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The Ocular Hypertension Treatment Study
Baseline Factors That Predict the Onset of Primary Open-Angle Glaucoma
Mae O. Gordon, PhD;
Julia A. Beiser, MS;
James D. Brandt, MD;
Dale K. Heuer, MD;
Eve J. Higginbotham, MD;
Chris A. Johnson, PhD;
John L. Keltner, MD;
J. Philip Miller, AB;
Richard K. Parrish II, MD;
M. Roy Wilson, MD;
Michael A. Kass, MD;
for the Ocular Hypertension Treatment Study Group
Arch Ophthalmol. 2002;120:714-720.
ABSTRACT
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Background The Ocular Hypertension Treatment Study (OHTS) has shown that topical
ocular hypotensive medication is effective in delaying or preventing the onset
of primary open-angle glaucoma (POAG) in individuals with elevated intraocular
pressure (ocular hypertension) and no evidence of glaucomatous damage.
Objective To describe baseline demographic and clinical factors that predict which
participants in the OHTS developed POAG.
Methods Baseline demographic and clinical data were collected prior to randomization
except for corneal thickness measurements, which were performed during follow-up.
Proportional hazards models were used to identify factors that predicted which
participants in the OHTS developed POAG.
Results In univariate analyses, baseline factors that predicted the development
of POAG included older age, race (African American), sex (male), larger vertical
cup-disc ratio, larger horizontal cup-disc ratio, higher intraocular pressure,
greater Humphrey visual field pattern standard deviation, heart disease, and
thinner central corneal measurement. In multivariate analyses, baseline factors
that predicted the development of POAG included older age, larger vertical
or horizontal cup-disc ratio, higher intraocular pressure, greater pattern
standard deviation, and thinner central corneal measurement.
Conclusions Baseline age, vertical and horizontal cup-disc ratio, pattern standard
deviation, and intraocular pressure were good predictors for the onset of
POAG in the OHTS. Central corneal thickness was found to be a powerful predictor
for the development of POAG.
INTRODUCTION
THE OCULAR Hypertension Treatment Study (OHTS) was a multicenter randomized
trial designed to evaluate the safety and efficacy of topical ocular hypotensive
medication in delaying or preventing the onset of primary open-angle glaucoma
(POAG) in individuals with elevated intraocular pressure (IOP) and no detectable
glaucomatous damage. The results of the OHTS are described in detail in our
companion article.1
The cumulative probability of developing POAG was reduced by 60% among
participants randomized to receive topical ocular hypotensive medication compared
with those randomized to observation (hazard ratio, 0.40; 95% confidence interval
[CI], 0.27-0.59). At 60 months, the cumulative probability of developing POAG
was 4.4% in the medication group and 9.5% in the observation group.
During the planning phase of the OHTS, we identified several baseline
demographic and clinical factors that might predict which participants in
the trial would develop POAG. If some of these factors proved to be good predictors,
clinicians could use this information to decide the appropriateness of initiating,
continuing, or discontinuing topical ocular hypotensive medication in patients
with ocular hypertension.
PARTICIPANTS AND METHODS
STUDY DESIGN
The protocol is described in detail in the study manual,2
in the baseline design article,3 and on the
World Wide Web at http://www.vrcc.wustl.edu. The protocol was approved by the institutional
review board of each participating clinic. In brief, 1636 participants who
had ocular hypertension, with an IOP between 24 mm Hg and 32 mm Hg in one
eye and between 21 mm Hg and 32 mm Hg in the other eye and no evidence of
glaucomatous damage, were randomized to either observation or treatment with
commercially available topical ocular hypotensive medication. The goal of
treatment with topical ocular hypotensive medication was to achieve an IOP
of 24 mm Hg or less and a minimum 20% reduction from the average of the qualifying
IOP and IOP at the baseline randomization visit, except that an IOP of less
than 18 mm Hg was not required. The primary outcome was the development of
reproducible visual field abnormality or clinically significant reproducible
optic disc deterioration attributable to POAG. Abnormalities were determined
by masked certified readers at the Visual Field and Optic Disc Reading Centers,
and attribution to POAG was decided by the masked Endpoint Committee.
Baseline demographic and clinical information was collected for each
participant prior to randomization. The baseline clinical examination included
refraction, best-corrected visual acuity, full-threshold white-on-white Humphrey
30-2 visual field tests, IOP measurement, a dilated fundus examination, and
stereoscopic optic disc photographs. Myopia was defined as a spherical equivalent
of -1.0 diopter (D) or more. Horizontal and vertical cup-disc ratios
by contour were estimated visually from stereoscopic optic disc photographs
by masked certified readers in the Optic Disc Reading Center.4
Information collected by participant report included ocular and medical history,
family history of glaucoma, current use of medications including oral calcium
channel blockers, and oral  -adrenergic antagonists. Medical history
was obtained by asking, "Has a doctor ever told you that you have any of the
following conditions?" and reading a list of medical conditions. Family history
of glaucoma was determined by asking, "Do any of your blood relatives (biological
mother or father, biological brother or sister, biological aunt or uncle,
or biological grandmother or grandfather) have glaucoma?" A first-degree relative
was defined as a biological parent or sibling.
During the planning phase of the OHTS, we identified several factors
as possible predictors for the development of POAG. These included age, self-identified
race, sex, vertical and horizontal cup-disc ratio, IOP, family history of
glaucoma, visual field indexes, myopia, heart disease, high blood pressure,
low blood pressure, treatment of medical conditions with oral calcium channel
blockers or oral -adrenergic antagonists, cerebrovascular accident,
diabetes mellitus, and migraine. During the course of the OHTS, increasing
information indicated that thick corneas could cause overestimation of the
true IOP and that individuals classified as having ocular hypertension had
thicker corneas on average. We began to collect central corneal thickness
measurements in early 1999, about 2 years after randomization of the last
participant. The protocol for the measurement of central corneal thickness
is described in a previously published article.5
New conditions or signs that occurred during follow-up, such as optic disc
hemorrhage, are not included in this article.
STATISTICAL ANALYSIS
For eye-specific variables, we calculated the mean for each eye and
then averaged these 2 values to determine the baseline predictive factor.
The IOP predictive factor was calculated from 4 to 6 baseline IOP measurements
per eye. The visual field predictive factors (mean deviation, pattern standard
deviation, and corrected pattern standard deviation) were calculated from
2 normal and reliable baseline visual fields per eye. The central corneal
thickness predictive factor was calculated from 5 measurements per eye obtained
during the same visit. Cox proportional hazards models as implemented in the
PHREG program in the SAS statistical software (SAS Institute Inc, Cary, NC)
were used to estimate and test factors for their association with the development
of POAG. The analysis sample for the proportional hazards models consisted
of 125 randomized participants who developed POAG and 1493 randomized participants
with at least 1 follow-up visit (18 of 1636 participants did not have any
follow-up visits) who did not develop POAG. The analysis data set included
all data through November 8, 2001, as recommended by the Data and Safety Monitoring
Committee. Median participant follow-up was 72 months. A parsimonious model
was selected using the score criterion in PHREG for comparing models containing
1 predictive factor with those containing combinations of all predictive factors.
We report hazard ratios from univariate models, which do not adjust for the
presence of other factors, as well as adjusted hazard ratios from the multivariate
Cox proportional hazards models. Univariate and multivariate hazard ratios
for developing POAG and their 95% CIs are reported for each putative predictive
factor. Statistical significance was defined as P<.05.
RESULTS
Baseline demographic and clinical factors of participants who did and
did not develop POAG in the OHTS are reported in Table 1 and Table 2.
The percentages in Table 1 were
calculated by dividing the number of participants who developed POAG by the
number of randomized participants with at least 1 follow-up visit (1618).
These values are not adjusted for duration of follow-up. Corneal thickness
measurements, which began in 1999, were completed in 1398 participants.
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Table 1. Putative Baseline Demographic and Clinical Predictors by POAG
Status*
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Table 2. Baseline Age and Putative Ocular Predictors by POAG Status*
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Univariate and multivariate Cox proportional hazards models were evaluated
in the observation group alone and in the entire study sample using randomization
group as a stratification variable. Both analyses identified similar predictive
factors; therefore, we report the results from models based on the entire
sample because that approach provides greater statistical power.
Univariate and multivariate hazard ratios with 95% CIs are reported
for each putative predictive factor for the development of POAG (Table 3). In univariate analyses, baseline
factors significantly predictive of the development of POAG were older age,
race (African American), sex (male), higher IOP, larger vertical cup-disc
ratio, larger horizontal cup-disc ratio, greater pattern standard deviation,
heart disease, and thinner central corneal measurement. Factors significantly
predictive of the development of POAG in both the univariate and multivariate
models included older age, higher IOP, greater pattern standard deviation,
thinner central corneal measurement, and larger vertical cup-disc ratio. Although
horizontal and vertical cup-disc ratios were highly correlated (r = 0.92), vertical cup-disc ratio was a slightly better predictor
for the development of POAG than horizontal cup-disc ratio. Therefore, vertical
cup-disc ratio was included in the multivariate risk model, and horizontal
cup-disc ratio was not.
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Table 3. Univariate and Multivariate Hazard Ratios and 95% Confidence
Intervals for the Development of POAG*
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A history of diabetes mellitus appeared to be significantly protective
against developing POAG in both univariate and multivariate models. Among
the 191 participants who reported a history of diabetes mellitus at baseline,
6 (3.1%) developed POAG compared with 119 (8.3%) of 1427 participants who
did not report a history of diabetes mellitus. The univariate hazard ratio
for diabetes mellitus was 0.40 (95% CI, 0.18-0.92), and the multivariate hazard
ratio was 0.37 (95% CI, 0.15-0.90).
Baseline factors associated with developing POAG that were statistically
significant in the univariate model but not in the multivariate model were
race, heart disease, and sex (male). In the univariate model, race (African
American) was associated with a 59% increase in the risk of developing POAG
(hazard ratio, 1.59; 95% CI, 1.09-2.32). In this study, African American participants
had a larger mean ± SD baseline vertical cup-disc ratio (0.45 ±
0.18) compared with other participants (0.37 ± 0.20) and a thinner
mean ± SD central corneal measurement (554.9 ± 38.5 µm)
than other participants (578.3 ± 36.5 µm). The inclusion of either
baseline vertical cup-disc ratio or corneal thickness caused race to become
statistically nonsignificant in the multivariate model.
The OHTS enrolled 56 participants who identified themselves as Hispanic.
Eight (14.3%) of these 56 participants (95% CI, 5%-23%) developed POAG during
follow-up. Hispanic participants resembled the other participants in terms
of demographic and baseline clinical features. Because of the small sample
size, we did not include Hispanic ethnic identity as a separate predictive
factor and grouped Hispanic participants with "others" in the analyses.
Baseline factors that were not associated with the risk of developing
POAG in both univariate and multivariate models included family history of
glaucoma (first-degree relative or any relative), mean deviation, corrected
pattern standard deviation, myopia, migraine, cerebrovascular accident, high
blood pressure, low blood pressure, and use of oral -adrenergic antagonists
or oral calcium channel blockers. No association with POAG was found for myopia
of -1.0 D or less, greater than -1.0 D to -3.0 D (moderate
myopia), or greater than -3.0 D (high myopia).
A thinner central corneal measurement predicted the development of POAG
in both univariate and multivariate models. Among participants who developed
POAG, the mean ± SD central corneal thickness was 553.1 ± 38.8
µm compared with 574.3 ± 37.8 µm among those who did not
develop POAG. We examined whether the effect of corneal thickness on the development
of POAG was present across the range of corneal thickness measurements observed
in the OHTS. We divided the entire sample into 3 approximately equal-sized
groups of participants (n = 450-480) with corneal thickness measurements of
555 µm or less (mean, 530.8 µm), greater than 555 µm to
less than or equal to 588 µm (mean, 571.7 µm), and more than 588
µm (mean, 613.5 µm). For each group, we computed the multivariate
hazard ratio for the development of POAG using the group with the thickest
corneas as a reference. Compared with the participants with the thickest corneas
(>588 µm), participants with intermediate central corneal measurements
(>555 µm to  588 µm) had a hazard ratio of 1.7 (95% CI, 0.97-3.0),
and participants with the thinnest central corneal measurements (555 µm)
had a hazard ratio of 3.4 (95% CI, 2.1-5.6). Similar analyses conducted using
4 to 8 categories of corneal thickness supported the conclusion that the risk
of developing POAG was inversely correlated with central corneal thickness,
with no apparent threshold effect.
Next we examined whether the effect of corneal thickness on the development
of POAG was present across the range of baseline IOP observed in the OHTS.
The entire sample was divided into 3 approximately equal groups of participants
(n = 531-567) with an IOP of 23.75 mm Hg or less (mean, 22.2 mm Hg), greater
than 23.75 mm Hg to less than or equal to 25.75 mm Hg (mean, 24.8 mm Hg),
and more than 25.75 mm Hg (mean, 27.9 mm Hg). For each IOP group, we computed
a multivariate hazard ratio for participants with the thinnest, intermediate,
and thickest central corneal measurements as described previously. The risk
of developing POAG was highest among participants with the thinnest central
corneal measurements within each IOP group. The relationship between corneal
thickness and risk of developing POAG did not differ substantially between
the 3 IOP groups (P = .14). Figure 1 illustrates the percentage of participants in the observation
group who developed POAG, grouped by central corneal measurements and IOP.
We then examined whether the effect of central corneal thickness on
the development of POAG was present across the range of baseline vertical
cup-disc ratios observed in the OHTS. We divided the entire sample into 3
approximately equal groups of participants (n = 524-569) with baseline vertical
cup-disc ratios of 0.30 or less (mean, 0.16), greater than 0.30 to less than
0.50 (mean, 0.40), and 0.50 or higher (mean, 0.60). For each vertical cup-disc
ratio group, we computed a multivariate hazard ratio for participants with
the thinnest, intermediate, and thickest central corneal measurements. The
risk of developing POAG was highest among participants with the thinnest central
corneal measurements within each vertical cup-disc ratio group. The relationship
between corneal thickness and the risk of developing POAG did not differ substantially
between the 3 cup-disc ratio groups (P = .32). Figure 2 illustrates the percentage of participants
in the observation group who developed POAG, grouped by central corneal measurements
and vertical cup-disc ratio.
We were concerned that the apparent predictive power of central corneal
thickness on the development of POAG could be explained by the correlation
between corneal thickness and other predictors of POAG. However, we found
little evidence for this. Pearson correlation coefficients for the association
between corneal thickness and other baseline factors were as follows: age
(r = -0.14), vertical cup-disc ratio (r = -0.12), IOP (r = -0.03),
pattern standard deviation (r = -0.07), and
mean deviation (r = 0.01). The correlations between
central corneal thickness and these baseline factors were also computed using
the Kendall  -b and Spearman rank order tests, with similar results.
COMMENT
Almost all previous studies of risk factors for POAG collected risk
factor data retrospectively or at the time that POAG was ascertained.6-17
In the OHTS, risk factors were measured at baseline prior to the onset of
POAG, so that predictive factors could be differentiated with greater precision.
Only corneal thickness was measured after randomization. Stringent eligibility
criteria ensured that each case of POAG detected during follow-up was a new
case and not one that had escaped detection at baseline. Determination of
abnormality was made independently by masked certified readers at the reading
centers, and confirmation of abnormality required multiple tests separated
by several weeks or months. Attribution of abnormality to POAG was made by
the masked Endpoint Committee. Thus, the OHTS protocol ensured that incident
cases of POAG were truly new cases and that the diagnosis of POAG was made
with high specificity.
The OHTS confirmed that age, cup-disc ratio, and IOP are predictive
factors for the development of POAG in individuals with ocular hypertension.
Similar findings have been reported previously in population surveys, case-control
studies, and prospective studies. Leske,18
Tielsch,19 and Wilson and Martone20
have published detailed articles on risk factors for glaucoma. The predictive
factors identified in our study are most likely to be helpful for assessing
the risk of patients who resemble the OHTS participants; that is, individuals
who have ocular hypertension, an IOP between 24 and 32 mm Hg, and no evidence
of glaucomatous damage.
Some scientists might argue that a larger cup-disc ratio is not a risk
factor for developing POAG but rather an indicator of early glaucomatous damage.
However, when a clinician examines a patient for the first time, there is
no way to determine whether the cup-disc ratio observed has been stable during
the patient's lifetime or has enlarged as part of the disease process, assuming
that no previous photographs or measurements are available for comparison.
A patient with a large cup-disc ratio unaltered by glaucoma may be at greater
risk for developing POAG. Thus, we decided to include baseline cup-disc ratio
in the predictive models. A similar reasoning process was followed to include
baseline visual field indexes in these models as well.
In the OHTS, 3 putative predictive factors (race, sex, and heart disease)
were identified in univariate analyses but were not statistically significant
in multivariate models. The statistical power to detect the association between
these factors and the development of POAG ranged from 0.50 to 0.90, assuming
conventional levels of statistical significance. Some of these factors might
have been statistically significant in multivariate models if a greater number
of participants with the risk factor had been enrolled (eg, only 101 participants
reported heart disease at baseline) or if a larger number of incident POAG
cases had occurred. On the other hand, the number of incident POAG cases in
the OHTS (125 of 1636 participants with ocular hypertension) exceeds that
in previous reports of large prospective studies of glaucoma, including the
Iowa Study (4 eyes of 1628 individuals),21
the Collaborative Glaucoma Study (93 eyes of 5886 subjects),22
the Dalby Study (12 eyes of 599 individuals),23
and the Barbados Incidence Study of Eye Diseases (67 of 3427 participants).24
Univariate analyses indicated that self-identified African American
participants had a 59% increase in the risk of developing POAG. Many studies
have reported a substantially higher prevalence and incidence of POAG in black
individuals compared with white individuals.11-12,24-26
However, African American participants in the OHTS had thinner central corneal
measurements and larger baseline vertical cup-disc ratios. In multivariate
analyses that adjusted for these factors, race was no longer a statistically
significant predictor.
In the OHTS, 8 of 56 Hispanic participants developed POAG. Although
this small sample size prevented detailed analysis, the results were consistent
with a recent population survey that found a higher prevalence of POAG in
Hispanic subjects.27
Family history of glaucoma is a well-established risk factor for POAG.28-31 Forty-seven
(8.5%) of 553 participants who reported at least 1 first-degree relative with
glaucoma developed POAG, compared with 78 (7.3%) of 1065 who did not. Of all
OHTS participants, 42% reported either a first-degree relative or any relative
with glaucoma. No attempt was made to verify the participants' reports or
to corroborate the diagnoses with family members or clinicians. The high proportion
of participants who reported a family history of glaucoma suggests that this
condition is not always distinguished from ocular hypertension. Population
surveys and genetic studies are likely to provide stronger tests of the heritability
of POAG.
In the OHTS, male sex predicted the development of POAG in the univariate
analyses but was of borderline significance in multivariate models. Other
studies of the relationship between sex and POAG have yielded conflicting
results, with some studies finding men at higher risk,12, 31-32
some finding women at higher risk,33 and some
finding no association.9, 19, 34
Myopia was not predictive of the development of POAG in the OHTS. In
contrast, several well-performed case-control and population-based studies
have reported an association between myopia, particularly high myopia, and
POAG.35-37
Low perfusion pressure has been associated with POAG30
and may be an important consideration in the decision to treat elevated IOP.38 However, in the OHTS, a history of low blood pressure
at baseline was ascertained only by self-report. We did not perform blood
pressure readings and are unable to test this interesting hypothesis.
In both our univariate and multivariate analyses, a history of diabetes
mellitus at baseline appeared to be protective against developing POAG. This
contradicts all previously published studies, which either found that diabetes
is associated with POAG39-41
or that there is no association.19, 30, 33, 42-43
We did not confirm the diagnosis of diabetes mellitus in OHTS participants
with blood tests or medication use. Because individuals with diabetic retinopathy
were excluded from the OHTS, we probably enrolled an unrepresentative group
of patients with diabetes. These factors may explain the paradoxical relationship
between diabetes mellitus and POAG in the OHTS.
We found that small differences in pattern standard deviation at baseline
predicted the development of POAG, even among participants who had normal
and reliable results on Humphrey 30-2 visual field tests. Such small differences
can be detected only by taking an average from multiple visual fields, as
was done in the OHTS. The visual field predictive factor was computed from
4 normal and reliable visual field test results (2 from each eye) per participant.
It is unlikely that pattern standard deviation would be a useful predictive
factor in general practice.
To our knowledge, the OHTS is the first study to prospectively document
that a thinner central corneal measurement predicts the development of POAG.
Corneal thickness appeared to be a strong predictive factor for the development
of POAG, even after adjusting for the effects of baseline age, IOP, vertical
cup-disc ratio, and pattern standard deviation. Participants with a corneal
thickness of 555 µm or less had a 3-fold greater risk of developing
POAG compared with participants who had a corneal thickness of more than 588
µm. This inverse relationship was found across the ranges of baseline
IOP and baseline vertical cup-disc ratios. It is well known that corneal thickness
influences the measurement of IOP. Eyes with thicker corneas have a true IOP
that is lower than the measured IOP. Conversely, eyes with thin corneas have
a true IOP that is greater than the measured IOP. Thus, individuals with thicker
corneas may be misclassified as having ocular hypertension. Cross-sectional
studies have documented that central corneal thickness is greater in individuals
with measured ocular hypertension compared with normotensive individuals or
those with glaucoma.44-51
It is likely that the predictive power of corneal thickness is due to
its effect on the measured IOP. However, we cannot exclude the possibility
that corneal thickness is related to other factors affecting susceptibility
to glaucomatous damage. Baseline IOP was not correlated with corneal thickness
in the OHTS, partly because of the narrow range of IOP. We did not use available
formulas to correct the IOP for corneal thickness because they are theoretical
in nature52 or derived from small samples with
limited racial variation.53-55
In the OHTS, the mean central corneal thickness among African Americans was
23.5 µm thinner than that of other participants.5
The central corneal thickness of the African American participants more closely
resembles the norm, whereas the other participants had thicker corneas than
the norm.47-51
We conclude that central corneal thickness provides new information about
the risk of developing POAG, and we recommend its measurement in the clinical
evaluation of patients with ocular hypertension.
In summary, the OHTS data suggest that a clinician caring for a patient
with ocular hypertension can assess that individual's risk of developing POAG
by considering age, IOP, cup-disc ratio, and central corneal thickness. By
combining these factors, the clinician can identify patients at moderate to
high risk for developing POAG and who are more likely to benefit from early
medical treatment.
AUTHOR INFORMATION
Submitted for publication March 6, 2002; final revision received April
10, 2002; accepted April 10, 2002.
This study was supported by grants EY09341 and EY09307 from the National
Eye Institute and the National Center for Minority Health and Health Disparities,
National Institutes of Health, Bethesda, Md; Merck Research Laboratories,
White House Station, NJ; and by an unrestricted grant from Research to Prevent
Blindness, New York, NY.
Drs Gordon and Kass take responsibility for authorship, financial disclosure,
and copyright transfer for the group.
Corresponding author and reprints: Mae O. Gordon, PhD, OHTS Coordinating
Center, Department of Ophthalmology and Visual Sciences, Washington University
School of Medicine, Box 8203, 660 South Euclid, St Louis, MO 63110 (e-mail: mae{at}vrcc.wustl.edu).
From the Department of Ophthalmology and Visual Sciences (Drs Gordon
and Kass and Ms Beiser) and Division of Biostatistics (Mr Miller), Washington
University School of Medicine, St Louis, Mo; Department of Ophthalmology,
University of California, Davis (Drs Brandt and Keltner); Department of Ophthalmology,
Medical College of Wisconsin, Milwaukee (Dr Heuer); Maryland Center for Eye
Care Associates and the Department of Ophthalmology, University of Maryland,
Baltimore (Dr Higginbotham); Devers Eye Institute, Portland, Ore (Dr Johnson);
Bascom Palmer Eye Institute, University of Miami School of Medicine, Miami,
Fla (Dr Parrish); and Creighton University School of Medicine, Omaha, Neb
(Dr Wilson).
REFERENCES
| |
1. Kass MA, Heuer DK, Higginbotham EJ, et al. The Ocular Hypertension Treatment Study: a randomized trial determines
that topical ocular hypotensive medication delays or prevents the onset of
primary open-angle glaucoma. Arch Ophthalmol. 2002;120:701-713.
FREE FULL TEXT
2. Gordon MO, Kass MA and the Ocular Hypertension Treatment Study Group (OHTS). Manual of Procedures. Springfield, Va: National Technical Information Service; 1997. Publication
PB97-148308NZ.
3. Gordon MO, Kass MA for the Ocular Hypertension Treatment Study Group. The Ocular Hypertension Treatment Study: design and baseline description
of the participants. Arch Ophthalmol. 1999;117:573-583.
FREE FULL TEXT
4. Feuer WJ, Parrish II RK, Schiffman JC, et al. The Ocular Hypertension Treatment Study: reproducibility of cup/disk
ratio measurements over time at an optic disc reading center. Am J Ophthalmol. 2002;133:19-28.
FULL TEXT
|
ISI
| PUBMED
5. Brandt JD, Beiser JA, Kass MA, Gordon MO for the Ocular Hypertension Treatment Study (OHTS) Group. Central corneal thickness in the Ocular Hypertension Treatment Study
(OHTS). Ophthalmology. 2001;108:1779-1788.
FULL TEXT
|
ISI
| PUBMED
6. Hollows FC, Graham PA. Intra-ocular pressure, glaucoma, and glaucoma suspects in a defined
population. Br J Ophthalmol. 1966;50:570-586.
FREE FULL TEXT
7. Kahn HA, Milton RC. Alternative definitions of open-angle glaucoma: effect on prevalence
and associations in the Framingham eye study. Arch Ophthalmol. 1980;98:2172-2179.
ABSTRACT
8. Tielsch JM, Sommer A, Witt K, Katz J, Royall RM. Blindness and visual impairment in an American urban population: the
Baltimore Eye Survey. Arch Ophthalmol. 1990;108:286-290.
ABSTRACT
9. Klein BEK, Klein R, Sponsel WE, et al. Prevalence of glaucoma: the Beaver Dam Eye Study. Ophthalmology. 1992;99:1499-1504.
ISI
| PUBMED
10. Coffey M, Reidy A, Wormold R, Xian WX, Wright L, Courtney P. Prevalence of glaucoma in the west of Ireland. Br J Ophthalmol. 1993;77:17-21.
FREE FULL TEXT
11. Mason RP, Kosoko O, Wilson MR, et al. National survey of the prevalence and risk factors of glaucoma in St
Lucia, West Indies, I: prevalence findings. Ophthalmology. 1989;96:1363-1368.
ISI
| PUBMED
12. Leske MC, Connell AM, Schachat AP, Hyman L for the Barbados Eye Study Group. The Barbados Eye Study: prevalence of open angle glaucoma. Arch Ophthalmol. 1994;112:821-829.
ABSTRACT
13. Shiose Y, Kitazawa Y, Tsukahara S, et al. Epidemiology of glaucoma in Japan: a nationwide glaucoma survey. Jpn J Ophthalmol. 1991;35:133-155.
PUBMED
14. Dielemans I, Vingerling JR, Wolfs RC, Hofman A, Grobbee DE, de Jong PT. The prevalence of primary open-angle glaucoma in a population-based
study in the Netherlands: the Rotterdam Study. Ophthalmology. 1994;101:1851-1855.
ISI
| PUBMED
15. Mitchell P, Smith W, Attebo K, Healey PR. Prevalence of open-angle glaucoma in Australia: the Blue Mountains
Eye Study. Ophthalmology. 1996;103:1661-1669.
ISI
| PUBMED
16. Wensor MD, McCarty CA, Stanislavsky YL, Livingston PM, Taylor HR. The prevalence of glaucoma in the Melbourne Visual Impairment Project. Ophthalmology. 1998;105:733-739.
FULL TEXT
|
ISI
| PUBMED
17. Bonomi L, Marchini G, Marraffa M, et al. Prevalence of glaucoma and intraocular pressure distribution in a defined
population: the Egna-Neumarkt Study. Ophthalmology. 1998;105:209-215.
FULL TEXT
|
ISI
| PUBMED
18. Leske MC. The epidemiology of open-angle glaucoma: a review. Am J Epidemiol. 1983;118:166-191.
FREE FULL TEXT
19. Tielsch JM. The epidemiology and control of open angle glaucoma: a population-based
perspective. Annu Rev Public Health. 1996;17:121-136.
ISI
| PUBMED
20. Wilson RM, Martone JF. The epidemiology of chronic open-angle glaucoma and ocular hypertension. In: Ritch R, Shields MB, Krupin T, eds. The Glaucomas:
A Multi-volume Reference. St Louis, Mo: Mosby-Year Book; 1996:753-768.
21. Armaly MF. Ocular pressure and visual fields: a ten-year follow-up study. Arch Ophthalmol. 1969;81:25-40.
ISI
| PUBMED
22. Armaly MF, Krueger DE, Maunder L, et al. Biostatistical analysis of the collaborative glaucoma study, I: summary
report of the risk factors for glaucomatous visual-field defects. Arch Ophthalmol. 1980;98:2163-2171.
ABSTRACT
23. Bengtsson B. Manifest glaucoma in the aged, I: occurrence nine years after a population
survey. Acta Ophthalmol (Copenh). 1981;59:321-331.
24. Leske MC, Connell AM, Wu SY, et al for the Barbados Eye Studies Group. Incidence of open-angle glaucoma: the Barbados Eye Studies. Arch Ophthalmol. 2001;119:89-95.
FREE FULL TEXT
25. Tielsch JM, Sommer A, Katz J, Royall RM, Quigley HA, Javitt J. Racial variations in the prevalence of primary open-angle glaucoma:
the Baltimore Eye Survey. JAMA. 1991;266:369-374.
ABSTRACT
26. Buhrmann RR, Quigley HA, Barron Y, West SK, Oliva MS, Mmbaga BB. Prevalence of glaucoma in a rural East African population. Invest Ophthalmol Vis Sci. 2000;41:40-48.
FREE FULL TEXT
27. Quigley HA, West SK, Rodriguez J, Munoz B, Klein R, Snyder R. The prevalence of glaucoma in a population-based study of Hispanic
subjects: Proyecto VER. Arch Ophthalmol. 2001;119:1819-1826.
FREE FULL TEXT
28. Armaly MF. On the distribution of applanation pressure, I: statistical features
and the effect of age, sex, and family history of glaucoma. Arch Ophthalmol. 1965;73:11-18.
29. Tielsch JM, Katz J, Sommer A, Quigley HA, Javitt JC. Family history and risk of primary open-angle glaucoma: the Baltimore
Eye Survey. Arch Ophthalmol. 1994;112:69-73.
ABSTRACT
30. Leske MC, Nemesure B, He Q, Wu SY, Hejtmancik J, Hennis A. Patterns of open-angle glaucoma in the Barbados Family Study. Ophthalmology. 2001;108:1015-1022.
FULL TEXT
|
ISI
| PUBMED
31. Weih LM, Nanjan M, McCarty CA, Taylor HR. Prevalence and predictors of open-angle glaucoma: results from the
Visual Impairment Project. Ophthalmology. 2001;108:1966-1972.
FULL TEXT
|
ISI
| PUBMED
32. Leibowitz HM, Krueger DE, Maunder LR, et al. The Framingham Eye Study monograph: an ophthalmological and epidemiological
study of cataract, glaucoma, diabetic retinopathy, macular degeneration, and
visual acuity in a general population of 2631 adults, 1973-1975. Surv Ophthalmol. 1980;24(suppl):335-610.
33. Bengtsson B. The prevalence of glaucoma. Br J Ophthalmol. 1981;65:46-49.
FREE FULL TEXT
34. Quigley HA, Enger C, Katz J, Sommer A, Scott R, Gilbert D. Risk factors for the development of glaucomatous visual field loss
in ocular hypertension. Arch Ophthalmol. 1994;112:644-649.
ABSTRACT
35. Ponte F, Giuffre G, Giammanco R, Dardononi G. Risk factors of ocular hypertension and glaucoma: the Casteldaccia
Eye Study. Doc Ophthalmol. 1994;85:203-210.
FULL TEXT
|
ISI
| PUBMED
36. Mitchell P, Hourihan F, Sandbach J, Wang JJ. The relationship between glaucoma and myopia: the Blue Mountains Eye
Study. Ophthalmology. 1999;106:2010-2015.
FULL TEXT
|
ISI
| PUBMED
37. Perkins ES, Phelps CD. Open angle glaucoma, ocular hypertension, low-tension glaucoma, and
refraction. Arch Ophthalmol. 1982;100:1464-1467.
ABSTRACT
38. Tielsch JM, Katz J, Sommer A, Quigley HA, Javitt JC. Hypertension, perfusion pressure, and primary open-angle glaucoma:
a population-based assessment. Arch Ophthalmol. 1995;113:216-221. |
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