Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT03322904
Other study ID # 09.03.2016/1100
Secondary ID
Status Completed
Phase N/A
First received October 10, 2017
Last updated October 23, 2017
Start date March 10, 2016
Est. completion date March 5, 2017

Study information

Verified date October 2017
Source Kecioren Education and Training Hospital
Contact n/a
Is FDA regulated No
Health authority
Study type Observational

Clinical Trial Summary

ABSTRACT BACKGROUND The existence of the retinohypothalamic pathway suggests that light may influence autonomic outflow activity. The objective of this study was to examine the correlation between the estimated iris muscle sympathetic‒parasympathetic area (IRIS) ratio and the sympathetic-parasympathetic ratio (low frequency [LF]/high frequency [HF] ratio).

METHODS The study population consisted of 200 females and 200 males (mean age, 32.4 ± 7.1 years). The IRIS ratio was determined from digital photographs of the iris in a computer setting. The LF/HF ratio was determined from records of heart rate variability obtained using a Holter implementation.


Description:

INTRODUCTION The iris is the only tissue in which simultaneous interactions among smooth muscles stimulated by sympathetic and parasympathetic nerves can be observed with the naked eye. The iris contains the neural crest, which is comprised of the autonomous nervous system (ANS) and dorsal root ganglia . Fibers from the hypothalamus join the parasympathetic system through the dorsal longitudinal fasciculus and the medial forebrain bundle and unite with the Edinger-Westphal nucleus or the lateral horns of the thoracic spinal cord. A portion of these parasympathetic fibers innervate the constrictor muscle fibers of a circular structure underneath the area up to the collarette and limit the iris pupil via the oculomotor nerve. The hypothalamus is the major control and integration center of the ANS. The sympathetic nerves emerging from the hypothalamus extend along the length of the carotid artery synapse with the superior cervical ganglion and subsequently innervate the mydriasis muscle fibers beneath the iris collarette and iris root.

Heart rate variability (HRV) refers to changes in the time interval between heartbeats and is regulated by the ANS. Sympathetic and parasympathetic activities can be determined at a certain sensitivity by HRV assessment using low frequency (LF) and high frequency (HF) measurements. Previous epidemiological studies have shown that HRV is associated with both cardiac and non-cardiac all-cause mortality.

.The ANS is activated when we open our eyes, and the amount of light is adjusted by the iris . Non-visual impacts of light are mediated by melanopsin-based photoreceptors in the retinal photosensitive ganglia cells . Melanopsin is also found in the melanophores of the iris and inner brain. Phtosensitive retinal ganglion cells transmit light stimuli to the suprachiasmatic nucleus (SCN; circadian center) via the retinohypothalamic tract. In the dark, melatonin released rhythmically from the pineal gland also strongly affects SCN neuronal activity. This area receives stimulation from the visual photoreceptor system and from various areas of the brain, including the brain stem, limbic system, and cerebral cortex and contains multiple synapses with the pineal gland. The input of light into the retina, which is adjusted by the iris, is associated with the areas of the brain that regulate the ANS. Light may cause acute physiological effects such as rapid melatonin suppression, increased alertness, and increased heart rate and sympathetic nerve tonus.

The anterior cingulate cortex, amygdala, parabrachial nucleus, hypothalamus, periaqueductal grey matter, anterior insula, and some areas of the medulla play significant roles in the regulation of cardiac function. These cerebral structures are associated with cardiac activity via the sympathetic and parasympathetic nervous systems.

The objective of the study was to determine the degree of reflection of the estimated iris muscle area (IRIS) ratio of iris muscles innervated by parasympathetic and sympathetic nerves and its relationship with HRV, which is an ANS indicator of the heart.

MATERIALS AND METHODS A total of 400 healthy volunteers (200 males and 200 females) with brown eyes were included in the study. The investigators enrolled apparently healthy subjects who had no history of diabetes mellitus, hypertension, coronary artery disease, heart failure, cigarette smoking, eye disease, psychological illness, or drug therapy affecting the ANS.

A three-channel standard ambulatory Holter recording system (DMS Software Cardioscan II Holter monitoring system, ver. 11.4.0054a) was used to measure the pulse rate by HRV frequency domain analysis after removing the artefacts. The LF (0.04-0.15 Hz) and HF (0.16-0.4 Hz) ratings were recorded for 24 hours (day and night average).

Photographs of both irises of the healthy volunteers were taken using a digital camera (5-megapixel camera, 1.75 μm pixels, 0.5× digital zoom, LED flash) in the same room in daylight, at the same time of day with the same flash. Patients with non-specific and interrupted collarette (peripupillar ring) limits were not included in the study. An image software program was used to draw circular limits over the iris exterior circle (IEC), coloretta circle (CC), and pupil circle (PC) on digital photographs. The areas between the circles were measured. IEC-PC refers to the estimated total area of the dilator plus constrictor muscles stimulated sympathetically and parasympathetically; CC-PC refers to the estimated area stimulated parasympathetically; and [IEC-PC¬]-[CC-PC] refers to the estimated area stimulated sympathetically. The likelihood that the IRIS ratio was equal to the LF/HF ratio was calculated using the formula [IEC-PC¬] ‒ [CC-PC] / [CC-PC]. The average of three measurements was calculated for each photograph.

The statistical analyses were carried out using SPSS for Windows 22 (IBM SPSS Inc., Chicago, IL, USA). The normality of the data distribution was assessed using the Kolmogorov-Smirnov test. Numerical variables with a normal distribution are presented as means ± standard deviation, while those with a nonnormal distribution are presented as medians (range). The t-test (for numerical variables displaying a normal distribution) and Mann-Whitney U-test (for numerical variables displaying an abnormal distribution) were used to determine differences between two independent groups. The association between the numerical parameters was determined by Pearson and Spearman correlation analyses. The Bland-Altman analysis was used to assess differences in compliance of the IRIS ratio and the LF/HF ratio in terms of ICC. A p-value < 0.05 was considered significant.

Studies were carried out in compliance with the Declaration of Helsinki after obtaining approval from the ethics committee. Informed consent was obtained from all subjects prior to participation.

The investigators identified a relationship between the IRIS ratio and HRV in 400 healthy subjects and demonstrated cardiac autonomic function. The IRIS ratio can also be applied to diseases accompanied by cardiac autonomic dysfunction. However, further studies are needed to demonstrate a relationship between the IRIS ratio and HRV in patients with cardiac disease.


Recruitment information / eligibility

Status Completed
Enrollment 400
Est. completion date March 5, 2017
Est. primary completion date March 5, 2017
Accepts healthy volunteers Accepts Healthy Volunteers
Gender All
Age group N/A and older
Eligibility Inclusion Criteria:

- We enrolled apparently healthy subjects

Exclusion Criteria:

- History of diabetes mellitus, hypertension, coronary artery disease, heart failure, cigarette smoking, eye disease, psychological illness, or drug therapy affecting the ANS

Study Design


Related Conditions & MeSH terms


Intervention

Diagnostic Test:
iris photography
The LF (0.04-0.15 Hz) and HF (0.16-0.4 Hz) ratings were recorded for 24 hours (day and night average) by Holter recording system Photographs of both irises of the healthy volunteers were taken . An image software program was used to draw circular limits over the iris exterior circle (IEC), coloretta circle (CC), and pupil circle (PC) on digital photographs. The areas between the circles were measured. The likelihood that the IRIS ratio was equal to the LF/HF ratio was calculated using the formula [IEC-PC¬] ? [CC-PC] / [CC-PC].

Locations

Country Name City State
Turkey Sahbender Koç Ankara

Sponsors (1)

Lead Sponsor Collaborator
Kecioren Education and Training Hospital

Country where clinical trial is conducted

Turkey, 

Outcome

Type Measure Description Time frame Safety issue
Primary Correlation between iris ratio and LF/HF ratio we have conducted with 400 healthly subjects iris muscle ratio associated with heart rate variability and it is demonstrated cardiac autonomic function. Iris muscle ratio can also be used in diseases accompanied by cardiac autonomic dysfunction.Correlation between pupil diameter and heart rate variability have also been investigated in some diseases where autonomic nervous system disorders are coincident. In Parkinson's disease (PD) is accompanied by autonomic nervous system dysfunction with neurodegenerative changes.. Jain et al. demonstrate simultaneous autonomic nervous system dysfunction in both pupillary diameter and in cardiac system via heart rate variability in PD Similarly, it has been shown that pupil functions in schizophrenia, which have previously been shown to be accompanied by cardiac autonomic dysfunction, may be proportional to the severity of the schizophrenia 11months
See also
  Status Clinical Trial Phase
Recruiting NCT05004857 - The Effect of Reading Therapy on Newborns N/A
Terminated NCT00547911 - Augmenting Effects of L-DOPS With Carbidopa and Entacapone Phase 1/Phase 2
Completed NCT03327493 - Impact of Adrenoreceptor Expressions on Inflammatory Pattern in Refractory Cardiogenic Shock Under VA ECMO N/A
Recruiting NCT05239065 - Personalized Stress Management With Application of Portable Devices in Occupational Populations N/A
Completed NCT03064256 - Aerobic Physical Training and Heart Rate Variability in Hypertersion N/A
Completed NCT02594488 - Implantable Cardiac Monitors in High-Risk Post-Infarction Patients With Cardiac Autonomic Dysfunction N/A
Completed NCT00775853 - Biomarkers of Risk of Parkinson Disease
Recruiting NCT03426085 - The Effects of Liraglutide on Sudomotor Function and Inflammation in Type 2 Diabetes Phase 2
Terminated NCT02963181 - Effects of Melatonin to Reduce Nocturnal Hypertension in Patients With Neurogenic Orthostatic Hypotension Early Phase 1
Not yet recruiting NCT02365974 - Transcutaneous Electrical Nerve Stimulation (TENS) on Arterial Stiffness and Blood Pressure N/A
Completed NCT00001418 - PET Scan in Patients With Neurocardiologic Disorders N/A
Not yet recruiting NCT06236945 - HUTT to Assess Cardiac Autonomic Nervous Function
Completed NCT02397681 - Autonomic Responses During the Valsalva Maneuver and Deep Breathing Test Depend on the Experimental Setup N/A
Completed NCT02584712 - Effect of Exercise Training in Autonomic Modulation in Breast Cancer Patients N/A
Recruiting NCT00422474 - Prognostic Significance of the Baroreflex Sensitivity Changes After Acute Ischemic Stroke N/A
Terminated NCT00581477 - Treatment of Orthostatic Hypotension Phase 2/Phase 3
Enrolling by invitation NCT02725060 - Autoimmune Basis for Postural Tachycardia Syndrome N/A
Completed NCT00748059 - The Pathophysiology of Orthostatic Hypotension Phase 1
Completed NCT02830022 - Sleep, Autonomic Nervous System and Cardiorespiratory Capacity in Autism Spectrum Disorders Children (APAUTRES) N/A
Enrolling by invitation NCT04100486 - Non-Invasive Bioelectronic Analytics