Relationship between intraocular pressure and glaucoma onset and progression

Open-angle glaucoma is a multifactorial disease, and among the several risk factors, a high intraocular pressure represents the most consistent and the only one that can be modified in order to provide a significant impact over the course of the disease. High intraocular pressure is significantly associated to the onset and the progression of open angle glaucoma, and the results of several randomised controlled clinical trials have consistently attributed a higher 10% higher risk for both the development and the progression of the disease to each higher single mmHg. Intraocular pressure has been studied in terms of mean value and short-term and long-term fluctuations. As of today the mean value represents the most significant factor whereas the importance of both short-term and long-term fluctuations is still debated.

Introduction

Open-angle glaucoma (OAG) is an optic nerve disease in which intraocular pressure (IOP) causes structural and functional damage.

‘Risk factors’ and ‘prognostic factors’ respectively describe characteristics that are statistically related to the onset and progression of a given disease. However, a risk factor is not only statistically associated with the typical structural and functional abnormalities of a disease, but should have been present before their occurrence and can conceivably play a role in incident disease. The concept of risk factors is very important in medicine because each could be a potential target for treatment: for example, evidence of a behavioural risk factor (such as the close association between smoking and lung cancer) makes it possible to prescribe behavioural changes as a treatment in order to minimise disease incidence in a population.

The etiology of OAG is still not completely understood, but the current literature suggests that factors other than IOP (e.g. vascular risk factors) play a role in the multifactorial disease process [1, 2, 3]. However, IOP is still the only known modifiable factor, and the relationship between it and optic nerve damage is clearly causal: randomised trials have repeatedly shown that treatment aimed at lowering baseline IOP can be effective in preventing OAG onset (Ocular Hypertension Treatment Study (OHTS), European Glaucoma Prevention Studies (EGPS)) [4, 5] and progression (Early Manifest Glaucoma Treatment Trial (EMGT), Collaborative Initial Glaucoma Treatment Study (CIGTS), Advanced Glaucoma Intervention Study (AGIS)) [6••, 7, 8]. Even in normal tension glaucoma, the Collaborative Normal Tension Glaucoma Study (CNGTS) [9] has shown that IOP lowering is essential to prevent worsening the damage. The other so-called ‘risk factors’ that have been found to be closely related to OAG in many statistical analyses, such as age, the cup-to-disc ratio, visual field indices or a family history of OAG [4, 10, 11] may be more an expression of cumulative damage or ‘fellow-travellers’ than causes.

This chapter will consider the best evidence indicating that IOP is a risk and prognostic factor in OAG and, as Information obtained from randomised, controlled clinical trials is the gold standard influencing clinical care decisions, clinical evidence from major, multicentred clinical trials or population-based studies will be preferentially taken into account.

Despite its limitations, such as the fact that the measurements are affected by corneal thickness and other ocular biomechanical parameters (corneal curvature, stiffness, and viscoelastic properties), it is important to bear in mind that Goldmann applanation tonometry (GAT) is still the only technique that can be used as a reference method [12]. Many alternative means of measuring IOP such as I-care tonometry, the Pascal contour dynamic tonometer and the ocular response analyser (ORA) have been developed and tested over the last few years, but the data are still controversial and so the only standardised device we can rely on is still the Goldmann tonometer.