Prevalence of Glaucoma The Beaver Dam Eye Study Barbara E. K. Klein, MD, MPH, 1 Ronald Klein, MD, MPH, 1 William E. Sponsel, ChB, MD,2 Todd Franke, PhD,l Louis B. Cantor, MD,2 James Martone, MD,3 Mitchell J. Menage, FRCS4 Purpose: The purpose of this study is to determine the prevalence of glaucoma in the population participating in the Beaver Dam Eye Study (n = 4926). Methods: All subjects were examined according to standard protocols, which included applanation tonometry, examination of the anterior chamber, perimetry, grading of fundus photographs of the optic disc, and a medical history interview. Visual field, cup-to-disc ratio, and intraocular pressure (lOP) criteria were used to define the presence of open-angle glaucoma. Definite open-angle glaucoma was defined by the presence of any two or all three of the following: abnormal visual field, large or asymmetric cupto-disc ratio, high lOP. Results: The overall prevalence of definite open-angle glaucoma was 2.1 %. The prevalence increased with age from 0.9% in people 43 to 54 years of age to 4.7% in people 75 years of age or older. There was no significant effect of sex after adjusting for age. Of the 104 cases of definite open-angle glaucoma, 33 had lOPs less than 22 mmHg in the involved eye. Hemorrhage on the optic disc was found in 46 people; 2 of these had glaucoma. Narrow-angle glaucoma was rare, with two definite cases in the population. Conclusion: The prevalence of open-angle glaucoma in Beaver Dam is similar to that in other white populations. Findings from this study re-emphasize the notion that estimates of glaucoma prevalence should be based on assessing multiple risk indicators. Ophthalmology 1992;99: 1499-1504

Glaucoma is one of the most frequent causes of visual loss in American adults. According to Leske, I it is the second most common single cause of blindness registrations in the United States and is a common reason for visits to ophthalmologists. In data from the Framingham, 2 Baltimore/ Ferndale,4 and Dalby studies,5 prevalence increased with increasing age. These studies were done in Originally received: April 22, 1992. Revision accepted: June 12, 1992. I Department of Ophthalmology, University of Wisconsin, Madison. 2 Glaucoma Service, Indiana University, Indianapolis. 3 Project Orbis, New York. 4 Bristol Eye Hospital, Bristol, England, United Kingdom. Supported by National Eye Institute/NIH grant EY06594, Bethesda, Maryland (Drs. Klein and Klein). Reprint requests to Barbara E. K. Klein, MD, MPH, Department of Ophthalmology, University of Wisconsin, 600 Highland Ave, E5/351 esc, Madison, WI 53792.

different geographic locations with populations of different ethnic and socioeconomic distributions. It is the purpose of this report to describe the distribution of glaucoma in a rural American community, Beaver Dam, Wisconsin.

Materials and Methods Population The Beaver Dam Eye Study population has been described in previous reports. 6 - 8 In brief, a private census of the population of Beaver Dam, Wisconsin was performed from September 15, 1987 to May 4, 1988. Eligibility criteria for study entry included living in the city or township of Beaver Dam and being 43 to 84 years of age at the time of the census. There were a total of 5925 individuals, of whom 4926 participated in the examination phase between March 1, 1988 and September 14, 1990. Comparisons between participants and nonparticipants have been

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published previously.s In brief, of the 999 nonparticipants, 225 died before the examination, 91 moved out of the area, 23 people could not be located, 391 refused all participation, and 269 permitted an interview only.

Procedures Study examinations were performed by ophthalmic technicians who were specially trained in the procedures and protocols used in this study. A quality assurance program was used to monitor consistency. As part of the study evaluation, each subject had a visual field screening test of each eye using a Henson CFS 2000 perimeter (Keeler Instrument Corp, Broomall, PA). This device performs threshold-related suprathreshold static perimetry using multiple stimulus patterns. 9 First, the threshold is established. The screening is performed using patterns of 2, 3, or 4 suprathreshold points within the central 25 0 of the visual field (26 stimuli in all). These points were selected based on prior studies indicating that they are missed more frequently in eyes with glaucoma than in eyes of similarly aged, visually normal people. 10, 1I If any point is not seen at the first attempt, it is retested to confirm or deny that it remains consistently unseen. Any point missed twice on three attempts is a confirmed miss. One such confirmed miss constitutes failure of the screening test. Those who failed the screen were immediately submitted to full perimetric testing, which involved testing 132 test points at 3 0 intervals across the central visual field. Insensitivity to a stimulus at any point is retested at progressively brighter light intensities, 0.5, 0.8, and 1.2 decibels brighter than the initial testing level. After testing was completed for each eye, a printout was produced. For those passing the screening test, only the threshold was recorded. The screening program in one study was found to have a sensitivity of 90% and specificity of 88% in detecting glaucoma visual field defects. 12 After visual field testing, the subject was seated at the slit lamp and the anterior segment was examined. Any abnormality was noted. The anterior chamber depth was assessed. If the examiner determined that the angle was too narrow, the pupil was not dilated unless recent previous dilation was reported by the subject or her/his eye care provider. Intraocular pressure (lOP) was measured according to a standard protocol using a Goldman applanation tonometer after instilling a drop of Flouress (Barnes-Hind Armour Pharmaceutical Co, Kankakee, IL) in each eye. The tonometer was set to 10 mmHg before taking the pressure in the right eye, and the value was not read until the examiner moved the tonometer back from the cornea. The tonometer was then reset to 10 mmHg and the measurement was taken in the left eye. Values were recorded on the form. If the examiner thought that the measurement was unreliable, it was indicated on the form. Such measurements were not included in the analyses reported here. While the pupils were dilating, a standardized history was obtained. Subjects were queried about whether they had ever been told that they had glaucoma, were taking medicines for glaucoma, or had had surgery for glaucoma.

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Responses to these questions and names of medications were recorded. When in doubt, the participant's ophthalmologist was consulted. After the medical history was complete and examinations of the lens and fundus were done, photographs were taken. Pertinent to this report, stereoscopic fundus photographs offield 1 (centered on the optic disc) as specified for the Early Treatment of Diabetic Retinopathy I 3,14 were taken with a Zeiss (Thornwood, NY) fundus camera using an Allen separator. The film was Kodachrome ASA25. Photographs were labeled, sent to Kodalux for processing, returned to the study offices, identified, and sorted for grading. There were 922 subjects who failed the initial visual field screening program in at least 1 eye, 71 of whom could not carry the full test to completion. The remaining 851 full fields were evaluated by 4 glaucoma specialists who were masked to subject characteristics and to each other's gradings. The grading classifications were as follows: 1 = normal; 2 = suspicious (equivocal changes); 3 = mild to moderate nerve fiber layer-type defect; 4 = severe nerve fiber layer-type defect; 5 = neurologic type visual field defect; 6 = other visual field abnormality. Consensus of 3 of 4 graders was obtained for 94.8% (807 of 851) of the visual fields (unpublished data, Sponsel WE; presented at the annual meeting of the Association for Research in Vision and Ophthalmology, Sarasota, 1992). For this report, consensus grading scores of suspicious, mild to moderate nerve fiber layer-type defects, and severe nerve fiber layer-type defects were included as abnormal visual fields, compatible with the diagnosis of glaucoma. Full visual field testing was not performed on subjects who passed the screening test; therefore, none could be evaluated by the glaucoma experts. Grading of optic discs and cups was performed according to a detailed standardized protocol. l5 ,16 In brief, the stereoscopic pairs were examined and both vertical and horizontal disc and cup diameters were measured with a template of graded circles. Specific anatomic characteristics were used to define both the disc and cup margins. Cup-ta-disc ratios were computed for vertical and horizontal meridians in each eye. The vertical ratio was arbitrarily chosen for these analyses. Definite hemorrhage on the optic disc was noted on the grading form.

Diagnostic Classification Table 1 shows the number of subjects in whom each of the diagnostic criteria were available for classification. Because not every characteristic was available for every eye of every subject, whenever combinations of characteristics were used for classification, the total number of subjects varied accordingly. Table 2 shows the characteristics used to define the presence of glaucoma. These factors in combination (or singly for history of glaucoma with treatment) were used to classify subjects as having definite or probable glaucoma. The senior author (BEKK) reviewed all charts, visual fields, and photographs of all subjects meeting these criteria to evaluate the suitability of the classification.

Klein et al . Prevalence of Glaucoma in Beaver Dam Table 1. Number of Subjects with Adequate Visual Fields, Fundus Photographs, Intraocular Pressure Measurements, and History of Glaucoma Characteristic

Number

Percent

4603 76 247

93.4 1.5 5.0

4441 335 150

90.2 6.8 3.0

4870 23 33

98.9 0.5 0.7

4923

99.9 0.1

Visual Fields Both eyes One eye Neither eye Optic Cup-to-disc Measurements Both eyes One eye Neither eye Intraocular pressure Both eyes One eye Neither eye History obtained regarding doctor's diagnosis of glaucoma and taking medications for glaucoma and/or having had surgery for glaucoma. Yes No

Statistics WISAR, an information processing system, was used to store all subject files. 17 The Statistical Analysis System was used for calculating prevalence, means, t tests, and for performing multiple logistic regression analyses. 18 Trends in proportions were tested for significance using the Mantel-Haenszel procedure. 19

Results The distribution ofIOP for right eyes in the Beaver Dam Eye Study population is shown in Figure 1 (the distribution of lOP in the left eye is similar). The distribution is slightly skewed to the right and the median lOP is approximately 15 mmHg. The distribution of vertical cupto-disc ratios for the right eye appears in Figure 2 (the distribution for the left eye is similar). The distribution is skewed and the median value is approximately 0.36. Table 3 shows the prevalence of various combinations of characteristics used to define cases of glaucoma. Characteristicshad to be present in the same eye. Frequencies

3

of most of the combinations increased with age; there was no consistent effect of sex (based on multiple logistic regression). The odds of having definite glaucoma, as defined by the four classifications in Table 4, increased 1.74 (95% confidence interval, 1.45,2.09) for each lO-year increment in age. Low-tension glaucoma was defined by the same visual field and cup-to-disc ratio criteria as for definite glaucoma, but in the absence of lOP greater than 21 mmHg. This condition accounted for 33 of the cases of definite openangle glaucoma. We considered among the diagnostic categories a history of glaucoma along with usage of medications and/ or past surgery for glaucoma. Table 4 shows the frequency of such history occurring alone or in the presence of one of the other first three characteristics listed in Table 2. Overall, 108 people had a history of medicine or surgery for glaucoma; only 10 of these people met the criteria for glaucoma, defined as having at least two abnormal parameters and they are included in Table 3, not in Table 4. There were 39 people who met none of the other criteria. Among the entire group, the average cup-to-disc

Table 2. Diagnostic Characteristics Characteristic

1. Visual field defect compatible with diagnosis of glaucoma 2. Cup-to-disc ratio of 0.8 or greater or difference in cup-to-disc ratio of 0.2 or more in involved eye. 3. Intraocular pressure ~22 mmHg in involved eye. 4. History of taking drops for or having surgery for glaucoma (excludes those with rubeosis iridis, history of trauma that is directly related to glaucoma).

Diagnostic Label Abnormal visual field Large or asymmetric cupto-disc ratio High intraocular pressure History of glaucoma

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35

0 .8

0·12

13·15

16-18

19·21

22·24

25+

Figure 1. Distribution of lOP, right eyes; Beaver Dam Eye Study, 1990 to 1992.

ratio was 0.51 and the average lOP in that eye was 17.6 mmHg. The average values in the Beaver Dam population without glaucoma were 0.36 for cup-to-disc ratio and 15.2 mmHg (right eyes) for lOP. The age and sex distribution of these probable cases is shown in Table 5. There were 45 subjects (30 women and 15 men) who were judged on examination to have shallow anterior chambers. A history of a prior attack of angle-closure glaucoma (substantiated by a physician) was obtained for two of these subjects. The presence of hemorrhage on the disc was noted at the time of grading. This characteristic occurred in 46 persons in the entire population; 2 of these had definite glaucoma in the same eye.

Discussion The prevalence of definite open-angle glaucoma in Beaver Dam (2. 1%) is only slightly higher than that recently reported for the white population participating in the Baltimore Eye Study (1.3%). 3 Previous data from the Framingham Eye Study2 and the study in Dalby5 found frequencies of 1.2% and 0.9%, respectively. These four studies used similar algorithms to arrive at the diagnosis and the small differences in prevalence suggests that so, ciocultural factors may not have great influence on the frequency of this disease. Definite open-angle glaucoma was diagnosed in 33 persons in Beaver Dam who had lOP less than 22 mmHg. This experience is consistent with findings of others4,20,2 1 and once again emphasizes the necessity to use parameters other than lOP to determine the prevalence of glaucoma. Furthermore, Tielsch et aJ2' demonstrated that neither lOP nor cup-to-disc ratio nor narrowest optic disc rim width, when taken alone, is a good indicator in a population of the presence of open-angle glaucoma. Because of the broad distribution of cup-to-disc ratios in the normal population, epidemiologic studies choose criteria that are believed to be definitely abnormal. However, even using the high threshold value for abnormality of 0.8 or

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greater or asymmetry of cupping, 45 persons who were otherwise classified as having glaucoma did not meet these criteria. Measurement of cup-to-disc ratios depends on the image (photographs in many studies) used to grade and the grading conventions. A standard method of grading was used in this study and its reliability and utility have been previously demonstrated. 15 Photography may be an imperfect, although economical, method to image the optic nerve. Visual field testing, currently being considered as a screening procedure, is also not ideal. Such testing may disclose abnormalities in normal subjects,22-24 and is attended by difficulties in administering this test in a field setting. Keltner and 10hnson24 report the variability in results of such testing in their experience with the huge populations that are tested for driving licenses. In the current study, the large number of persons failing the visual field screening test (n = 922) who were finally classified as not having definite glaucoma (n = 818) suggest that using this test alone in this study would have over estimated the frequency of glaucoma. We are unable to calculate the predictive power of the measure we ultimately used for visual field abnormality (consensus of four graders) as we have no other independent estimate of sensitivity and specificity of this technique. If the sensitivity of this method was as good as 95% and specificity was somewhat less, perhaps 90%, and if the true prevalence of glaucoma was 2%, then the predictive power of this method to identify glaucoma would be about 16%. Therefore, because of the imprecision of using anyone parameter in epidemiologic studies, an approach using more than one parameter, and best using all available relevant characteristics, has been adopted in the population studies of Bedford, Dalby, Des Moines, Ferndale, Sk6vde, I Baltimore,3 Barbados (unpublished data, Leske MC; presented at the annual meeting of the Association for Research in Vision and Ophthalmology, Sarasota, 1992), and Beaver Dam. Considering the data in Tables 3 and 4 together, it seems that lOP probably was an important factor in establishing a prior diagnosis of glaucoma in the Beaver 35 30.8

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Prevalence of glaucoma. The Beaver Dam Eye Study.

The purpose of this study is to determine the prevalence of glaucoma in the population participating in the Beaver Dam Eye Study (n = 4926)...
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