Decreased retinal capillary density as a beneficial response to 24-week high-speed circuit resistant training in healthy older adults.

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

Impaired Retinal Capillary Function in Patients With Alzheimer Disease.

BACKGROUND: Extensive evidence indicates that vasculopathy, especially the level of microcirculation, contributes to neurodegeneration in Alzheimer disease (AD). However, it is not easy to directly monitor cerebral microcirculation. The retinal microvasculature has been proposed as a surrogate measure to study cerebral vascular changes. Indeed, decreased retinal microvascular network densities were reported in patients with AD. We sought to determine the retinal capillary function (RCF, the efficiency of blood flow transferring in the capillary network) in patients with AD. METHODS: Twenty patients (age 60-84 years, mean ± SD: 72.8 ± 7.7 years) with AD and 14 age-matched cognitively normal controls (CN, age 62-81 years, mean ± SD: 68.6 ± 6.7 years.) were recruited. There were no differences in vascular risk factors, including smoking, hypertension, hyperlipidemia, Type 2 diabetes, and cardiovascular disease, between the groups. One eye of each subject in both groups 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. RESULTS: RCF was 1.62 ± 0.56 nl/s/Dbox (mean ± SD) in the AD group, which was significantly lower than that (2.56 ± 0.25 nl/s/Dbox, P < 0.01) in the CN group. The change of RCF in the AD group represented 28% lower than in the CN group. RCF was significantly and positively correlated with RBF in the AD group (r = 0.98, P < 0.05) and in the CN group (r = 0.65, P < 0.05). CONCLUSIONS: Our study is the first to demonstrate impaired retinal capillary function in patients with AD. The alteration of RCF was mainly due to decreased retinal blood flow, which is transferred by the capillary network. The RCF may be developed as a biomarker of impaired cerebral microcirculation in patients with AD.

Age-related alterations in retinal capillary function.

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

Improvement of Retinal Capillary Function After High-Speed Circuit Resistance Training in Healthy Older Adults.

BACKGROUND: To determine the retinal capillary function (RCF, the efficiency of blood flow transferring in the capillary network) and its relation to cognitive function in healthy older people without known cognitive impairment following an 8-week high-speed circuit resistance training program (HSCT). METHODS: Eleven subjects in the HSCT group and 7 age-matched nontraining controls (CON) were recruited. The HSCT group trained 3 times per week for 8 weeks, whereas CON performed no formal training. One eye of each subject from both groups was imaged at baseline and 8-week follow-up. 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. Cognitive function was assessed during both visits using the NIH Toolbox Fluid Cognition Battery. RESULTS: RCF was 2.07 ± 0.64 nL⋅s -1 ·Dbox -1 (mean ± SD) at baseline, and significantly increased to 2.59 ± 0.54 nL⋅s -1 ·Dbox -1 after training ( P = 0.0003) in the HSCT group, reflecting an increase of 25%. The changes of RBF were not related to the changes of RCD in the HSCT group (r = -0.18, P = 0.59). There was no significant change of RCF in the CON group ( P = 0.58). In the HSCT group, the Pattern Comparison Processing Speed Test and Fluid Cognition Composite Score were significantly increased after HSCT ( P = 0.01). Furthermore, the changes in Flanker Inhibitory Control and Attention Test (FLNK) were positively correlated to increases in RCF (r = 0.77, P = 0.005). CONCLUSIONS: This is the first prospective study to demonstrate that the increased RCF after HSCT was related to improved cognition in cognitively normal older adults.

Multi-Center Repeatability of Macular Capillary Perfusion Density Using Optical Coherence Tomography Angiography.

Background/Aims: This study was to determine the test-retest repeatability in quantifying macular capillary perfusion density (CPD, expressed as fractal dimension) using optical coherence tomography angiography (OCTA) in a multi-center setting. Methods: OCTA data were obtained in self-reported healthy subjects from Bascom Palmer Eye Institute at the University of Miami (UM, N = 18) and the University of Pennsylvania (UPenn, N = 22). The right eye of each subject was imaged twice at the first visit and then again at an interval of one week to assess intra-visit and inter-visit repeatability. The macular area of the OCTA-derived capillary perfusion density (OCTA-CPD) was analyzed by custom-made image processing and fractal analysis software. Fractal analysis was performed on the skeletonized microvascular network to yield OCTA-CPD by box-counting to the fractal dimension (Dbox) in the superficial vascular plexus (SVP). Repeatability was assessed by three measures: within-subject standard deviation (Sw), coefficient of variation (CoV) of repeated measures, and intraclass correlation coefficient (ICC). Results: OCTA-CPD from both sites (UM and UPENN) showed good to excellent intra-visit repeatability, as demonstrated by the Sw ≤0.004, CoVs ≤0.23%, and ICCs ≥0.61. Similarly, both sites had good to excellent inter-visit repeatability, as shown by the Sw ≤0.005, CoVs ≤0.28%, and ICCs ≥0.61. The Bland-Altman plots of the intra-visit and inter-visit measurements showed excellent agreements between the paired measurements with minimal biases. Conclusion: Our data showed that comparable high repeatability of OCTA-CPD can be achieved in both research sites using the same device, scan protocol, and image analysis.

Age-related focal thinning of the ganglion cell-inner plexiform layer in a healthy population.

Background: Given the aging of the population worldwide, to learn the underlying age-related biological phenomena is important to improve the understanding of the ageing process. Neurodegeneration is an age-associated progressive deterioration of the neuron. Retinal neurodegeneration during aging, such as the reduction in thickness of the retinal nerve fiber layer (RNFL) and ganglion cell-inner plexiform layer (GCIPL) measured by optical coherence tomography (OCT), has been reported, but no studies have provided their specific alteration patterns with age. Therefore, this study is to provide visualization of the evolution of various tomographic intraretinal layer thicknesses during aging and to document age-related changes in focal thickness. Methods: A total 194 healthy subjects were included in this cross-sectional study. The subjects were divided into four age groups: G1, <35 years; G2, 35-49 years; G3, 50-64 years; and G4 ≥65 years. One eye of each subject was imaged using a custom-built ultrahigh-resolution optical coherence tomography (UHR-OCT). Volumetric data centered on the fovea were segmented to obtain the thickness maps of six intraretinal layers, including the macular retinal nerve fiber layer (mRNFL) and GCIPL. Results: There were alterations visualized in thickness maps in these intraretinal layers. The GCIPL showed a thickness reduction localized in the inner annulus in elder subjects (G4). Within the inner annulus, the most profound alteration in G4, an oval zone (length 0.76 mm and width 0.52 mm), appeared to be in the inferior sector about 0.61 mm below the fovea, named "A zone". The average thickness reduction of the A zone was 14.4 µm in the elderly group (G4). Age was significantly related to the GCIPL thickness of the inner annulus (ρ =-0.48; P<0.001) and of the A zone (ρ =-0.39, P<0.001). Conclusions: This is the first study to apply UHR-OCT for visualizing the age-related alteration of intraretinal layers in a general population. The most profound change of the optic nerve fiber is an oval-like focal thinning in GCIPL, which occurred in the inferior sector within the inner annulus and was strongly related to increased age.

Associations Between Lid Wiper Microvascular Responses, Lens Fit, and Comfort After One Day of Contact Lens Adaptation by Neophytes.

PURPOSE: To determine associations between lid wiper microvascular responses, lens fit, and comfort after 1 day of contact lens adaptation by neophytes. METHODS: Functional slitlamp biomicroscopy was used to image the microvascular network of the upper tarsal conjunctiva, lid wiper, and bulbar conjunctiva. Fractal dimension was obtained to represent vessel density. Ultra-high-resolution optical coherence tomography was used to image the lens edge and fitting characteristics, including lens movement and lens-induced conjunctival indentation. Ocular comfort was rated using a 50-point visual analogue scale (VAS). Forty-nine healthy subjects without a history of contact lens wear were recruited. A contact lens was then fitted in the right eye. Imaging was taken at baseline and 6 hr after lens wear. RESULTS: The changes of VAS comfort score were negatively related to the changes of the vessel density in the lid-wiper (R 2 =0.18, P =0.002) and bulbar conjunctiva (R 2 =0.13, P =0.009). However, the changes of VAS were positively related to the changes in vessel density of the tarsal conjunctiva (R 2 =0.11, P =0.02). The changes of ocular microvasculature were not related to the objective metrics of the lens-fitting characteristics ( P >0.05). Similarly, the changes in the VAS comfort score were not related to the objective metrics of the lens-fitting characteristics ( P >0.05). CONCLUSION: Contact lens discomfort seemed to relate to lid wiper microvascular responses rather than fitting characteristics after 1 day of contact lens adaptation by neophytes.