the presence of 2 claims for ICD-9-CM code 362.52, which
carries high specificity for neovascular AMD and is not
shared with any other eye condition. In addition, nearly
all diagnoses (94%) were made by a specialist. Control
patients were also excluded if other macular disorders
that may progress to neovascular AMD were diagnosed.
Variables such as race/ethnicity, smoking, exercise, or
diet were not available for analysis. In particular, smok-
ing has been linked to neovascular AMD, heart disease,
Other studies have shown a higher preva-
lence of neovascular AMD among white individuals than
black individuals, but black individuals were more likely
to develop MI or CVA.
According to the 2005 US Cen-
sus Bureau, about 81.5% of people older than 45 years
Among individuals without diabetes older
than 50 years, Centers for Disease Control and Preven-
tion data from the 2002 National Health Interview Sur-
vey show that 74.4% (95% CI, 60.8%-88.1%) of patients
with macular degeneration were white.
Thus, the ob-
served and expected proportions are not remarkably dif-
ferent and variations in race distribution between pa-
tients with neovascular AMD and controls are not likely
to have a significant impact on the outcomes. Smoking,
exercise, or dietary habits may be different between the
cohorts in this study and the impacts of these variables
on the outcomes are unknown.
As with all claims studies, limitations exist in the re-
liability of the ICD-9-CM codes selected to detect events.
In published analyses of ICD-9-CM–coded MI events,
PPVs of 87% to 97% have been reported when validated
by medical record reviews, denoting a high specificity of
the outcome when it is coded.
dent–coded events in the literature have shown a wider
PPV range from 62% to 92%.
The claims profile re-
view in this study resulted in PPVs of 71% for MI and
66% for CVA. Claims profiles and not medical records
were reviewed by 3 physicians in this study. Lower PPVs
and interrater agreement are expected since claims data
do not contain clinical notes or laboratory and diagnos-
tic results that aid in the confirmation of the outcomes
(ie, cardiac enzymes, electrocardiogram, imaging stud-
ies, angiography). The greater variability in the CVA group
may be because of the use of different ICD-9-CM code
groups to define CVA, which would cause a change in
the sensitivity and specificity of case ascertainment. Lastly,
only hospitalized events were included as outcomes to
improve the reliability of detecting a true outcome.
Event rates for MI or CVA in this study are limited by
the ability to detect these events through hospitaliza-
tion. Events that occur outside the hospital setting may
not have been counted, such as those resulting in death
prior to admission. The mortality rate is not known in
our sample. Loss of events because of preadmission deaths
or nonhospitalized events could result in an underesti-
mate of event rates for both groups. Although the mag-
nitude and direction of missed events on the outcome is
unknown, if undetected MI and CVA were to occur se-
lectively more often in the neovascular AMD group, then
this could explain some of the difference. Finally, the re-
liability of event rates in this study is supported by their
similarity to those in the Cardiovascular Health Study
(CHS). The CHS evaluated 5288 participants 65 years or
older and reported the incidence of MI and CVA at 13.7
per 1000 PY and 11.5 per 1000 PY, respectively. The in-
cidence rates in our study were similar to that of the CHS
at 11.3 MIs per 1000 PY and 9.7 CVAs per 1000 PY.
Few studies have been conducted in a large sample
of subjects with a diagnosis of neovascular AMD describ-
ing and comparing the rates of cardiovascular out-
comes. Two recent studies on the association of neovas-
cular AMD to MI or CVA outcomes have yielded mixed
results. In the current study, the risk of hospitalized MI
and CVA was found to be inversely associated with the
diagnosis of neovascular AMD. The relationship be-
tween neovascular AMD and cardiovascular disease re-
mains unclear and warrants further study.
Submitted for Publication: March 19, 2007; final revi-
sion received February 19, 2008; accepted February 20,
Correspondence: Bao-Anh Nguyen-Khoa, PharmD,
MPH, 1616 N Fort Myer Dr, Ste 1430, Arlington, VA 2220
Author Contributions: The Degge Group had full ac-
cess to all of the data in the study and takes responsibil-
ity for the integrity of the data and the accuracy of the
data analyses. Dr Werther provided feedback in the con-
ception and design of the study, participated in critical
revision of the manuscript for important intellectual con-
tent, and provided supervision of the internal manu-
script review process.
Financial Disclosure: Dr Jones is president of The Degge
Group. Dr Nguyen-Khoa and Mr Goehring are employ-
ees of The Degge Group. Dr Werther is an employee of
Funding/Support: The Degge Group received funding for
the conduct of this study from Genentech, Inc. Dr Wer-
ther, senior epidemiologist at Genentech Inc, repre-
sents the study sponsor.
Role of the Sponsor: Neither Genentech Inc nor any rep-
resentative of the sponsor took part in the collection, man-
agement, analysis, or interpretation of the data. Study re-
sults were shared with the study sponsor.
Additional Contributions: Varinder P. Singh, MS, per-
formed data management and analysis and John C. Pez-
zullo, PhD, performed statistical analysis.
1. Klein R, Wang Q, Klein BE, Moss SE, Meuer SM. The relationship of age-related
maculopathy, cataract, and glaucoma to visual acuity. Invest Ophthalmol Vis Sci.
2. Leibowitz HM, Krueger DE, Maunder LR, et al. The Framingham Eye Study mono-
graph: an ophthalmological and epidemiological study of cataract, glaucoma, dia-
betic retinopathy, macular degeneration, and visual acuity in a general popula-
tion of 2631 adults, 1973-1975. Surv Ophthalmol. 1980;24(suppl):335-610.
3. Friedman DS, O’Colmain BJ, Munoz B, et al. Prevalence of age-related macular
degeneration in the United States. Arch Ophthalmol. 2004;122(4):564-572.
4. Klein R, Klein BE, Tomany SC, Meuer SM, Huang GH. Ten-year incidence
and progression of age-related maculopathy: The Beaver Dam eye study.
5. Snow KK, Seddon JM. Do age-related macular degeneration and cardiovascular dis-
ease share common antecedents? Ophthalmic Epidemiol. 1999;6(2):125-143.
6. Klein R, Clegg L, Cooper LS, et al. Prevalence of age-related maculopathy in the
Atherosclerosis Risk in Communities Study. Arch Ophthalmol. 1999;117(9):
(REPRINTED) ARCH OPHTHALMOL / VOL 126 (NO. 9), SEP 2008 WWW.ARCHOPHTHALMOL.COM
©2008 American Medical Association. All rights reserved.
at Johns Hopkins University, on June 14, 2010 www.archophthalmol.comDownloaded from