Dr Zheng He*
BMed China PhD
Dr Christine T Nguyen*
Dr Bang V Bui*
BScOptom MOptom PGCertOcTher PhD
Dr James A Armitage
BScOptom MOptom PhD,
Professor Algis J Vingrys*
BScOptom PGCertOcTher PhD FARVO FAAO
*University of Melbourne
High blood pressure (> 140/90 mmHg) is probably the most common comorbidity in glaucoma patients presenting to optometry clinics. In Australia, the prevalence of hypertension is 28.6 per cent.1 This number increases to 59.5 per cent in men and 70.0 per cent in women above the age of 70 years.2 Chronic high blood pressure leads to structural remodeling in the small arteries and arterioles, increasing resistance in the peripheral blood vessels and promoting the risk of multiple end organ damage.
While chronic arterial hypertension is a well-documented risk factor for stroke, the link between hypertension and open angle glaucoma remains uncertain. The National Health and Medical Research Council guidelines for glaucoma (2011) state that the link between glaucoma and hypertension ‘is likely to be a complex relationship as the patient’s age and duration of systemic hypertension both impact upon the hypertensive state.’3
As the prevalence of both systemic hypertension and glaucoma increase with age, an association between the two diseases may merely be incidental. We need to consider whether there is a true interaction that modifies the risk of glaucoma in those suffering from systemic hypertension. For example, the difference between intraocular pressure and blood pressure determines ocular perfusion pressure. Any blood pressure reduction treatment will inadvertently reduce ocular perfusion pressure and may have the potential to produce detrimental effects for the optic nerve.
Short term vs long term systemic hypertension
The Baltimore Eye Survey4 (5,308 participants) compared young and older patients with hypertension and found that young patients with high blood pressure had less risk of glaucoma. Paradoxically, systemic hypertension in older subjects increases the risk of glaucoma.
A lower risk of glaucoma with hypertension is consistent with the idea that higher blood pressure provides better perfusion pressure to the eye. In contrast, in older patients with a longer duration of systemic hypertension and more severe vascular changes (thicker, narrower and more rigid arteries) the benefits of improved perfusion pressure are not apparent.
These data suggest that the way systemic blood pressure modifies the susceptibility of glaucoma depends on the patient’s vascular status. As shown in Figure 1A, high blood pressure within normal arteries acts as a driving force for blood flow into the eye and therefore helps to counteract high intraocular pressure. However, as arteries becomes rigid and narrow with older age and long term hypertension, local blood flow to the eye can be compromised such that high blood pressure is no longer beneficial or protective against glaucoma (Figure 1B).
Figure 1. A schematic of the central retinal artery under normal conditions (A) and following changes of thickening, narrowing and impaired reactivity in chronic hypertension (B). These structural changes will compromise blood flow autoregulation and lead to partial ocular ischaemia. The insets show the experimental evidence for increased wall-to-lumen ratio of the ophthalmic artery in rats with chronic high blood pressure.
This idea is supported by our laboratory studies.5 We have found that rats with transient high blood pressure (one hour) can withstand acute intraocular pressure elevation better than those with normal blood pressure. However, the functional ‘protection’ afforded by improved ocular perfusion pressure was compromised when the duration of high blood pressure was extended from one hour to four weeks, which was associated with damage to the vascular walls.5
This finding is consistent with epidemiological data from the Los Angeles Latino Eye Study,6 which showed that the relationship between blood pressure and the prevalence of glaucoma is a ‘J-curve’. That is, patients at both the high and low end of the blood pressure spectrum are at increased risk of glaucoma. This suggests that patients with hypotension can be at increased risk of glaucoma due to insufficient ocular perfusion pressure, whereas those with long-term hypertension may suffer greater glaucoma risk due to structural vascular changes.
Hypertension and blood flow autoregulation
Our experimental data suggest that the association between chronic hypertension and increased risk for glaucoma is not merely incidental; the prevalence of the two independent entities do not simply increase in parallel with ageing. Chronic hypertension may compound the risk for glaucoma.
Ocular perfusion pressure shows normal physiological variation due to a host of factors such as circadian fluctuation (both in intraocular pressure and blood pressure), postural changes or physical activity. Despite such variation, retinal blood flow can be maintained relatively stable thanks to the intrinsic capacity of the small arteries and arterioles to adjust diameter and thereby buffer any changes in pressure or metabolic demand.7 This process, known as autoregulation, acts to ensure a constant supply of oxygen and nutrients to the retina.
In chronic hypertension, when atherosclerosis and arterial remodeling compromise the vascular elasticity and therefore the capacity to autoregulate, even a small reduction in ocular perfusion pressure can result in blood flow deficiency. Our recent study showed that in rats with chronic high blood pressure, the retina is less able to maintain blood flow during intraocular pressure challenge.5
These results highlight the need for primary eye care providers to not only screen for hypertensive retinopathy in patients with high blood pressure, but also to be mindful to include the blood pressure status in the glaucoma risk assessment along with other risk factors. The Thessaloniki Eye Study has shown that while high blood pressure is detrimental, over-zealous treatment of blood pressure can also lead to increased risk of glaucoma.8 This latter finding suggests that the eye in hypertensive individuals becomes accustomed to higher ‘ocular perfusion pressure’ and that abrupt reductions in blood pressure do not give the eye enough time to adjust, leading to relative ischaemia.
Further studies are needed to develop an algorithm to optimise individual blood pressure ranges for patients with glaucoma and coexisting high blood pressure.
- Briganti EM, Shaw JE, Chadban SJ et al. Untreated hypertension among Australian adults: the 1999-2000 Australian Diabetes, Obesity and Lifestyle Study (AusDiab). Med J Aust 2003; 179: 135-139.
- Kearney PM, Whelton M, Reynolds K, Muntner P, Whelton PK, He J. Global burden of hypertension: analysis of worldwide data. Lancet 2005; 365: 217-223.
- NHMRC. A Guide to Glaucoma for Primary Health Care Providers. Canberra, ACT, Australia: National Health and Medical Research Council; 2011.
- Tielsch JM, Katz J, Sommer A, Quigley HA, Javitt JC. Hypertension, perfusion pressure, and primary open-angle glaucoma. A population-based assessment. Arch Ophthalmol 1995; 113: 216-221.
- He Z, Vingrys AJ, Armitage JA, Nguyen CT, Bui BV. Chronic hypertension increases susceptibility to acute IOP challenge in rats. Invest Ophthalmol Vis Sci 2014; 55: 7888-7895.
- Memarzadeh F, Ying-Lai M, Chung J, Azen SP, Varma R. Blood pressure, perfusion pressure, and open-angle glaucoma: the Los Angeles Latino Eye Study. Invest Ophthalmol Vis Sci 2010; 51: 2872-2877.
- He Z, Vingrys AJ, Armitage JA, Bui BV. The role of blood pressure in glaucoma. Clin Exp Optom 2011; 94: 133-149.
- Topouzis F, Coleman AL, Harris A et al. Association of blood pressure status with the optic disk structure in non-glaucoma subjects: the Thessaloniki eye study. Am J Ophthalmol 2006; 142: 60-67.