age 55.6 ± 8.1 years; 56% female) without a history of diagnosed CHD were included. During a median follow-up of 11.0 (interquartile range, 10.88 to 11.19) years, 3211 incident CHD events occurred. In multivariable Cox proportional hazards models, we found decreasing Df (adjusted HR = 0.80, 95% CI, 0.65–0.98, p = 0.033), lower NS of arteries (adjusted HR = 0.69, 95% CI, 0.54–0.88, p = 0.002) and venules (adjusted HR = 0.77, 95% CI, 0.61–0.97, p = 0.024), and reduced arterial VSD (adjusted HR = 0.72, 95% CI, 0.57–0.91, p = 0.007) and venous VSD (adjusted HR = 0.78, 95% CI, 0.62–0.98, p = 0.034) were related to an increased risk of incident CHD. ConclusionsOur study revealed a significant association between retinal microvascular parameters and incident CHD. As the lower complexity and density of the retinal vascular network may indicate an increased risk of incident CHD, this may empower its prediction with the quantitative measurements of retinal structure.

Microvascular changes in obese adults detected by Optical Coherence Tomography Angiography.

Aim: The aim of this prospective, controlled, non-randomized study was the comparison of the retinal microvascular parameters of obese and nonobese adults. Methods: 184 eyes of 92 subjects were separated to 3 groups. 68 eyes were in the normal weight group, with a body mass index between 18.5 and 24.5 kg/ m2, 60 eyes were in the overweight group, with a body mass index between 25-29.9 kg/ m2, and 56 eyes were in the obese group, with a body mass index ≥ 30 kg/ m2. All the volunteers were applied visual acuity, ocular motility testing, and slit lamp and mydriatic fundus examination. Optical Coherence Tomography Angiography (OCT-A) scanning was practiced with Optovue (Optovue, Inc; Fremont, CA) on a 6.00 x 6.00 mm macular region, in the central fovea. Results: 184 eyes of ninety-two patients were involved in this prospective study. The vessels' density (VD) in the optic nerve head (ONH) were significantly lower in the overweight and obese adult volunteers compared to the normal weight control group. However, other OCTA parameters (including macular VDs, Foveal avascular zone (FAZ), choriocapillaris plexus (CCP) area) did not demonstrate any significant difference between groups. Subfoveal choroidal thickness (SCT) was higher in the overweight and obese patients when compared to the normal weight control group. Central macular thickness (CMT) did not reveal any significant difference between groups. Conclusion: Even though clinicians are limited in pointing out any differential findings in obese patients only by fundus examination, OCT-A provides a predictable view of the microvascular changes in the retina and choroid in obese patients. Abbreviations: BMI = Body mass index, WHO = World Health Organization, AMD = Age-related macular degeneration, CT = Choroidal thickness, OCTA = Optical Coherence Tomography Angiography, (W/H) ratio = Waist-hip ratio, ETDRS = Early Treatment Diabetic Retinopathy Study, VD = Vessel density, SCP = Superficial capillary plexus, DCP = Deep capillary plexus, CCP = Flow area of the choriocapillaris, FAZ = Avascular zone, CMT = Central macular thickness, ONH = Optic nerve head.

Impaired retinal microcirculation in patients with non-obstructive coronary artery disease.

To quantitatively investigate alterations of retinal microcirculation in patients with non-obstructive coronary artery disease (NOCAD) using optical coherence tomography angiography (OCTA), and to identify the ability of retinal microcirculation parameters in differentiating coronary artery disease (CAD) subtypes. All participants with angina pectoris underwent coronary computed tomography angiography. Patients with lumen diameter reduction of 20-50% in all major coronary arteries were defined as NOCAD, while patients with at least one major coronary artery lumen diameter reduction ≥ 50% were recruited as obstructive coronary artery disease (OCAD). Participants without a history of ophthalmic or systemic vascular disease were recruited as healthy controls. Retinal neural-vasculature was measured quantitatively by OCTA, including peripapillary retinal nerve fiber layer (RNFL) thickness and vessel density (VD) of the optic disc, superficial vessel plexus (SVP), deep vessel plexus (DVP), and foveal density (FD 300). p<0.017 is considered significant in multiple comparisons. A total of 185 participants (65 NOCAD, 62 OCAD, and 58 controls) were enrolled. Except for the DVP fovea (p=0.069), significantly reduced VD in all other regions of SVP and DVP was detected in both the NOCAD and OCAD groups compared to control group (all p<0.017), while a more significant decrease was found in OCAD compared to NOCAD. Multivariate regression analysis showed that lower VD in superior hemi part of whole SVP (OR: 0.582, 95% CI: 0.451-0.752) was an independent risk factor for NOCAD compared to controls, while lower VD in the whole SVP (OR: 0.550, 95% CI: 0.421-0.719) was an independent risk factor for OCAD compared to NOCAD. Using the integration of retinal microvascular parameters, the area under the receiver operating characteristic curve (AUC) for NOCAD versus control and OCAD versus NOCAD were 0.840 and 0.830, respectively. Significant retinal microcirculation impairment, while milder than that in OCAD was observed in NOCAD patients, indicating retinal microvasculature assessment might provide a new systemic microcirculation observation window for NOCAD. Furthermore, retinal microvasculature may serve as a new indicator to assess the severity of CAD with good performance of retinal microvascular parameters in identifying different CAD subtypes.

Differences in rate of change of retinal structural and microvasculature parameters in parkinson’s disease compared to controls

AbstractBackgroundPrior cross‐sectional studies have revealed decreased macular perfusion density (PFD) and increased peripapillary PFD in Parkinson’s disease (PD). We assess longitudinal rate of change of retinal microvascular and structural parameters in PD vs controls with normal cognition.MethodSubjects were imaged using Zeiss Cirrus HD‐5000 AngioPlex. Those with confounding medical or ocular comorbidities were excluded. Superficial capillary plexus (SCP) PFD and vessel density (VD) were assessed within ETDRS 6×6 circle, inner ring, outer ring and 3×3 circle and inner ring. SCP foveal avascular zone (FAZ) area was assessed. PFD, VD, FAZ, peripapillary retinal nerve fiber layer (RNFL), ganglion cell‐inner plexiform layer (GCIPL), and central subfield thickness (CST) were measured at 2 time points 1 year apart. Rate of change per year was calculated. Generalized estimating equations analyzed associations between rate of change of imaging parameters and PD.Result74 eyes of 40 patients with PD (60% male, mean age 67.47.9 years) &amp; 149 eyes of 78 controls (28% male, mean age 70.35.8 years) were included. No demographic differences were observed between groups except higher proportion of females in controls (p = 0.001). PD had a greater decline in PFD in 6×6 circle (mean change per year = 0.021, control = 0.00, p = 0.001), 6×6 inner ring (PD = 0.018, control = 0.001, p = .007), 6×6 outer ring (PD = 0.022, control = 0.00, p = 0.001), 3×3 circle (PD = 0.016, control = 0.002, p&lt;.001), 3×3 inner ring (PD = 0.016, control = 0.002, p&lt;0.001). PD had greater decline in VD in 6×6 circle (mean change per year in PD = 0.72/mm, control = 0.054/mm, p = 0.006), 6×6 inner ring (PD = 0.636/mm, control = 0.048/mm, p = 0.03), 6×6 outer ring (PD = 0.746/mm, control = 0.054/mm, p = 0.005), 3×3 circle (PD = 0.939/mm, control = 0.006/mm, p&lt;0.001), 3×3 inner ring (PD = ‐0.942/mm, control = 0.013/mm, p&lt;0.001). PD had greater decrease in GCIPL (mean change per year in PD = 0.403µm, control = 0.128µm control, p = 0.01). There were no significant differences in rate of change in FAZ area, RNFL thickness, CST, and no significant differences in rate of change when stratified by PD severity.ConclusionPD may be associated with more rapid loss of retinal microvascular perfusion and vessel densities and more rapid thinning of GCIPL compared to normal aging in controls with normal cognition.

Retinal vessel geometry in patients with idiopathic epiretinal membrane

We investigated the associations between retinal vascular geometric measurements and idiopathic epiretinal membrane (ERM). Whether changes in retinal vascular geometry are independent of systemic cardiovascular risk factors was also evaluated. This retrospective, cross sectional study included 98 patients with idiopathic ERM, and 99 healthy age-matched controls. Quantitative retinal vascular parameters were measured from digital retinal fundus photographs using a semi-automated computer-assisted program. Multivariate logistic regression analyses were performed to evaluate associations between retinal vascular geometric parameters and the presence of idiopathic ERM after adjusting for systemic cardiovascular risk factors. There was no significant difference in the baseline characteristics of the two groups, except that the ERM group had a higher proportion of females than the control group. In multivariate regression analyses, female sex (odds ratio [OR] 0.402; 95% CI 0.196–0.802; P = 0.011), wider retinal venular caliber (OR 16.852; 95% CI 5.384–58.997; P < 0.001) and decreased total fractal dimension (OR 0.156; 95% CI 0.052–0.440; P = 0.001) were associated with idiopathic ERM. Idiopathic ERM was associated with alterations in global retinal microvascular geometric parameters, wider retinal venules, and less complex vascular branching patterns, independent of cardiovascular risk factors.

Sleeve gastrectomy improved microvascular phenotypes from obesity cohort, detected with optical coherence tomography angiography.

To examine how metabolic status is associated with microvascular phenotype and to identify variables associated with vascular remodeling after bariatric surgery, using noninvasive optical coherence tomography angiography (OCTA). The study included 136 obese subjects scheduled for bariatric surgery and 52 normal-weight controls. Patients with obesity were divided into metabolically healthy obesity (MHO) and metabolic syndrome (MetS) groups according to the diagnosis criteria of the Chinese Diabetes Society. Retinal microvascular parameters were measured by OCTA, including superficial capillary plexus (SCP) and deep capillary plexus (DCP) vessel densities. Follow-ups were performed at the baseline and 6months after bariatric surgery. Fovea SCP, average DCP, fovea DCP, parafovea DCP, and perifovea DCP vessel densities were significantly lower in the MetS group, compared to controls (19.91% vs. 22.49%, 51.60% vs. 54.20%, 36.64% vs. 39.14%, 56.24% vs. 57.65% and 52.59% vs. 55.58%, respectively, all p < .05). Parafovea SCP, average DCP, parafovea DCP, and perifovea DCP vessel densities significantly improved in patients with obesity 6months after surgery, compared to baseline (54.21% vs. 52.97%, 54.43% vs. 50.95%, 58.29% vs. 55.54% and 55.76% vs. 51.82%, respectively, all p < .05). Multivariable analyses showed that baseline blood pressure and insulin were independent predictors of vessel density changes 6months after surgery. Retinal microvascular impairment occurred mainly in MetS rather than MHO patients. Retinal microvascular phenotype improved 6months after bariatric surgery and baseline blood pressure and insulin status may be key determinants. OCTA may be a reliable method to evaluate the microvascular complications associated with obesity.

Combining retinal neuronal and microvascular measurements improves discriminative power for multiple sclerosis patients without previous optic neuritis

AbstractPurpose: Quantitative thinning of optic nerves and changes in retinal microvasculature have been detected in multiple sclerosis patients without optic neuritis (MSNON). However, data on how both retinal neuronal and microvascular parameters jointly influence the diagnostic performance is lacking. To investigate the diagnostic performance of neuronal and microvascular changes to detect the presence of MSNON from normal controls.Methods: This is a cross‐sectional study of 51 MS participants (n = 76 eyes) and 71 age‐ and sex‐matched healthy controls (n = 117 eyes). Retinal macular ganglion cell complex (GCC) and retinal nerve fibre layer (RNFL) thicknesses and capillary densities from the superficial (SCP) and deep capillary plexuses (DCP) were obtained from the optical coherence tomography (Cirrus AngioPlex model HD‐OCT 5000). We also compensated RNFL thickness for ocular anatomical factors. Thickness and vascular measurements and their corresponding areas under the receiver operating characteristic curves (AUCs) were compared between groups.Results: All retinal structural and vascular parameters were significantly altered in MS (p ≤ 0.012). The best neuronal parameter for detecting MS was compensated RNFL from the optic nerve head region (AUC = 0.85), followed by GCC from the macular region (AUC = 0.79) while the best microvasculature parameter was the SCP (AUC = 0.66). Combining retinal neuronal and microvascular parameters improved its diagnostic performance for MS detection (AUC = 0.90; P &lt; 0.001). The joint model including both neuronal and microvasculature significantly improved the discrimination between MS and normal compared with each parameter separately (p = 0.027).Conclusions: Combining retinal neuronal and microvasculature parameters improved the discrimination of MSNON. Further studies may be warranted to evaluate the clinical utility of retinal parameters in risk prediction for disease progression.

Choriocapillaris Flow Deficit as a Biomarker for Diabetic Retinopathy and Diabetic Macular Edema: 3-Year Longitudinal Cohort

To investigate the relationship between choriocapillaris flow deficit percentage (CC FD%) by swept-source optical coherence tomography angiography (SS-OCTA) and 3-year risk of diabetic retinopathy (DR) progression and diabetic macular edema (DME) development. Prospective, observational cohort study. A total of 903 participants with type 2 diabetes mellitus (T2DM) without DR or with mild nonproliferative DR (NPDR) free of DME at baseline were followed up annually for 3 years. All participants underwent standard 7-field fundus photography and spectral-domain OCT. SS-OCTA was used for retinal and choriocapillaris imaging and 3×3-mm2 macular CC FD% was quantified. Univariate and multivariate logistic models were used to evaluate the association between CC FD% and 2 or more steps of DR progression and DME development. The additional predictive value of CC FD% for outcome events was assessed using C statistic, net reclassification index (NRI), and integrated discrimination improvement index (IDI). Over 3 years, 295 of 1805 eyes (16.34%) developed DR progression, and 118 eyes (6.54%) developed DME. A higher average CC FD% was correlated with DR progression (odds ratio [OR], 3.41 per SD increase, 95% CI: 2.65-4.39, P < .001) and DME development (OR, 1.37 per SD increase, 95% CI: 1.06-1.77, P=.016) after adjusting for confounders. In the ETDRS regions, increased CC FD% in all fields was associated with DR progression; however, increased CC FD% in the inferior field was associated with DME development. Compared with the models based on established risk factors, the addition of average CC FD% significantly improved the C statistics for DR progression (0.712 to 0.777, P < .001) and DME occurrence (0.743 to 0.773, P=.044). The estimated NRIs and IDIs (all >0) indicated that the addition of CC FD% led to a significant improvement in the discriminative performance for end points. CC FD% is independently associated with DR progression and DME development in the Chinese T2DM population and provides incremental predictive value beyond traditional risk factors and retinal microvascular parameters. Further inclusion of CC FD% in DR prediction models helps guide population-based screening and personalized management.

Association of cognitive function with Neurofilament light chain in the aqueous humor of human eye.

To evaluate the predictive clinical role of neurofilament light chain (NfL), amyloid-β (Aβ), glial fibrillary acidic protein (GFAP), and phosphorylated tau at threonine 181 (p-tau181) proteins in human aqueous humor (AH) and quantify the retinal macular microvascular parameters by optical coherence tomography angiography (OCTA) as early diagnostic markers of Alzheimer's disease (AD). This prospective, single-site, cross-sectional, cohort study enrolled 55 participants, including 38 patients with neovascular age-related macular degeneration (nAMD) and 17 individuals with senile cataracts. The single-molecule array platform was used to quantitatively measure the levels of AH NfL, Aβ40, Aβ42, GFAP, and p-tau181 proteins in AH. The mini-mental state examination (MMSE) score was used to assess the global cognitive function. OCTA scan with 6 × 6 mm macular area was used to quantify the retinal thickness and microvascular densities of superficial retinal capillary plexuses and deep retinal capillary plexuses. NfL, Aβ40, Aβ42, GFAP, and p-tau181 were detected in all AH samples by Simoa platform. Individuals with cataract had higher concentrations of NfL and p-tau181 but lower Aβ40 and Aβ42 and similar GFAP compared to those with nAMD. Lower MMSE scores showed a negative correlation with NfL concentration of AH not only in the nAMD group (p = 0.043), but also in the cataract group (p = 0.032). However, the MMSE scores were not associated with the levels of Aβ40, Aβ42, GFAP, or p-Tau181. Further analysis found that the Aβ40 and Aβ42 concentrations showed a strong positive correlation (p < 0.0001). In addition, the NfL concentration showed a mild positive correlation with that of GFAP in the cataract group (p = 0.021). Although it has not reached statistical significance, there was a correlation between the levels of NfL and Aβ42 in the nAMD group (p = 0.051). Moreover, the macular superficial vessel density values had a negative correlation with the concentration of NfL (p = 0.004) but a positive correlation with MMSE scores (p = 0.045). The macular deep vessel density values were negatively correlated with the concentration of p-tau181 (p = 0.031) and positively correlated with MMSE scores (p = 0.020). The examination of AD-related biomarkers in human AH and OCTA may improve the ocular-based AD detection methods and contribute to forestalling the progression of preclinical AD.

Retinal Neurovascular Changes in Patients With Ischemic Stroke Investigated by Optical Coherence Tomography Angiography.

BackgroundTo investigate retinal neurovascular structural changes in patients with ischemic stroke (IS) using optical coherence tomography angiography (OCTA).Materials and MethodsThe cross-sectional study was conducted in Guangdong Provincial People’s Hospital, China, consisting of 159 eyes from IS patients and 109 eyes from age-matched control subjects. Retinal microvascular parameters including the vessel density (VD) of the superficial capillary plexus (SCP), deep capillary plexus (DCP) and radial peripapillary capillary (RPC), and neural parameters such as ganglion cell complex thickness (GCCt) and retinal nerve fibre layer thickness (RNFLt) were measured by OCTA.ResultsThe VD of SCP and DCP in the macular area were significantly reduced in IS patients compared to the control group (all p < 0.001). The VD of RPC at the optic disc was also significantly reduced in IS patients (all p < 0.05). IS patients showed reduced GCCt and RNFLt and increased GCC focal loss volume and global loss volume compared with the controls (all p < 0.05). Among patients with IS, the parafovea SCP VD was positively correlated with GCCt (r = 0.346–0.408, all p < 0.001) but not with DCP VD (all p > 0.1). In the optic disc region, the whole image RPC VD was positively correlated with mean RNFLt (r = 0.467–0.548, all p < 0.001).ConclusionReduction of retinal VD, GCCt and RNFLt was observed in patients with IS. The parafovea SCP VD and RPC VD were positively correlated with GCCt and RNFLt, respectively.

Retinal Neurovascular Impairment in Non-diabetic and Non-dialytic Chronic Kidney Disease Patients.

Background: Widespread neural and microvascular injuries are common in chronic kidney disease (CKD), increasing risks of neurovascular complications and mortality. Early detection of such changes helps assess the risks of neurovascular complications for CKD patients. As an extension of central nervous system, the retina provides a characteristic window to observe neurovascular alterations in CKD. This study aimed to determine the presence of retinal neurovascular impairment in different stages of CKD.Methods: One hundred fifteen non-diabetic and non-dialytic CKD patients of all stages and a control group of 35 healthy subjects were included. Retinal neural and microvascular parameters were obtained by optical coherence tomography angiography (OCTA) examination.Results: CKD 1–2 group (versus control group) had greater odds of having decreased retinal ganglion cell-inner plexiform layer thickness (GC-IPLt) (odds ratio [OR]: 0.92; 95% confidence interval [CI]: 0.86–0.98), increased ganglion cell complex-focal loss volume (GCC-FLV) (OR: 3.51; 95% CI: 1.27–9.67), and GCC-global loss volume (GCC-GLV) (OR: 2.48; 95% CI: 1.27–4.82). The presence of advanced stages of CKD (CKD 3–5 group versus CKD 1–2 group) had greater odds of having decreased retinal vessel density in superficial vascular plexus (SVP)-WholeImage (OR: 0.77, 95% CI: 0.63–0.92), SVP-ParaFovea (OR: 0.83, 95% CI: 0.71–0.97), SVP-ParaFovea (OR: 0.76, 95% CI: 0.63–0.91), deep vascular plexus (DVP)-WholeImage (OR: 0.89, 95% CI: 0.81–0.98), DVP-ParaFovea (OR: 0.88, 95% CI: 0.78–0.99), and DVP-PeriFovea (OR: 0.90, 95% CI: 0.83–0.98). Besides, stepwise multivariate linear regression among CKD patients showed that β2-microglobulin was negatively associated with GC-IPLt (β: –0.294; 95% CI: –0.469 ∼ –0.118), and parathyroid hormone was positively associated with increased GCC-FLV (β: 0.004; 95% CI: 0.002∼0.006) and GCC-GLV (β: 0.007; 95% CI: 0.004∼0.01). Urine protein to creatinine ratio was positively associated with increased GCC-FLV (β: 0.003; 95% CI: 0.001∼0.004) and GCC-GLV (β: 0.003; 95% CI: 0.001∼0.006).Conclusion: Retinal neuronal impairment is present in early stages of CKD (stages 1–2), and it is associated with accumulation of uremic toxins and higher UACR, while retinal microvascular hypoperfusion, which is associated with worse eGFR, was only observed in relatively advanced stages of CKD (stages 3–5). The results highlight the importance of monitoring retinal neurovascular impairment in different stages of CKD.