Migraine Headache and Its Association With Open-Angle
Glaucoma: The Beaver Dam Eye Study
Barbara E. K. Klein, Ronald Klein, Stacy M. Meuer, and Lisa A. Goetz
Purpose. To investigate the relationship of a history of migraine headache to open-angle glaucoma.
Methods. In an epidemiologic study of age-related eye disease, subjects were asked if they had
migraine headaches. The diagnosis of glaucoma was based on visual field, intraocular pressure,
cup/disc ratio, and history.
Results. Those younger than 65 years were significantly more likely to report a history of
migraine (P = 0.001) as were women (P < 0.001). There was no difference in the frequency of
open-angle glaucoma between those with and those without migraine headache (P = 0.87).
Multivariate analyses did not alter the conclusion.
Conclusion. In this population-based study there is no evidence of a relationship between
open-angle glaucoma and migraine headache. Invest Ophthalmol Vis Sci. 1993;34:
3024-3027.
Institutional review board approved the protocol,
which conformed to the Declaration of Helsinki. Informed consent was obtained from each subject.
l^orbett et al investigated a potential relationship between primary open-angle glaucoma, low-tension
glaucoma, and a history compatible with migraine
headache. 1 A relationship with low-tension glaucoma
was found particularly in older persons. We had an
opportunity to evaluate relationships between history
of migraine headache and open-angle glaucoma in a
large population of adults.
MATERIALS AND METHODS
Population
The Beaver Dam Eye Study population has been described in previous reports.2'3 In brief, a private census of Beaver Dam, Wisconsin was performed from
September 15, 1987 to May 4, 1988. There was a total
of 5,925 persons in the target age range (43-84 years);
4,926 of them participated in the examination phase.
Comparisons between participants and nonparticipants have been published.4
From the University of Wisconsin, Department of Ophthalmology, Madison,
Wisconsin.
This research was supported by NIH National Eye Institute grants EYO6594 and
EYO80I2.
Submitted for publication fuly 30, 1992; accepted March 12, 1993.
Proprietary interest category: N.
Reprint requests: Barbara E. K. Klein, Department of Ophthalmology, University of
Wisconsin-Madison, 600 Highland Avenue, E5/351 CSC, Madison, Wt 537923220.
3024
Procedures
Examinations were performed by technicians who
were trained in the study protocols. As part of the
examination, a screening visual field test using the
Henson CFS 2000 (Tinsley, Croydon, UK) was performed.5 Persons who failed the screening test were
tested with full perimetric test consisting of 132 test
points at 3° intervals across the central visual field.
There were 922 subjects who failed the screen in at
least one eye of whom 71 could not carry the full test
to completion. There were 851 persons for whom full
fields were available. These fields were evaluated by
four glaucoma specialists who were masked to subject
characteristics and to one another's gradings. Specifics of the testing procedures and grading algorithm
have been published elsewhere.6
After visual field testing, the anterior segment was
examined to assess its depth and the intraocular pressure was measured with a Goldmann applanation tonometer by protocol.6 Thereafter, pupils were dilated
with 1% tropicamide and 2.5% phenylephrine. While
the pupils were dilating, a standardized medical history was obtained. As part of that history, subjects
were asked, "Have you ever had migraine headaches
Investigative Ophthalmology & Visual Science, September 1993, Vol. 34, No. 10
Copyright © Association for Research in Vision and Ophthalmology
Downloaded From: http://iovs.arvojournals.org/pdfaccess.ashx?url=/data/journals/iovs/933169/ on 06/15/2017
Migraine and Glaucoma
TABLE
3025
i. Diagnostic Characteristics
RESULTS
The frequencies of migraine by age and sex are given
in Table 2. People younger than 65 years were more
likely to report migraine headache (444 of 2811) than
people 65 years or older (256 of 2069; P < 0.001).
Women were more likely to be affected (555 of 2729)
than men (145 of 2151; P < 0.001). The effect of sex
was still apparent after adjusting for age (P < 0.001,
logistic regression, not shown).
The frequencies of definite open-angle glaucoma
appear in Table 3. There is an increase in frequency
with increasing age but there was no effect of sex. Of
those reporting a history of migraine headache, 2.0%
had definite open-angle glaucoma (14 of 700),
whereas for those without migraine headache, 2.1%
had open-angle glaucoma (88 of 4180). Heavy
drinkers were less likely to report migraine (5 of 116)
than others (693 of 4735; P< 0.001); the relationship
was of borderline significance after adjusting for age
and sex (P = 0.09, logistic regression, not shown).
Current smokers were more likely to report migraine
headache (358 of 2182) than others (341 of 2697) (P =
0.003); the relationship was no longer significant after
adjusting for age and sex (P = 0.32, logistic regression,
not shown). Reported stroke or heart attack and hypertension were unrelated to migraine headache. This
was unchanged after adjusting for age and sex (not
shown).
Multivariate logistic regression analyses were employed to evaluate the relationships of age, migraine
headache, cigarette smoking, and drinking behavior
simultaneously with the prevalence of open-angle
glaucoma (Table 4). Models developed for each sex
were similar in the direction and significance levels.
Because the number of cases in each sex is small, the
last model uses data from both sexes. In this model,
only age was a significant variable in explaining the
prevalence of open-angle glaucoma.
Diagnostic Label
Characteristic
Visual field defect compatible
with diagnosis of glaucoma
Cup-to-disc ratio of 0.8 or
greater or difference in cupto-disc ratio of 0.2 or more
in involved eye.
Intraocular pressure >22
mmHg in involved eye.
History of taking drops for or
having surgery for glaucoma
(excludes those with rubeosis
iridis, history of trauma that
is directly related to
glaucoma).
Abnormal visual field
Large or asymmetric
cup-to-disc ratio
High intraocular
pressure
History of glaucoma
(with vomiting, light flashes, or severe enough to keep
you in bed)?" Positive responses to this query are included as cases. Subjects were also asked, "Did a doctor ever tell you that you had a stroke or a brain hemorrhage?" Persons responding positively to this question
are included as cases of stroke in the relevant analyses.
After the medical history was complete, photographs of the eyes, including stereoscopic photographs of the optic disc were taken. They were graded
according to a detailed standardized protocol.7 The
presence of definite hemorrhage on the optic disc was
noted.
Definite glaucoma was defined as two or all three
of the criteria defined in Table 1 in the same eye. If
two parameters were met, the person was included as a
subject. This was true even if data on one of the three
parameters were missing.
Statistics
An information processing system was used to store all
subject files. The Statistical Analysis System was used
for calculating prevalence, means, and f-test.8 Tendency for trends in proportions were tested for significance using the Mantel-Haenszel procedure.9
TABLE 2.
DISCUSSION
Migraine headache was not a rare condition, occurring in 14.3% of the population in the Beaver Dam Eye
Frequency (%) of Migraine Headache
Age
43-54 yr
Women
Men
792
718
65-74 yr
55-64yr
25.9
8.1
690
611
19.9
7.2
736
536
History of migraine missing for 33 women and 13 men.
Downloaded From: http://iovs.arvojournals.org/pdfaccess.ashx?url=/data/journals/iovs/933169/ on 06/15/2017
75+ yr
18.8
6.0
511
286
14.7
3.9
3026
TABLE 3.
Investigative Ophthalmology 8c Visual Science, September 1993, Vol. 34, No. 10
Prevalence of Definite Open Angle Glaucoma Characteristics*
Women
55-64yr
(n = 701)
43-54 yr
(n = 798)
65-74 yr
(n = 743)
75+yr
(n = 520)
Total
(n = 2762)
Characteristics
n
%
n
%
n
%
n
%
n
%
1. Abnormal visual field; large or
asymmetric cup-to-disc ratio;
high intraocular pressure
(criteria 1, 2, 3; Table 1)
2. Abnormal visual field; large or
asymmetric cup-to-disc ratio
(criteria 1, 2; Table 1)
3. Abnormal visual field; high
intraocular pressure (criteria 1,
3; Table 1)
4. Large or asymmetric cup-to-disc
ratio; high intraocular pressure
(criteria 2, 3; Table 1)
Total
0
0.00
0
0.00
0
0.00
0
0.00
0
0.00
2
0.25
4
0.57
4
0.54
9
1.73
19
0.69
4
0.50
2
0.29
9
1.21
12
2.31
27
0.98
5
0.63
3
0.43
3
0.40
4
0.77
15
0.54
11
1.38
9
1.28
16
2.15
25
4.81
61
2.21
Men
43-54yr
(n = 722)
55-64yr
(n = 615)
65-74 yr
(n = 540)
75+ yr
(n = 287)
Total
(n = 2164)
Characteristics
n
%
n
%
n
%
n
%
n
%
1. Abnormal visual field; large or
asymmetric cup-to-disc ratio;
high intraocular pressure
(criteria 1, 2, 3; Table 1)
2. Abnormal visual field; large or
asymmetric cup-to-disc ratio
(criteria J, 2; Table 1)
3. Abnormal visual field; high
intraocular pressure (criteria 1,
3; Table 1)
4. Large or asymmetric cup-to-disc
ratio; high intraocular pressure
(criteria 2, 3; Table 1)
Total
0
0.00
0
0.00
3
0.56
2
0.70
5
0.23
1
0.14
5
0.81
4
0.74
4
1.39
14
0.65
2
0.28
2
0.33
9
1.67
5
1.74
18
0.83
1
0.14
1
0.16
2
0.37
2
0.70
6
0.28
4
0.55
8
1.30
18
3.33
13
4.53
43
1.99
Subjects excluded from this analyses were those with neovascular glaucoma and persons whose visual field abnormality was the result of
panretinal pholocoagulalion or "severe macular degeneration (n = 14) and those with definite narrow-angle glaucoma (n = 2).
Study. Most epidemiologic studies specifically designed to investigate migraine headache compute rates
based on reported responses to a series of questions.10"12 The current study was aimed primarily at
describing prevalence in the context of a study of agerelated eye disease. Therefore, the classification is limited to the response to a single question. However, the
question contained a description of migraine similar
to that used in another study.1 There is potential, if
our question were broadly interpreted, to include persons with nonmigrainous headaches. This could serve
to obscure a weak association. We may, however, be
somewhat reassured about the frequency of migraine
we found in the current study when we review preva-
lence from the large study reported by Stewart et al (n
= 20,468).10 They found that 17.6% of women and
5.7% of men reported migraine headache. Sex-specific rates in the current study are of a similar magnitude (20.3% of women, 6.7% of men). In addition, we
too found an age effect, with decreased prevalence at
older ages.
The classification used to define primary open-angle glaucoma in this population was based on combinations of two from the triad of abnormal visual field,
high intraocular pressure, and large or asymmetric
cup-to-disc ratio (Table 3). Each parameter was measured once in each eye of each subject. Therefore, we
were able to approach the question of a relationship of
Downloaded From: http://iovs.arvojournals.org/pdfaccess.ashx?url=/data/journals/iovs/933169/ on 06/15/2017
Migraine and Glaucoma
3027
TABLE 4.
Logistic Regression Model of Variables Associated
with Definite Open Angle Glaucoma
Sex
Women
Variable
Intercept
Age
Men
Migraine
Heavy drinking
Smoking
Intercept
Age
Both
Migraine
Heavy drinking
Smoking
Intercept
Age
Sex
Migraine
Heavy drinking
Smoking
Parameter Estimate
-6.86
0.05
0.13
0.48
0.02
-8.44
0.07
-0.95
-0.17
-0.06
-7!50
0.06
0.02
-0.01
-0.04
0.02
migraine headache with normal-tension glaucoma
based on intraocular pressure <21 mm Hg in the presence of a characteristic visual field defect and a large
or asymmetric cup-to-disc ratio between eyes. In this
population, the rate was 0.7% and was unrelated to a
history of migraine headache. Detecting such a relationship would be difficult because of the infrequency
of normal-tension glaucoma and the inherent difficulty of detecting it in this field study setting. Similarly,
we found no association between migraine headache
and open-angle glaucoma. The rarity of this more prevalent condition restricted our power to detect a significant association. However, if a relationship exists, one
would expect to see evidence of at least a trend from
prevalence survey data. We found no indication of a
positive relationship.
Key Words
glaucoma, migraine headache, low-tension glaucoma, epidemiology
Acknowledgments
The authors thank the Beaver Dam Scientific Board (Frederick Ferris III, MD, Leslie Hyman, PhD, Natalie Kurinij,
PhD, Robert Sperduto, MD, Robert Wallace, MD, and
Sheila West, PhD); Scot E. Moss, MA, for statistical advice;
and Colleen Comeau and Luann Soule for manuscript preparation.
References
1. Corbett JJ, Phelps CD, Eslinger P, Montague PR. The
neurologic evaluation of patients with low-tension
glaucoma. Invest Ophlhalmol Vis Sci. 1985; 26:11011105.
2. Campbell JA, Palit CD. Total digit dialing for a small
Standard Error
Probability
0.91
0.01
0.33
0.45
0.19
1.14
0.02
1.02
0.33
0.25
0.71
0.01
0.22
0.15
0.27
0.15
<0.01
<0.01
0.69
0.29
0.94
<0.01
<0.01
0.35
0.59
0.81
<0.01
<0.01
0.94
0.96
0.89
0.91
area census by phone. In: American Statistical Association. Proceedings of the Survey Research Methods Section.
Alexandria, VA: The Association; 1988:549-551/
3. Linton KLP, Klein BEK, Klein R. The validity of selfreported and surrogate-reported cataract and age-related macular degeneration in the Beaver Dam Eye
Study. Am J Epidemiol. 1991; 134:1438-1446.
4. Klein R, Klein BEK, Linton KLP, De Mets DL. The
Beaver Dam Eye Study: visual acuity. Ophthalmology.
1991;98:1310-1315.
5. Langerhorst CT, Bakker D, Raakman MAC. Usefulness of the Henson Central Field Screener for the detection of visual field defects, especially in glaucoma.
Doc Ophthalmol. 1989; 72:279-285.
6. Klein BEK, Klein R, Sponsel WE, et al. Prevalence of
Glaucoma. The Beaver Dam Eye Study. Ophthalmology. 1992;99:1499-1504.
7. Klein BEK, Magli YL, Richie KA, et al. Quantitation
of optic disc cupping. Ophthalmology. 1985; 92:16541656.
8. SAS Institute Inc. SAS/STAT User's Guide. Version 6
(4th edition). Cary, North Carolina: SAS Institute,
1989; Vol 1-2.
9. Mantel N. Chi-square tests with one degree of freedom: extensions of the Mantel-Haenszel procedure, f
AmStatAssoc. 1963;58:690-700.
10. Stewart WF, Lipton RB, Celentano DD, Reed ML.
Prevalence of migraine headache in the United States.
Relation to age, income, race and other sociodemographic factors. fAMA. 1992; 267:64-69.
11. Stang PE, Yanagihara T, Swanson JW, Beard CM,
Melton LJ: A population-based study of migraine
headaches in Olmsted County, Minnesota. Neuroepidemiology. 1991; 10:297-307.
12. Taylor PJ, Pocock SJ, Hall SA, Waters WE: Headaches
and migraine in colour retouchers. Br J Ind Med.
1970;27:364-367.
Downloaded From: http://iovs.arvojournals.org/pdfaccess.ashx?url=/data/journals/iovs/933169/ on 06/15/2017