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

Abstract

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.

Introduction

Vascular alterations affect the neurovascular-hemodynamic balance. These changes characterize the development of cardiovascular¹ and geriatric degenerative diseases. One effect of this hemodynamic imbalance is hypoperfusion to tissues with great metabolic demand, such as the retina.¹ With advancing age, there is a decrease in retinal vessel area density² and blood flow velocity.^1,3 This occurs because aging causes oxidative stress and inflammation which are important factors that negatively affect the microcirculation, microvasculature, and microstructure of the retina.⁴

Major systemic health benefits have been found associated with resistance training.⁵ Recommendations for healthy, older adults include: resistance training performed at least twice per week, on non-consecutive days.⁵ High-speed circuit resistance training (HSCT) in older adults improves retinal blood flow, retinal tissue perfusion, capillary function as well as improves physiological and performance parameters.^6,7 Exercise is known to affect the retinal circulatory flow both directly and indirectly.⁸ Therefore, changes in the microcirculation are expected after HSCT.

Optical coherence tomography angiography (OCTA) is a non-invasive imaging modality that can generate retinal angiography (i.e., blood vessels) by tracking motion contrast of moving red blood cells in the vessels.⁹ It has been used to study retinal microvascular responses to physical exercise in both the young¹⁰ and the aging population.⁷ The goal of this present study was to determine retinal vessel densities in healthy older people after 24 weeks of HSCT.

Methods

Subjects

The study was approval by the institutional review board for human research at the University of Miami Miller School of Medicine. Written informed consent was prepared, explained, and then signed by each study participant, who was treated in accordance with the Declaration of Helsinki. Healthy older adults (age > 60 years) were recruited by the Department of Kinesiology and Sports Sciences at the University of Miami. The following subjects were excluded from the study; subjects with congestive heart diseases, uncontrolled chronic illnesses such as diabetes and hypertension, a history of stroke, malignancies within the last five (5) years, and any systemic inflammatory or autoimmune diseases. Patients with a history of ocular surgeries except for cataract; cataract surgery less than six (6) months were excluded from the study. Also, cataracts obscuring the ocular media, refractive error greater than ± 6 diopters (D), and eyes with the retinal disease were not included. All study subjects had an ophthalmic screen which included best-corrected visual acuity, intraocular pressure (IOP), and a slit-lamp examination. Individuals who had participated regularly (at least twice per week) in a resistance training program were also excluded. A total of 30 eligible subjects were recruited and randomly assigned into two groups: 15 subjects in the training group (HSCT) and 15 in the non-training group (CON). The HSCT group performed HSCT training and the non-training participants were allowed to continue simple physical activities (such as gardening or walking their pets) that were already part of their lifestyle.

The HSCT

Supervised training was performed in the mornings, three times per week, on non-consecutive days for 24 weeks by the subjects in the HSCT group. The present study employed a HSCT protocol that has been proven to improve oxidative capacity.¹¹ The training center was fitted with ten (10) computerized Keiser Pneumatic Resistance Machines (Keiser Corp., Fresno, CA, USA) set up in a circuit. The study subjects moved through the circuit where they performed 1 set of 10–12 repetitions on each machine. In the first week, one circuit was completed, two circuits were done during week two, and three circuits were completed in weeks 3–24. Details of the training sessions have been previously described.⁷ Briefly, before training, the maximum weights suitable for each study subject on each machine were established. The exercises were performed in the following order: chest press (CP), leg press (LP), seated row (SR), leg curl (LC), overhead press (OP), hip adduction (HAD), lat pulldown (LAT), hip abduction (HAB), triceps extension (TE), and arm curl (AC) (Fig. 1). The National Strength and Conditioning Association’s 1-Repetition Maximum (1RM) testing protocol was adopted for leg press and chest press which was used to determine exercise values. The Borg Modified Rating of Perceived Exertion (RPE) scale was used to assess effort¹². Minimal recovery time was allowed between exercises, and 1–2 min break was provided after each circuit was completed. The foregoing and the alternation between upper and lower body exercises reduced muscle fatigue. Once suitable baseline weights were selected, study subjects began training with movement-specific warm-ups, then the circuit commenced. Study subjects were encouraged to move “as quickly as possible” during the concentric phase of the exercises with exhalation. A controlled eccentric phase was mirrored by inhalation. Exercise progress was monitored by trained research assistants using the digital display screen on the machines. Once power values plateaued within 5% of the preceding day’s work out, additional loads were added by 5% until the next power plateau, this occurred after week 4 of training. The time taken to complete the exercise (all circuits) was 40–45 mins.

Figure 1.

The exercise order of each circuit.

The power testing was carried out in a randomized sequence, utilizing loads of 40%, 50%, 60%, 70%, and 80% of each participant at 1- repetition maximum (1RM). Prior to the testing, a warm-up consisting of ten repetitions at 30% of the 1RM was performed, followed by a one-minute rest period. To prepare for the power testing, a set of five repetitions was completed at 30% of the 1RM, focusing on power-based movements. During the power testing, participants were instructed to execute the concentric phase of the lift as quickly as possible while taking two to three seconds for the eccentric portion. After the final warm-up set and a one-minute rest, the pneumatic machines were set in the appropriate randomized order, and participants performed three repetitions at each load, with a countdown for each repetition. The peak power output was recorded from the display device of each machine and cross-referenced using electronic spreadsheets that were stored in the master computer of the Keiser pneumatic system. Aerobic fitness was assessed using the 6-Minute Walk Test (6MWT). The test was designed to estimate aerobic fitness in older adults.^13,14 Subjects were instructed to walk as far as possible along an outlined track in the laboratory for 6 minutes. The total distance covered was measured and used to compute peak oxygen consumption (VO_2Peak) employing the equation developed by Ross et al.¹⁴

OCTA

The OCTA device (AngioVue, Optovue, Inc., Fremont, CA, USA) was used to measure the retinal microvasculature. The OCTA system has a scan speed of 70,000 A-scan per second, and it produces an axial resolution of 5 µm.⁷ The machine has a high scan speed requiring only 3–4 seconds per scan. Two scans are needed to generate one angiogram.⁹ In this present study, a 3 × 3 mm scan protocol was used to scan the macula centered on the fovea. Image qualities of ≥ 7/10 were used. Angiographic (i.e., en face view) images of the total vascular network (RVN), superficial vascular plexus (SVP), and deep vascular plexus (DVP) were exported (Fig. 2), processed, and analyzed using fractal analysis for vessel density. The superficial layer was defined from the inner limiting membrane (ILM) to the outer boundary of the inner plexiform layer (IPL). The deep layer was outlined from the outer boundary of the IPL to the outer boundary of the outer plexiform layer (OPL). The segmentation boundaries were manually adjusted to the zero offset on the OCTA imaging device.

Fig. 2. OCTA enface images.

The macula centered on the fovea was scanned with a field of view 3 × 3 mm. The enface images in different slabs were exported for analysis of vessel densities in total retinal vascular network (RVN), superficial vascular plexus (SVP and deep vascular plexus (DVP). Note: there are mainly capillaries in the DVP image, while there are small vessels and capillaries in the RVN and SVP images.

Fractal analysis has been extensively used to investigate changes in retinal vascular trees in fundus photos^15,16 and OCTA angiographies.^17–19 With the analysis of fractal dimensions which represent the vessel density, skeletonization of the vessel giving an equal weight to capillaries and small vessels regardless their diameter (i.e., width) is commonly used.^20,21 While it is possible to obtain vessel densities in percentage of the area covered by vessels via the AngioVue Software in the OCTA device (i.e., Optovue), the software does not provide the function of skeletonization of the vessels and custom definition of the annulus (diameter 0.6 – 2.5 mm). We have developed fully automatic software that has been used in our previous studies.^1,4,7,21 In brief, OCTA enface images with an image size of 304 × 304 pixels were resized to 1,024 × 1,024 pixels for vessel segmentation by a custom software program in Matlab (The MathWorks, Inc., Natick, MA, USA). This was done to facilitate the measurement of vessel density (VD). A series of image processing procedures were used to create a binary image of the vessels. The procedures included: inverting, equalizing, removal of non-vessel structures, and background noise.¹ Using this binary image, vessels with a diameter of ≥ 25 μm were classified as large and were extracted from the OCTA images. The vessels that remained were classified as small vessels and were analyzed. The foveal avascular zone (FAZ) was detected based on the intensity gradient of the image. That is, the change in the grayscale image with the contrasting dark and light areas was used to determine the center of the fovea. The FAZ is approximately 0.6 mm in diameter.²² The annulus from 0.6 to 2.5 mm was analyzed. Using the fractal analysis toolbox (TruSoft Benoit Pro 2.0, TruSoft International, Inc., St. Petersburg, FL, USA), the box-counting method was used to calculate the fractal dimension (Dbox) of the annulus, representing VD. The VD measurements included VD in the RVN (RVD), SVP (SVD), and DVP (DVD). All participants were imaged at baseline and at the 24-week follow-up (within three days of training) during office hours (9 AM to 5 PM).

Sample Size and Statistical Analyses

Sample size was estimated using a software program (Gpower, Ver. 3.0) developed by Erdfelder et al.²³ To detect a difference of 0.01 in fractal dimension (Dbox) in SVP between baseline and follow-up, a sample size of 11 subjects is needed with a detection power of 0.9. In the present study, 15 subjects were recruited in each group.

Descriptive statistics and data analyses were conducted using a statistical software package (SPSS for Windows 25.0; SPSS Inc., Chicago, Illinois, USA). The distribution of the quantitative parameters was determined using Kolmogorov-Smirnov Normal Test. T-tests and Chi-square tests were used to determine if differences existed in the demographic variables between baseline and follow-up.

Results

Demographic characteristics of the study subjects by group are presented in Table 1. There were no significant differences in any variables, except for heartbeat rate. Additionally, there were no significant differences between groups for baseline fitness measures including body mass index (BMI) (P=0.235), body fat percentage (P=0.157), resting heart rate (P=0.815), and peak oxygen uptake (VO_2peak) (P=0.961)

Table 1.

Demographic Characteristics of the study groups.

	HSCT			CON
	Baseline	Follow-up	P Value	Baseline	Follow-up	P Value
Subject, n	15			15		n.a
Age, y	73.3±7.8			72.2±6.0		0.66
Sex, M:F	4:11			5:10		0.70
HTN, n	8			4		0.14
Diabetes, n	3			0		n.a
Dyslipidemia, n	7			5		0.46
Education, n	17±1			17±2		0.75
SBP (mmHg)	135.3±19.0	126.1±12.2	0.10	135.2±16.2	132.9±17.8	0.64
DBP (mmHg)	77.1±8.6	75.5±9.0	0.48	79.9±6.8	78.9±9.2	0.58
HR (beats/min)	65.1±7.9	72.3±12.0	0.002	68.5±9.2	67.7±6.6	0.74
MAP	96.5±9.6	92.4±6.3	0.06	98.4±9.0	96.9±10.0	0.50
MOPP	54.1±6.3	52.2±4.5	0.17	55.5±5.9	54.7±6.8	0.57
IOP (mmHg)	15.3±1.3	14.0±2.5	0.05	15.1±2.5	14.9±1.7	0.61
VO2Peak (ml/kg/min)	17.0±2.2	16.8±2.2	0.69	16.4±3.2	16.5±1.6	0.84
BMI (kg/m2)	27.8±4.1	27.6±4.0	0.45	29.6±4.7	29.4±4.2	0.30
BF (%)	33.9±7.0	33.5±7.2	0.68	36.9±6.9	38.5±9.3	0.13

Results are presented as the mean ± standard deviation. Abbreviations: M = male; F = female; SBP = systolic blood pressure; DBP = diastolic blood pressure; H.R. = heart rate; MAP = mean arterial pressure; MOPP = mean ocular perfusion pressure; IOP = intraocular pressure; HSCT: high-speed circuit training group; CON: control group; M: F: male: female; HTN, hypertension; n.a, not applicable; VO_2peak = peak oxygen uptake; BMI = body mass index; BF= body fat; Bold P values indicate P < 0. 05.

The retinal vessel density measurements were found to have normal distributions (Kolmogorov-Smirnov Test, P > 0.05). There were significant decreases in the retinal vessel densities of RVN, SVP, DVP, and in the HSCT group (P < 0.05, Fig. 3). 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, Fig. 4).

Fig. 3. Retinal vessel densities of the HSCT and CON groups at baseline and 24-week follow-up.

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. HSCT: high-speed circuit training group; CON: control group VD: vessel density; RVD: VD in the total retinal vascular network; SVD: VD in the superficial vessel plexus; DVD: VD in the deep vessel plexus. The values are the means. Bars = standard errors.

Fig. 4. Changes of retinal vessel densities between baseline and 24-week follow-up in both HSCT and CON groups.

The decreased vessel densities in all vascular measurements (i.e., SVP, RVN, and DVP) were approximately double in the HSCT group in comparison to the CON group. However, the differences between groups did not reach a significant level (P > 0.05) in all three measurements. HSCT: high-speed circuit training group; CON: control group, VD: vessel density; RVD: VD in the total retinal vascular network; SVD: VD in the superficial vessel plexus; DVD: VD in the deep vessel plexus. Bars = standard errors.

Discussion

To the best of our knowledge, this is the first study to reveal the changes in retinal microvascular density after a relatively long training period (i.e., 24-week) of HSCT in unique healthy older adults. This finding added a critical piece of information into the puzzle whether the retinal microvasculature can be used as an imaging marker for physical exercise. The key finding is a significant decrease in the retinal microvascular density of the overall inner retina (including SVP, RVN, and DVP) after 24-week HSCT, which supports the notion that retinal vessel density may be a sensitive marker for gauging the vascular response to physical exercise. Indeed, the findings validated the alteration trend demonstrated in our previous pilot study with a shorter HSCT training period.⁷ Using the same HSCT program for eight weeks, a trend of decline in retinal vessel density was found in a group of healthy older people. However, the changes did not reach a significant level.⁷ The HSCT group showed a significant increase in cognitive function tested as pattern comparison processing speed and fluid composition score, which were negatively related to retinal vessel density.⁷ Together with the current study, decreased retinal vessel density may be beneficial as a positive response to the programed exercise. Moreover, retinal blood flow,⁶ tissue perfusion,⁶ and retinal capillary function³ were found improved in the same group after eight weeks of HSCT. The previous study, with a period of 8 weeks, pointed out that improvements can be expected in retinal circulation, tissue perfusion, and capillary function, as well as cognitive function. However, the previous study with the 8-week HSCT did not conclude whether the decrease in retinal vessel density is a response to physical exercise in older people. The unanswered question was addressed in the present study, that the decrease of retinal vessel density reached a significant level after 24-week HSCT, which was three times longer than the previous study.⁷ This supports that a longer training period (i.e., dose) might be necessary for the changes in the microvasculature in older adults.

Decreased retinal vessel density in response to physical exercise has been explained with some speculations, such as blood redistribution,^24,25 vascular autoregulation dysfunction,²⁶ impaired neurovascular coupling,²⁷ and vasoconstriction.²⁸ Vessels visualized using OCTA are those with blood flow (i.e., blood moving). However, the device does not measure blood flow velocity nor flow volume.¹⁰ As such, the retinal microvascular density measured using OCTA mainly denotes the functional capillaries needed for transporting blood needed for tissue perfusion.²⁹ Therefore, the decrease in vessel density found in the present study may imply that a lower quantity of recruited (i.e., needed) capillaries are sufficient to achieve efficient blood flow or increased blood flow as shown previously for effective tissue perfusion, suggesting a possible benefit due to physical exercise.⁶ In addition, the utilization of a lower quantity of recruited capillaries for blood transportation may indicate a larger reservation of capillaries ready for recruitment to meet the higher demand of blood flow. Physical exercise has been found to improve retinal capillary function, meaning increased ability to transfer blood flow.³ Jiang et al. reported the function of the capillary bed to transfer blood flow per unit of capillaries was increased after 8-week HSCT in older adults.³ The calculation was based on measured retinal blood flow and capillary density in the macula, which provided an opportunity to gauge the retinal capillary function. In the present study, it could be speculated that retinal capillary function would improve, which resulted in fewer capillaries required to transport needed blood flow, although we did not measure the blood flow in the present study. The decreased retinal vessel density may therefore be interpreted as a beneficial effect in response to the HSCT program with a related long duration.

The effect of physical exercise has been widely studied, especially in the aging population.^3,6,7,19,30 Increased oxidative stress and inflammation are associated with the aging process and are referred to as “inflamm-aging”.³¹ These factors cause dysfunction of the vascular system, including vessel structure, capillary function, and circulation, which are regarded as precursors for illnesses.³² Exercise has direct vasoprotective benefits, including anti-inflammatory effects, increasing the availability of nitric oxide, relieving oxidative stress, improved endothelial function,³³ and increasing systemic metabolism.³⁰ There is a strong correlation between vascular health and physical fitness. Acute exercise impacts vascular function, whereas long-term exercise induces vascular functional adaptation and structural remodeling.³⁴ These long-term changes allow the vessels to transport blood more effectively and efficiently, even during the aging process. The body may, therefore, not need to increase vessel density with this adaptation, which was found in the present study. In fact, the ability to transport blood with increased efficiency occurs by virtue of repeated hemodynamic stimulation during each exercise session.³⁴ On the other hand, vasoconstriction in the retina may occur to prevent overflow with increased blood flow velocity and flow rates throughout the body during exercise. This adaptation, along with effective neuro-vascular coupling function may have eventually resulted in less vessel recruitment while maintaining efficient tissue perfusion. Therefore, the decreased vessel density in response to chronic physical exercise may also indicate the integrity of neuro-vascular coupling, which may be a warrant for further exploration. Additionally, regular exercise training may involve certain precise exercise-induced circulatory microRNAs of endothelial origin, like miR-126, known to promote retinal endothelial repair and survival, likely resulting in improved capillary function.¹⁹ In the present study, the healthy older study subjects had an improvement in neuromuscular exercise performance which implies the mitigation of “inflamm-aging.”

Different from previous literature reports (Table 2),^10,18,24 OCTA was repeated within three days after completing the HSCT training program in older adults in the present study, whereas other studies reported decreased retinal vessel density immediately after the physical training in young adults.^18,24 Alnawaiseh et al. observed a decrease in peripapillary and parafoveal vessel density immediately after engaging in a specific training program in young adults.²⁴ The excerise program included sit-ups, push-ups, squats, lunges, and jumping a skipping rope. This phenomenon was suggested to attribute to the increased systemic energy consumption and redistribution of blood to other more vital organs during exercise.²⁴ Other studies within the field have been done that observed a decrease in retinal microvascular density after continuous cycling for 20 mins in healthy adults ages 18–40 yrs.¹⁸ Similarly, Schmitz et al. found a decrease in the SVP after a 4-week high-intensity interval training program in healthy young adults with a average age of 20 years old.¹⁰ Therefore, a rest period after the training prior to the OCTA scan may eliminate the direct systemic cardiovascular effects on retinal vascular data and demonstrate a sustained effect.

Table 2:

Retinal measurements in response to physical exercise

Study	Sample	Age, yrs (range)	Exercise Type	Exercise duration	Test Time	Ocular Measurements	Ocular Findings	Explanation of Findings
Present Study, 2023	15 healthy	73.3±7.7 (61–87)	HSCT	24 weeks (3x per week)	Within 3 days	RVD, SVD, DVD	SVD↓, RVD↓, DVD↓	Retinal Vessel Constriction, Efficient neurovascular coupling
Jiang et al., 20223	11 healthy	70.1±5.9 (62–83)	HSCT	8 weeks (3x per week)	One day after	RCF, RBF, RCD	RCF↑. RBF↑ No changes in RCD	Improved retinal capillary function due to improved retinal blood flow per capillary unit
Brinkmann et al., 202126	34 healthy	32.4±7.9	Isometric (grip strength) and dynamic (ascending and descending 3x of 20 stairs)	2 min for isometric exercise then dynamic	Immediately	SCCP, DCCP, CCP. SLP, HLP	CCP↑, SLP↑ and HLP↑− after dynamic activity; No changes in SCPP & DCPP	Auto regulatory mechanisms; myogenic and local metabolites; choroidal blood flow has low autoregulation and depends on systemic MAP
Mauget-Faysse et al., 202128	29 runners	43.4±8.1	Marathon	several hours	Within one hour	RVDI, CMT, SFCT	RVDI↓	Dehydration, Retinal Vessel Constriction
Karakucuk et al., 20218	15 football players	18.1±0.4 18–20	HIIT	6 weeks	One day after	FAZ, VDd, VDs, VDcc	VDd↑, VDcc↑	Improved blood flow
Hua et al., 202125	23 healthy	26.9±3.7 18–30	ICRT	Day 1, no masks; Day 2, surgical masks; Day 3, N95 makes	Within 3 minutes	SVD, DVD, VD of ONH, CCF	SVD↓, DVD↓, VD of ONH↓ in all days	Blood supply redistribution
Alten et al., 202027	20 healthy, 20 T1DM	Healthy: 21.8±2.9 (20–31) T1DM: 41.3±15.0 (18–65)	HIIT	4 weeks (2x per week)	Within 3 days	Flow deficit in CC	Flow deficit↑ in CC in healthy; No changes in T1DM	Neurovascular coupling
Zinn et al., 202019	20 T1DM	41.3±15.0	HIIT	4 weeks	Within three days; 2 weeks; & 5 weeks after	FAZ, VD, VDI, FD (SVP, DVP & RPC)	No change	Impaired neurovascular coupling
Fang et al. 20207	12 healthy	70.8±5.8	HSCT	8 weeks (3x per week)	One day after	RVD, SVD, DVD	A trend of ↓ in SVD, RVD & DVD	Vascular effects
Galina et al., 202037	29 healthy	51±14.2	yoga	10 mins	Same day	SVP,DVP, VDcc, AMT, CMT,CCT	AMT↑	Related to decreased IOP and a decrease in axial length secondary to exercise
Karakucuk et al., 202038	16 football players	18.2± 0.3	Wingate test	30 sec	Immediately after	VDs, VDd, VDcc, FAZ, SFCT and CMT	FAZd ↓	Autoregulation, Local compensatory mechanisms
Zhang et al., 20206	11 healthy	70.1±5.7	HSCT	8 weeks (3x per week)	One day after	RTP, RBF	RTP↑, RBF↑	Improvement of neurovascular coupling
Vo Kim et al., 201939	32 healthy	Group 1: 20.6 (18–29) Group 2: 33.5 (30–40)	biking	20 mins	Immediately after	DVD, SVD, FAZ area, and FD	SVD↓; FD in DCP	Retinal autoregulation
Schmitz et al., 201810	58 healthy	22.0±2.0	HIIT	4 week (2x per week)	One day after	FAZ, FD (SVP, DVP, ONH)	FAZd↓, FDsM↓, FDnhPP↑	Autoregulation
Alnawaiseh et al., 201724	13 healthy	27.3±3.5	sit-ups, push-ups, squats, lunges, rope skipping	Minutes	Immediately	FAZ, FD (macula & ONH)	FD of RPC↓, FD of SVP↓, No changes in FAZ	Redistribution of blood; Increased blood pressure.

Abbreviations

AMT: average macular thickness;

cc: choriocapillaris.

CCF: choriocapillaris flow area

CCP: choriocapillaris perfusion;

CCT: central choroidal thickness;

CMT: central macula thickness;

DCPP: deep capillary plexus perfusion;

DVD: deep vascular density

DVP: deep vascular plexus;

FAZ: foveal avascular zone area

FAZd: FAZ in deep vascular plexus;

FAZd: FAZ in deep vascular plexus;

FD: flow density;

FD: fractal dimension

FDnhPP: FD peripapillary area

FDsM: FD in superficial layer;

HIIT: high intensity interval training;

HLP: Haller’s layer perfusion.

ICRT: incremental continuous running test;

ONH: optic nerve head;

RBF: retinal blood flow

RCD: retinal capillary density

RCF: retinal capillary function;

RPC: radial peripapillary capillaries

RTP: retinal tissue perfusion;

RVD: retinal vascular density;

RVDI: retinal vascular density index

SCCP: superficial capillary plexus perfusion;

SFCT: subfoveal choroidal thickness

SLP: Sattlers’s layer perfusion:

HSCT: high speed circuit training;

SVD: superficial vascular density;

SVP: superficial vascular plexus.

T1DM: type 1 diabetes

VD: vessel density;

VDcc: choriocapillaris vessel density

VDd: deep vascular density;

VDI: vessel diameter index;

VDs: superficial vascular density;

There are many exercise programs from which to choose. In the present study, normal healthy older adults participated in HSCT. Engaging in this type of exercise improves retinal blood flow, retinal tissue perfusion, and cognition in older adults.⁶ Not only does HSCT enhance both strength and power, but it is also effective in improving cardiovascular and neuromuscular performance. However, the effects of strain during exercise yield different effects on healthy persons versus persons with altered blood supply to organs such as retinal artery occlusion or glaucoma. It has been reported that patients with advanced glaucoma suffered from visual loss during exercise due to “vascular steal”.³⁵ Therefore, the selection of an exercise program is critical.

There are some limitations to the present study. First, the sample size was relatively small. However, the responses of the retinal vessel density reached a significant level within the relatively long study period, which appeared to have sufficient power to determine the effect of HSCT on the retinal microvasculature. Second, a wider age range of participants may have been included as this would have added more value to our database. The present study is the first study to determine the retinal vessel density in response to 24-week HSCT in older adults who are at risk of vascular dysfunction. Third, blood flow measurements were not a part of this study, although retinal blood flow has been found to increase in older adults after eight weeks of HSCT in our previous study.⁶ Nevertheless, blood flow measurements would facilitate the calculation of the capillary function with the consideration of the blood flow and its carrying capillary bed. Fourth, there were no restrictions on daily exercise in the control group. As such, some CON participants may maintain active lifestyles, which may have had an impact on retinal vessel densities. Fifth, in the present study, we imaged all study subjects during office hours from 9 AM to 5 PM. Although we found significant differences in retinal vessel densities in the HSCT group, diurnal variation may induce some random errors in the measurements, which may have had limited effects compared to the 6-month physical exercise program provided. Lastly, the number of women in the present study was more than twice as mean (i.e., 21 women vs. 9 men). The difference in response to physical exercise between men and women may have impact on overall outcomes; however, the impact of these differences (≈3ml·kg⁻¹·min⁻¹) was small compared to the changes typically produced by circuit resistance training³⁶ and is reflective of the greater survival rates in women versus men, thereby increasing the generalizability of our results.

In summary, this is the first study to reveal decreased retinal vessel densities after the 24-week HSCT program in older adults. OCT retinal vascular measurements may be further developed as an imaging marker for the effects of physical exercise.

Highlights.

• Retinal capillary density in healthy older adults

• High-speed circuit resistant training

• Decreased as a beneficial response to 24-week high-speed circuit resistant training