must confess at the outset that the title of this section — What in Blazes is Glaucoma!? — is misleading since it implies that this section will explain to the reader what primary open angle glaucoma (POAG) is. Unfortunately, what follows will not do that; though it will help you to understand what glaucoma isn’t. This is not to say that we don’t know anything about glaucoma — we do. But we cannot tell you what it is. Flatly — we don’t know. Nor do we know what causes glaucoma, if ‘cause’ (etiology) is the correct term here. Nor do we fully understand the mechanism that produces the loss of vision, or for that matter whether increased intraocular pressure (IOP) is in some way implicated in neuronal damage or merely a symptom/sign of the problem. Because not all patients showing what are commonly termed glaucomatous visual field changes have abnormally elevated IOP.

Secondary glaucoma — that due to ocular injury, ocular inflammation, or system/local medication — is another matter entirely and will be dealt with in another part of this section. Herein, we will only deal with POAG.

Incidence and Distribution of
Primary Open Angle Glaucoma

Increased intraocular pressure (IOP) is common in glaucoma and is believed to contribute to the damage to the optic nerve.  The incidence of ocular hypertension (OHT — usually defined as an IOP >22 mm Hg), is much higher than the incidence of glaucoma.  Ocular hypertension is present in 7-13% of the general population, and its prevalence increases with age.[5]  However, while elevated IOP may be the most important risk factor for the development or progression of glaucomatous damage, it is no longer generally considered a diagnostic criterion for glaucoma and does not, in itself, indicate the presence of glaucoma.  Moreover, other risk factors, such as insufficient ocular blood supply, can lead to glaucomatous damage even if IOP is within normal limits.[3]

The risk of progressing to glaucoma, however, varies directly with the magnitude and duration of IOP elevation.  The proportion of persons developing visual deficits within 5 years is less than 1% for those with normal IOP (< 21 mm Hg), 3 to 10% for those with IOP 21 mm Hg, 6-16% for those with IOP > 25 mm Hg, and 33% for those with IOP > 30 mm Hg.[5] Untreated individuals with moderate ocular hypertension (mean IOP 24-26 mm Hg) developed new visual deficits (based on sensitive measures) at a rate of 3-4% per year in recent trials.[6-8] Among patients with untreated ocular hypertension followed for 17-20 years in older series, over 30% developed clinical glaucoma.[9, 10]

Of the various forms of glaucoma (e.g., congenital, open-angle, closed-angle, secondary [see also Types of Glaucoma]), primary open-angle glaucoma (POAG) is the most common in the U.S. (80-90% of cases)[11] and is estimated to be responsible for impaired vision in 1.6 million Americans and blindness in 150,000.[4, 11] POAG generally refers to patients with elevated IOP and visual damage, while the term ‘ocular hypertension’ refers to persons with elevated IOP but no detectable disc or visual field damage.  POAG is usually asymptomatic until irreversible visual field loss has occurred.

The prevalence of glaucoma is 4-6 fold higher in blacks than whites: among whites, glaucoma is present in 0.5 - 1.5% of persons under age 65 and 2 - 4% of those over 75;[12, 13] among blacks, 1.2% of 40 - 49-year-olds and 11.3% of those over 80 have glaucoma.[11] The prevalence of POAG increases with age generally. Leske, in a review of data from various sources, estimated prevalence was less than 1 per 100 for persons younger than age 65, approximately 1 per 100 for persons age 70, and about 3 per 100 for persons older than age 75.[1,2] Prevalence of glaucoma is increased in patients with diabetes mellitus, myopia, and a family history of glaucoma.[4]

What glaucoma isn’t

Firstly glaucoma isn’t cataract. That may seem perfectly obvious to anyone with a smattering of medical knowledge but it wasn’t at all obvious from ancient times up to about the 1700’s. In point of fact, the exact condition of cataract was not properly described until 1708 by Boerhaave and glaucoma itself correctly categorized until around 1855 (by von Græfe). But considering that the lens itself was not really correctly placed within the eye until around that time (1700's), the error is understandable. Not to put too fine a point on it but the eye is a difficult organ to study without proper magnification and preparation. After death, if not refrigerated immediately, it will deteriorate exceedingly rapidly destroying the delicate tissue within and totally obscuring the relationships of the various parts.

What's in a name?

Hence the terms glaucome and cataract were often used to describe the same condition. It is assumed that glaucome was used because of the appearance of the dense cataract through the pupil gave the eye a bluish green/grayish blue look. The word glaucoma itself is from the Greek describing the colors just mentioned while the word cataract is also from the Greek and refers to ‘water falling down’. Since the onset of cataract was often described as just that — ‘water falling down’ — the use is apt. The Romans used the term suffusio, but in time most physicians employed either cataract or glaucome/glaucoma to describe the same condition. Which ‘ignorance’ continued until 1855.

Some writers today take umbrage with the ignorance displayed by ancient and near-ancient physicians and some natter on about how very little modern physicians seem to have learned since. I can only say in answer, that those writers who take that tone are themselves woefully ignorant of the facts and should heed the advice of Abraham Lincoln who said: “It is better to remain silent and merely be thought a fool, than to speak and remove all doubt.”

Having said that, I cannot deny that much of the mystery of the human organism escapes even those of us who have had the privilege and the responsibility of its care — even today in our age of ‘enlightenment’ and technical marvels.

Glaucoma is one of these mysteries. Because, frankly, we don’t know what it is. We know what it does — it causes the afflicted to lose vision. But why or how it does that has eluded our grasp to this point in time.

What glaucoma does

Glaucoma is a disorder defined by slowly progressive loss of vision in association with characteristic signs of damage to the optic nerve. Selective death of retinal ganglion cells leads to the gradual enlargement of the optic cup (the small depression in the head of the optic nerve) and loss of vision (beginning with peripheral vision) that are typical of glaucoma. Increased intraocular pressure (IOP) is common in glaucoma and is believed to contribute to the damage to the optic nerve, but it is no longer considered a diagnostic criterion for glaucoma.

'tis a puzzlement ...

Glaucoma presents a unique challenge to the ophthalmic practitioner. This challenge is manifested in several ways — not the least of which stems from misunderstanding of this condition by patient and physician alike.

It is important to note that many specialists hold that glaucoma is not a disease. A disease has a specific etiology, mode of onset, pathophysiology, and course, or natural history. Intervention can potentially occur at a number of different stages, from prevention, to intervention to limit progression, to cure, and to reversal of damage caused by the disease. Glaucoma does not fit this paradigm since it has no specific etiology, cannot be prevented or at this stage — ‘cured’.

I can’t buy argument entirely. Cardiovascular disease (CVD) is still called a disease even though it has complex causes, many of them not clearly understood or even known. The same is true of Chronic Obstructive Pulmonary Disease (COPD) and of course — HIV cannot (at this juncture) be cured. I think it the height of hubris to disdain applying the appellation: disease, to a human condition of which we know very little. Hence I will continue to call it a disease — out of convenience if not out of ignorance — much as did my earlier brethren when they ‘confused’ glaucoma and cataract.

A mechanistic theory of glaucomatous damage

One of the earlier concepts of glaucoma was the so-called mechanical theory. That is — the damage of glaucoma is due to the direct mechanical effect of increased IOP upon the optic nerve. This concept is illustrated by the following two figures:

The cause of elevated pressure was deemed to be some difficulty in the outflow mechanism of the aqueous, analogous to the picture of a kitchen faucet always on and a drain that is clogged. A vivid picture and easily understood but the picture is not entirely correct. In point of fact — it may not be apt at all. It is altogether too simplistic and led many then (and still today) to believe that the essence of glaucoma is elevated IOP. In fact, for many, the definition of glaucoma is elevated IOP. Which concept underscores something H.L Mencken said many years ago:

“For every complex problem, there is always someone who has a simple solution — which is invariably wrong.”

Over the last 150 years, what could be called the central dogma has held sway in which primary open angle glaucoma is characterized as a disease caused by elevated IOP. In this dogma it is this elevated IOP that damages and destroys the axons of the optic nerve, leading to progressive blindness. This dogma has played a major role in retarding thinking and inhibiting new approaches to understanding and therapy and should be discarded.

It seems logical enough: plugged drain; fluid can’t get out; pressure goes up; pressure damages optic nerve by pressing it against the edge of the stiff outer shell of the eye (the sclera); nerve cells die off; blindness ensues. The problem with this concept is that it doesn’t explain ‘low tension’ glaucoma (more on this later). The trouble is that in medicine at least, logic is not always your friend and can lead you to make bad choices. Some wag once said:

Logic is a systematic method of coming to the wrong conclusion with confidence.

What glaucoma appears to be

Glaucoma is an end stage condition, analogous to congestive heart or liver failure. It is an optic neuropathy characterized by a specific pattern of optic nerve head and visual field damage, which represents a final common pathway resulting from a number of different conditions which can affect the eye. Elevated IOP may the most important risk factor for the development or progression of glaucomatous damage, but it is still only a risk factor and not the condition itself.

Other risk factors can lead to glaucomatous damage even in the face of a normal IOP. The hot topic at the present time is that of blood supply to the eye and its regulation. An insufficient blood supply is believed to be a major risk factor for glaucomatous damage but even this is not a given.

The way the term ‘glaucoma’ is used also creates confusion in the minds of physicians and patients alike. For instance, we use the term primary open-angle glaucoma (POAG) to refer to a patient with elevated IOP and visual damage, while reserving the term ‘ocular hypertension’ (OHT) for persons with elevated IOP but no detectable disc or visual field damage. We can also use the term ‘glaucoma suspect’, which includes ocular hypertensives and persons with large cup/disc ratios who may have normal-tension glaucoma but still have normal visual fields.

However, not all patients with elevated IOP develop glaucoma-related eye damage. It is also possible to have been diagnosed with glaucoma and have a ‘normal’ IOP. This is not a rare occurrence because it may be identified in approximately one-third of all individuals diagnosed with glaucoma. In fact, as many as 50% of the patients with ‘high tension glaucoma’, or glaucoma associated with elevated intraocular pressure, will have presented without increased IOP at the time of initial diagnosis.

Low-tension glaucoma or, as ophthalmologists now call it, normal-tension glaucoma, has been classically defined as open-angle glaucoma developing in a person in whom the IOP never goes above 21 mm Hg. It is now realized that the number of persons with low-tension glaucoma has been grossly underestimated. It is this disease (or really, group of diseases waiting to be elucidated) in which risk factors other than IOP account for damage.

In summary, the terms high-tension and low-tension glaucoma are misleading. Glaucomatous damage can be thought of as consisting of two basic forms — mechanical and non-mechanical (vascular and other). The higher the intraocular pressure, the greater the component of mechanical damage. The lower the intraocular pressure at which damage occurs or progresses, the greater the non-mechanical component. In the coming decades, these factors will hopefully become better understood. In the meantime, there is no magic number cutting off one form from another.

1. Leske, M.C., The epidemiology of open-angle glaucoma: a review. Am J Epidemiol, 118(2): p. 166-91; 1983. 
2. Sommer, A., et al., Racial differences in the cause-specific prevalence of blindness in east Baltimore [see comments]. N Engl J Med, 325(20): p.1412-7; 1991. 
3. Grant, W.M. and J.F. Burke, Jr., Why do some people go blind from glaucoma? Ophthalmology, 89(9): p.991-8; 1982. 
4. Quigley, H.A., Open-angle glaucoma [see comments]. N Engl J Med, 328(15): p.1097-106; 1993. 
5. Office of Technology Assessment, Congress of the United States, Screening for open-angle glaucoma in the elderly, 1988. 
6. Epstein, D.L., et al., A long-term clinical trial of timolol therapy versus no treatment in the management of glaucoma suspects [see comments]. Ophthalmology, 96(10): p.1460-7; 1989. 
7. Kass, M.A., Timolol treatment prevents or delays glaucomatous visual field loss in individuals with ocular hypertension: a five-year, randomized, double- masked, clinical trial. Trans Am Ophthalmol Soc, 87: p.598-618; 1989. 
8. Schulzer, M., S.M. Drance, and G.R. Douglas, A comparison of treated and untreated glaucoma suspects [see comments]. Ophthalmology, 98(3): p.301-7; 1991. 
9. Lundberg, L., K. Wettrell, and E. Linner, Ocular hypertension. A prospective twenty-year follow-up study. Acta Ophthalmol (Copenh), 65(6): p.705-8; 1987. 
10. Hovding, G. and H. Aasved, Prognostic factors in the development of manifest open angle glaucoma. A long-term follow-up study of hypertensive and normotensive eyes. Acta Ophthalmol (Copenh), 64(6): p.601-8; 1986. 
11. Tielsch, J.M., et al., A population-based evaluation of glaucoma screening: the Baltimore Eye Survey. Am J Epidemiol, 134(10): p.1102-10; 1991. 
12. Klein, B.E., et al., Prevalence of glaucoma. The Beaver Dam Eye Study. Ophthalmology, 99(10): p.1499-504; 1992. 
13. Podgor, M.J., M.C. Leske, and F. Ederer, Incidence estimates for lens changes, macular changes, open-angle glaucoma and diabetic retinopathy. Am J Epidemiol, 118(2): p.206-12; 1983.