Intraocular Pressure and Glaucoma

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EDITORIAL Intraocular

Pressure and Glaucoma Alfred Sommer

Ever since von Graefe noticed that patients with a characteristic form of optic nerve damage had increased intraocular pressure, the two conditions have been inexorably linked in what is generally assumed to be a cause and effect relationship. We have even invented terminology and sought alternative explanations for seeming inconsistencies: "low tension" glaucoma for glaucomatous optic nerve damage in the absence of increased intraocular pressure and "ocular hypertension" for increased intraocular pressure in the absence of glaucomatous optic nerve damage. Whole volumes could be filled with arguments raised for and against the existence of these entities, their proper nomenclature, and perceived differences in origin and expression. Survey data that suggest a third or more "glaucoma" patients have "normal" intraocular pressure'< are largely ignored. A review of original clinical observations, from an epidemiologic perspective, suggests our present confusion may stem from precon-

ceived notions that obscure basic unifying principles. First, it is apparent that glaucomatous optic nerve damage is most common in eyes with high intraocular pressure. The validity of this conclusion is obvious among individuals in whom the pressure in one eye is considerably higher than in the other (from blunt trauma, uveitis, congenital abnormalities, and the like). If one of the two eyes has glaucomatous optic nerve damage, almost invariably it is the eye with the higher intraocular pressure. It is also apparent, but not nearly so obvious, that patients with primary open-angle glaucoma (by definition with glaucomatous optic nerve damage) rarely have pressures that are truly "low" (that is, several standard deviations below the population mean of 16 to 17 mm Hg). Hence, intraocular pressure is associated with glaucomatous optic nerve damage. In epidemiologic parlance, high intraocular pressure is a risk factor for glaucomatous optic nerve damage, 186

Editorial

Vol. 107, No.2

TABLE 1 RISK OF SUBSEQUENT GLAUCOMATOUS FIELD LOSS BASELINE INTRAOCULAR PRESSURE (MM HG)

PERCENT DEVELOPING FIELDDEFECT'

RELATIVE RISK

187

TABLE 2 RISK OF SUBSEQUENT GLAUCOMATOUS FIELD LOSS BASELINE INTRAOCULAR PRESSURE (MM HG)

PERCENT DEVELOPING FIELDDEFECT'

RELATIVE RISK

< 16

0.8

1.0

21-25

2.7

1.0

16-19

1.4

1.7

26-30

12.0

4.4

20-23

3.1

4.0

>

41.2

15.3

24

8.4

10.5

~

30

'Mean follow-up of 43 months. Modified from David, Livingston,

'Over a one- to 13-year follow-up period. and assoctates."

Modified from Armaly

just as smoking is for lung cancer or high blood pressure is for stroke. As with cancer and stroke, there seems to be a dose-response relationship between the risk factor (intraocular pressure) and the disease (glaucomatous optic nerve damage). Though available data are less than ideal, they are consistent: the higher the baseline intraocular pressure, the greater the risk of subsequently developing glaucomatous optic nerve damage. The Collaborative Glaucoma Study! permits estimation of subsequent risk of glaucomatous optic nerve damage for intraocular pressure below 16 to above 25 mm Hg. While the numbers are small and the interval of follow-up variable, the trend is obvious (Table 1). Subjects with intraocular pressure ranging between 16 and 19 mm Hg were at almost twice the risk of those whose pressure was lower; when pressure exceeded 23 mm Hg, the risk increased tenfold. Reinterpretation of data from David, Livingston, and Luntz' indicates this dose-response relationship persists at higher levels' (Table 2). These and other studies'" permit rough estimation of the relative risk of glaucomatous optic nerve damage among subjects whose original (baseline) pressure was above or below a single cutoff point. Again, the data are less than ideal, but their implications are consistent (Table 3). These interpretations provide two important insights. Firstly, the direct relationship between intraocular pressure and risk of subsequent optic nerve damage strengthens the importance of intraocular pressure as a risk factor for glaucomatous optic nerve damage; as with cigarette smoking for cancer or systemic hypertension for stroke, it also suggests the relationship is causal. Secondly, it explains why a large proportion of all glaucomatous optic nerve damage occurs among individuals with

and LunlZ" by Sommer. 5

"lower" intraocular pressure; it is simply because they comprise the bulk of the population. The risk of glaucomatous optic nerve damage at pressures below 22 mm Hg may be only one sixth that at higher pressures, but they apply to almost 20 times as many people (Table 3). These extrapolations would suggest that most glaucomatous subjects have intraocular pressure lower than 22 mm Hg. There are many potential explanations for why, in reality, more might be related to "increased" intraocular pressure, including intermittent increases in intraocular pressure not detected at baseline measurement and (an unrecorded) sustained rise in intraocular pressure between baseline and subsequent development of glaucomatous optic nerve damage. There are also many reasons why patients with "lower" intraocular

TABLE 3 HYPOTHETICAL PROPORTION OF GLAUCOMA PATIENTS WITH PRESSURES ABOVE AND BELOW 21 MM HG INITIALINTRAOCULAR PRESSURE

> 21 MM HG

,,;21MMHG

Relative risk of subsequent field defect (A) Proportion of population (B)

1

6

.92

.08

Relative risk of glaucoma (A x B) Ratio of glaucoma cases

.92

2

.48 to

1

Adjusted ratio of glaucoma cases'

to

'Assuming half of the glaucoma patients with an initial intraocular pressure of ,,; 21 mm Hg are subsequently found, on careful follow-up, to have (or develop) higher intraocular pressure.

188

February, 1989

AMERICAN JOURNAL OF OPHTHALMOLOGY

pressures might appear to represent so small a component of clinical practice. Most importantly these include the biased referral and examination of patients detected by health fairs, optometrists, and even ophthalmologists because intraocular pressure was noted to be "increased." It is also probable that the rate at which axonal death occurs is directly related to intraocular pressure, and the higher the intraocular pressure, the more axons destroyed by any age. As a result, a greater proportion of subjects with "high" intraocular pressure will have clinically detectable glaucomatous optic nerve damage, the glaucomatous optic nerve damage will be more severe, and a larger proportion will ultimately become blind. The foregoing indicates that there is no fixed intraocular pressure boundary below which one never develops glaucomatous optic nerve damage and above which one always does. The only intraocular pressure boundaries fixed are the extremes: the minimal pressure needed to prevent atrophy and the very high intraocular pressure resulting in venous and arterial occlusion. Between those extremes exists a broad range of pressure that is compatible (for varying durations in different individuals) with normal ocular physiology. How then did we come to define 22 mm Hg, 25 mm Hg, 28 mm Hg, and the like, as "abnormal"? Recall that population surveys locate the "average" pressure at 16 to 17 mm Hg. If one wished to identify individuals at the greatest risk of glaucomatous optic nerve damage (present or future), it was most efficient to concentrate on the 5% or 1% of individuals with the highest pressures, which happen to coincide with pressures greater than 21 and 24 mm Hg, respectively. They were not chosen because they defined abnormal; they were chosen because they made the search for glaucomatous optic nerve damage more efficient. If there is no such thing as an abnormal pressure, only pressures at which the risk of glaucomatous optic nerve damage is higher or lower than average, then there is no basis for the term low-tension glaucoma and no reason to search for a discrete mechanism to explain it. Nor does it make sense to wake patients at hourly intervals in search of a pressure exceeding 21 mm Hg (although establishing diurnal pressure curves may be useful for management), nor any value in choosing one specific intraocular pressure as a criterion for successful intervention or adequacy of control.

Intraocular pressure is not the only risk factor for glaucomatous optic nerve damage; the risk of primary open-angle glaucoma increases with age, is higher in some racial groups than in others, and may be associated with refractive status. While the close dose-response relationship between intraocular pressure and glaucomatous optic nerve damage supports other data suggesting a causal relationship, it does not explain why some people with high pressure never develop glaucomatous optic nerve damage any more than it explains why some people with low pressures do. Obviously other factors, genetic, medical, or environmental, playa modulating role. These urgently require f}.uther elucidation. From the Dana Center for Preventive Ophthalmology of the Wilmer Institute and School of Public Health, Johns Hopkins University, Baltimore. Reprint requests to Alfred Sommer, M.D., Wilmer 120, Johns Hopkins Hospital, 600 N. Wolfe St., Baltimore, MD 21205.

References 1. Hollow, F. c., and Graham, P. A.: Intraocular pressure, glaucoma and glaucoma suspects in a defined population. Br. J. Ophthalmol. 50:570, 1966. 2. Kahn, H. A., and Milton, R. c.: Alternative definitions of open-angle glaucoma. Effect on prevalence and association in the Framingham Eye Study. Arch. Ophthalmol. 98:2172, 1980. 3. Armaly, M. F., Krueger, D. E., Maunder, L., Becker, B., Hetherington, J., [r., Kolker, A. E., Levene, R. Z., Maumenee, A. E., Pollack, I. P., and Shaffer, R. N.: Biostatistical analysis of the collaborative glaucoma study. I. Summary report of the risk factors for glaucomatous visual-field defects. Arch. Ophthalmol. 98:2163, 1980. 4. David, R., Livingston, D. G., and Luntz, M. H.: Ocular hypertension. A long-term following of treated and untreated patients. Br. J. Ophthalmol. 61:668, 1977. 5. Sommer, A.: Epidemiology and Statistics for the Ophthalmologist. New York, Oxford University Press, 1980, pp. 8-11. 6. Perkins, E. S.: The Bedford glaucoma survey. I. Long-term follow-up of borderline cases. Br. J. OphthaI mol. 57:179, 1973. 7. Perkins, E. S.: The Bedford glaucoma survey. II. Rescreening of normal population. Br. J. Ophthalmol. 57:186, 1973. 8. Bengtsson, B.: Aspects of the epidemiology of chronic glaucoma. Acta Ophthalmol. 146(suppl.):4, 1981.