Investigative Ophthalmology & Visual Science, Vol. 33, No.

7, June 1992
Copyright Association for Research in Vision and Ophthalmology

Intraocular Pressure in an American Community

The Deover Dom Eye Study
Barbara E. K. Klein, Ronald Klein, and Karhryn L. P. Linron
The Beaver Dam Eye Study is a population-based study of age-related eye diseases in persons 43-86 yr of age. Applanation tonometry was done on all study subjects. Mean intraocular pressure (IOP) increased significantly with age. Mean IOP differed little between the sexes and was not significantly different after age adjustment (in right eyes of 2721 women, it was 15.5 mm Hg, and in right eyes of 2135 men, it was 15.3 mm Hg). There was an association of IOP with systolic and diastolic blood pressures, body mass index, hematocrit, serum glucose, glycohemoglobin, cholesterol level, pulse, nuclear sclerosis, season, and time of day of measurement. These data confirm that, in a general population, IOP is associated with important systemic and ocular characteristics. Those characteristics should be considered in further research on determinants of IOP. Invest Ophthalmol Vis Sci 33:2224-2228, 1992

Intraocular pressure (IOP) is an inherent physiologic characteristic of importance in maintaining structure and function of the eye. Correlates of this measurement include other important physiologic parameters that may need to be considered in investigating determinants of IOP. Because IOP is the ocular parameter that is associated most commonly with glaucoma,1"4 it may be important to evaluate these physiologic correlates of IOP; they may confound relationships between IOP and glaucoma. We briefly describe the distribution of IOP and investigate its correlates in the population participating in the Beaver Dam Eye Study. Materials and Methods A private census of Beaver Dam was done, and the procedures have been published elsewhere.5 In brief, 6612 households were identified, of which 3715 had at least one occupant 43-84 yr of age. Thereafter, each individual in the target age range was contacted for a study appointment. Three subjects were examined whose age was 86 yr at the time of testing. Their data are included in this report. Of the total of 5925
From the Department of Ophthalmology, University of Wisconsin Madison, Madison, Wisconsin. Supported by National Institutes of Health (Bethesda, Maryland) grant 5U10 EY 10 6594 (RK and BEKK). Presented in part at the Annual Meeting of the Association for Research in Vision and Ophthalmology, Sarasota, Florida, April 28 to May 3, 1991. Submitted for publication: October 2, 1991; accepted December 21, 1991. Reprint requests: Barbara E. K. Klein, MD, MPH, Department of Ophthalmology, 600 Highland Avenue, Madison, WI 53792.

persons in the target age range, 4926 were evaluated (83.14%). Relevant parts of the study evaluation included the date of birth and a history of ocular trauma, surgery, medications, glaucoma, and diabetes. Most of the participants were white (99.4%). Blood pressure was measured according to the Hypertension Detection and Follow-up Program protocol.6 Height and weight were measured with a Health-o-Meter scale (Continental Scale Corp., Bridgewater, IL). The IOP was measured with a Goldmann applanation tonometer. A drop of Fluress (Armour, Kankakee, IL) was instilled in each eye. The tonometer was set at 10. The measurement was taken as the examiner viewed the mires through the prism. When the end point was reached, the examiner moved the slit lamp away from the eye and recorded the reading. The procedure was repeated for the other eye. The time of measurement was recorded. Iris pigmentation was evaluated and compared with three standard color 35-mm slides. The protocol specifies categories of pigmentation from a lightly pigmented iris (blue) through a heavily pigmented one (brown).7 After assessing anterior chamber depth, the pupils were dilated with one drop each of tropicamide 1% and phenylephrine 2.5%. When the pupils were dilated, a clinical assessment of the presence and severity of cataract was made, and photographs were taken with the illuminating beam at 45 to the viewing system.7 These photographs subsequently were graded by comparison with standard photographs according to the protocol.7 A blood specimen was obtained, and glucose and glycosylated hemoglobin were measured. The subjects were classified as having no diabetes if there was a negative history of

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diabetes, blood glucose was less than 200 mg/dl, and glycosylated hemoglobin was within two standard deviations of the mean for the particular age-sex subgroup. Informed consent was obtained for each subject. We used the Statistical Analysis System (SAS, Cary, NC) to analyze the data.8 Because the distribution of IOP does not differ from normality, parametric tests were chosen where applicable. Univariate associations with IOP were detected by Student's t-test, and analysis of variance techniques were used for categoric factors, with Pearson correlation coefficients for continuous factors. Confidence intervals for the correlation coefficients were calculated using the method developed by Fisher.9 Results There was little difference between the mean IOP of right and left eyes (0.14 2.11 m m Hg) or their association s with other variables. Therefore, data for right eyes only are presented. The distribution of IOP in the right eye by sex and age is given in Table 1. There was a small but significant change in mean IOP with increasing age (P < 0.05). We found IOP greater than 21 mm Hg to be more frequent in older age groups (P < 0.01, by test for trends). Women had higher mean IOP than did men, but the difference was not great and was only borderline significant (P = 0.06) when adjusted for age (by multiple-linear regression). During the interview, the participants were asked whether they had glaucoma or were receiving medication for this disease. The mean IOP was significantly higher (20.1 mm Hg) in those with a positive compared with a negative history (15.3 mm Hg).

We investigated the relationship between nuclear sclerosis and IOP (Table 2). There was a significant trend of increasing IOP with increasing severity of nuclear sclerosis. In those eyes that were either aphakic or had intraocular lens implants, the mean IOP was between the mean for those eyes in thefirsttwo categories of severity of nuclear sclerosis (Table 2). A history of other eye surgery or trauma was not associated with increased mean IOP. The participants were categorized as to definite, possible, or no history of diabetes. There was a significant difference between the IOP means among these groups (Table 2). There also was a seasonal effect on IOP; measurements during the summer months (July, August, and September) were significantly lower (15.2 mm Hg) than those during the winter months (January, March, and April; 15.7 mm Hg). There was no significant effect of iris color, refractive error, cigarette smoking, or alcohol consumption on IOP. A history of cardiovascular disease was not related to IOP. Table 3 describes the multiple linear-regression analysis for the variables significantly associated with IOP. Data for persons who reported receiving medicine for glaucoma or who had had surgery for glaucoma were excluded from this analysis. Systolic blood pressure, time of day of examination, body mass index, glaucoma history, refractive error, cholesterol level, hematocrit, female sex, month of examination, pulse rate, severity of nuclear sclerosis, diastolic blood pressure, and glycosylated hemoglobin were all selected in the stepwise analysis. Age did not enter as a significant factor when considered with the other variables.

Table 1. Percent distribution of intraocular pressure in right eyes by age and sex
IOP (mm Hg) Age (years) 43-49 50-54 55-59 60-64 65-69 70-74 75-79 80-86 TOTAL Sex F M F M F M F M F M F M F M F M F M N 448 385 340 327 347 287 348 325 391 299 340 233 276 168 231 111 2721 2135 0-12 21.9 22.9 21.8 24.2 23.6 16.4 17.8 15.1 12.5 20.1 15.3 15.9 16.3 19.6 18.2 22.5 18.5 19.6 13-15 35.5 37.4 33.2 39.1 29.4 40.8 28.5 32.9 29.4 32.4 32.7 36.1 31.2 30.4 36.8 31.5 32.0 35.4 16-18 32.6 31.2 32.4 24.2 34.9 27.2 38.2 36.0 39.4 30.8 32.9 31.8 31.5 32.7 29.4 33.3 34.2 30.5 19-21 6.9 6.2
9.7 9.5 7.5

22-24 2.7 1.3 2.7 2.1 4.3 2.4 3.2 4.0 4.9 4.7 3.5 5.6 6.2 6.0 3.5 2.7 3.8 3.4

25+ 0.5 1.0 0.3 0.9 0.3

1.1

Mean 15.0 14.7 15.1 14.9 15.1 15.4 15.6 15.8 16.0 15.4 15.9 15.6 15.9 15.8 15.5 14.9 15.5 15.3

SD 2.9 3.1 3.0 3.3 3.2 3.4 3.1 3.3 3.4 3.4 3.3 3.3 3.6 4.2 3.6 3.9 3.3 3.4

12.2 11.8 10.5 12.3 11.4 14.7 10.3 13.4 9.5 9.5 9.0 10.6 9.7

0.6 1.5 1.5 0.7 0.9 0.4 1.5 1.8 2.6 0.9 0.9 1.0

Twenty-seven "unreliable" and 43 "not obtainable" excluded from the analyses.

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Table 2. Mean intraocular pressure in right eyes by subject characteristics

Variable Nuclear sclerosis <Stdl <Std2 <Std3 <Std4 >Std4 GC Aphakic or IOL Glaucoma Hx No Yes Diabetes status No Hx, but no meds/symptom Yes Trends test. N 847 1790 1251 625 25 64 258 4743 113 4418 55 383 Mean (mm Hg) 15.0 15.2 15.7 15.9 16.0 16.5 15.1 15.3 20.1 15.3 16.1 16.0 SD 3.0 3.2 3.3 3.7 3.3 3.8
3.9
J

P value*

<0.0001

3.2 1 4.4 3.3 1 4.0

<0.0001

0.0003

3.6 J

Discussion The Beaver Dam Eye Study is a current large population-based study in American adults. It provides information about ocular and systemic parameters. Thus, it is possible to evaluate independent relationships of other physiologic features with IOP. In the future, such data will provide the opportunity to determine whether the other characteristics also influence or confound the relationship of IOP to disease (eg, glaucoma, altered retinal sensitivity, and decreased contrast sensitivity). There was a small positive relationship of age and IOP in the adults in Beaver Dam, Wisconsin. Positive correlations of age and IOP in America and Europe have been reported in most studies of this relationship.10"16 Both black and white Americans participated in the Health and Nutrition Examination Survey. A positive relationship was found in both groups. A negative association between these variables was seen in Japanese studies.1718 Whether this difference is related directly to specific ocular characteristics that

differ between ethnic groups o mental effect is not known. Eye color was defined according to a scale of increasing pigmentation in the Beaver Dam Eye Study. Standard 35-mm slide photographs were used by the examiner for comparison with the subject's iris. No relationship was seen between the degree of pigmentation and IOP. Although pigmentary glaucoma may be related to mechanical obstruction from pigment in the trabeculum, there is no evidence in these analyses to suggest that iris pigment plays a role in the height of the IOP level in the absence of characteristics of pigmentary glaucoma. Others reported an effect of iris color on IOP.19 The difference between our findings and theirs may reflect differences in ethnicity between the study populations or chance. The severity of nuclear sclerosis was based on gradings of slit-lamp photographs according to the study protocol.7'20 It was correlated with a higher mean IOP. The finding that mean IOP in aphakic eyes or those with lens implants was similar to that found in those with less severe nuclear sclerosis is compatible with

Table 3. Multiple regression analysis for intraocular pressure in right eyes

Variable

Coefficient 0.019 -0.001 3.883 8.791 -0.107 0.004 0.075 0.473 -0.053 0.019 0.172 0.018 0.074

P value 0.0001 0.0001 0.0001 0.0001 0.0001 0.0007 0.0001 0.0001 0.0002 0.0157 0.0016 0.0014 0.0162

Partial R2 0.039 0.024 0.007 0.006 0.006 0.005 0.004 0.005 0.003 0.002 0.002 0.002 0.001

Total R2

Systolic blood pressure (mm Hg) Time of day of exam (hr) Body mass index Glaucoma history (yes/no) Refractive error (diopters) Cholesterol (mg/dl) Hematocrit (mm) Sex (F) Month of exam (1-12) Pulse (beats/min) Nuclear sclerosis Diastolic blood pressure (mm Hg) Glycosylated hemoglobin (%)

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the hypothesis that there is a mechanical effect if a larger lens compromises aqueous outflow; this would be relieved by lens removal. Such an interpretation was suggested by some authors who observed amelioration of phacomorphic glaucoma after cataract surgery.21 An alternative explanation may be that cataract surgery influences the aqueous physiology and leads to lower IOP. A history of diabetes and medications to lower blood sugar was elicited during the study interview. Those who said they had diabetes or were suspected of having it had a significantly higher mean IOP than those without diabetes. The IOP among the study participants in the Wisconsin Epidemiologic Study of Diabetic Retinopathy were slightly higher than the mean of a nondiabetic comparison group evaluated at the same time.13 Other investigators have found an increased frequency of elevated IOP in people with diabetes.2223 Although a physiologic explanation is unclear, the health care implication is that persons with diabetes may be at increased risk of glaucoma, and ophthalmologists who follow such persons should be evaluating the patient for the possible development of glaucoma. Other systemic factors may influence IOP. Blood pressure has been found in several studies to be associated significantly with 1OP.121319-31 There may be a direct effect of systolic blood pressure on ultrafiltration and, through this mechanism, on IOP.1827 Body mass index, a measure of obesity, was correlated positively with IOP. Others found a similar relationship of obesity with IOP.25 Because corticosteroid secretion is increased in obese persons, this may explain this relationship.30 Mechanically, it has been suggested that orbital pressure from excess fat may cause a rise in episcleral venous pressure and decreased outflow facility.18*27 Diurnal IOP variation could not be assessed in our study; the participants only underwent one study examination. The time of the appointment depended only on scheduling concerns. Nevertheless, a pattern emerged of mean IOP tending to be higher earlier in the day. This finding was compatible with the report on the Bedford Glaucoma Survey;32 positive screenings for glaucoma were more likely to occur in the morning. This relationship has important implications for those who treat people with glaucoma and who tailor this treatment to the IOP level. The pulse rate was found to be correlated to IOP in earlier studies.12-27 An association of IOP with cholesterol level also was reported previously.12-30 In addition, we found hematocrit was significantly related to IOP; similarly, hemoglobin and erythrocyte count were associated with IOP in another study.25 The biologic importance of the association of these cardiovas-

cular risk variables with IOP is unclear, but they appear to be more universal than just an ethnic variation. Seasonal variations were reported by others,28'33 with slightly higher pressures found in the winter months. We found a similar pattern in Beaver Dam. From these earlier studies, we might question whether this represents a response of people from a northern European ethnic background or is related to the northern latitudes. However, one of these studies was conducted in Israel.34 The seasonality may be related to the light, temperature, and humidity changes. There are other annual rhythms affecting physiologic systems.33 The variation in IOP may be a result of these other physiologic changes or may be intrinsic to the regulatory systems in the eye. The relationships reported emphasize the physiologic interdependence of the eye with other organ systems. These relationships and the influence of external environmental conditions indicate that these too must be considered when studying IOP and its relationship to eye disease. Key words: intraocular pressure, epidemiology, Beaver Dam Eye Study, age-related eye diseases Acknowledgments
The authors thank the community of Beaver Dam, Wisconsin, and their health care providers for their enthusiastic cooperation throughout all phases of the study; Moneen Meuer and Sarah Baumgart for project coordination; Stacy Meuer for photograph management; Barbara Houser for data management; Ann Varda, Anik Ganguly, and Karl Jensen for programming and computing; Yvonne M. Bellay, Dayna S. Dalton, Norma Dorn, Kathy Peterson, and Kathryn Burke for examining all subjects; Michael Neider for photography training and equipment design; Carol Hoyer, Deborah Reiderer, Maria Swift, and A. Jeffrey Whitehead for photograph grading; Helen Soldner for reception; David L. DeMets for statistical advice; and Julie K. Olson, Kristine A. Tway, and Luann Soule for manuscript preparation.

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21. Jaffe NS, Jaffe MS, and Jaffe GF: Cataract Surgery and Its Implications, 5th ed. St. Louis, CV Mosby, 1990, pp. 385-411. 22. Traisman HS, Alfano JE, Andrews J, and Gatti R: Intraocular pressure in juvenile diabetics. Am J Ophthalmol 64:1149, 1967. 23. Carel RS, Korczyn AD, Rock M, et al: Association between ocular pressures and health parameters. Ophthalmology 91:311, 1984. 24. Christiansson J: Intraocular pressure in diabetes mellitus. Acta Ophthalmol (Copenh) 39:155, 1961. 25. Shiose Y: The aging effect on intraocular pressure in an apparently normal population. Arch Ophthalmol 102:883, 1984. 26. Leske MC and Podgor MJ: Intraocular pressure: Cardiovascular risk variables and visual field defects. Am J Epidemiol 118:280, 1983. 27. Bulpitt CJ, Hodes C, and Everitt MG: Intraocular pressure and systemic blood pressure in the elderly. Br J Ophthalmol 59:717, 1975. 28. Bengtsson B: Some factors affecting the distribution of intraocular pressure in a population. Acta Ophthalmol (Copenh) 50:33, 1972. 29. McLeod SD, West SK, Quigley HA, and Fozard JL: A longitudinal study of the relationship between intraocular and blood pressure. Invest Ophthalmol Vis Sci 31:2361, 1990. 30. Schteingart DE: Characteristics of increased adrenocortical function observed in many obese persons. Ann N Y Acad Sci 131:388, 1965. 31. Kahn LA, Leibowitz HM, Ganley JP, et al: The Framingham Eye Study: 2. Association of ophthalmic pathology with single variables previously measured in the Framingham Heart Study. Am J Epidemiol 106:33, 1977. 32. Perkins ES: The Bedford Glaucoma Survey II: Rescreening of normal population. Br J Ophthalmol 57:186, 1973. 33. Blumenthal M, Blumenthal R, Peritz E, and Best M: Seasonal variation in intraocular pressure. Am J Ophthalmol 69:608, 1970.