Chorioretinal Imaging, Vascular Biomarkers, and Ultra-Trail: A Pilot Study

Overview

Retinal and choroidal microcirculation is a relevant biomarker of systemic vascular health and lies at the heart of eye-heart interactions. Noninvasive retinal imaging, particularly OCT angiography (OCT-A), now makes it possible to examine retinal and choroidal microvascularization in vivo and to study its relationship with systemic cardiovascular and neurovascular mechanisms. Ultra-endurance activities, such as ultra-trail races, induce significant systemic hemodynamic changes, including dehydration, variations in perfusion pressure, prolonged sympathetic activation, and redistribution of blood flow. These physiological adaptations could lead to acute and reversible changes in retinal and choroidal vascular parameters as measured by retinophotography and OCT angiography. Several studies suggest that intense physical exercise may be accompanied by significant changes in retinal and choroidal microvascular perfusion. In particular, a significant decrease in the vascular density of the superficial retinal plexus has been observed following intense exercise in a healthy population, suggesting a transient change in retinal microcirculation. Similarly, following a marathon, a decrease in the retinal vascular density index (RVDI) has been reported, likely related to exercise-induced vasoconstriction and a transient reduction in retinal blood flow. This decrease may also be exacerbated by the drop in systemic blood pressure and the relative dehydration observed after the race. More broadly, intense endurance exercise is accompanied by cardiovascular and neurohormonal adaptations, particularly through activation of the renin-angiotensin-aldosterone system, which may modulate ocular perfusion. Scott et al. demonstrated, following a 160-km ultramarathon, significant alterations in left ventricular function and a major elevation in NT-pro-BNP, indicating systemic cardiovascular stress that was markedly greater than that observed after a standard marathon. Furthermore, a multi-omics study conducted during the Ultra-Trail du Mont-Blanc (171 km) revealed systemic oxidative stress, marked inflammation with elevated IL-6 levels, and profound metabolic changes affecting red blood cells-mechanisms recognized as being involved in microvascular dysfunction. However, these variations primarily reflect functional changes in perfusion related to hemodynamic status and autonomic tone, rather than true structural microvascular remodeling or angiogenesis. Metrics derived from OCT angiography, such as vascular density or perfusion density, are in fact sensitive to systemic variations in circulating volume, perfusion pressure, and the quality of the acquired signal. In this context, the effects of ultra-endurance exercise on the eye remain poorly characterized. Research in this area is necessary to better understand the acute physiological adaptations of ocular microcirculation and to highlight the value of retinal imaging as a tool for cardiovascular research and prevention within an integrated eye-heart approach.

Interventions

• Other Retinal imaging evaluation of both eyes without dilation before and after the Mont Afrique Ultra Trail
  Retinal imaging evaluation of both eyes without dilation before and after the Mont Afrique Ultra Trail
• Other Retinal imaging evaluation of both eyes without dilation, performed in two stages (T0 and T0+11/24H)
  Retinal imaging evaluation of both eyes without dilation, performed in two stages (T0 and T0+11/24H)

Primary outcome measures

• Difference in macular vascular density of the superficial capillary plexus between the pre-race and immediate post-race examinations [Time frame: When measuring vascular biomarkers on Day 1]

Eligibility criteria

Inclusion criteria

• Participant who has given free, informed, and verbal consent
• Participant of legal age
• Participant registered for the UTMA 100 km solo ultra-trail race (for the "ultra-trail" group)
• Active subject not exposed to intense physical exertion (>6 hours of exercise) within the 7 days prior to the enrollment visit (for the "active control" group)
• Participant with an estimated physical activity level of 4-6 hours per week (for the "active control" group)
• Participant agreeing to undergo ophthalmological examinations on the same schedule as the ultra-trail group (for the "active control" group)

Exclusion criteria

• Myopia > 6 diopters
• Type 1 or Type 2 diabetes
• Protected individuals: Minors, individuals under legal protection (guardianship, conservatorship, court order), individuals unable to give informed consent
• Individuals not enrolled in a social security program
• Pregnant or breastfeeding women
• Participants with a systemic or inflammatory vascular condition and cardiovascular risk
• Participants with an ocular condition or ophthalmological history likely to impair retinal/choroidal microcirculation or the quality of imaging (vascular and degenerative macular conditions, cataracts)
• Participants being treated with vasoconstrictors
• Tobacco use within 4 hours prior to enrollment
• Caffeine consumption within 1 hour prior to enrollment

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Other

Study locations

France · 1 center

• Chu Dijon Bourgogne — Dijon

Identifiers

NCT: NCT07748936 · ARNOULD 2026

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗