Chronic open angle glaucoma: Risk factors in addition to intraocular pressure

Our concepts of open angle glaucoma originated largely from patients with symptoms of angle closure who almost always presented with high and severely damaging intraocular pressures. The elevated pressure constituted glaucoma as was clearly expressed some 150 years ago by Priestley Smith when he wrote “Glaucoma is characterized by one constant and essential symptom, increased tension of the eyeball. Let this physical condition be added to any eye, healthy or diseased, and straightaway it becomes glaucomatous. Let the excess of intraocular pressure be taken away from the glaucoma eye and whatever structural or morbid change may be left, glaucoma exists no longer”. This concept was challenged some 35 years ago by the first population studies, which showed that elevated intraocular pressure was indeed a risk factor for the prevalence of glaucoma and that there was a clear relationship between the prevalence and the height of the intraocular pressure. However, these studies also showed that glaucoma patients with perfectly normal, and occasionally even low pressures constituted a sizeable group and subsequently it appeared that in Japan they formed the majority of the disease. Populations, which were followed over long periods of time, demonstrated that a large group of people with elevated intraocular pressures did not appear to develop obvious glaucomatous damage. It has therefore become clear that elevated intraocular pressure does not constitute the disease and that there must be additional risk factors, which by themselves, or in combination with other risk factors including pressure, could be responsible for damage. In order to cling to our traditions we refer to these other factors as an increased susceptibility of the optic nerve (presumably to pressure) without knowing the true nature of the mechanism by which these factors influence the disease. Some of these risk factors, in addition to intraocular pressure, have been known or suspected for a long time. Ethnic origin, family history, age and myopia were among them. In the current Acta, Grodum and colleagues confirm, in the large population whom they screened for the disease, that age, intraocular pressure and myopia are such risk factors. They also show that the greater the myopia the greater the prevalence of glaucoma but that at high intraocular pressures the association with myopia is no longer evident. This apparent lack of association at high intraocular pressures does not necessarily indicate that the association ceases at these pressure levels but rather that the great prevalence of pressure induced damage at these high pressures masks the myopic contribution. There are almost certainly many other risk factors including the many vascular risk factors such as low perfusion pressures, vascular hypertension, shock-like states, intermittent dysrhythmias, vasospasm, vascular occlusive disease and therefore all the many risk factors for vascular diseases such as diabetes, obesity, smoking, sedentary life styles and elevations in homocysteine which may play a part. Some of these may interrelate with one another and others may be quite intermittent and difficult to identify between events. Some of these may have a low prevalence compared to the more major ones such as intraocular pressure and there is a danger that they might not be confirmed even by the large population studies unless they are specifically looked for. It is of course a truism that we can usually only see what we look for. The collaborative Normal Tension Glaucoma Study points out that risk factors which account for the prevalence of the disease, discussed above, may not be the same as those which determine the subsequent course of the disease. Glaucoma remains a complicated, multifactorial disease which requires both the meticulous studies of selected populations to identify the many possible risk factors, some currently probably not even suspected, followed by the large population based studies and costly clinical trials to confirm their significance. Until all the genes underlying the many risk factors are found and can be identified, and I suspect even long after that, the attempts to influence and understand the disease must go on in order to better the quality of life of our patients. Correspondence: Stephen Drance, MD, OCVancouver, BCCanadae-mail: [email protected]