Académique Documents
Professionnel Documents
Culture Documents
PAUL P. LEE, JOHN W. WALT, LISA C. ROSENBLATT, LISA R. SIEGARTEL, AND LEE S. STERN, ON BEHALF
OF THE GLAUCOMA CARE STUDY GROUP
G
PURPOSE: To evaluate whether greater intraocular LAUCOMA CURRENTLY AFFECTS MORE THAN TWO
pressure (IOP) variation between visits was associated million people in the United States. This number
with higher likelihood of glaucoma progression. is expected to grow as the number of aging
DESIGN: Cohort study. individuals rises steadily in the United States, with an
METHODS: A five-year minimum of data (June 1, 1990 estimated 3.36 million individuals affected by 2020.1
through January 22, 2002) was collected on 151 patients Although it is known that old age, thin corneas, and
(302 eyes) from 12 United States specialty centers. A elevated or variable intraocular pressure (IOP) are factors
post hoc analysis of visual field (VF) progression, glau- associated with the progression of visual field loss (VFL)
coma medication, intraocular pressure (IOP), and other from glaucoma,1 half of the individuals affected with
ocular data was conducted for two nonmutually exclusive glaucoma are not aware that they have the disease,
cohorts based on retrospective data abstracted well after leaving them at greater risk for vision loss.1 Better
actual patient visits. Mean IOP and standard deviations detection of the disease and an understanding of what
(SD) were calculated before treatment (medication or contributes to progression of glaucoma are needed to
surgery) or progression, whichever occurred first, and prevent vision loss effectively.
before progression regardless of treatment. IOP variables The course of primary open-angle glaucoma (POAG)
were assessed in a univariate fashion; Cox proportional has been associated largely with IOP, with the progression
hazards models evaluated glaucoma progression as an of POAG directly related to elevated IOP.25 Numerous
outcome measure and IOP SD as a main predictor, studies have explored the predictors for progression of
controlling for covariates. POAG. The degree of optic nerve damage, resulting from
RESULTS: In cohort 1 (55 patients; 84 eyes), mean age
factors such as varying optic nerve sensitivities to IOP and
was 63 years (range, 37 to 85 years), 58% were female, vascular insufficiencies, has been noted as a key predictor
and 19% of eyes underwent VF progression. In cohort 2 of glaucoma progression.6 Other factors such as age, type
(129 patients; 251 eyes), mean age was 66 years (range, and length of treatment provided, and existing visual field
19 to 88 years), 55% were female, and 27% of eyes (VF) damage also are among the prominent predictors of
underwent VF progression. Mean IOP was 16.5 mm Hg POAG progression.4,6 8
(IOP SD, 2.0 mm Hg), and 16.4 mm Hg (IOP SD, 2.7 The Early Manifest Glaucoma Trial (EMGT) was de-
mm Hg) in cohorts 1 and 2, respectively. Controlling for signed to evaluate the effect of immediate treatment on
age, mean IOP, VF stage, and other covariates, each unit glaucoma progression compared with no initial treatment
increase in IOP SD resulted in a 4.2 times and 5.5 times or later treatment.4 The EMGT showed an association
higher risk of glaucoma progression for cohort 1 (95% between higher baseline IOP and an increased rate of
confidence interval [CI], 1.3 to 12.9) and cohort 2 (95%
glaucoma progression.1 Specific IOP parameters, such as
CI, 3.4 to 9.1), respectively.
mean IOP and IOP variability, recently were examined for
CONCLUSIONS: IOP variability is an important predic-
their influence on POAG progression.6,7 Continuous sup-
tor of glaucoma progression; SD is a convenient measure
pression of IOP has been found necessary in those with
of variability to assess glaucoma progression risk. (Am
POAG to minimize disease progression that eventually can
J Ophthalmol 2007;144:901907. 2007 by Elsevier
lead to blindness.9 Various medical and surgical treatments
Inc. All rights reserved.)
have focused on lowering a subjects IOP.
Nonetheless, studies have indicated that, although a
Accepted for publication Jul 30, 2007.
lower IOP exhibits a protective effect regarding glaucoma
From the Duke University Eye Center, Durham, North Carolina progression, it does not necessarily indicate that one is free
(P.P.L.); Allergan, Inc, Irvine, California (J.W.W.); and Analytica of risk. In a study by Oliver and associates, patients
International, New York, New York (L.C.R., L.R.S., L.S.S.).
Inquiries to Lee S. Stern, Analytica International, 450 Park Avenue becoming legally blind from glaucoma were compared with
South, 12th Floor, New York, NY 10016; e-mail: lstern@analyticaintl.com those who did not go blind.6 It was found that progression
CPSD corrected pattern standard deviation; MD mean deviation; OHT ocular hypertension; PSD pattern standard deviation; VF
visual field.
IOP intraocular pressure; SD standard deviation. IOP intraocular pressure; SD standard deviation.
Cohort 1 consisted of patients with two or more IOP measure- Cohort 2 consisted of patient with two or more IOP measure-
ments before treatment or progression (whichever occurred ments before progression, regardless of whether they had
first); n 55 patients, 84 eyes. undergone treatment; n 129 patients, 251 eyes.
MULTIVARIATE ANALYSES: A multivariate model was family history of glaucoma (n 109, or 72%), 53% had a
developed for cohort 1 with POAG VFL progression as the positive family history for the disease.
outcome variable and SD of IOP as a key predictor
variable. Several eye- and patient-level variables were UNIVARIATE ANALYSES: Univariate analyses of cohort
tested in the model. Eye-level variables included SD of 1 were performed to determine IOP variation, as measured by
IOP, mean IOP, absolute difference between best (lowest) SD of IOP, before treatment or VF progression, whichever
and worst (highest) IOP (also referred to as range of IOP occurred first; this cohort consisted of 55 patients (84 eyes).
in the literature), absolute difference between first and last More than half of these individuals (58.2%) were female. The
IOP, stage before progression, medication use before pro- patients ranged in age from 37 to 85 years, with the mean age
gression (tested as two variables: yes or no and number of of this population being 62.9 years (SD, 11.4 years). Among
medications), and whether treatment with medication the eyes examined, 19% were found to have had VF progres-
preceded surgery. Patient-level variables tested were age, sion (Table 2). Before progression or treatment, mean IOP
gender, lowest overall VFL stage per person, and first was found to be 16.5 mm Hg, with a mean SD of IOP of 2.0
calendar year of follow-up. The final model was a Cox mm Hg (range, 14.2 to 22.1 mm Hg; Table 2).
proportional hazards model with progression (time to Univariate analyses of cohort 2 were performed to
progression) as the outcome measure and SD of IOP as the determine IOP variation, as measured by SD of IOP,
main predictor, while controlling for covariates. Mean IOP before VF progression, regardless of treatment; this
was included as a continuous variable in the model. All cohort consisted of 129 patients (251 eyes). Demographics
independent variables of interest with adequate sample size were similar to those of cohort 1: 55% were female, and
were tested in a model. Variables with P .2 were mean age was 66 years (SD, 12 years; range, 19 to 88
removed from the final model. Although nonsignificant in years). Among these eyes, 27% were found to have had VF
the cohort 1 model, gender was retained because of progression (Table 3). Before progression, mean IOP was
previously demonstrated associations between gender and found to be 16.4 mm Hg, with a mean SD of IOP of 2.7
glaucoma treatment. The Cox proportional hazards model mm Hg (range, 4.6 to 27.3 mm Hg; Table 3).
for cohort 2 was based on the same variables as were used
in cohort 1 as a means of comparison. MULTIVARIATE ANALYSES: The Cox proportional haz-
ards model for cohort 1, with VF progression (time to
progression) as the outcome measure and SD of IOP as the
RESULTS main predictor while controlling for key covariates, found
both the mean and SD of IOP before treatment or progression
DESCRIPTIVE STATISTICS: This study evaluated data to be associated significantly with the likelihood of progres-
from a chart review of 302 eyes among 151 patients. Mean sion. Each 1-mm Hg unit increase in IOP SD increased the
age was 66.3 years (SD, 11.9 years). Sixty-three individuals likelihood for glaucoma progression by a factor of 4.2 (95%
(42%) in the study population were male, and 86 (57%) confidence interval [CI], 1.3 to 12.9). Each 1-mm Hg increase
were female. Breakdown by race revealed that 70 patients in mean IOP resulted in a 20% increase in likelihood of
(46%) were White, 33 (22%) were Black, and seven (5%) glaucoma progression (95% CI, 1.0 to 1.4). An increased
were Asian; no data on race were available for the difference between highest and lowest IOP was associated
remaining 27%. Of those patients with data available on with a decreased likelihood of progression (odds ratio [OR],
THIS STUDY WAS SUPPORTED BY AN UNRESTRICTED GRANT FROM ALLERGAN, INC, IRVINE, CALIFORNIA. DR LEE IS A
consultant and has received research support and travel funds from Allergan, Inc. Dr Walt is an employee of Allergan, Inc. Drs Rosenblatt and Stern
are employees of Analytica International and were employed by Allergan, Inc, to conduct research and analyses. Dr Siegartel was an employee of
Analytica International at the time this study was conducted. Involved in the design of study (P.P.L., J.W.W.); conduct of study (P.P.L., J.W.W.,
L.C.R.); data collection (P.P.L., L.C.R.); management (J.W.W., L.S.S.); and analysis, interpretation, manuscript preparation, review, and approval
(P.P.L., J.W.W., L.C.R., L.R.S., L.S.S.).
THE GLAUCOMA CARE STUDY GROUP
Paul P. Lee, Duke University Medical Center, Durham, NC John G. Walt, Allergan, Inc, Irvine, CA John J. Doyle, The Analytica Group, New
York, NY Sameer V. Kotak, The Analytica Group, New York, NY Stacy J. Evans, The Analytica Group, New York, NY Donald L. Budenz,
University of Miami, Miami, FL Philip P. Chen, University of Washington, Seattle, WA Anne L. Coleman, University of Washington, Seattle, WA
Robert M. Feldman, University of Texas, Houston, TX Henry D. Jampel, Johns Hopkins University, Baltimore, MD L. Jay Katz, Wills Eye Hospital,
Philadelphia, PA Richard P. Mills, University of Kentucky, Lexington, KY Jonathan S. Myers, Wills Eye Hospital, Philadelphia, PA Robert J.
Noecker, University of Arizona, Tucson, AZ Jody R. Piltz-Seymour, University of Pennsylvania Health System, Philadelphia, PA Robert R. Ritch,
New York Eye & Ear Infirmary, New York, NY Paul N. Schacknow, Palm Beach Eye Foundation, Lake Worth, FL Janet B. Serle, Mount Sinai School
of Medicine, New York, NY Gary L. Trick, Henry Ford Health System, Detroit, MI.