The work is devoted to the study of the physiological variability of the microcirculatory-tissue system (MTS) parameters under normal conditions and during functional tests. The results were obtained in vivo using multimodal wearable analyzers implementing methods of laser Doppler flowmetry and fluorescence spectroscopy. Comprehensive data analysis and calculation of the coefficients of variation of the MTS parameters of the human body for various topographic and anatomical areas of the skin were carried out. The obtained results showed higher values of the coefficient of variation of MTS parameters in the area of the toes and wrists, while the fingers and forehead skin showed lower levers of variation. In all areas of the study, reproducibility of the parameters obtained for the right and left areas of the study is observed.

To assess changes in radial peripapillary capillary (RPC) microvasculature and their impact on visual function, measured by visual acuity (VA) and contrast sensitivity, in diabetic retinopathy (DR).

This was a cross-sectional study in 96 eyes of 67 patients, including controls, diabetes without DR (DMnoDR), nonproliferative DR (NPDR), and proliferative DR (PDR) groups. Participants underwent same-day quantitative contrast sensitivity function (qCSF) and 6 × 6 mm OCT angiography (OCTA) centered on the optic disc. The Peripapillary Nerve Fiber Layer Microvasculature Density algorithm (ARI Network) was used to calculate capillary perfusion density (total area of perfused microvasculature per unit area), capillary flux index (CFI, total weighted area of perfused microvasculature per unit area), and retinal nerve fiber layer (RNFL) thickness surrounding the optic disc. Mixed-effects multivariable regression models, controlling for age, hypertension, and lens status, evaluated associations between RPC OCTA metrics, DR severity, VA, and qCSF.

Significant RPC microvascular changes were observed across DR stages. Capillary perfusion density decreased with DR severity and even before retinopathy onset in DMnoDR versus controls (βavg = -0.42, P = 0.021). PDR compared to NPDR showed a significant decrease in CFI (β = -1.02 to -0.92, P < 0.01) and in RNFL (βavg = -0.71, P = 0.033). CFI had significant associations with qCSF at various spatial frequencies (β = 0.20 to 0.34, P = 0.002 to 0.042), but not with VA.

Radial peripapillary capillary perfusion density worsens with onset of diabetes and increasing severity of DR while capillary flux index is more significantly affected later in disease. Structure-function associations suggest that DR-induced peripapillary microvascular changes are more strongly associated with contrast sensitivity changes than with visual acuity.

To evaluate the significance of age and gender on macular retinal and choroidal thicknesses (RT and CT) and related vascular density (VD) using optical coherence tomography angiography (OCTA) in a wide spectrum of normal participants.

This was a cross-sectional study of 435 eyes of 234 normal healthy children and adults aged 5-97 years old who performed macular 3 × 3 mm scans using Optovue RTVue OCTA.

A statistically meaningful relationship was detected between age and macular layered VD and RT parameters. The middle retinal thickness (MRT) experiences minimal alterations throughout the lifespan. The mean foveal superficial capillary plexus density (SVD), deep capillary plexus density (DVD), and parafoveal SVD had the most density between the 20-40 years and tended to decrease to lowest point by the seventies. Foveal choriocapillaris vascular density (CVD), parafoveal CVD and parafoveal DVD had a decreasing course during the life course. There was no significant difference in choroidal vascular index between age groups. FAZ revealed relatively insignificant minor changes across age groups. The male participants had higher VD than the female participants in all measured parameters, except for parafoveal DVD.

RT of different layers as well as the whole retina is known to be influenced by age while the MRT experiences minimal alterations throughout the lifespan. The VD of male participants exceeded that of female participants across all measured parameters, except parafoveal DVD. Differential retinal and choroidal vascular plexuses have different course during a man's life.

Aging affects the eyes and is a major risk factor for ocular diseases. The purpose of this study was to determine the effect of age on retinal oxygen and blood flow metrics in mice.

Forty-seven C57BL/6 mice were included in four age groups (3-month-old (m): N = 18, 9m: N = 13, 15m: N = 8, and 21m: N = 8). Retinal arterial and venous diameters (DA, DV), venous blood velocity (VV), and arterial and venous oxygen contents (O2A, O2V) were measured by our established multimodal imaging system. Average blood flow (BF), oxygen delivery (DO2), metabolism (MO2), and extraction fraction (OEF) were calculated. ANOVA, and Tukey post-hoc analyses were performed to determine the effect of age on variables.

We found significant differences in VV, BF, O2A, O2V, and DO2 among the age groups. VV was significantly lower in the 21m (p = 0.004) and marginally lower in 15m (p = 0.06) compared to the 3m group, representing reductions of 41% and 30%, respectively. BF was lower in the 21m than the 3m group (p = 0.007), a 42% reduction. Additionally, O2A and O2V were significantly lower in 21m compared to the 9m group (p ≤ 0.05), indicating reductions of 30% and 65%, respectively. DO2 was significantly decreased in the 21m compared to 15m (p = 0.05) and 9m (p = 0.04) groups, representing reductions of 46% and 44%, respectively. Differences in MO2, OEF, DA, and DV did not reach statistical significance (p ≥ 0.07).

Our results showed that retinal vascular oxygen content, oxygen delivery rate, and blood flow were significantly reduced in older mice and established baselines for retinal physiological biomarkers according to age.

Retinal aging has been recognized as a significant risk factor for various retinal disorders, including diabetic retinopathy, age-related macular degeneration, and glaucoma, following a growing understanding of the molecular underpinnings of their development. This comprehensive review explores the mechanisms of retinal aging and investigates potential neuroprotective approaches, focusing on the activation of transcription factor EB. Recent meta-analyses have demonstrated promising outcomes of transcription factor EB-targeted strategies, such as exercise, calorie restriction, rapamycin, and metformin, in patients and animal models of these common retinal diseases. The review critically assesses the role of transcription factor EB in retinal biology during aging, its neuroprotective effects, and its therapeutic potential for retinal disorders. The impact of transcription factor EB on retinal aging is cell-specific, influencing metabolic reprogramming and energy homeostasis in retinal neurons through the regulation of mitochondrial quality control and nutrient-sensing pathways. In vascular endothelial cells, transcription factor EB controls important processes, including endothelial cell proliferation, endothelial tube formation, and nitric oxide levels, thereby influencing the inner blood-retinal barrier, angiogenesis, and retinal microvasculature. Additionally, transcription factor EB affects vascular smooth muscle cells, inhibiting vascular calcification and atherogenesis. In retinal pigment epithelial cells, transcription factor EB modulates functions such as autophagy, lysosomal dynamics, and clearance of the aging pigment lipofuscin, thereby promoting photoreceptor survival and regulating vascular endothelial growth factor A expression involved in neovascularization. These cell-specific functions of transcription factor EB significantly impact retinal aging mechanisms encompassing proteostasis, neuronal synapse plasticity, energy metabolism, microvasculature, and inflammation, ultimately offering protection against retinal aging and diseases. The review emphasizes transcription factor EB as a potential therapeutic target for retinal diseases. Therefore, it is imperative to obtain well-controlled direct experimental evidence to confirm the efficacy of transcription factor EB modulation in retinal diseases while minimizing its risk of adverse effects.

Aging is a complex process marked by various changes at both cellular and systemic levels, impacting the functioning and lifespan of organisms. Over time, researchers have pinpointed several significant hallmarks of aging that lead to the gradual deterioration of tissue function, regulation, and homeostasis associated with aging in humans. Despite this, the intricate interactions and cumulative effects of these hallmarks are still mostly uncharted territory. Understanding this complex web is a major challenge in Geroscience, yet it is crucial for developing effective strategies that promote healthy aging, reduce medical costs, and ensure the sustainability of health systems. Gaining insights in this area is essential for creating interventions that can slow the aging process, enhance healthspan, and decrease the likelihood of age-related diseases. The integration of knowledge from various fields concerning the middle-aging nitric oxide (NO)-mediated hypovascularity hypoxia hemodynamic hypothesis points to a systems-based approach to the biological hallmarks of aging. Key evidence suggests a systemic connection between the endocrine system (specifically sex hormones), endogenous NO deficiency, and the vascular system, which serves as a network of microvascular structures crucial for tissue perfusion functions at cellular level. These processes also involve oxidative stress and inflammation triggered by hypoxia.

Despite the promising capabilities of 3D transformer architectures in video analysis, their application to high-resolution 3D medical volumes encounters several challenges. One major limitation is the high number of 3D patches, which reduces the efficiency of the global self-attention mechanisms of transformers. Additionally, background information can distract vision transformers from focusing on crucial areas of the input image, thereby introducing noise into the final representation. Moreover, the variability in the number of slices per volume complicates the development of models capable of processing input volumes of any resolution while simple solutions like subsampling may risk losing essential diagnostic details.

To address these challenges, we introduce an end-to-end transformer-based framework, variable length feature aggregator transformer rollout (VLFATRollout), to classify volumetric data. The proposed VLFATRollout enjoys several merits. First, the proposed VLFATRollout can effectively mine slice-level fore-background information with the help of transformer's attention matrices. Second, randomization of volume-wise resolution (i.e. the number of slices) during training enhances the learning capacity of the learnable positional embedding (PE) assigned to each volume slice. This technique allows the PEs to generalize across neighboring slices, facilitating the handling of high-resolution volumes at the test time.

VLFATRollout was thoroughly tested on the retinal optical coherence tomography (OCT) volume classification task, demonstrating a notable average improvement of 5.47% in balanced accuracy over the leading convolutional models for a 5-class diagnostic task. These results emphasize the effectiveness of our framework in enhancing slice-level representation and its adaptability across different volume resolutions, paving the way for advanced transformer applications in medical image analysis. The code is available at https://github.com/marziehoghbaie/VLFATRollout/.

We examined the relationship between genetic risk for schizophrenia (SZ), using polygenic risk scores (PRSs), and retinal morphological alterations. Retinal structural and vascular indices derived from optical coherence tomography (OCT) and color fundus photography (CFP) and PRSs for SZ were analyzed in N = 35,024 individuals from the prospective cohort study, United Kingdom Biobank (UKB). Results indicated that macular ganglion cell-inner plexiform layer (mGC-IPL) thickness was significantly inversely related to PRS for SZ, and this relationship was strongest within higher PRS quintiles and independent of potential confounders and age. PRS, however, was unrelated to retinal vascular characteristics, with the exception of venular tortuosity, and other retinal structural indices (macular retinal nerve fiber layer [mRNFL], inner nuclear layer [INL], cup-to-disc ratio [CDR]). Additionally, the association between greater PRS and reduced mGC-IPL thickness was only significant for participants in the 40-49 and 50-59 age groups, not those in the 60-69 age group. These findings suggest that mGC-IPL thinning is associated with a genetic predisposition to SZ and may reflect neurodevelopmental and/or neurodegenerative processes inherent to SZ. Retinal microvasculature alterations, however, may be secondary consequences of SZ and do not appear to be associated with a genetic predisposition to SZ.

To investigate associations between quantitative vascular measurements derived from intravenous fluorescein angiography (IVFA) and baseline characteristics on optical coherence tomography (OCT) in neovascular age-related macular degeneration (nAMD) patients.

The authors prospectively recruited patients with active choroidal neovascularization secondary to AMD over 50 years old, presenting to a single center in Toronto, Canada from 2017 to 2023. Ultra-widefield IVFA images were processed using the artificial intelligence RETICAD FAassist system to extract quantitative information on blood flow, perfusion, and blood-retinal-barrier (BRB) permeability. Associations between IVFA parameters with functional and anatomical outcomes were examined using univariable and multivariable regression models.

Eighty-one nAMD eyes and seven healthy control eyes were included. Compared with healthy controls, BRB permeability in the central and peripheral retina was significantly higher in nAMD patients (P < 0.001). On univariable analysis, BRB permeability measured centrally was significantly associated with central macular thickness (P = 0.035), whereas perfusion and blood flow measured centrally were significantly associated with macular volume (P = 0.043 and 0.037, respectively). On multivariable analysis, BRB permeability remained significantly associated with central macular thickness (P = 0.026).

Central BRB permeability measured on IVFA was significantly associated with baseline central macular thickness in nAMD patients. Future work should longitudinally explore associations between IVFA parameters and clinical characteristics in diverse nAMD populations.

Introduction: To evaluate longitudinal peripapillary changes in cognitively normal older adults using optical coherence tomography (OCT) and OCT angiography (OCTA). Methods: Participants older than 50 years with no history of neurodegenerative disease or cognitive impairment were prospectively enrolled. OCT and OCTA images were obtained at the first visit and 2 years later. Results: The study comprised 189 eyes of 111 adults with a mean age (±SD) of 69.3 ± 5.8 years and mean follow-up of 2.1 ± 0.5 years. Woman experienced slower rate of decline than men in capillary perfusion density (0.000% ± 0.005% vs -0.002% ± 0.004%; P = .038) and retinal nerve fiber layer (RNFL) thickness (0.133 ± 1.617 µm vs -0.659 ± 1.431 µm; P = .008). At both timepoints, after controlling for sex, the capillary perfusion density (P < .001), capillary flux index (P < .001), and RNFL thickness (P = .005) were lower in older participants. The mean capillary perfusion density was higher in women than in men at both timepoints (P = .01 and P = .002, respectively), with no significant differences in the capillary flux index and RNFL thickness. Conclusions: In cognitively normal adults, there is a significant reduction in peripapillary capillary perfusion density, the capillary flux index, and RNFL thickness associated with aging beyond 50 years. Women had higher capillary perfusion density values with slower rates of change in capillary perfusion density and RNFL thickness. These values can serve as benchmarks, and variations could be suspicious for a pathologic process.

This study aims to investigate the impact of axial elongation on ganglion cell complex thickness (GCCT) and retinal capillary density (CD) using wide-field swept-source optical coherence tomography angiography.

A retrospective cross-sectional analysis was conducted involving 506 eyes. Fovea-centered scans were obtained to assess the subregional GCCT and capillary density across the whole retina, the superficial capillary plexus (SCP), and deep capillary plexus (DCP) among three groups: normal control, high myopia (HM) eyes with axial length < 28 mm, and HM eyes with axial length > 28 mm. Regional variations (central vs. peripheral, quadrants difference [superior, inferior, nasal, and temporal]) were analyzed.

In HM eyes with axial length > 28 mm, GCCT and retinal CD exhibit a general decline in most regions (P < 0.05). In HM eyes with axial length < 28 mm, significant reductions were observed specifically in peripheral regions, as in the GCCT beyond the 3 × 3 mm2 area and CD in the 9-12 mm whole retina, 9-12 mm superior SCP, and 6-12 mm DCP (P < 0.05). Maximum GCCT and retinal CD reduction with axial elongation was observed in subregions beyond 6 × 6  mm2.

GCCT beyond the 3 × 3 mm2 area and peripheral retinal CD beyond the 6 × 6  mm2 area were more susceptible to axial elongation and are thereby deserving of particular attention.

It is necessary to evaluate different regions during the clinical assessment of the effect of myopia on the fundus and pay close attention to the peripheral retina.

Diabetes, a health crisis afflicting millions worldwide, is increasing rapidly in prevalence. The microvascular complications triggered by diabetes have emerged as the principal cause of renal disease and blindness. The retinal microvascular network may be sensitive to early systemic vascular structural and functional changes. Therefore, this research endeavored to discern the systemic determinants influencing the retinal microvascular network in patients with and without diabetes.

The Kailuan Eye Study is a cross-sectional study based on the community-based cohort Kailuan Study. Participants underwent optical coherence tomography angiography (OCTA) (Zeiss Cirrus 5000; Carl Zeiss Meditec) and comprehensive systemic examination. Metrics such as perfusion density (PD), vascular density (VD), foveal avascular zone (FAZ) parameters of the superficial capillary plexus (SCP) in the macula were assessed.

This study included 860 eligible participants (average age = 62.75 ± 6.52 years; 21.9% female), of which 449 were diabetics. People with diabetes had diminished PD and VD in the entire macular and parafoveal regions compared to people without diabetes. Reduced PD in the whole macular region was correlated with higher fasting plasma glucose (FPG, mmol/L) concentration (Beta = -0.19, 95% CI = -0.42 to -0.36, P < 0.001), longer axial length (AL, mm) (Beta = -0.13, 95%CI = -0.48 to -0.25, P = 0.002), and elevated heart rate (Beta = -0.10, 95%CI = -0.14 to -0.19, P = 0.014), after adjusting for younger age (Beta = -0.18, 95%CI = -0.24 to -0.35, P < 0.001), consistent with VD of the whole macular region. A higher FPG level was significantly correlated with lower SCP density of both PD and VD in the macular and parafoveal region (P < 0.05 for all), as well as increased systolic blood pressure and low-density lipoprotein cholesterol concentration (P < 0.01 for all).

In this large-sample cross-sectional study, OCTA evaluation revealed that high prevalence of diabetes and elevated FPG levels were correlated with reduced retinal VD and PD. Hypertension and hyperlipidemia are important risk factors for the development of atherosclerotic cardiovascular disease but have no significant effect on retinal microvascular abnormalities.

To determine the changes in retinal microvascular density after a 24-week high-speed circuit resistance training program (HSCT) in healthy older adults.

Thirty healthy older adults were recruited and randomly assigned to either a training group (HSCT) or a non-training (CON) group. Fifteen subjects (age 73.3 ± 7.76 yrs) in the HSCT group exercised three times per week on non-consecutive days for 24 weeks. Fifteen subjects in the CON group (age 72.2 ± 6.04 yrs) did not have formal physical training. Both eyes of each subject were imaged using optical coherence tomography angiography (OCTA) at baseline and at the 24-week follow-up. The vessel densities of the retinal vascular network (RVN), superficial vascular plexus (SVP), and deep vascular plexus (DVP) were measured.

There were no demographic differences between the study groups. There were significant decreases in the retinal vessel densities of RVN, SVP and DVP in the HSCT group (P < 0.05). However, there were no significant changes in all three vascular measurements in the CON group (P > 0.05), although the changes showed a decreasing trend. The decreased vessel densities were doubled in the HSCT group in comparison to the CON group. However, the differences between groups did not reach a significant level (P > 0.05).

This is the first study to reveal the decreased retinal vessel densities as a possible imaging marker for the beneficial effects of the 24-week HSCT program in older adults.

Acknowledged as a significant pathogenetic driver for numerous diseases, aging has become a focal point in addressing the profound changes associated with increasing human life expectancy, posing a critical concern for global public health. Emerging evidence suggests that factors influencing vascular aging extend their impact to choroidal and retinal blood vessels. The objective of this work is to provide a comprehensive overview of the impact of vascular aging on ocular blood vessels and related diseases. Additionally, this study aims to illuminate molecular insights contributing to vascular cell aging, with a particular emphasis on the choroid and retina. Moreover, innovative molecular targets operating within the domain of ocular vascular aging are presented and discussed.

The aim of this article is to describe sustained myopic eye growth's effect on astrocyte cellular distribution and its association with inner retinal layer thicknesses. Astrocyte density and distribution, retinal nerve fiber layer (RNFL), ganglion cell layer, and inner plexiform layer (IPL) thicknesses were assessed using immunochemistry and spectral-domain optical coherence tomography on seventeen common marmoset retinas (Callithrix jacchus): six induced with myopia from 2 to 6 months of age (6-month-old myopes), three induced with myopia from 2 to 12 months of age (12-month-old myopes), five age-matched 6-month-old controls, and three age-matched 12-month-old controls. Untreated marmoset eyes grew normally, and both RNFL and IPL thicknesses did not change with age, with astrocyte numbers correlating to RNFL and IPL thicknesses in both control age groups. Myopic marmosets did not follow this trend and, instead, exhibited decreased astrocyte density, increased GFAP+ spatial coverage, and thinner RNFL and IPL, all of which worsened over time. Myopic changes in astrocyte density, GFAP+ spatial coverage and inner retinal layer thicknesses suggest astrocyte template reorganization during myopia development and progression which increased over time. Whether or not these changes are constructive or destructive to the retina still remains to be assessed.

This study seeks to build a normative database for the vessel density of the superficial retina (SVD) and evaluate how changes and trends in the retinal microvasculature may be influenced by age and axial length (AL) in non-glaucomatous eyes, as measured with optical coherence tomography angiography (OCTA).

We included 500 eyes of 290 healthy subjects visiting a county hospital. Each participant underwent comprehensive ophthalmological examinations and OCTA to measure the SVD and thickness of the macular and peripapillary areas. To analyze correlations between SVD and age or AL, multivariable linear regression models with generalized estimating equations were applied.

Age was negatively correlated with the SVD of the superior, central, and inferior macular areas and the superior peripapillary area, with a decrease rate of 1.06%, 1.36%, 0.84%, and 0.66% per decade, respectively. However, inferior peripapillary SVD showed no significant correlation with age. AL was negatively correlated with the SVD of the inferior macular area and the superior and inferior peripapillary areas, with coefficients of -0.522%/mm, -0.733%/mm, and -0.664%/mm, respectively. AL was also negatively correlated with the thickness of the retinal nerve fiber layer and inferior ganglion cell complex (p = 0.004).

Age and AL were the two main factors affecting changes in SVD. Furthermore, AL, a relative term to represent the degree of myopia, had a greater effect than age and showed a more significant effect on thickness than on SVD. This relationship has important implications because myopia is a significant issue in modern cities.

The present article serves as a comprehensive review of the published research literature surrounding the retinal microvasculature, characterized through the optical coherence tomography angiography (OCTA) and its potential clinical value for understanding and detecting cerebrovascular diseases.

Studies from the past 3 years (2020-2023) have identified a degeneration of the retinal microvasculature, commonly defined through the loss of vascular density, in ischemic stroke, dementia, carotid artery stenosis, cerebral small vessel disease, and a series of rare, potentially inherited cerebrovascular disorders. These retinal microvascular changes often correlate with structure and functional changes in the brain and sometimes occur prior to debilitating neurodegeneration.

While further investigations with longitudinal data and larger sample sizes are necessary, OCTA shows promising results for characterizing the retinal microvasculature as a potential imaging biomarker in reflecting the changes in the cerebral microvasculature for early detection, prevention, and treatment of cerebrovascular diseases.

Diabetic retinopathy (DR) is the most common microvascular complication of diabetes mellitus, leading to visual impairment if left untreated. This review discusses the use of optical coherence tomography angiography (OCTA) as a diagnostic tool for the early detection and management of DR. OCTA is a fast, non-invasive, non-contact test that enables the detailed visualisation of the macular microvasculature in different plexuses. OCTA offers several advantages over fundus fluorescein angiography (FFA), notably offering quantitative data. OCTA is not without limitations, including the requirement for careful interpretation of artefacts and the limited region of interest that can be captured currently. We explore how OCTA has been instrumental in detecting early microvascular changes that precede clinical signs of DR. We also discuss the application of OCTA in the diagnosis and management of various stages of DR, including non-proliferative diabetic retinopathy (NPDR), proliferative diabetic retinopathy (PDR), diabetic macular oedema (DMO), diabetic macular ischaemia (DMI), and pre-diabetes. Finally, we discuss the future role of OCTA and how it may be used to enhance the clinical outcomes of DR.

To assess the long-term variability of macular optical coherence tomography (OCT)/OCT angiography (OCTA) and visual field (VF) parameters.

Healthy and glaucoma eyes with ≥1-year follow-up were included. 24-2 VF and macular OCT/OCTA parameters, including VF mean deviation (MD), whole-image vessel density (wiVD) and ganglion cell complex thickness (wiGCC) were analysed. Intraclass correlation coefficient (ICC), root mean squared error (RMSE), within-subject test-retest SD (Sw) and test-retest variability were calculated for stable eye cohort (max follow-up=1.5 years). Rates of change and RMSE were evaluated in the extended cohort including all eyes (unlimited follow-up).

From a total of 230 eyes (150 participants; age=67.7 years), 86 eyes (37%, 62 participants) were stable. In stable eyes, OCT parameters showed the highest mean (95%) ICC (wiGCC=0.99 (0.99, 0.99)), followed by VF (VF MD=0.91 (0.88, 0.93)) and OCTA (wiVD=0.82 (0.75, 0.87)). RMSE and Sw for VF MD were 0.92 dB and 0.81 dB, respectively, for wiVD were 1.64% and 1.48%, respectively, and for wiGCC, 0.91 µm and 0.78 µm, respectively. The long-term test-rest variability of VF MD, wiVD and wiGCC was 2.2 dB, 4.1% and 2.2 µm, respectively. In the extended cohort (mean follow-up=3.0 years), all parameters had significant rates of change (p<0.001), and compared with the stable cohort, only slightly higher RMSE (VF MD=1.07 dB; wiGCC=2.03 µm; wiVD=2.57%) were found.

VF and macular OCT/OCTA, particularly OCT parameters, showed small long-term variability in all eyes, including stable ones, supporting the use of these instruments in glaucoma follow-up. Changes in macular VD and GCC greater than 4%-5% and 2 µm, respectively, indicate possible progression.

NCT00221897.

Huntington's Disease (HD) is a fully penetrant neurodegenerative disease leading to cognitive and motor disturbances. The retina may serve as a structural and functional extension of the central nervous system to identify biomarkers of HD using noninvasive imaging technology such as optical coherence tomography angiography (OCTA) and dark adaptometry.

This case-control study included 12 HD participants (24 eyes) recruited from the Huntington's Disease Society of America Center of Excellence at Washington University in St. Louis along with 16 control participants (31 eyes). Disease-positive participants underwent imaging testing of retinal capillary density and foveal avascular zone utilizing OCTA along with dark adaptometry testing. Data were collected from November 2020 to February 2022.

Individuals with HD had a lower mean age-adjusted superficial foveal capillary density and a higher mean deep foveal capillary density compared to control subjects. There was no significant difference in the mean foveal avascular zone or in dark adaptometry testing between the two groups.

This study suggests that changes in retinal biomarkers may exist in patients with HD and that additional investigations using multimodal techniques are warranted.

This study measured normal ranges of microcirculatory parameters in healthy individuals and investigated differences in parameters by age and sex.

Participants were enrolled into three groups with equal numbers of male and female: young (20-39 years), middle-aged (40-59 years), and elderly (60-79 years). Sublingual microcirculation images were obtained using the incident dark field (IDF).

A total of 75 female and 75 male healthy individuals were enrolled. The elderly group had a higher TVD (26.5 [2] vs. 25.2 [1.8]; p = 0.019) and a lower PPV (97 [2] vs. 98 [3]; p = 0.03) than did the young group. In the elderly group, systolic blood pressure (SBP) and mean arterial pressure (MAP) were moderately and positively correlated with MFI score (r = 0.407, p < 0.05, and r = 0.403, p < 0.05, respectively). The female participants had a lower MFI score than did the male participants (2.9 [2.8-3] vs. 3.0 [2.9-3]; p = 0.015).

This study revealed the range of microcirculatory parameters between different ages and sexes in healthy individuals. We found that blood pressure levels were correlated with microcirculatory parameters, especially in elders and female.

Quantitative changes in retinal microvasculature are associated with subclinical cardiac alterations and clinical cardiovascular diseases (i.e., heart failure and coronary artery disease). Nonetheless, very little is known about the retinal vascular and structural changes in patients with atrial fibrillation (AF). Our study aims to characterize the microvasculature and structure of the retina in AF patients and explore their differences in different types of AF (paroxysmal and sustained AF).

This cross-sectional study was conducted at the Departments of Neurology and Cardiology in West China Hospital, Chengdu, China. Individuals aged 40 years or older with a diagnosis of AF were eligible for inclusion and underwent an evaluation and diagnosis confirmation before enrollment. Control individuals aged 40 years or older and without a history of AF, ocular abnormalities/disease, or any significant systemic illness were recruited. The retinal vascular and structural parameters were assessed using swept-source optical coherence tomography (SS-OCT)/SS-OCT angiography. Echocardiographic data of left atrium (LA) diameter were collected in patients with AF at the time of inclusion.

A total of 242 eyes of 125 participants [71 men (56.8%); mean (SD) age, 61.98 (8.73) years] with AF and 219 eyes of 111 control participants [53 men (47.7%); mean (SD) age, 62.31 (6.47) years] were analyzed. In our AF cohort, 71 patients with paroxysmal AF and 54 patients with sustained AF (i.e., persistent/permanent AF) were included. Decreased retinal microvascular perfusion (β coefficient = -0.08; 95% CI, -0.14 to -0.03) and densities (β coefficient = -1.86; 95% CI, -3.11 to -0.60) in superficial vascular plexus (SVC) were found in the eyes of the participants with AF. In regard to retinal structures, thinner ganglion cell-inner plexiform layer (GCIPL; β coefficient = -2.34; 95% CI, -4.32 to -0.36) and retinal nerve fiber layer (RNFL) thicknesses (β coefficient = -0.63; 95% CI, -2.09 to -0.18) were observed in the eyes of the participants with AF. The retinal parameters did not significantly differ between paroxysmal and sustained AF (all P > 0.05). However, significant interactions were observed between LA diameter and AF subtypes with the perfusion and densities in SVC (P < 0.05).

This study found that individuals with AF had decreased retinal vascular densities and perfusion in SVC, as well as thinner GCIPL and RNFL thickness compared with age- and sex-matched control participants. The differences of the retinal microvasculature in SVC between paroxysmal and sustained AF depend on the LA diameter. Given our findings, further longitudinal studies with our participants are of interest to investigate the natural history of retinal microvascular and structural changes in individuals across the clinical process of AF and AF subtypes.

To identify how the inner retinal layer and microvasculature change with age by analyzing the relationships of ganglion cell-inner plexiform layer (GC-IPL) thickness, vessel density (VD), and the ratio of these measurements with age in healthy eyes.

Participants were divided into five groups according to age. The GC-IPL thickness, VD, and GC-IPL/VD ratio were compared among the groups. Linear regression analyses were performed to identify relationships of GC-IPL/VD ratio with age.

The average GC-IPL thicknesses were 84.84 ± 5.28, 84.22 ± 5.30, 85.20 ± 6.29, 83.29 ± 7.06, and 82.26 ± 5.62 μm in the 20s, 30s, 40s, 50s, and 60s age groups, respectively. The VDs were 20.94 ± 1.50, 21.06 ± 1.50, 20.99 ± 1.03, 20.71 ± 0.93, and 19.74 ± 1.73 mm-1 in the 20s, 30s, 40s, 50s, and 60s age groups, respectively. The GC-IPL/VD ratio was 4.05, 4.00, 4.06, 4.02, and 4.17 in each group, respectively, and the ratio of the 60s age group was significantly higher than that of other groups. In linear regression analyses, the GC-IPL/VD ratio was significantly associated with age in the participants aged ≥ 50 years (B = 0.014, P = 0.013), whereas it was not in the participants aged < 50 years (B = 0.003, P = 0.434).

GC-IPL thickness and macular VD showed a tendency to decrease beginning in the 50s age group and the GC-IPL/VD ratio was significantly increased in the 60s age group. Additionally, the GC-IPL/VD ratio was positively associated with age in subjects aged ≥ 50 years, which implies a more pronounced decline over time in VD rather than GC-IPL thickness.

To evaluate the frequency and associated factors of artifacts in swept-source optical coherence tomography (SS-OCT) imaging.

This was a population-based cross-sectional study. Individuals aged 35 years or older, residing in the Yuexiu district of Guangzhou, China, were recruited by random cluster sampling. Nearly half of the participants were randomly selected for SS-OCT imaging centered on the optic nerve head. Six types of artifacts in the peripapillary choroidal layer and retinal nerve fiber layer (RNFL) were graded and identified. Univariate and multivariate logistic regression analyses were used to investigate the association between the presence of artifacts and clinical characteristics.

Out of the 616 eligible individuals who underwent SS-OCT imaging, 18.3% and 13.6% of subjects exhibited at least one artifact in peripapillary RNFL (pRNFL) and peripapillary choroidal thickness (pCT) measurements, respectively, with posterior segmentation error and off-center artifact ranked as the most common artifacts. The presence of artifacts was significantly associated with age (odds ratio [OR], 1.03; 95% confidence interval [CI], 1.01-1.06; p = .003), refractive error (OR, 0.80; 95% CI, 0.71-0.89; p < .001), and signal strength (OR, 0.95; 95% CI, 0.90-0.997; p = .039) in pRNFL thickness measurement. Similarly, the presence of artifacts in pCT measurement was significantly associated with age (OR, 1.05; 95% CI, 1.03-1.08; p < .001), and refractive error (OR, 0.76; 95% CI, 0.68-0.86; p < .001).

Nearly one-fifth of the eyes were noted with at least one artifact in the population-scale SS-OCT study. Age was a risk factor for the presence of artifacts and should be considered in clinical settings.

Because the central nervous system is largely nonrenewing, neurons and their synapses must be maintained over the lifetime of an individual to ensure circuit function. Age is a dominant risk factor for neural diseases, and declines in nervous system function are a common feature of aging even in the absence of disease. These alterations extend to the visual system and, in particular, to the retina. The retina is a site of clinically relevant age-related alterations but has also proven to be a uniquely approachable system for discovering principles that govern neural aging because it is well mapped, contains diverse neuron types, and is experimentally accessible. In this article, we review the structural and molecular impacts of aging on neurons within the inner and outer retina circuits. We further discuss the contribution of non-neuronal cell types and systems to retinal aging outcomes. Understanding how and why the retina ages is critical to efforts aimed at preventing age-related neural decline and restoring neural function.

Several biological markers are believed to reflect accelerated aging in schizophrenia spectrum disorders; however, retinal neural changes have not yet been explored as potential CNS biomarkers of accelerated aging in this population. The aim of this study was to determine whether retinal neural layer thinning is more strongly related to age in schizophrenia and schizoaffective disorder patients (SZ) than in a psychiatrically healthy control group (CON).

Schizophrenia (n = 60) and CON participants (n = 69) underwent spectral domain optical coherence tomography (OCT) scans to examine the following variables in both eyes: retinal nerve fiber layer (RNFL) thickness, macula central subfield (CSF) thickness, macula volume, ganglion cell layer-inner plexiform layer (GCL-IPL) thickness, optic cup volume, and cup-to-disc ratio. Eleven participants in each group had diabetes or hypertension.

Significant negative relationships between age and RNFL thickness, macula volume, and GCL-IPL thickness were observed in the SZ group, while no significant relationships were observed in the CON group. However, many of the findings in the SZ group lost significance when participants with diabetes/hypertension were removed from analyses. A notable exception to this was that the age × SZ interaction accounted for a unique proportion of variance in GCL-IPL thinning over and above the effect of diabetes/hypertension.

The results suggest that retinal atrophy occurs at an increased rate in schizophrenia spectrum disorders, potentially reflecting accelerated aging inherent to these conditions, with considerable contributions from systemic medical diseases closely linked to this population.

Optical coherence tomography angiography (OCTA) is a new and reliable machine used to evaluate retinal structure and macular perfusion in children. The use of OCTA under bad condition such as high altitude, low atmospheric oxygen, and low humidity, in children is rarely.

To quantify the macular micro-vasculature in healthy children of various ages using OCTA in Qamdo.

Design: Prospective cross-sectional, school-based study. Three hundred and forty-seven normal students from 9 schools in 4 different areas in Qamdo were included. OCTA was performed on a 3 mm × 3 mm area centered on the macular region and macular cube 512 × 128 showed details in macular. Early treatment of diabetic retinopathy study Vessel Flow Density (VD) of the macular central vascular plexus density (CVD), inner vascular plexus density (IVD), full vascular plexus density (FVD), and the size of the foveal avascular zone (FAZ) were measured. All these results corrected by t/s = 3.382 × 0.01306 × (axial length-1.82). The differences were compared among various ages, sexes and living environments.

The mean FAZ area in all eyes was 0.27 mm2 ± 0.12 mm2. The mean foveal thickness (MFT) in the macular cube was 227.64 μm ± 23.51 μm. Compared with girls, boys had a lager FAZ (P = 0.0029). Among the different age groups, MFT (P < 0.001) and FVD (P < 0.0001), IVD (P < 0.0001), and CVD (P = 0.0050) increased with age. FAZ areas were not correlated with age (P = 0.8853) or others (MFT, area).

OCTA can use to evaluate macular perfusion in children. Our data bridge the gap between structural OCT and perfusion density in children in high altitude. Even though these were not a longitudinal study, it may provide us with hints about retina development during puberty and clinical implications of OCTA in children.

The purpose of this study was to examine the sensitivity of quantitative metrics of the retinal vasculature derived from optical coherence tomography angiography (OCT-A) images.

Full retinal vascular slab OCT-A images were obtained from 94 healthy participants. Capillary loss, at 1% increments up to 50%, was simulated by randomly removing capillary segments (1000 iterations of randomized loss for each participant at each percent loss). Thirteen quantitative metrics were calculated for each image: foveal avascular zone (FAZ) area, vessel density, vessel complexity index (VCI), vessel perimeter index (VPI), fractal dimension (FD), and parafoveal intercapillary area (PICA) measurements with and without the FAZ (mean PICA, summed PICA, PICA regularity, and PICA standard deviation [PICA SD]). The sensitivity of each metric was calculated as the percent loss at which 80% of the iterations for a participant fell outside of two standard deviations from the sample's normative mean.

The most used OCT-A metrics, FAZ area and vessel density, were not significantly different from normative values until 27.69% and 16.00% capillary loss, respectively. Across the remaining metrics, metric sensitivity ranged from 6.37% (PICA SD without FAZ) to 39.78% (Summed PICA without FAZ).

The sensitivity of vasculature metrics for detecting random capillary loss varies substantially. Further efforts simulating different patterns of capillary loss are needed for comparison. Additionally, mapping the repeatability of metrics over time in a normal population is needed to further define metric sensitivity.

Quantitative metrics vary in their ability to detect vascular abnormalities in OCT-A images. Metric choice in screening studies will need to balance expected capillary abnormalities and the quality of the OCT-A images being used.

The purpose of this study was to validate a new automated method to locate the fovea on normal and pathological fundus images. Compared to the normative anatomic measures (NAMs), our vessel-based fovea localization (VBFL) approach relies on the retina's vessel structure to make predictions.

The spatial relationship between the fovea location and vessel characteristics is learnt from healthy fundus images and then used to predict fovea location in new images. We evaluate the VBFL method on three categories of fundus images: healthy images acquired with different head orientations and fixation locations, healthy images with simulated macular lesions, and pathological images from age-related macular degeneration (AMD).

For healthy images taken with the head tilted to the side, the NAM estimation error is significantly multiplied by 4, whereas VBFL yields no significant increase, representing a 73% reduction in prediction error. With simulated lesions, VBFL performance decreases significantly as lesion size increases and remains better than NAM until lesion size reaches 200 degrees2. For pathological images, average prediction error was 2.8 degrees, with 64% of the images yielding an error of 2.5 degrees or less. VBFL was not robust for images showing darker regions and/or incomplete representation of the optic disk.

The vascular structure provides enough information to precisely locate the fovea in fundus images in a way that is robust to head tilt, eccentric fixation location, missing vessels, and actual macular lesions.

The VBFL method should allow researchers and clinicians to assess automatically the eccentricity of a newly developed area of fixation in fundus images with macular lesions.

To determine age-related alterations in the retinal capillary function (RCF, the ability to transport blood flow) in healthy subjects.

A total of 148 healthy subjects (aged 18 to 83 years) were enrolled, and one eye of each subject was imaged. Retinal blood flow (RBF) was measured using a Retinal Function Imager, and retinal capillary density (RCD, expressed as fractal dimension Dbox) was measured using optical coherence tomography angiography. RCF was defined as the ratio of RBF to RCD, representing the ability to transport blood flow. The relationship between RCF and age was analyzed. In addition, the cohort was divided into four groups (G1, <35 years, G2, 35-49 years, G3, 50-64 years, and G4, ≥65 years) for further analysis.

With all data, the relation between the RCF and age had a trend of a quadratic model (G1-4: r = 0.16, P = 0.14). After 35 years (i.e., G2-4), the relation had a trend between the RCF and age fitted into a negative linear model (r = -0.23, P = 0.05). Moreover, after 50 years (i.e., G3-4), the negative linear model became stronger (r = -0.37, P = 0.03). The average RCF was 2.24 ± 0.22 μl/s/Dbox in G4, significantly lower than that in G2 (2.65 ± 0.56 μl/s/Dbox, P = 0.018) and G3 (2.64 ± 0.70 μl/s/Dbox, P = 0.034), but did not reach a significant level compared to that in G1 (2.55 + 0.51 μl/s/Dbox, P = 0.056).

This is the first study to determine age-related alterations in the RCF in a healthy population. Decreased RCF in the older group may represent a characteristic pattern of normal aging.

Aging-related hypoxia, oxidative stress, and inflammation pathophysiology are closely associated with human age-related carcinogenesis and chronic diseases. However, the connection between hypoxia and hormonal cell signaling pathways is unclear, but such human age-related comorbid diseases do coincide with the middle-aging period of declining sex hormonal signaling. This scoping review evaluates the relevant interdisciplinary evidence to assess the systems biology of function, regulation, and homeostasis in order to discern and decipher the etiology of the connection between hypoxia and hormonal signaling in human age-related comorbid diseases. The hypothesis charts the accumulating evidence to support the development of a hypoxic milieu and oxidative stress-inflammation pathophysiology in middle-aged individuals, as well as the induction of amyloidosis, autophagy, and epithelial-to-mesenchymal transition in aging-related degeneration. Taken together, this new approach and strategy can provide the clarity of concepts and patterns to determine the causes of declining vascularity hemodynamics (blood flow) and physiological oxygenation perfusion (oxygen bioavailability) in relation to oxygen homeostasis and vascularity that cause hypoxia (hypovascularity hypoxia). The middle-aging hypovascularity hypoxia hypothesis could provide the mechanistic interface connecting the endocrine, nitric oxide, and oxygen homeostasis signaling that is closely linked to the progressive conditions of degenerative hypertrophy, atrophy, fibrosis, and neoplasm. An in-depth understanding of these intrinsic biological processes of the developing middle-aged hypoxia could provide potential new strategies for time-dependent therapies in maintaining healthspan for healthy lifestyle aging, medical cost savings, and health system sustainability.

The aim was to detect subclinical structural retinal abnormalities in optical coherence tomography (OCT) in ophthalmologically asymptomatic systemic lupus erythematosus (SLE) patients without signs of lupus retinopathy or drug toxicity in fundus examination and in OCT and to assess the relationship between OCT parameters and disease activity, therapy type and burden on other organs to demonstrate the utility of OCT in early retinal impairment in SLE patients.

Cross-sectional study. Thirty-three SLE patients (57 eyes) and 31 healthy individuals (56 eyes) were enrolled in the study. We excluded patients with evidence of lupus retinopathy or hydroxychloroquine (HCQ) toxicity on OCT or fundus examination to reveal any subclinical changes. All patients underwent full ophthalmologic examination in the slit lamp including best corrected visual acuity, tonometry, and OCT. The Kolmogorov-Smirnov distribution test was used to assess the normal distribution in quantitative values. The differences between the individual measured parameters in the groups were analyzed using the Mann-Whitney U test. Spearman's rank correlation test was used to assess the correlation between the measured parameters and quantitative clinical data.

There was no difference in the OCT findings between SLE and healthy control groups. Among the study group a negative correlation was found between disease duration and age and retinal nerve fiber layer thickness in the inferior quadrant (p = 0.0063, p = 0.0036). No correlations were observed between examined retinal parameters and duration of hydroxychloroquine therapy, hydroxychloroquine as well as chloroquine cumulative dose and disease activity indices.

Optical coherence tomography is a widespread ophthalmic modality used for SLE retinopathy and HCQ toxicity screening. Our study did not demonstrate its clinical potency in diagnosis of subclinical retinal involvement. An optical coherence tomography device seems to be less sensitive in subclinical retinal impairment detection than optical coherence tomography angiography.

The benign public perception of myopia (nearsightedness) as a visual inconvenience masks the severity of its sight-threatening consequences. Myopia is a significant risk factor for posterior pole conditions such as maculopathy, choroidal neovascularization and glaucoma, all of which have a vascular component. These associations strongly suggest that myopic eyes might experience vascular alterations prior to the development of complications. Myopic eyes are out of focus because they are larger in size, which in turn affects their overall structure and function, including those of the vascular beds. By reviewing the vascular changes that characterize myopia, this review aims to provide an understanding of the gross, cellular and molecular alterations identified at the structural and functional levels with the goal to provide an understanding of the latest evidence in the field of experimental and clinical myopia vascular research. From the evidence presented, we hypothesize that the interaction between excessive myopic eye growth and vascular alterations are tipping-points for the development of sight-threatening changes.

To assess the normative values and parameters of optical coherence tomography angiography (OCTA) influencing the best corrected visual acuity (BCVA) in adults aged 50 and above.

This was a prospective cross-sectional study from an eye screening programme in Hong Kong for 4188 citizens aged 50 and above. Images were analysed using a validated quantification software calculating vessel density and capillary perfusion density (CPD), along with other OCTA parameters, such as the foveal avascular zone area (FAZ) and circularity. OCTA data was collected from May 2019 to December 2020, including a total of 4188 healthy eyes from 4188 subjects.

Mean superficial vessel density (MSVD) was 14.48 ± 3.60 mm^- 1, while the mean capillary perfusion density (MCPD) was 0.41 ± 0.06. Multivariate analysis revealed ageing (β = 0.321, p < 0.001), being male (β=-0.089, p < 0.001), having a high body mass index (BMI) (β = 0.039, p = 0.006), high FAZ area and low FAZ circularity (β = 0.039 and - 0.034, p = 0.01 and 0.024 respectively), low MSVD in the outer ring (β=-0.513, p < 0.001), specifically in the nasal and temporal outer quadrants (β = -0.226 and - 0.259, p < 0.001 for both), and low MCPD in the outer superior quadrant (β= -0.123, p = 0.016) being independently associated with BCVA.

High FAZ area and low FAZ circularity, low MSVD in the outer ring, specifically the nasal and temporal outer quadrants, and low MCPD in the outer superior quadrant can be used as biomarkers in predicting a low visual acuity in adults aged 50 and above.

Neurodegeneration and cognitive decline in aging are growing public health concerns. This study investigates associations between central retinal arteriolar and venular equivalents (CRAE, CRVE) and brain-aging, a sensory and cognitive test composite measure, and macular ganglion cell-inner plexiform layer (mGCIPL) thickness, a biomarker of neurodegeneration.

Beaver Dam Offspring Study (BOSS) participants are adult children (baseline (2005-2008) age 21-84 years) of the population-based Epidemiology of Hearing Loss Study participants. Follow-up occurred every 5 years. In 2010-2013, fundus photographs were used to measure retinal vessels. A brain-aging score was constructed by principal component analysis using sensorineural and cognitive data. Associations between incident brain-aging and vessel measures were investigated using logistic regression. Associations between CRAE and CRVE and mGCIPL thickness, measured in 2015-2017, were also investigated.

Participants (N = 2381; mean age: 53.9 years (SD = 9.8); 54% women) had a mean CRAE and CRVE of 148.8 µm (SD = 14.5) and 221.7 µm (SD = 20.7), respectively. Among those without ocular conditions, wider CRAE was associated with decreased 5-year brain-aging risk (33% per SD CRAE increase). Both vessel measures were independently associated with mGCIPL thickness. The mGCIPL thickness increased by approximately 1.7 µm and 2.0 µm per SD increase in CRAE and CRVE, respectively.

The association of CRAE with incident brain-aging indicates its potential use as a screening tool among those without eye disease. The associations between CRAE and CRVE and mGCIPL thickness indicate narrower vasculature could affect neuronal health. These associations point to potential usefulness of retinal vessel measurements to identify people at higher risk of sensorineural declines and neurodegeneration.

To analyze the correlation of age, spherical equivalent (SE), and axial length (AL) with the microcirculation of optic nerve head (ONH) in high myopia (HM).

In this cross-sectional clinical study, 164 right eyes were included. Optical coherence tomography angiography (OCTA) was used to detect ONH vessel density. Eyes were classified based on age, SE, and AL. Groups of Age1, Age2, and Age3 were denoted for age classification (Age1<20y, 20y≤Age2<30y, Age3≥30y); Groups SE1, SE2, and SE3 for the SE classification (-9≤SE1<-6 D, -12≤SE2<-9 D, SE3<-12 D); Groups AL1, AL2, AL3, and AL4 for the AL classification (AL1<26 mm, 26≤AL2<27 mm, 27≤AL3<28 mm, AL4≥28 mm).

No significant difference was observed in vessel density among the Age1, Age2, and Age3 groups (all P>0.05) and the SE1, SE2, and SE3 groups (all P>0.05). No significant difference was observed in the intrapapillary vascular density (IVD) among AL1, AL2, AL3, and AL4 groups (P>0.05). However, a significant decrease was found in the peripapillary vascular density (PVD) in the AL1, AL2, AL3, and AL4 groups (F=3.605, P=0.015), especially in the inferotemporal (IT; F=6.25, P<0.001), temporoinferior (TI; F=2.865, P=0.038), and temporosuperior (TS; F=6.812, P<0.001) sectors. The IVD was correlated with age (r=-0.190, P<0.05) but not with SE or AL (P>0.05). The PVD was correlated with AL (r=-0.236, P<0.01) but not with age or SE (P>0.05).

With the increase of AL, the IVD remains stable while the PVD decreases, especially in the three directions of temporal (IT, TI, and TS). The main cause of microcirculation reduction may be related to AL elongation rather than an increase in age or SE.

This cross-sectional study compared optical coherence tomography angiography (OCTA) parameters between older Black and White adults with systemic comorbidities in an effort to further understand racial differences in the retinal microvasculature. We analyzed vessel density at the superficial (SCP), intermediate (ICP), and deep capillary plexuses (DCP), foveal avascular zone (FAZ) parameters, and blood flow area (BFA) at the choriocapillaris. We used a mixed-effects linear regression model, controlling for hypertension and two eyes from the same subject, to compare OCTA parameters. Black subjects had lower foveal vessel density at the SCP and ICP, while no differences were observed at the parafovea or 3x3 mm macular area of any capillary layer. Black subjects had greater FAZ area, perimeter, and FD-300, a measurement of vessel density in a 300 μm wide ring around the FAZ. Black subjects also had lower BFA at the choriocapillaris. Within a cohort of subjects without hypertension, these differences remained statistically significant, with the exception of foveal vessel density at the SCP and foveal BFA of the choriocapillaris. These findings suggest that normative databases of OCTA parameters must strive to be diverse in nature to adequately capture differences across patient populations. Further study is required to understand if baseline differences in OCTA parameters contribute to epidemiological disparities in ocular diseases.

Optical coherence tomography angiography (OCT-A) is a novel method in the dementia field that allows the detection of retinal vascular changes. The comparison of OCT-A measures with established Alzheimer's disease (AD)-related biomarkers is essential to validate the former as a marker of cerebrovascular impairment in the AD continuum. We aimed to investigate the association of macular vessel density (VD) in the superficial plexus quantified by OCT-A with the AT(N) classification based on cerebrospinal fluid (CSF) Aβ1-42, p181-tau and t-tau measurements in individuals with mild cognitive impairment (MCI).

Clinical, demographic, ophthalmological, OCT-A and CSF core biomarkers for AD data from the Neuro-ophthalmology Research at Fundació ACE (NORFACE) project were analyzed. Differences in macular VD in four quadrants (superior, nasal, inferior, and temporal) among three AT(N) groups [Normal, Alzheimer and Suspected non-Alzheimer pathology (SNAP)] were assessed in a multivariate regression model, adjusted for age, APOE ε4 status, hypertension, diabetes mellitus, dyslipidemia, heart disease, chronic obstructive pulmonary disease and smoking habit, using the Normal AT(N) group as the reference category.

The study cohort comprised 144 MCI participants: 66 Normal AT(N), 45 Alzheimer AT(N) and 33 SNAP AT(N). Regression analysis showed no significant association of the AT(N) groups with any of the regional macular VD measures (all, p > 0.16). The interaction between sex and AT(N) groups had no effect on differentiating VD. Lastly, CSF Aβ1-42, p181-tau and t-tau measures were not correlated to VD (all r < 0.13; p > 0.13).

Our study showed that macular VD measures were not associated with the AT(N) classification based on CSF biomarkers in patients with MCI, and did not differ between AD and other underlying causes of cognitive decline in our cohort.

Lupus retinopathy is the second most common eye involvement in systemic lupus erythematosus (SLE), associated with significant visual deterioration and well-known negative prognostic factor for survival. Ocular manifestation in SLE, relating the retina, ranges from asymptomatic vascular involvement to vision devastating vascular occlusions. Subclinical microvascular changes are undetectable in slit lamp examination, hence are underdiagnosed. Optical coherence tomography angiography (OCTA) is a novel, easy to interpret and non-invasive technique that allows retinal vessels visualization. OCTA simplifies clinical approach and measures the severity of decreased perfusion. The aim of the study was to demonstrate the retinal vascularization in a subclinical stage of ocular involvement in a cohort of SLE patients. Thirty-three patients (57 eyes) diagnosed with SLE were enrolled into the study group and 31 healthy individuals (56 eyes) into the control group. Vessel density reduction in parafovea, inferior and nasal quadrants of superficial retinal capillary plexus in a cohort of SLE patients was found. Among study group kidney involvement was associated with further microvasculature reduction. Knowing that retinal involvement may precede other organs impairment, early detection of retinal impairment and use of OCTA as a screening modality, may decrease overall disease morbidity.

To establish normative data on morphological characteristics and quantitative parameters of Foveal Avascular Zone (FAZ) as well as their systemic and ocular associations using OCT angiography (OCT-A) in healthy Nepalese subjects.

A prospective, cross-sectional, population-based study recruiting 210 healthy samples (420 eyes) aged 10 to 70 years was conducted. All the samples underwent detailed comprehensive eye examination followed by Optical Coherence Tomography Angiography (OCTA) and Enhanced Depth Imaging performed in each eye using Spectral Domain Optical Coherence Tomography. Foveal avascular zone area and vessel density in superficial and deep retinal plexus and Sub foveal Choroidal Thickness (SFCT) were evaluated. Ocular and systemic associations of these parameters were also studied in a multivariate analysis utilizing linear regression.

The mean superficial and deep FAZ area was 459.96 ± 124.75 μm (95% confidence interval [CI], 443.08-476.83) and 589.0 ± 141.39 μm (95% CL, 570.77-609.02), respectively. The vessel density in superficial capillary plexus was 54.03 ± 9.34% (95% CL, 53.98-54.11) while the vessel density in deep capillary plexus was 25.91 ± 38% (95% CL, 25.85-25.96). The mean SFCT in this study was 308.89 ± 68.87μm (95% CL, 299.64-318.14 μm). There was no statistically significant inter-eye difference in the FAZ parameters. Myopic eyes had smaller FAZ, lesser vessel density and thinner SFCT. Association was observed between superficial FAZ area and systolic blood pressure, and deep FAZ area and diastolic blood pressure.

This study reports the normative data on FAZ parameters in healthy Nepalese subjects which can serve as references for interpreting these parameters in different retinal-choroidal diseases.

The purpose of the study was to investigate the long-term effects of uncomplicated phacoemulsification on macular perfusion using optical coherence tomography angiography (OCTA) in healthy aging subjects. OCTA was performed before phacoemulsification and 1 week, 1 month, 3 months, and 6 months after. Superficial vascular complex (formed of nerve fiber layer vascular plexus and superficial vascular plexus), deep vascular complex (formed of intermediate capillary plexus and deep capillary plexus), as well as choriocapillaris (CC) and large choroidal blood vessels were recorded. Significant changes of vascular parameters in 95 eyes of 95 patients reached plateau 1 week after surgery and remained stable up to 6 months, occurring in all retinal layers but not in choroid and CC. Statistically significant increases in retinal vessels area, vessels percentage area, total number of junctions, junctions density, and total and average vessels length were found, followed by the total number of end points and mean lacunarity decline, proving an increase in blood supply. The study confirmed that uncomplicated phacoemulsification leads to a long-term increase in macular retinal perfusion. The results might ease the decision regarding timing for cataract surgery as long-term perfusion benefits can be achieved. Furthermore, study results provide a normative database of retinal and choroidal vasculature in healthy aging patients.

To assess the macular capillary networks and foveal avascular zone (FAZ) with swept-source optical coherence tomography angiography in healthy eyes.

This cross-sectional, prospective, observational study enrolled 222 eyes of 116 healthy participants with no ocular or systemic disease. SS-OCTA images were captured using the PLEX Elite 9000 (Carl Zeiss Meditec Inc., Dublin, CA, USA) with a 6 × 6 mm pattern centered on the foveal center. Vessel length density (VLD), perfusion density (PD), and FAZ parameters were analyzed using the manufacturer's automated software.

A significant negative correlation was observed between age and average VLD in the superficial plexus, and average PD in both the superficial plexus and the whole retina. A significant positive correlation between age and foveal avascular zone perimeter and area was also noted. Age-wise comparisons showed a trend for an increase in VLD and PD until 40 years of age, with a subsequent decrease in the older age in the macular region. The central subfield showed a decrease in the vessel density measurements in the 21-40 age group. FAZ area and perimeter were the mirror inverse of the central subfield vessel density measurements with a numerically greater area and perimeter in the 21-40 age group compared to the 0-20 and 41-60 age groups. FAZ circularity was significantly reduced after 40 years of age.

Age-related changes in the vessel density and FAZ parameters in the healthy macula are complex and vary with the macular location. These results carry significance when interpreting the data from diseased eyes.

Microcirculation facilitates the blood-tissue exchange of nutrients and regulates blood perfusion. It is, therefore, essential in maintaining tissue health. Aberrations in microcirculation are potentially indicative of underlying cardiovascular and metabolic pathologies. Thus, quantitative information about it is of great clinical relevance. Photoacoustic imaging (PAI) is a capable technique that relies on the generation of imaging contrast via the absorption of light and can image at micron-scale resolution. PAI is especially desirable to map microvasculature as hemoglobin strongly absorbs light and can generate a photoacoustic signal. This paper reviews the current state of the art for imaging microvascular networks using photoacoustic imaging. We further describe how quantitative information about blood dynamics such as the total hemoglobin concentration, oxygen saturation, and blood flow rate is obtained using PAI. We also discuss its importance in understanding key pathophysiological processes in neurovascular, cardiovascular, ophthalmic, and cancer research fields. We then discuss the current challenges and limitations of PAI and the approaches that can help overcome these limitations. Finally, we provide the reader with an overview of future trends in the field of PAI for imaging microcirculation.