Circadian variation in arterial blood pressure and glaucomatous optic neuropathy – a systematic review and meta-analysis

Methodological quality of the review: Low Confidence

Authors: Bowe A, Grünig M, Schubert J, Demir M, Hoffmann V, Kutting F, Pelc A, Steffen HM

Region: Europe, Japan

Sector: Glaucoma

Sub-sector: Blood pressure

Equity focus:  None specified

Review type: other review

Quantitative synthesis method: Meta-analysis

Qualitative synthesis method: Not applicable


Epidemiological studies have led to equivocal results concerning the role of arterial blood pressure as a risk factor for the development of glaucomatous damage and progressive visual field loss in glaucoma has been attributed to low night-time blood pressure, especially when oral antihypertensives have been combined with beta-blocking eyedrops. In order to answer the question whether nocturnal blood pressure or blood pressure dip during ambulatory blood pressure monitoring (ABPM) are associated with progressive visual field loss, the authors performed a systematic review and meta-analysis of studies in patients with primary open-angle glaucoma and normal tension glaucoma.



To ascertain whether nocturnal systolic and diastolic blood pressure or blood pressure dips are associated with progressive glaucomatous optic neuropathy.

Main findings:

A total of five studies were included in the review. The included studies were all retrospective cohort studies of no more than moderate quality. Two studies used exclusively a Humphrey field analyser (program 30–2) where deterioration of visual fields was defined as a significant difference in mean deviation or corrected pattern SD, one study used either the Humphrey system or a Goldmann perimeter with newly developed or extended scotoma as definition of progressive field loss. An Octopus G1 perimeter with an increase of at least 3dB of the mean defect as indication of field loss progression was used together with a Goldmann perimeter and in another study visual fields were analysed by all 3 systems. The types of ABPM monitor, as well as the definition of daytime and night-time differed between studies and was 6 am to 10 pm and 10 pm to 6 am, respectively, and 8 am to 10 pm and 10 pm to 8 am, respectively. Daily activity was recorded in one study in order to define waking and sleeping periods. The age of included patients ranged from 28 to 85 years, the proportion of patients with accompanying arterial hypertension varied between 0% and 44%. From the study of Kashiwagi et al. only mean values for systolic and diastolic blood pressure as well as nocturnal dips could be retrieved, while Detry et al. published only the distribution of blood pressure dips for patients with and without progressive visual field defects. A 10% fall in systolic or diastolic blood pressure during the night as criterion for the definition of dipping was available for 4 studies.


The authors found no difference in mean systolic or diastolic diurnal and nocturnal blood pressure between patients with or without progressive visual field loss. The odds ratio for deteriorating visual fields over 2 years with nocturnal dips >10% in systolic or diastolic blood pressure was 3.32 (1.84–6.00) and 2.09 (1.20–3.64), respectively. Data allowing a separate analysis of over-dipping were not available.


Based on findings, the authors concluded that “Nocturnal blood pressure fall is a risk factor for progressive visual field loss in glaucoma. However, prospective studies are needed to define a tolerable degree of dipping. Antihypertensive therapy in glaucomatous patients should be controlled with ambulatory blood pressure monitoring.”



The authors’ meta-analysis was conducted according to the Quorum statement. Using the terms “open-angle glaucoma,” “normal tension glaucoma,” “circadian blood pressure,” “blood pressure variation,” and “ambulatory blood pressure”.  They searched the databases of MEDLINE, EMBASE, and the Cochrane Library as well as the reference lists of the retrieved studies in adult glaucoma patients with no language constraints. Inclusion criteria were defined as follows:

1) description of the method of

ambulatory blood pressure measurements (ABPM),

2) separate data for daytime and nighttime blood pressure reported,

3) a definition of nocturnal blood pressure dip is mentioned or can be derived, and

4) assessment of visual fields over a study period of at least 2 years of follow-up.


Study quality was assessed independently by 2 investigators using the STROBE Statement checklist establish from von Elm et al. for cohort studies excluding the final item concerning the financing of studies. Disagreement was resolved by discussion.


The primary outcome evaluated by the authors was visual field defects on at least two occasions, two years apart, assessed with the same technique. The effect of diurnal and nocturnal systolic and diastolic blood pressure, as well as systolic and diastolic blood pressure dip on the defined outcome was calculated from the extracted quantitative data and analysed with the Cochrane Review Manager. Statistical heterogeneity between studies was evaluated by Cochran Chi2 test and was considered to exist when P < 0.05.


Applicability/external validity:

The authors note that is important to consider the fall in nocturnal blood pressure as a risk factor for progressive glaucomatous optic neuropathy despite adequate intraocular pressure control, especially in patients with concomitant cardiovascular risk factors or diseases and antihypertensive or vasoactive medication.


Geographic focus: None specified

Summary of quality assessment:

Overall, low confidence was attributed in conclusions about the effects of this study. The authors did not conduct a thorough search of the literature to ensure that all relevant studies were included in the review, which on the other hand can affect the validity of study findings. In addition, the authors do not report methods used to screen studies for inclusion and extract data of included studies.

Publication source:

Bowe A, Grunig M, Schubert J, Demir M, Hoffmann V, Kütting F, Pelc A, Steffen HM (2015) Circadian Variation in Arterial Blood Pressure and Glaucomatous Optic Neuropathy—A Systematic Review and Meta-Analysis. American Journal of Hypertension, 28(9), pp. 1077 – 1082