Research Article: Carbohydrate ingestion induces differential autonomic dysregulation in normal-tension glaucoma and primary open angle glaucoma

Date Published: June 7, 2018

Publisher: Public Library of Science

Author(s): Lei Cao, Stuart L. Graham, Paul M. Pilowsky, Manabu Sakakibara.


It is reported that glaucoma may be associated with vascular dysregulation. Normal tension glaucoma (NTG) and primary open angle glaucoma (POAG), which feature different intraocular pressure levels, may manifest differential features of systemic autonomic dysregulation.

We investigated autonomic regulation to carbohydrate ingestion and postural change in 37 glaucoma patients (19 NTG and 18 POAG) and 36 controls. Subjects were age and gender-matched, normotensive, and had normal comparable insulin sensitivity. Continuous finger arterial pressure and ECG was recorded in supine and standing positions before and after carbohydrate ingestion. Low frequency (LF, 0.04–0.15Hz) and high frequency (HF, 0.15–0.4Hz) spectral power of heart rate and systolic blood pressure variability (HRV and SBPV) were calculated to estimate sympathovagal function. Overall comparison glaucoma (N = 37) and controls (N = 36) showed an increased sympathetic excitation, vagal withdrawal and unstable mean arterial pressure after carbohydrate ingestion in glaucoma patients. Glaucoma severity by retinal nerve fibre layer (RNFL) thickness is positively correlated to autonomic responses (HRV LF power and HF power in normalised units (nu), and HRV LF/HF ratio) after carbohydrate ingestion. Early (30 minutes) following carbohydrate ingestion, SBP LF power and HRV parameters remained unchanged in controls; while POAG showed abnormal autonomic responses, with a paradoxical vagal enhancement (increased HRV HF power in nu) and sympathetic inhibition (decreased HRV LF power nu and HRV LF/HF ratio), and associated hypotension. Later (60–120 minutes) following carbohydrate ingestion, HRV parameters remained unaltered in controls; whereas NTG manifested vagal withdrawal (reduced HRV HF power nu) and sympathetic hyper-responsiveness (increased HRV LF power nu and HRV LF/HF ratio), despite increased SBP LF power in both controls and NTG. Both NTG and POAG exhibited attenuated autonomic responses to postural stress.

NTG and POAG both manifest some systemic autonomic cardiovascular dysregulation. However, the two forms of glaucoma respond differentially to carbohydrate ingestion, irrespective of insulin resistance.

Partial Text

Glaucoma is one of the most common causes of blindness, with a loss of retinal ganglion cells leading to visual field defects [1]. Growing evidence indicates that vascular risk underlies the pathogenesis of glaucoma [2], regardless of the pathological role of elevated intraocular pressure (IOP) [3, 4]. From a vascular perspective the eye (retina) provides a window to the cardiovascular system, and often manifests features of target organ damage of cardiovascular disease [5]. In clinical practice, primary open angle glaucoma (POAG) refers to glaucoma patients with elevated IOP (> 21mmHg); whereas those with IOP always < 21mmHg are termed normal tension glaucoma (NTG). While it remains controversial whether the two types are distinct entities, but rather more likely a spectrum of glaucomatous disease, it has been suggested that they may share a similar pathogenic pathway from a vascular perspective [4, 6–8]. The new findings of this study are that while glaucoma patients were found to manifest features of systemic autonomic dysregulation, there was a difference in the characteristics of the response to carbohydrate ingestion in different sub-types of glaucoma, and this was irrespective of insulin resistance. RNFL thickness is positively correlated to autonomic response to carbohydrate ingestion; attenuated autonomic responses may be associated with RNFL loss, i.e. advanced glaucomatous disease [42]. In the early postprandial state, POAG patients showed autonomic failure with associated hypotension (mean arterial pressure). Later following carbohydrate ingestion, NTG patients exhibited cardiac vagal withdrawal and sympathetic over-activation (Table 5. A summary for study findings). The current study provides new experimental evidence that differential global autonomic dysregulation may underlie, and correlate with, the pathogenesis of vascular mediated changes in NTG and POAG. The current study demonstrates that POAG patients manifested a cardiac autonomic failure associated with a significant depressor response soon after eating. Following carbohydrate ingestion, NTG patients exhibited a cardiac sympathetic hyper-responsiveness and vagal inhibition in the later phase of the postprandial state, irrespective of insulin resistance. In addition, both NTG and POAG showed blunted cardiac autonomic responses to postural challenge. Therefore, the current study provides important experimental evidence that glaucoma is associated with a systemic cardiovascular disorder. It provides a new mechanistic insight that the distinct autonomic dysregulation may underlie, or correlate with, the pathogenesis of the two forms of glaucoma. Clinically, it is worth noting that the assessment procedure is simple and non-invasive, and may be useful as a tool for monitoring responses to treatment in individual patients.   Source:


0 0 vote
Article Rating
Notify of
Inline Feedbacks
View all comments