EAL

FNOA: Antioxidants (2011-2012)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

The purpose of this study was to examine overall diet quality using the Healthy Eating Index (HEI) and Alternate Healthy Eating Index (AHEI) in relation to advanced age-related macular degeneration (AMD).

Inclusion Criteria:

Examined at Duke University Eye Center (DUEC), Vanderbilt University Medical Center (VUMC) or other collaborating retinal specialty clinics
At least 55 years of age and likely to receive eye exams at DUEC or VUMC
All study participants provided informed consent prior to participation.

Exclusion Criteria:

Participants were excluded if they were missing more than 25 items on the food frequency questionnaire
Participants were excluded if they reported unusually low (<500Kcal for women; <800Kcal for men) or high (>3,500Kcal for women; >4,000Kcal for men) daily energy intake
Controls who were spouses of the cases (N=17, 2%) and participants who were missing essential covariate information (N=9, 1%) were also excluded
Participants that identified as grade 3 (early AMD) were not included in the analysis.

Description of Study Protocol:

Recruitment

Examined at Duke University Eye Center (DUEC), Vanderbilt University Medical Center (VUMC) or collaborating retinal specialty clinics
AMD patients who attended these clinics were recruited as cases
Study advertisements in center-specific newsletters, AMD-related seminars for the general public, and presentations at local retirement centers were used to recruit controls who were likely to receive eye exams at DUEC or VUMC.

Design

Case-control study

Blinding used

Implied with measurements

Intervention

Not applicable

Statistical Analysis

Pearson correlation coefficients were used to estimate correlation
Odds ratios and 95% confidence intervals were estimated using unconditional multiple logistic regression
Age (under 65, 65-69, 70-74, 75-79, 80-84, 85 and older), smoking (ever/never), study site, sex, total energy intake (quartiles) and education (less than high school, high school graduate or General Education Diploma, some college, college graduate) were included as covariates in fully adjusted models
Statistical analyses were conducted using SAS version 9.1 (SAS Institute Inc., Cary, NC).

Data Collection Summary:

Timing of Measurements

Participants had their vision examined at retinal clinics and completed FFQs.

Dependent Variables

Presence or absence of age-related macular degeneration (AMD)
Prior to enrollment a complete ophthalmoscopic examination of all study participants included slit-lamp examination and biomicroscopy with a handheld 90-diopter indirect ophthalmoscopy of the peripheral retina
35mm color fundus photographs with a minimum of three standard fields were obtained including stereo photographs of the disk and macula
Photographs were graded by two of the authors according to a slightly modified Age-Related Eye Disease Study (AREDS) grading system
All cases and controls were assigned an AMD grade of 1 through 5 in the more severely affected eye
Advanced AMD cases were defined as grades 4 and 5, whereas controls included grades 1 and 2.

Independent Variables

Overall diet quality
Participants completed a 97-item block food frequency questionnaire to collect information on dietary history over the year prior to study enrollment
Diet scores were calculated using both the Healthy Eating Index (HEI) and the Alternate Healthy Eating Index (AHEI).

Control Variables

Participants also completed a self-administered health and activities survey which included information on level of education, frequency and duration of smoking, and use of vitamins and mineral supplements
Age (under 65, 65-69, 70-74, 75-79, 80-84, 85 and older)
Smoking (ever/never)
Study site
Sex
Education
Sex-specific total energy intake.

Description of Actual Data Sample:

Initial N: 840 men and women
Attrition (final N):
- 437 advanced AMD patients
  - 153 male and 284 female
- 259 unrelated controls
  - 103 male and 156 female
Age: 55 years of age or older
- Age at exam:
  - Under 65 years: 5% of cases, 49% of controls
  - Aged 65-69 years: 12% of cases, 19% of controls
  - Aged 70-74 years: 22% of cases, 14% of controls
  - Aged 75-79 years: 24% of cases, 15% of controls
  - Aged 80-84 years: 22% of cases, 3% of controls
  - Aged 85+ years: 16% of cases, 2% of controls
Ethnicity: Non-Hispanic white men and women
Other relevant demographics:
Anthropometrics:
Location: Participants were examined at Duke University Eye Center (DUEC), Vanderbilt University Medical Center (VUMC) or another retinal specialty clinic in North Carolina and Tennessee.

Summary of Results:

Key Findings

Variables

Healthy Eating Index

Alternate Healthy Eating Index

Odds ratios for advanced Age-Related Macular Degeneration by diet scores

0.75
(0.41, 1.38)

P=0.0541*

0.54
(0.30-0.99)

P=0.1543**

Participants in the highest quartile of diet quality had non-significantly reduced odds of AMD according to the healthy eating index
Participants in the highest quartile of diet quality had significantly reduced odds of AMD according to the alternate healthy eating index
The odds of age-related macular degeneration were also 51% lower in the highest quartile of fish intake compared to the lowest quartile (OR=0.49, 0.26-0.90), P=0.1174.

Author Conclusion:

This study provided evidence that overall diet quality may play an important role in modulating the risk of AMD. The results also support the general hypothesis that AMD shares multiple risk factors with cardiovascular disease. The study also suggests that the Alternate Healthy Eating Index may be a useful instrument for identifying diet patterns associated with lower AMD risk.

Funding Source:

Government:	Grant EY12118 from the National Eye Institute, National Institute of Health (NIH)
University/Hospital:	General Clinical Research award (RR 00095) to Vanderbilt University

Reviewer Comments:

Authors note the following limitations:

Average age of cases was older than that of controls. Age could be a potential confounder of the association between diet and AMD if it was associated with both diet and AMD.
Sample size was small and the findings are considered preliminary because of this.

Quality Criteria Checklist: Primary Research
Relevance Questions
	1.	Would implementing the studied intervention or procedure (if found successful) result in improved outcomes for the patients/clients/population group? (Not Applicable for some epidemiological studies)	Yes
	2.	Did the authors study an outcome (dependent variable) or topic that the patients/clients/population group would care about?	Yes
	3.	Is the focus of the intervention or procedure (independent variable) or topic of study a common issue of concern to dieteticspractice?	Yes
	4.	Is the intervention or procedure feasible? (NA for some epidemiological studies)	Yes

Validity Questions
1.	Was the research question clearly stated?		Yes
	1.1.	Was (were) the specific intervention(s) or procedure(s) [independent variable(s)] identified?	Yes
	1.2.	Was (were) the outcome(s) [dependent variable(s)] clearly indicated?	Yes
	1.3.	Were the target population and setting specified?	Yes
2.	Was the selection of study subjects/patients free from bias?		???
	2.1.	Were inclusion/exclusion criteria specified (e.g., risk, point in disease progression, diagnostic or prognosis criteria), and with sufficient detail and without omitting criteria critical to the study?	Yes
	2.2.	Were criteria applied equally to all study groups?	Yes
	2.3.	Were health, demographics, and other characteristics of subjects described?	Yes
	2.4.	Were the subjects/patients a representative sample of the relevant population?	No
3.	Were study groups comparable?		No
	3.1.	Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT)	N/A
	3.2.	Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline?	No
	3.3.	Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.)	Yes
	3.4.	If cohort study or cross-sectional study, were groups comparable on important confounding factors and/or were preexisting differences accounted for by using appropriate adjustments in statistical analysis?	N/A
	3.5.	If case control study, were potential confounding factors comparable for cases and controls? (If case series or trial with subjects serving as own control, this criterion is not applicable.)	No
	3.6.	If diagnostic test, was there an independent blind comparison with an appropriate reference standard (e.g., "gold standard")?	N/A
4.	Was method of handling withdrawals described?		Yes
	4.1.	Were follow-up methods described and the same for all groups?	Yes
	4.2.	Was the number, characteristics of withdrawals (i.e., dropouts, lost to follow up, attrition rate) and/or response rate (cross-sectional studies) described for each group? (Follow up goal for a strong study is 80%.)	Yes
	4.3.	Were all enrolled subjects/patients (in the original sample) accounted for?	Yes
	4.4.	Were reasons for withdrawals similar across groups?	Yes
	4.5.	If diagnostic test, was decision to perform reference test not dependent on results of test under study?	N/A
5.	Was blinding used to prevent introduction of bias?		Yes
	5.1.	In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate?	N/A
	5.2.	Were data collectors blinded for outcomes assessment? (If outcome is measured using an objective test, such as a lab value, this criterion is assumed to be met.)	Yes
	5.3.	In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded?	N/A
	5.4.	In case control study, was case definition explicit and case ascertainment not influenced by exposure status?	Yes
	5.5.	In diagnostic study, were test results blinded to patient history and other test results?	N/A
6.	Were intervention/therapeutic regimens/exposure factor or procedure and any comparison(s) described in detail? Were interveningfactors described?		Yes
	6.1.	In RCT or other intervention trial, were protocols described for all regimens studied?	N/A
	6.2.	In observational study, were interventions, study settings, and clinicians/provider described?	Yes
	6.3.	Was the intensity and duration of the intervention or exposure factor sufficient to produce a meaningful effect?	Yes
	6.4.	Was the amount of exposure and, if relevant, subject/patient compliance measured?	Yes
	6.5.	Were co-interventions (e.g., ancillary treatments, other therapies) described?	Yes
	6.6.	Were extra or unplanned treatments described?	N/A
	6.7.	Was the information for 6.4, 6.5, and 6.6 assessed the same way for all groups?	Yes
	6.8.	In diagnostic study, were details of test administration and replication sufficient?	N/A
7.	Were outcomes clearly defined and the measurements valid and reliable?		Yes
	7.1.	Were primary and secondary endpoints described and relevant to the question?	Yes
	7.2.	Were nutrition measures appropriate to question and outcomes of concern?	Yes
	7.3.	Was the period of follow-up long enough for important outcome(s) to occur?	Yes
	7.4.	Were the observations and measurements based on standard, valid, and reliable data collection instruments/tests/procedures?	Yes
	7.5.	Was the measurement of effect at an appropriate level of precision?	Yes
	7.6.	Were other factors accounted for (measured) that could affect outcomes?	Yes
	7.7.	Were the measurements conducted consistently across groups?	Yes
8.	Was the statistical analysis appropriate for the study design and type of outcome indicators?		Yes
	8.1.	Were statistical analyses adequately described and the results reported appropriately?	Yes
	8.2.	Were correct statistical tests used and assumptions of test not violated?	Yes
	8.3.	Were statistics reported with levels of significance and/or confidence intervals?	Yes
	8.4.	Was "intent to treat" analysis of outcomes done (and as appropriate, was there an analysis of outcomes for those maximally exposed or a dose-response analysis)?	N/A
	8.5.	Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)?	Yes
	8.6.	Was clinical significance as well as statistical significance reported?	Yes
	8.7.	If negative findings, was a power calculation reported to address type 2 error?	N/A
9.	Are conclusions supported by results with biases and limitations taken into consideration?		Yes
	9.1.	Is there a discussion of findings?	Yes
	9.2.	Are biases and study limitations identified and discussed?	Yes
10.	Is bias due to study's funding or sponsorship unlikely?		Yes
	10.1.	Were sources of funding and investigators' affiliations described?	Yes
	10.2.	Was the study free from apparent conflict of interest?	Yes