Cost-effectiveness of Vitamin Therapy for
Age-Related Macular Degeneration
David B. Rein, PhD,1Jinan B. Saaddine, MD, MPH,2John S. Wittenborn, BS,1Kathleen E. Wirth, BA,1
Thomas J. Hoerger, PhD,1K. M. Venkat Narayan, MD,2Traci Clemons, PhD,3Stephen W. Sorensen, PhD2
patients diagnosed with age-related macular degeneration (AMD).
We compared the impacts of vitamin therapy with those of no vitamin therapy using a computerized,
stochastic, agent-based model. The model simulated the natural history of AMD and patterns of ophthalmic
service use in the United States in a cohort from age 50 years until 100 or death.
Participants and/or Controls:
The model created 20 million simulated individuals. These individuals each
received both the intervention (vitamin therapy after diagnosis) and the control (no vitamin therapy). Expected
outcomes generated when vitamins were taken after diagnosis were compared with the expected outcomes
generated when they were not.
The model created individuals representative of patients in the U.S. Incidence of early AMD was
based on published studies, as was vision loss and response to choroidal neovascularization therapies.
Post–incident disease progression was governed by previously unpublished data drawn from the Age-Related
Eye Disease Study.
Main Outcome Measures:
Extent of disease progression, years and severity of visual impairment, cost of
ophthalmic care and nursing home services, and quality-adjusted life years (QALYs). Costs and benefits were
considered from the health care perspective and discounted using a 3% rate. The analysis was run for 50 years
starting in 2003.
Compared with no therapy, vitamin therapy yielded a cost-effectiveness ratio of $21 387 per QALY
gained and lowered the percentage of patients with AMD who ever developed visual impairment in the
better-seeing eye from 7.0% to 5.6%.
Our model demonstrates that vitamin therapy for AMD improves quality of life at a reasonable
cost. Ophthalmology 2007;114:1319–1326 © 2007 by the American Academy of Ophthalmology.
To determine the cost-effectiveness of vitamin therapy (antioxidants plus zinc) for all indicated
Age-related macular degeneration (AMD) is the leading
cause of blindness and visual impairment among ?65-year-
olds in the United States and the industrialized world. Ap-
proximately 1.75 million Americans over age 50 are living
with advanced vision-threatening AMD, and this number is
expected to increase 50% to 2.95 million by 2020.1Recent
evidence has found that AMD patients who take high-dose
antioxidant plus zinc vitamin supplements* during the early
stages of AMD are at a reduced risk of choroidal neovas-
cularization and geographic atrophy (GA), the advanced
vision-threatening symptoms of AMD.2
Although 2 studies3,4have evaluated the potential impact
of vitamin supplements, neither has estimated the cost-
effectiveness within the context of the U.S. health care
system. The first, the Age-Related Eye Disease Study
(AREDS),3estimated that as many as 300 000 cases of
advanced AMD could be avoided in the U.S. over 5 years if
all eligible patients took vitamin supplements containing
antioxidants plus zinc; however, the study did not consider
the economic impact. The second, Hopley et al,4did esti-
mate the cost-effectiveness ratio (CER) of vitamins (ap-
proximately $31 800 [£18 948] in March 2003—per quality-
adjusted life year [QALY]) but presented results only for
patients 65 years and older, used data from Australia and
Great Britain, and included the cost of diagnostic screening
as part of the vitamin intervention.
This study is the first to assess the independent incre-
mental cost-effectiveness of prescribing antioxidants plus
zinc for cases of AMD diagnosed in the course of routine
ophthalmic eye care compared with no use of vitamins for
those same patients. We look at the impact for all patients
older than 50 years with AMD using U.S. cost and preva-
Originally received: May 2, 2006.
Accepted: October 26, 2006.
1RTI International, Research Triangle Park, North Carolina.
2Division of Diabetes Translation, National Center for Chronic Disease
Prevention and Health Promotion, Centers for Disease Control and Pre-
vention, Atlanta, Georgia.
3Emmes Corp., Rockville, Maryland.
Funding for this research was provided by the Division of Diabetes
Translation, Centers for Disease Control and Prevention (contract no.
2957 Flowers Road, Suite 119, Atlanta, GA 30341. E-mail: email@example.com.
*Age-Related Eye Disease Study antioxidant plus zinc vitamin supple-
ments contained 500 mg of vitamin C, 400 IU of vitamin E, and 15 mg of
?-carotene, plus 80 mg of zinc as zinc oxide and 2 mg of copper as cupric
oxide to prevent potential anemia.
Manuscript no. 2006-502.
© 2007 by the American Academy of Ophthalmology
Published by Elsevier Inc.
ISSN 0161-6420/07/$–see front matter
lence data. As a result, this study can be used to provide
cost-effectiveness information to inform normal ophthalmic
practice for patients diagnosed with AMD in the U.S. This
study also presents a new natural history model of AMD,
based on the symptoms of large drusen and retinal pigment
epithelium (RPE) abnormalities and driven by previously
unpublished evidence from the AREDS.
Materials and Methods
We developed a stochastic agent-based model in which simulated
individuals are created at age 50 years and observed until death or age
100. The model simulated 20 million discrete individuals who varied
in terms of their demographic characteristics, longevity, and use of
normal ophthalmologic care. Stochastic microsimulation models have
been used in the past to evaluate the cost-effectiveness of interven-
tions to treat diabetic retinopathy and retinopathy of prematurity.5–7
All individuals in the model also could develop AMD, of course. The
model tracked each patient’s costs, incidence and subsequent progres-
sion of AMD (if any), visual impairment resulting from AMD, and
patient QALYs lived. Visual impairment and blindness were deter-
mined based on the functionality of an individual’s better-seeing eye,
accounting for losses of acuity, and contrast sensitivity (CS). Patient
quality of life decreased based on the extent of visual impairment. For
each simulated person, the model tracked years of visual loss and
blindness, QALYs, and ophthalmologic costs related to routine oph-
thalmologic care, AMD vitamin prophylaxis and medical treatment,
and nursing home placement. For this analysis, we evaluated costs
from the health care perspective and excluded such costs as the time
of informal caregivers and lost productivity due to visual impairment.
The AMD simulation is part of a larger Multiple Eye Disease Simu-
lation model [Rein DB, Wittenborn JS, Wirth KE, et al. Developing
a multiple eye disease simulation model (no. 28). Presented at: 3rd
RTI Fellows Symposium, April 3–4, 2006, Chapel Hill, North Caro-
lina] and is programmed in AnyLogic (XJ Technologies Co., Ltd., St.
Upon model initiation, the model simulated a certain percentage of
patients with GA and choroidal neovascularization and early
preadvanced AMD, based on the percentage of the population with
these conditions at age 50 years.1The vast majority of patients
were not assigned AMD at initiation and instead experienced an
annual probability of incident AMD in subsequent years of the
model. Patient AMD progression was evaluated based on a joint
assessment of both eyes until the patient’s first eye progresed to
advanced AMD, after which the model simulated disease progres-
sion in each eye independently.
Our conceptual model of AMD and the probabilities of patient
progression from one stage to another were based on previously
unpublished data obtained from the AREDS.8Groups of patient
symptoms were categorized into discrete states with the same
probability of progression to advanced AMD (GA or choroidal
neovascularization) in the AREDS data. In the AREDS, progres-
sion to advanced AMD was best predicted based on a joint assess-
ment of both eyes of the patient. Consequently, in our model
patient disease states were based on the presence or absence of
large drusen (?125 ?m) or RPE abnormalities in one or both eyes.
Patients with early and intermediate AMD were categorized into
mutually exclusive states numbered 0 to 4. State 0 patients had no
large drusen or RPE abnormalities in either eye; state 1 patients
had either large drusen in one eye or RPE abnormalities in one eye,
with no other symptoms; state 2 patients had large drusen in both
eyes, with no RPE abnormalities, RPE abnormalities in both eyes
with no large drusen, or large drusen and RPE abnormalities in one
eye each; state 3 patients had large drusen in both eyes, with RPE
abnormalities in one eye, or RPE abnormalities in both eyes with
large drusen in one eye; and state 4 patients had large drusen and
RPE abnormalities in both eyes (Table 1).
Patients in states 1 through 4 had an estimated yearly proba-
bility of moving to any other state, including the advanced AMD
states of GA and choroidal neovascularization (Fig 1). Contrary to
popular perceptions of AMD, AREDS patients were observed
moving forward and backward among all preadvanced AMD
states. Our model incorporated both forward and backward tran-
sitions (backward transitions not shown in Fig 1). Eyes with GA
also could develop choroidal neovascularization, whereas eyes that
developed choroidal neovascularization remained there until a
patient’s death.9,10Based on its proximity to the fovea, choroidal
neovascularization was classified as extrafoveal, juxtafoveal, or
subfoveal, with treatment options and the annual probability of
visual loss depending on type.11
Loss of visual function occurred only from advanced AMD.
Eyes with GA or choroidal neovascularization had an annual
probability of losing 0.3 or 0.6 log units of acuity2,12,13and 0.3 or
0.75 log units of CS, which could be mediated by treatment.12At
the end of each year, based on the worse impairment level of acuity
or CS, eyes were categorized into 1 of 6 impairment categories: none,
mild, moderate, U.S.-defined blindness, World Health Organization–
defined blindness, and severe blindness based on the best-corrected
visual function of the better-seeing eye.14
Progression Parameters, Care and Costs
of Complications, and Health Utilities
Age-related macular degeneration prevalence at model initiation
(age 50 years) was based on a meta-analysis of population-based
study data.1Subsequent incidence of AMD (movement from state
0 to state 1 or higher) was set according to age using incidence
estimates obtained from population-based studies.15–19Transitions
among states 1 through 4 and from those states to GA and cho-
roidal neovascularization were based on a data matrix of transition
probabilities estimated by the AREDS group.20All patients diag-
nosed with AMD were assumed to have received medical treat-
ment and services recommended by the American Academy of
Ophthalmology’s preferred practice patterns.11For example, all
patients with extrafoveal or juxtafoveal choroidal neovasculariza-
tion received photocoagulation or focal laser surgery. Costs for
these services were assigned based on the Centers for Medicare &
Medicaid Services fee schedule.20,21Because patients with visual
impairment and blindness are at an elevated risk of using nursing
home services,22the model also tracked the use and costs of
nursing home services.23
Table 1. Risk States for the Development of Advanced Age-
Related Macular Degeneration (AMD) in the First Eye Based
on the Large Drusen and Pigment Abnormality Status of Both
Eyes with Large Drusen
Eyes with Pigment Abnormalities
Volume 114, Number 7, July 2007
Patient QALYs were calculated annually by multiplying the
value of 1 minus patients’ visual impairment–related health utility
decrement (if any) by a uniform background utility of 0.87 (the
average health utility of people at age 50 years). Annual health
utilities were discounted to the base year and summed for all years
of life. Health utility decrements were based on published studies
of QALY decrements associated with visual impairment calculated
using a time-tradeoff approach.24
Normal Use of Ophthalmic Services
Based on a National Center for Health Statistics–suggested meth-
odology,25we used the 2002 National Ambulatory Medical Care
Survey data26to identify the annual number of patients with any
ophthalmologist visit and assumed that a diagnostic screen for
AMD (slit-lamp biomicroscopy) would occur at all visits for
patients in this age range. Our resulting estimated rates of service
use were similar to those found in other studies.27
Calibration and Validation
To calibrate the model, we compared its results to the proportion of
patients with intermediate AMD (states 1–4), advanced AMD (GA
and choroidal neovascularization), visual impairment, and blindness
reported by a National Eye Institute (NEI)–sponsored meta-analysis
of population-based epidemiological studies.1We then altered the
model’s age-specific transition probabilities from state 0 to state 1
(incidence of AMD) within the range of possible values reported in
the literature while holding all other transition probabilities constant
until our model resulted in the best fit of the NEI data. Because the
model underpredicted cases of GA, we increased all transitions to GA
in the model by 10%. This adjustment still resulted in an underpre-
diction of GA relative to the NEI data, but one that was less extreme
than first observed.20
outlined by the International Society for Pharmacoeconomics and
Outcomes Research Task Force.28Internal testing was conducted by
altering parameters to extreme values and assessing the impact on
results. A degree of external validation was gained through our
calibration of results against the NEI data because our model gener-
ates prevalence values similar to those of the NEI study after cali-
brating only the parameters governing progression from state 0 to
state 1 and subsequent progressions from states 1 through 4 to GA.
We evaluated the impact of treating all patients diagnosed with
AMD in either eye in states 1 through 4 with antioxidant plus zinc
Figure 1. Natural history of age-related macular degeneration shown in disease states (boxes) and possible transitions between states (lines) for a patient’s
first eye and second eye (backward transitions not shown). CNV ? choroidal neovascularization; EF ? extrafoveal; GA ? geographic atrophy; JF ?
juxtafoveal; SF ? subfoveal.
Rein et al ? Cost-effectiveness of Vitamins to Prevent Advanced AMD
vitamin supplements as recommended by the AREDS research
group.2The AREDS identified a 25% risk reduction of disease
progression among patients taking vitamin supplements, compared
with those taking a placebo. In our intervention scenario, patients
diagnosed with AMD received vitamin therapy, with the effect of
reducing their annual forward transition probabilities from states 1
through 4 by 25%. Vitamin therapy was assumed to have no
impact on backward transitions or transitions from GA to choroi-
Cost-effectiveness Analysis and Other Outcomes
We report the costs of vision-related medical care, vision-related
nursing home placements, and total costs. Vision-related medical
care includes the cost of the normal use of ophthalmic services,
cost of additional ophthalmologic services needed to monitor
AMD after a diagnosis, cost of vitamin therapy for AMD, and
costs of laser therapy and photodynamic therapy to treat choroidal
neovascularization. Vision-related nursing home costs include the
incremental nursing home placements attributable to visual impair-
ment and blindness. We also report the percentage of AMD pa-
tients who ever entered AMD states 2, 3, and 4 (all incident AMD
patients are assumed to enter state 1), percentage of AMD patients
with choroidal neovascularization or GA in either eye, percentage
of AMD patients who had visual impairment or blindness in at
least one eye, and percentage of AMD patients who had visual
impairment or blindness in the better-seeing eye.
One-Way Sensitivity Analysis
To test the sensitivity of the model to uncertain parameters, we
increased and decreased the risk-reduction benefit of vitamins by
10 percentage points (15%–35%) and doubled and nearly halved
the cost of vitamins. The base vitamin costs were based on the
average prices observed in a survey of online and retail prices and
redbook average wholesale prices for each vitamin component.
Recently, a branded single daily pill vitamin meeting the AREDS
dosing recommendations was marketed at a price similar to or
higher than our baseline price. Doubling the cost of vitamins
reflects the higher price of daily vitamin supplements targeting
AMD and also may capture additional unobserved costs of any
rare adverse complications of intensive vitamin therapy. The lower
vitamin price was calculated based on the minimum observed
vitamin price ($59.06), slightly over half the baseline cost. We
varied the probability of developing GA and choroidal neovascu-
larization by adjusting all transitions in the model to GA and
choroidal neovascularization upward and downward by 25% and
considered the cost-effectiveness of vitamins when long-term care
costs were excluded. We also varied the discount rate from 0% to
5%. We report full results for the discount rate and risk reduction
associated with vitamins. For other variables, we report only the
result that could challenge the conclusion of the model’s point
Vitamin therapy offered to all patients diagnosed with AMD in
states 1 through 4 led to an undiscounted decrease of 0.036 years
of visual loss per person in the model and an increase of dis-
counted QALYs of 0.004. When considering only those with
AMD, as opposed to the entire population, visual loss per person
decreased by 0.095 years and QALYs increased by 0.011. Includ-
ing the cost of vitamins, treatment costs per person in the sample
increased from $583 to $721, whereas per-person nursing home
costs decreased from $266 to $217. Total costs, compared with no
vitamin therapy, increased by $88 per person. The CER was
$21 387 per QALY gained (Table 2). Relative to no vitamin
therapy, the percentage of patients with AMD who ever developed
GA in either eye dropped from 10.1% to 8.1%, and the percentage
who ever developed choroidal neovascularization in either eye
dropped from 16.0% to 13.0%. The percentage of patients with
AMD who ever developed visual impairment or blindness in either
eye dropped from 21.4% to 17.4%, and the percentage who ever
developed visual impairment or blindness in the better-seeing eye
dropped from 7.0% to 5.8% (Fig 2).
Exclusion of long-term care costs had a relatively minor impact on
the cost-effectiveness of vitamin therapy. Decreasing the risk-
reduction benefit of vitamin therapy to 15% and decreasing the
baseline probability of developing GA and/or choroidal neovascu-
larization by 25% had a moderate impact on the cost-effectiveness
of vitamin therapy. Changes in the discount rate and cost of
vitamins had a more dramatic impact on results (Fig 3). Excluding
nursing home costs increased the CER to $33 250. Decreasing the
impact of vitamins increased the CER to $47 351. Similarly,
decreasing the probability of GA and choroidal neovascularization
by 25% increased CERs to $43 424 and $47 085 per QALY,
respectively. Changing the annual cost of vitamins had the most
substantial impact. Doubling vitamin costs from $114.23 to
$228.46 increased discounted costs per person by $279 (with no
corresponding increase in QALYs), resulting in a CER of $61 683.
Using the minimum observed prices for vitamins resulted in a
slightly cost-saving CER of ?$865.
Vitamin therapy improves visual outcomes by delaying or
preventing the onset of advanced AMD while also increas-
ing health care costs. The cost-effectiveness of vitamin
therapy ($21 387/QALY) compares favorably with other
interventions and treatments to prevent AMD-related visual
impairment and blindness. For example, laser photocoagu-
lation therapy for extrafoveal choroidal neovascularization
Table 2. Incremental Cost-Effectiveness by Intervention
Years of Visual
Impairment and BlindnessQALYs
Ratio (Total Cost/QALY)
AMD Nursing HomeTotal
Vitamin therapy for all diagnosed
AMD ? age-related macular degeneration; QALY ? quality-adjusted life years.
Volume 114, Number 7, July 2007
was found to have a CER of $24 720 per QALY (2004
dollars),29similar to our finding for vitamins. The cost-
effectiveness of photodynamic therapy with verteporfin to
treat subfoveal choroidal neovascularization was estimated
at $92 499 (2004 dollars) per QALY in the U.S.30and, more
recently, at approximately $70 000 per QALY in Great
Britain.31Vitamin therapy for AMD appears to be a rea-
sonable investment of health resources compared with other
Figure 2. Cumulative incidence of age-related macular degeneration (AMD) states and complications among those with AMD (i.e., those who ever
reached AMD state 1). CNV ? choroidal neovascularization; GA ? geographic atrophy; VI ? visual impairment.
Figure 3. Sensitivity of cost-effectiveness ratio to changes in major model assumptions. CNV ? choroidal neovascularization; GA ? geographic atrophy;
LTC ? long-term care; QALY ? quality-adjusted life year.
Rein et al ? Cost-effectiveness of Vitamins to Prevent Advanced AMD
interventions, although there is no consensus regarding
what constitutes an acceptable CER other than a cost-saving
Vitamin therapy also compared favorably to many public
health preventive services using the comparative methodol-
ogy employed by the National Commission on Prevention
Priorities.33Assuming a compliance rate among those pre-
scribed above 85%, vitamin therapy for patients diagnosed
with early and intermediate AMD would be considered as
high a priority as breast cancer screening for women older
than 50 years, Chlamydia screening for sexually active
women younger than 25, calcium chemoprophylaxis for
adolescent and adult women to prevent fractures, and vision
screening for children to detect amblyopia, strabismus, and
defects in visual acuity (VA).33Even at compliance rates as
low as 30%, vitamin therapy is as desirable as the use of
folic acid to prevent birth defects and routine screening for
obesity with behavioral interventions for obese patients.33
At both compliance levels, vitamin therapy is more fa-
vorable than several other interventions such as screenings
for depression, hearing, cholesterol risk, osteoporosis, or
diabetes or counseling to prevent injury. Vitamin therapy is
not as favorable as some low-cost high-benefit interventions
such as screening for VA defects among adults older than
65 years or aspirin chemoprophylaxis to prevent cardiovas-
cular events. However, the marginal impact of promoting
the policy may be quite large even in comparison with these
interventions, because the percentage of those diagnosed
with early or intermediate AMD who are prescribed and use
vitamins may be well below 50%. A study of eligible
Australian AMD patients found that 53% of participants
were aware of the availability of a vitamin formula to
prevent advanced AMD, 38% were taking the supplement,
and only 1% were taking the correct dose.34The level of
knowledge of and compliance with vitamin therapy in the
U.S. is unknown, but if it is similar to Australian levels, then
promoting vitamin therapy for patients diagnosed would
qualify as a top prevention priority (tied for sixth highest)
by the National Commission on Prevention Priorities.
Our model’s results were most sensitive to estimates of
the discount rate and price of vitamin therapy. Sensitivity to
the discount rate is a result of many of the benefits of
vitamin therapy being realized at late ages. We observed a
cost-neutral to cost-saving CER using the minimum ob-
served market prices for vitamins. However, it is very
unlikely that consumers could obtain this price, and in fact,
they may be more likely to purchase single-pill AMD sup-
plements that typically cost as much as or more than the
average observed price used in the analysis. Our model also
assumed no direct effect of vitamin therapy on backward
transitions (improvements in symptoms). If vitamins lead to
improvements in symptoms as well as simply slow forward
progression, their cost-effectiveness would be even better.
After adjusting for differences in the definition of AMD,
our model35adequately replicates the prevalence of AMD
reported in the NEI meta-analysis.1The model also closely
reproduces the combined prevalence of advanced AMD,
although it does so by somewhat overpredicting choroidal
neovascularization and underpredicting GA.
Several therapies, excluded from our model, are or will
shortly be available to treat AMD-related choroidal neovas-
cularization. Drugs to treat vascular endothelial growth fac-
tor, such as pegabtanib sodium injections and ranibizumab,
have demonstrated effectiveness as treatments for choroidal
neovascularization.36Other possible choroidal neovascular-
ization treatments include corticosteroids with antiangio-
genic properties and juxtasclerally administered intravitreal
triamcinolone and anecortave.36These technologies may be-
come integrated into the treatment of choroidal neovascular-
ization, likely resulting in better long-term visual outcomes but
possibly at substantially increased costs. Future research
should evaluate the cost-effectiveness of these treatments rel-
ative to existing treatments and incorporate these results into
models such as ours that evaluate the cost-effectiveness of
prophylactic treatments given to those diagnosed with early
and intermediate disease.
Our study finds a CER similar to that found by its closest
counterpart ($31 800),4despite several key differences be-
tween the 2 studies. These differences include the fact that
the former study considered the joint benefits of vitamins
and screening; reported results only for those older than 65
years, whereas this study supports the use of vitamins for all
patients 50 and over; used Australian epidemiological, med-
ical cost, and life expectancy data; assumed no screening
occurred in the absence of the intervention; and did not
include the cost of nursing home care. The similarity of our
results, despite these differences, adds evidence supporting
vitamin therapy as a cost-effective treatment for AMD. Of
note, this study evaluated the cost-effectiveness of treating
only those patients diagnosed during the course of routine
ophthalmic care. The incremental cost-effectiveness of add-
ing additional screening to hasten diagnosis is likely to be
less favorable. However, any such screenings also might
identify other ocular disorders, thus increasing their overall
This research is limited by several assumptions. First, our
model considers cost from the health care perspective and
does not include such costs as time of informal caregivers,
hired home assistance workers, social assistance payments,
rehabilitative equipment and training, and lost productivity
due to visual impairment (although some economists argue
that productivity losses are incorporated within the QALY
value).32Second, all patients in our model diagnosed with
advanced AMD receive guideline-recommended standards
of care,11which likely results in increased and timelier laser
therapy and photodynamic therapy for choroidal neovascu-
larization than actual real-world treatment. If real-world
patients actually receive suboptimal laser therapy and pho-
todynamic therapy, then episodes of choroidal neovascular-
ization will result in greater levels of visual impairment,
associated greater QALY losses, but lower medical costs
than those observed in our model. Third, we have assumed
that the risk reductions currently observed only over the
duration of the AREDS trial would continue for as many
years as a patient took vitamins. If the effectiveness of
vitamins wanes over time, the cost-effectiveness of their use
would be less favorable. Fourth, our model tested the effec-
Volume 114, Number 7, July 2007
tiveness of the vitamin combination suggested by the
AREDS.3Emerging evidence suggests that intake of lutein
and zeaxanthin in addition to the AREDS supplement also
may further inhibit the progression to advanced AMD.37
Despite these limitations, our model is the only simula-
tion model of AMD that has been calibrated against external
U.S. prevalence data, uses U.S. practice patterns and costs,
incorporates losses of CS as well as acuity, and makes
use of the most recent AREDS data on AMD progression.
The limitations and assumptions embedded in this anal-
ysis were chosen to derive the most informative results,
given limitations in knowledge, while focusing the risk of
parameter uncertainty toward a conservative conclusion.
Our model demonstrates that vitamin therapy compares
favorably with other medical therapies to prevent visual
impairment from AMD and to improve health more gener-
ally. Readers should be aware that antioxidant formulations
used in the AREDS contain ?-carotene and therefore should
never be recommended to patients who smoke.38,39* Our
results support the use of vitamin therapy for all indicated
patients diagnosed with AMD and 50 years or older.
Acknowledgments. The authors acknowledge Frederick L.
Ferris III for allowing access to the AREDS data and providing
key conceptual input in the development of the natural history
model of AMD.
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