It is commonly accepted that increased IOP either directly or indirectly causes optic nerve cupping.The evidence for this can be summarized as follows:

1.Most patients with POAG have increased IOP, which generally predates by years the development of cupping and visual field loss.

2.Elevated IOP is a major risk factor for the development of POAG in glaucoma suspects.

3.Elevated IOP is the only known common element to a wide variety of secondary glaucomas.

4.In all animal models of glaucoma, elevated IOP precedes optic nerve damage and visual loss.248

5.Even in normal-pressure glaucoma, in which IOPs do not

exceed the statistically ‘normal’ range, the degree of cupping is related to the level of IOP.46,47,259

6.Mechanical changes in the topography of the optic nerve and in the lamina cribrosa are seen early in experimental glaucoma

with elevated IOP in monkeys and are not seen in other forms of optic nerve damage.260,261

Although IOP is certainly one risk factor, most investigators point to other factors that also affect glaucomatous cupping.248,262,263 They

point to the observations that (1) a significant per cent of patients develop optic nerve cupping and visual field loss at normal levels of IOP; (2) some patients maintain normal optic nerves and visual function despite elevated IOP, and (3) the level of IOP does not correlate well with the progression of established POAG. However, these observations do not refute a linkage between IOP and optic nerve damage; rather they imply variable resistance of the optic nerve to pressure-induced damage.That is, some nerves are more sensitive to pressure than are others.

More than 130 years ago, Mueller264 proposed that elevated IOP led to direct compression and death of axons, whereas von Jaeger265 stated that ischemia was the cause of progressive glaucomatous cupping.Yamazaki and Drance reported abnormal retrobulbar circulation by color Doppler imaging in eyes with progressively worsening normal-tension glaucoma compared to those with stable glaucoma.266 Other studies have supported some abnormality in ocular circulation in patients with primary open-angle glaucoma and normal-tension glaucoma compared to secondary glaucomas. Although the debate over the role of mechanical versus circulatory factors continues to the present, most would agree that no one theory explains all of the observed phenomena and that each plays some role in at least some patients. The optic nerve damage from glaucoma is multifactorial and, at different times and in different eyes, may involve genetic susceptibility factors, mechanical forces, ischemia, loss of neurotrophic factors, and neurotoxicity. It also may be that actual ganglion cell death depends on the inability of astroglial cells to prevent or repair injury to the cell or its extracellular matrix regardless of the source of the initial trauma.267

Clinical features

Symptoms

Primary open-angle glaucoma is usually described as an insidious, slowly progressive, bilateral condition. The adjective ‘insidious’ is appropriate because most patients are asymptomatic until the late stages of the disease. The few exceptions to this rule include

the occasional patient who notices a scotoma when performing a monocular visual task and the young patient who has sudden, severe elevations in IOP that cause corneal edema, halo vision, and discomfort. If patients are not diagnosed until they develop extensive glaucomatous damage, they become symptomatic from loss of fixation in one or both eyes or from loss of peripheral vision, which interferes with activities such as driving. The early stages of POAG usually develop slowly over months to years. As glaucoma advances, however, the pace accelerates. In a recent study from Melbourne, Australia, the prevalence of glaucoma increased from 0.1% in the 40to 49-year-old age group to 9.7% in the 80to 89-year-old age group; 50% of those found to have glaucoma were previously undiagnosed.268 Untreated open-angle glaucoma can and does lead to significant vision loss and blindness. The 10-year incidence, in an untreated Afro-Caribbean population, of unilateral blindness was 16% and of bilateral blindness was 11%.269 In another study of a treated Afro-Caribbean population, open-angle glaucoma was responsible for approximately one-fifth of the prevalent blindness.270

Quality of life is generally not affected early in glaucoma, but as the disease progresses or as treatment becomes more aggressive, quality of life may be impacted.271 In fact, patients with glaucoma also tend to have other medical conditions which directly or indirectly through the required treatment may affect quality of life and even the ability to apply glaucoma medications;272 this situation should be kept in mind when prescribing additional glaucoma medications.

Findings

Primary open-angle glaucoma is generally a bilateral disease of adult onset; however, a juvenile-onset type is seen that is indistinguishable from the adult-onset variety except for a stronger genetic factor and a more aggressive course. At least one eye should have either characteristic damage to the optic nerve or retinal nerve fiber layer or characteristic visual field changes, open angles with no obvious abnormality, and absence of any other condition known to cause glaucoma. Primary open-angle glaucoma often is asymmetric on presentation, however, so that one eye may have moderate or advanced damage, whereas the fellow eye may have minimal or no detectable damage. In this situation, the clinician must not be fooled and mistakenly conclude that the patient has a unilateral secondary glaucoma.

Most patients of European or African ancestry with POAG have elevated IOPs in the range of 22–40 mmHg. A few patients may have much higher pressures, which occasionally reach levels of 60 or even 80 mmHg. Some patients will never have IOPs over 18 mmHg.These patients are said to have normal-tension glaucoma (low-tension glaucoma). It is important to remember that IOP fluctuates throughout the day and that patients with glaucoma undergo wider fluctuations than do normal individuals. Although most people reach their highest IOPs in the morning, others may reach their peaks in the afternoon or evening or follow no consistent pattern. Diurnal IOP measurements may be useful in some situations, including diagnosing POAG, explaining progressive damage despite apparent good pressure control, evaluating the efficacy of therapy, and distinguishing normal-tension glaucoma from POAG.

Most individuals have fairly symmetric IOP readings although asymmetric POAG does occur reasonably frequently. When pressure is higher in one eye, that eye usually has a larger cup and a more damaged visual field than the fellow eye. Marked differences in IOPs between the two eyes should raise suspicion of exfoliative syndrome or another form of secondary glaucoma.