Clinical trial NCT01192061: Autonomic Nervous System Activity and Normal Tension Glaucoma
Official title: Autonomic Nervous System Activity, Peripheral Microcirculation and Retrobulbar Hemodynamics in Normal Tension Glaucoma Patients.
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Normal Tension Glaucoma
Keywords: autonomic nervous system
heart rate variability
blood pressure variability
retrobulbar hemodynamics
vascular dysregulation
Lead sponsor: Military Institute od Medicine National Research Institute
Sponsor class: OTHER
Collaborators: name: Polish Academy of Sciences
name: Indiana University School of Medicine
name: Medical University of Warsaw
First posted: 2010-08-31
Enrollment: 97
Sex: ALL
Minimum age (years): 30
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: NTG group: out-patient clinic of the Ophthalmology Department of the Military Medical Institute (MMI), control group: hospital stuff, family and friends of hospital stuff and patients

Brief summary: Evidence has accumulated that systemic and ocular mechanisms, responsible for regulating blood flow in the area of the optic disc, such as reduced ocular perfusion pressure, abnormal autoregulation and vascular dysregulation may be involved in the pathogenesis of normal tension glaucoma (NTG). Defective cardiovascular neuroregulation has been advocated as a possible one of the main systemic contributing factors in the etiology of NTG. Based on the results of previous studies, the hypothesis has been posed that patients with NTG have an impaired diurnal heart rate variability (HRV) or high activity of the sympathetic component of autonomic nervous system (ANS) and endothelial dysfunction. Impaired balance of ANS, resulting in increased demand for oxygen in the tissues and subsequent low threshold of hypoxia in all organs (including the eye) can be an important link in the pathogenetic pathway of NTG, making the optic nerve more sensitive to small and short-term changes in perfusion pressure and prone to damage even under a statistically "normal" intraocular pressure (IOP).

The aim of this study is to evaluate the activity and characteristics of the following systems: the central ANS (through a 24-hour analysis of heart rate variability and blood pressure), peripheral vascular system (through the analysis of the post-occlusive hyperemia reaction within the distal part of left upper limb) and the local retrobulbar circulation as measured by color Doppler imaging (CDI) in patients with NTG and healthy volunteers. The correlations between all above systems, as well as between them and the structural and functional parameters of the optic nerve, and the retina in both groups will be also analyzed.

Detailed description: Fifty patients with NTG and 50 age and gender-matched control subjects will be recruited. All patients will be underwent eye examination (medical history, best corrected visual acuity, slit-lamp and stereo optic disc evaluation, Goldmann applanation tonometry, central corneal thickness measurement , Humphrey central 24-2 threshold perimetry test and optical coherence tomography of the optic nerve head, retinal nerve fibre layer and macula. CDI examination of the retrobulbar vessels will be performed. 24-hour ambulatory electrocardiogram and blood pressure monitoring will be performed simultaneously. Time- and frequency-domain measures of HRV will be calculated. BP will be measured in 20 minutes intervals during the day and 30 minutes intervals at night. The occlusive provocative test and finger hyperemia will be assessed by two-channels laser-Doppler flowmeter.

Eligibility criteria: Inclusion Criteria:

NTG group

* both gender
* early to moderate NTG
* without significant cardiac or pulmonary conditions. Glaucoma is diagnosed on the basis of a glaucomatous appearance of the optic disc (cup-to-disc ratio greater than 0.6 or an interocular cup-to-disc ratio asymmetry greater than or equal to 0.2, and at least one of the following abnormalities: thinning of the rim, notching, nerve fiber layer defects, or peripapillary atrophy), correlating with visual field defects in two consecutive central 24-2 program of Humphrey threshold perimetry, according to the European Glaucoma Society (EGS) diagnostic criteria (abnormal glaucoma hemifield test or cluster of three non-edge contiguous points at the \<5% level on the pattern deviation plot with at least one point at the \<1% level, with \< 25% fixation losses and false positives and false negatives responses). Early and moderately glaucomatous loss is defined according to the Hodapp et al. classification, based on the Mean Defect (MD) index of visual fields less than - 6 dB (decibels) and - 12 dB but more than -6 dB, respectively, and on the basis of a vertical cup/disc ratio less than 0.8.

Control group

* both gender
* age and gender-matched
* without glaucoma
* without significant cardiac or pulmonary conditions.

Exclusion Criteria:

* ocular hypertension
* primary open angle glaucoma (high pressure glaucoma, IOP\>21mmHg)
* secondary open angle glaucoma
* angle closure glaucoma
* history of eye surgery
* history of eye trauma
* myopia above -6.0 diopters (D)
* corneal dystrophies
* uncontrolled arterial hypertension
* atrial fibrillation
* atrial flutter
* pacemaker
* history of cardiac arrest
* vasovagal syndrome
* diabetes mellitus
* primary damage to the autonomic nervous system
* Shy-Drager syndrome
* encephalomyelitis, multiple sclerosis
* brain and spinal cord tumors
* renal failure
* carotid sinus hypersensitivity syndrome carotid sinus
* carotid artery stenosis
* pregnancy
* breast-feeding

Primary outcomes:
measure: Time and spectral-domain measures of heart rate variability
timeFrame: baseline
Secondary outcomes:
measure: retrobulbar hemodynamic parameters of ophthalmic (OA), central retinal (CRA) and short ciliary posterior arteries (SCPA)
timeFrame: baseline
measure: measures of blood pressure (BP) diurnal variability
timeFrame: baseline
measure: parameters of postocclusive hyperemia response
timeFrame: baseline
measure: optical coherence tomography parameters of optic nerve head
timeFrame: baseline
measure: optical coherence tomography parameters of the retinal nerve fibre layer (RNFL)
timeFrame: baseline
measure: optical coherence tomography parameters of macula
timeFrame: baseline
measure: Parameters of visual field examination
timeFrame: baseline
Other outcomes:
Locations:
city: Warsaw
country: Poland
facility: Military Medical Institute
Study officials:
affiliation: Military Medical Institute, Department of Ophthalmology, 128 Szaserow Str. 04-141 Warsaw, Poland
name: Joanna Wierzbowska, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Wierzbowska J, Wierzbowski R, Stankiewicz A, Robaszkiewicz J. [Autonomic nervous system and primary open angle glaucoma--pathogenetic and clinical correlations]. Klin Oczna. 2009;111(1-3):75-9. Polish.
citation: Brown CM, Dutsch M, Michelson G, Neundorfer B, Hilz MJ. Impaired cardiovascular responses to baroreflex stimulation in open-angle and normal-pressure glaucoma. Clin Sci (Lond). 2002 Jun;102(6):623-30.
citation: Riccadonna M, Covi G, Pancera P, Presciuttini B, Babighian S, Perfetti S, Bonomi L, Lechi A. Autonomic system activity and 24-hour blood pressure variations in subjects with normal- and high-tension glaucoma. J Glaucoma. 2003 Apr;12(2):156-63. doi: 10.1097/00061198-200304000-00011.
citation: Kashiwagi K, Tsumura T, Ishii H, Ijiri H, Tamura K, Tsukahara S. Circadian rhythm of autonomic nervous function in patients with normal-tension glaucoma compared with normal subjects using ambulatory electrocardiography. J Glaucoma. 2000 Jun;9(3):239-46. doi: 10.1097/00061198-200006000-00007.