- Email: [email protected]
Reprint of: Survey of patients with age-related macular degeneration: knowledge and adherence to recommendations
ORIGINAL ARTICLE
Reprint of: Survey of patients with age-related macular degeneration: knowledge and adherence to recommendations Sanket U. Shah, MD, Suman Pilli, MD, David G. Telander, MD, PhD, Lawrence S. Morse, MD, PhD, Susanna S. Park, MD, PhD ABSTRACT ● RÉSUMÉ Objective: To evaluate the patient’s understanding of the importance and adherence to the various lifestyle and Age-Related Eye Disease Study (AREDS) supplement recommendations for age-related macular degeneration (AMD). Design: Cross-sectional study. Participants: Patients with AMD treated at the vitreoretinal service clinic. Methods: Telephone questionnaire survey was administered to assess knowledge and adherence to various recommendations made to patients with AMD about lifestyle and AREDS supplements in this single-institution study. Results: Among 92 patients with AMD contacted, dietary modification, exercise and weight reduction, smoking cessation, and AREDS supplementation recommendations were recalled by 47 (51%), 21 (23%), 5 (5%), and 90 (98%) patients, respectively. The necessity of making these interventions was believed by 29 (62%), 16 (76%), 4 (80%), and 67 (74%) patients, respectively. Patient adherence to dietary modification was 81%, to exercise and weight reduction was 76%, to smoking cessation was 0%, and to AREDS supplementation was 88% (71% on correct dose). Financially, 29% of the patients noted a mean increase of $88 per month in expenditure because of making dietary modifications, but most reported such as justified; 61% noted a mean increase of $25 per month in expenditure from consumption of AREDS supplements, and most (96%) believed this was justified. Conclusions: Patients with AMD recalled recommendations for AREDS supplementation more often than other lifestyle changes but generally felt recommendations were necessary and affordable. Adherence to smoking cessation recommendation was poor (0%), but to other recommendations was good. Objet : Évaluation de la compréhension par les patients de l'importance et de l'adhésion aux divers modes de vie et des recommandations supplémentaires de l'étude sur les maladies oculaires liées à l'âge (AREDS) (en anglais seulement) pour la dégénérescence maculaire liée à l'âge (DMLA). Nature : Étude transversale. Participants : Des patients atteints de DMLA examinés dans une clinique vitro-rétinienne. Méthodes : Administration d'un questionnaire d'enquête par téléphone pour évaluer la connaissance et l'adhésion à diverses recommandations faites aux patients de DMLA quant au mode de vie et aux suppléments AREDS dans une seule étude institutionnelle. Résultats : Parmi les 92 patients atteints de DMA contactés, 47 (51 %), 21 (23 %), 5 (5 %) et 90 (98 %) se sont souvenus respectivement des modifications alimentaires, des exercices et de la réduction du poids, de l'abandon du tabagisme et des recommandations supplémentaires d'AREDS. Par ailleurs, 29 (62 %), 16 (76 %), 4 (80 %) et 67 (74 %) patients ont ressenti respectivement la nécessité de faire ces interventions. En outre, 81 % des patients adhéraient aux modifications alimentaires, 76 % à l'exercice et à la réduction du poids, 0 % à l'abandon du tabagisme et 88% aux suppléments d'AREDS (71 % à la dose appropriée). Financièrement, 29 % des patients ont noté une hausse moyenne de 88 $ par mois des dépenses visant à modifier l'alimentation mais la plupart ont trouvé cela justifié; 61 % ont noté une hausse moyenne de 25 $ par mois des dépenses de consommation des suppléments d'AREDS et la plupart (96 %) ont trouvé cela justifié. Conclusions : Les patients atteints de DMLA ont rappelé les recommandations concernant les suppléments d'AREDS plus souvent que les autres modifications du mode de vie, mais ils ont généralement estimé que les recommandations étaient nécessaires et abordables. L'adhésion à la recommandation de l'abandon du tabagisme était nulle, mais l'adhésion aux autres recommandations était bonne.
Age-related macular degeneration (AMD) affects more than 1.75 million individuals in the United States and accounted for 54% of the blindness among white Americans in the year 2000.1,2 Smoking and body mass index are modifiable risk factors associated with progression to advanced AMD in patients with intermediate AMD.3 Healthy lifestyles such as nutritious diet, physical activity,
and not smoking were found to be associated with 71% lower odds of development of AMD.4 Advanced AMD has been significantly related with overall diet quality, and factors such as fish intake have been suggested to be protective against it.5,6 In addition, the Age-Related Eye Disease Study (AREDS) showed that a specifically formulated vitamin supplement consisting of antioxidants
This article is a reprint of a previously published article. For citation purposes, please use the original publication details; Sanket U. Shah, Suman Pilli, David G. Telander, et al., Survey of patients with age-related macular degeneration: knowledge and adherence to recommendations. Can J Ophthalmol 2013;48:204–209. **DOI of original item: http://dx. doi.org/10.1016/j.jcjo.2013.01.013
Correspondence to Susanna S. Park, MD PhD, Department of Ophthalmology and Vision Science, University of California Davis Eye Center, 4860 Y Street, Suite 2400, Sacramento, CA 95817; susanna. [email protected]
From the Vitreoretinal Service, Department of Ophthalmology and Vision Science, University of California Davis Eye Center, Sacramento, Calif
Can J Ophthalmol 2015;50:S23–S28 0008-4182/15/$-see front matter & 2015 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.jcjo.2015.04.005
Originally received Oct. 2, 2012. Final revision Jan. 16, 2013. Accepted Jan. 24, 2013 CAN J OPHTHALMOL — VOL. 50, NO. S1, JUNE 2015
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Survey of patients with age-related macular degeneration—Shah et al. Table 1—Contents of various Age-Related Eye Disease Study supplements
β-Carotene Vitamin C Vitamin E Zinc oxide Cupric oxide No. of pills daily
Ocuvite PreserVision (daily dose)
ICaps AREDS Formula (daily dose)
Ocu-Plus Formula (daily dose)
RetinaVites (daily dose)
VisiVite original AREDS formula (daily dose)
Vitalux AREDS (daily dose)
28 640 IU/17.2 mg 452 mg 400 IU 69.6 mg 1.6 mg 2 or 4‡
28 640 IU/17.2 mg 452 mg 400 IU 69.6 mg 1.6 mg 2 or 4‡
25 000 IU/15 mg 1000 mg 400 IU 50 mgn 2 mgn 2
25 000 IU/15 mg 500 mg 400 IU 80 mg 2 mg 2
25 000 IU/15 mg 500 mg 400 IU 80 mg 2 mg 2
9548 IU/5.73 mg 500 mg 400 IU 80 mg† 2 mg† 2
AREDS, Age-Related Eye Disease Study. n Zinc gluconate and copper gluconate (not oxide); additional ingredients in Ocu-Plus Formula include selenium, chromium, citrus bioflavonoid complex, N-acetylcysteine, quercetin, rutin, bilberry extract, eyebright, α-lipoic acid, ginkgo biloba, L-glutathione, lutein, and zeaxanthin. † Zinc gluconate and copper hydrolyzed vegetable protein chelate (not oxide); additional ingredients in Vitalux AREDS include lutein and zeaxanthin. ‡ Two soft gels daily or 4 tablets daily.
and zinc (15 mg β-carotene, 500 mg vitamin C, 400 IU vitamin E, 80 mg zinc oxide, and 2 mg cupric oxide) reduced the risk for progression to advanced AMD in patients with extensive intermediate-size drusen, at least 1 large druse, noncentral geographic atrophy in 1 or both eyes, or advanced AMD or vision loss caused by AMD in 1 eye.7 Based on these criteria, recommendations of lifestyle modification and AREDS supplementation are made to patients with AMD. In spite of the potential for considerable public health impact, low adherence to use of AREDS supplements in patients with AMD has been reported.8–10 The purpose of this study was to assess from the patient’s perspective the necessity to follow these recommendations, the patient adherence, and the financial difficulty faced by the patients in following various recommendations.
METHODS A questionnaire was designed (S.U.S., S.P.) and approved (S.S.P., L.S.M., D.G.T.) by the authors to assess the necessity of, the adherence to, and the financial difficulty regarding the various recommendations in AMD from the patient’s perspective. No previously validated questionnaires to specifically address this study’s objective could be identified. The recommendations included lifestyle changes (increase in the intake of fruits, vegetables, and fish; decrease in the intake of processed food, sugar, and red meat; exercise and weight reduction; smoking cessation) and supplementation with AREDS formula products. The study protocol including the questionnaire was prospectively approved by the Institutional Review Board of University of California (UC) Davis Medical Center, Sacramento, Calif. The electronic medical records were reviewed to generate a database of patients with the diagnosis of AMD treated in the Vitreo-retinal service at UC Davis Eye Center from January 1, 2007, to May 30, 2009. Telephone interview was used to obtain and record response of the patients to the questionnaire in this single-centre study. If the patient could not be contacted the 1st time, 2 additional attempts were made at different times of the day after work hours.
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Patients were explained the purpose of the study, and their consent was obtained verbally before proceeding with the interview. Demographic information including medical record number, age, sex, diagnosis, and best corrected visual acuity were recorded from the most recent eye clinic encounter documented in the medical record. The various recommendations made to the patients were recorded, and the qualification of the person who made those recommendations (vitreoretinal specialist, comprehensive ophthalmologist, optometrist, other) was noted. Questions directed to judge patient awareness and knowledge included whether the patients knew about having the condition of AMD and whether they think it was necessary to modify their lifestyle and to consume AREDS supplements as recommended to prevent the progression of AMD. Questions directed to assess patient adherence included whether the patients made any changes after being given the recommendations. The quantification of changes such as the number of servings of fruits, vegetables, fish, processed food, sugar, and red meat before and after obtaining recommendations, the amount of weight loss (if any), and the number of days in the week that patients adhered to the recommendation of diet and exercise were used to record patients’ adherence. Financial difficulty in terms of additional expenditure incurred because of following of any of the recommendations was noted. Comfort level associated with following of each of the recommendations was noted on a scale from 1 to 10, with 1 meaning “uncomfortable” and 10 meaning “totally comfortable” with following the recommendation. Questions regarding smoking included whether currently smoking, whether smoked in the past, the number of years smoked for, the number of years since cessation (where applicable), and the average number of packs of cigarettes smoked per day. Questions regarding AREDS supplements included the commercial brand of product used, number of pills consumed daily, regularity, adverse effects such as yellowing of skin, dysgeusia, headache, gastritis, fatigue, thyroid dysfunction, easy bruisability, urinary tract infections, or cognitive changes and use of other vitamins or dietary supplements at present or in the past. The definition of “AREDS supplement” in this study was slightly liberal in terms of exact dose of contents.
Survey of patients with age-related macular degeneration—Shah et al. Table 2—Recommendations and adherence regarding lifestyle and Age-Related Eye Disease Study recommendations in patients with age-related macular degeneration
Recommendations Increased intake of fruits and vegetables Increased intake of fish Decreased intake of processed food Decreased sugar intake Decreased red meat intake Exercise Weight reduction Smoking cessation AREDS vitamin supplements
Patients recommended, n (% of total)
Patients adherent to recommendations, n (% of those recommended)
37 (40)
33 (89)
30 18 17 18 20 17 6 90
23 16 16 15 14 4 0 79
(33) (20) (18) (20) (22) (18) (7) (98)
(77) (89) (94) (83) (70) (24) (0) (88)
AREDS, Age-Related Eye Disease Study.
The contents of various AREDS supplements in this study are summarized in Table 1. For comparing patient adherence in dry versus wet AMD, patients with wet AMD in at least 1 eye were considered to have wet AMD. Statistical analysis was performed with SPSS software version 16.0 (SPSS Inc, Chicago, Ill.) using χ2 test, unpaired t test, and 1-way ANOVA test as appropriate to evaluate associations of factors.
RESULTS Of 157 consecutive patients with AMD who were contacted by telephone, 65 (41%) were excluded because of hearing loss, dementia, debilitating comorbidities, or refusal to participate in the study. Ninety-two (59%) patients qualified for and consented to participating in the questionnaire survey. Of these 92 patients, 26 (28%) were male and 66 (72%) were female. The mean patient age was 79 years (SD, 9 years; range, 51–95 years). The patients had last seen the retina specialist, on average, 3 months (SD, 3 months; range, 1–12 months) before the time of the phone interview. Most patients (n ¼ 91, 99%) were aware of their diagnosis of AMD. The diagnosis included intermediate to advanced dry AMD in 1 or both eyes (n ¼ 124 eyes, 67%) and wet AMD in at least 1 eye (n ¼ 60 eyes, 33%). Recommendations about dietary modification and exercise, AREDS supplements, and smoking cessation were made by a retinal specialist (n ¼ 69, 75%),
a comprehensive ophthalmologist (n ¼ 22, 24%), and an optometrist or a primary care physician (n ¼ 1, 1%). The various recommendations made and the number of patients adherent to them are summarized in Table 2. Patient knowledge and perceived need to adhere to recommendations are summarized in Table 3. Of 47 patients given dietary recommendations, 38 (81%) modified their diet with a comfort level of 8.4 on a scale of 1 to 10. The specific dietary recommendations are summarized in Table 2. Adherence to the recommended diet was for less than 3 days per week in 6 (16%), 3 to 5 days per week in 10 (26%), and more than 5 days per week in 22 (58%) patients. Financial difficulty caused by following dietary recommendation was reported by 11 (29%) patients. A mean increase of $88 per month in their expenditure was reported, and most patients (91%) believed that such an increase was justified. Of 21 patients given recommendations on weight reduction and exercise, 16 (76%) adhered to the recommendation with a comfort level of 9.4 on a scale of 1 to 10. Of 90 patients given AREDS supplement recommendations, 79 (88%) adhered to the recommendation with a comfort level of 9.4 on a scale of 1 to 10. Among these patients, 28% were taking 1 pill daily, 56% were taking 2 pills daily, 1% were taking 3 pills daily, 9% were taking 4 pills daily, 5% were taking 5 pills daily, and 1% were taking 6 pills daily. The correct number of pills includes 2 Ocu-Plus Formula tablets (Rebuild Your Vision LLC, Woodinville, WA) daily, 2 RetinaVites tablets (American Vitamin Supply LLC, Southfield, MI) daily, 2 Ocuvite PreserVision soft gels (Bausch & Lomb) daily, 2 ICaps AREDS Formula soft gels (Alcon Laboratories Inc, Fort Worth, TX) daily, 4 Ocuvite PreserVision tablets (Bausch & Lomb) daily, or 4 ICaps AREDS Formula tablets (Alcon Laboratories) daily as noted in Table 1. Patients quantified adherence as being regular (n ¼ 68, 86%), mostly regular (n ¼ 9, 11%), or irregular (n ¼ 2, 3%) with taking the AREDS supplements. After accounting for the total number and type of pills consumed and the reported adherence, the effective daily dose of vitamins A, C, and E, zinc, and copper was inadequate to meet AREDS criteria in 29% of patients. The formulations used by the patients included tablet or soft gel formulation of Ocuvite PreserVision (78%), tablet or soft gel formulation of ICaps AREDS Formula (8%), and others (3%) including Ocu Plus Formula (n ¼ 1) and
Table 3—Patients’ knowledge and perceived need regarding lifestyle and AREDS supplementation recommendations for agerelated macular degeneration Recommendations Diet Weight reduction or exercise Smoking cessation AREDS supplements
Patients recommended, n (%) 47 21 5 90
(51) (23) (5) (98)
Recommendation felt necessary, n (%) 29 15 4/5 67
(62) (71) (80) (74)
Recommendation felt unnecessary, n (%) 5 1 1/5 6
(11) (5) (20) (7)
Uncertain about recommendation, n (%) 13 5 0 17
(28) (24) (0) (19)
AREDS, Age-Related Eye Disease Study.
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Survey of patients with age-related macular degeneration—Shah et al. Table 4—Consumption of additional vitamins and/or dietary supplements besides Age-Related Eye Disease Study supplements in patients with age-related macular degeneration Additional vitamins/dietary supplements Multivitamin Calcium Fish oil Omega-3-fatty acid Other herbal/nutritional supplementsn Total
Patients, n (%) 50 29 20 6 4 66
(63) (37) (25) (8) (5) (84)
*Soy lecithin, bilberry, garlic, ginseng, flax seeds, lysin, and forskohlii.
RetinaVites (n ¼ 1). Some of the patients (9%) were on AREDS II study supplements. Few patients (3%) used non-AREDS supplements. Few patients used lutein (29%) and zeaxanthin (4%) separately in addition to Ocuvite PreserVision or ICaps AREDS Formula. Financial difficulty caused by AREDS supplements was reported by 48 (61%) of the patients, with a mean increase of $25 per month in their expenditure because of AREDS supplements, but most (96%) felt that such an increase was justified. None of the patients reported any adverse effects from taking AREDS supplements. Other vitamins and/or dietary supplements besides AREDS supplements were consumed by 66 (84%) of 79 patients who were on AREDS supplements and are summarized in Table 4. We compared the adherence to AREDS supplementation in patients with dry AMD in both eyes (n ¼ 46 patients, 85%) with patients with wet AMD in at least 1 eye (n ¼ 44 patients, 91%) among the 90 patients who recalled receiving AREDS supplementation recommendation. No statistically significant difference (p40.05) between the 2 groups was observed. Based on history, 5 (5%) patients were currently smoking an average of 1 pack a day for the past 41 months. They were recommended to quit smoking. A positive smoking history was present in 46 (50%) patients who smoked an average of 1 pack a day in the past for 24 months and had quit, on average, 31 months ago. Forty-one patients (45%) had never smoked. None of the patients adhered to the recommendation of smoking cessation. Among the patients who followed any of the lifestyle or AREDS supplementation recommendations, 42 (49%) patients reported subjective improvement in vision, whereas 43 (51%) reported no such effect. Statistical analysis showed significant associations between multivitamin use and perceived need for adherence to AREDS supplementation (p ¼ 0.037, χ2 test), multivitamin use and adherence to weight reduction and exercise (p ¼ 0.007, Fisher’s exact test), and multivitamin use and adherence to AREDS supplements (p ¼ 0.009, Fisher’s exact test). Other factors such as sex, mean age, person making the recommendation (vitreoretinal specialist versus others), and smoking status (current or past smoker versus nonsmoker) were not associated with perceived need or with adherence to any recommendations.
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DISCUSSION The adherence to recommendations of lifestyle modifications in AMD has not been well studied previously. Smoking is one of the most important risk factors, and its cessation is an important recommendation with the potential to alter AMD progression.11 In our study, although very few patients warranted smoking counseling, the adherence to smoking cessation was 0%. This indicates that alternative measures of patient education about smoking cessation may need to be explored. Behavioral interventions and pharmacologic treatments with nicotine replacement therapy, bupropion, and varenicline may be appropriate alternatives to consider given the possible addictive nature of smoking. Other lifestyle modifications such as diet and physical activity were well received by most patients. Although most patients recalled recommendations for AREDS supplementation in our study, fewer patients recalled being given lifestyle recommendations. It is unclear whether the physician decided that the lifestyle recommendations were not necessary for some of the patients based on history and physical examination, or the patients did not recall dietary and exercise recommendations considering that a pill would be easier to take and may seem to be more effective from the patient’s point of view. Because the recommendations may not have been uniform, it is also possible that in a typical busy retinal practice with limited time for each patient, the ophthalmologist may find it easier to recommend a pill and omit lifestyle changes. Nevertheless, vitreoretinal specialists and ophthalmologists should remember to provide recommendations on lifestyle modification, together with AREDS supplements. The adherence to AREDS supplements has been reported to be low in previous studies (36–43%).9,10 However, the adherence was higher (88%) in our study. This may be because most of the patients had more advanced disease and were recruited from the retina subspecialty clinic. Our patients might have been more concerned about their retinal condition and prospects of going blind than a patient with milder disease seen in a general ophthalmology setting; however, statistical analysis in our study showed no correlation between adherence to AREDS supplement and the type of specialist making the recommendation. In addition, there was no difference in rate of adherence to AREDS supplementation recommendation among patients with dry versus wet AMD. Multivitamin users were more likely to feel the need to be adherent to AREDS supplements in our study because these patients are likely to be more health conscious. Multivitamin or multimineral use was reported in 35% of U.S. adults because of expectation to improve their health with these supplements.12 Concomitant multivitamin use may be an indicator of health-conscious attitude, and the finding of our study may be related to such an attitude.
Survey of patients with age-related macular degeneration—Shah et al.
Fig. 1 — Sample of patient handout summarizing Age-Related Eye Disease Study and lifestyle recommendations given to patients with age-related macular degeneration treated in the retinal clinic.
Whether regional differences in the United States in terms of lifestyle and multivitamin use would explain our study results is unknown. In evaluating patients taking AREDS supplements, it is important to find out the specific brand and formulation that the patient chooses to use because some patients may take non-AREDS formulations inadvertently. Our study shows that although a high percentage of patients were on true AREDS supplements, a wide range of doses was being
consumed. As noted in our study, 29% of the patients who were adherent to AREDS supplements did not consume adequate daily dose. Different formulations such as tablet and soft gel available for the same brand of AREDS supplements may further complicate this issue. Certain formulations available exclusively in Canada, such as Vitalux and Macula 2, are noteworthy with regard to dosage of individual ingredients. Although Vitalux resembles the AREDS formula (Table 1), Macula 2 is a distinct CAN J OPHTHALMOL — VOL. 50, NO. S1, JUNE 2015
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Survey of patients with age-related macular degeneration—Shah et al. vitamin–mineral formulation that does not meet AREDS criteria. Therefore, it is crucial to stress to the patient the exact dose and frequency based on the formulation and the brand that the patient agrees to use. This is important not only to realize the full effect of these supplements (by preventing underusage), but also to prevent potential adverse effects (by preventing overusage). Although written take-home instructions are commonly dispensed in our clinic (Fig. 1), such a strategy seems inadequate. Poor patient adherence seems to be multifactorial in origin. Some of the factors include patient failure to comprehend the importance of AMD-related recommendations, little understanding among general internists regarding significance of lifestyle modifications in AMD, inadequate nursing involvement, inadequate explanation and reinforcement from ophthalmologists, and lack of nutritionist support and referral. Welldesigned, prospective studies may shed light on some of these hitherto unknown factors. Some of the shortcomings of this study include a relatively small sample size (especially the size of patients with history of smoking), problems inherent to a questionnaire survey, and outcomes based on subjective patient responses. The primary purpose of this study was to investigate how the patient perceived and implemented the lifestyle and AREDS supplement recommendations for AMD. Although several epidemiologic studies have focused on the objective risk factors for AMD progression and suggested specific recommendations to minimize the risk for progression of AMD, our study suggests that there remains a significant gap between the recommendations made by the ophthalmologist and the recommendations actually practiced by the patients with AMD. This study highlights the importance of proper patient education of the recommendations and regular follow-up to the recommendations to ensure that the recommendations are being implemented correctly.
Disclosure: The authors have made the following disclosures: Dr. Telander has received research funds from Genentech via UC Davis. Dr. Morse has received compensation for lecture from Genentech and for consulting from Genentech and Allergan; he has also received research funds for university from Genentech, EMMES, Allergan, Iridex, and Bausch & Lomb. Dr. Park has
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received compensation for lecture from Allergan and for consulting from Regeneron, Healthnet, Genentech, Oraya, and Allergan; she has also received research funds for university from Allergan and Genentech. Drs. Shah and Pilli declare no potential conflict of interest. Supported by: This study was supported by Research to Prevent Blindness, Unrestricted Departmental Grant, New York, N.Y. REFERENCES 1. Friedman DS, O’Colmain BJ, Muñoz B, et al. Eye Diseases Prevalence Research Group. Prevalence of age-related macular degeneration in the United States. Arch Ophthalmol. 2004;122: 564-72. 2. Congdon N, O’Colmain B, Klaver CC, et al. Eye Diseases Prevalence Research Group. Causes and prevalence of visual impairment among adults in the United States. Arch Ophthalmol. 2004;122:477-85. 3. Clemons TE, Milton RC, Klein R, Seddon JM, Ferris FL 3rd. AgeRelated Eye Disease Study Research Group. Risk factors for the incidence of advanced age-related macular degeneration in the AgeRelated Eye Disease Study (AREDS). AREDS report. Ophthalmology. 2005;112:533-9. 4. Mares JA, Voland RP, Sondel SA, et al. Healthy lifestyles related to subsequent prevalence of age-related macular degeneration. Arch Ophthalmol. 2011;129:470-80. 5. Montgomery MP, Kamel F, Pericak-Vance MA, et al. Overall diet quality and age-related macular degeneration. Ophthalmic Epidemiol. 2010;17:58-65. 6. Swenor BK, Bressler S, Caulfield L, West SK. The impact of fish and shellfish consumption on age-related macular degeneration. Ophthalmology. 2010;117:2395-401. 7. Age-Related Eye Disease Study Research Group. A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E, beta carotene, and zinc for advanced age-related macular degeneration and vision loss: AREDS report no. 8. Arch Ophthalmol. 2001;119:1417-36. 8. Bressler NM, Bressler SB, Congdon NG, et al. Age-Related Eye Disease Study Research Group. Potential public health impact of Age-Related Eye Disease Study results: AREDS report no. 11. Arch Ophthalmol. 2003;121:1621-4. 9. Ng WT, Goggin M. Awareness of and compliance with recommended dietary supplement among age-related macular degeneration patients. Clin Exp Ophthalmol. 2006;34:9-14. 10. Hochstetler BS, Scott IU, Kunselman AR, Thompson K, Zerfoss E. Adherence to recommendations of the age-related eye disease study in patients with age-related macular degeneration. Retina. 2010;30: 1166-70. 11. Age-Related Eye Disease Study Research Group. Risk factors associated with age-related macular degeneration. A case-control study in the age-related eye disease study: Age-Related Eye Disease Study Report Number 3. Ophthalmology. 2000;107:2224-32. 12. Radimer K, Bindewald B, Hughes J, Ervin B, Swanson C, Picciano MF. Dietary supplement use by US adults: data from the National Health and Nutrition Examination Survey, 1999-2000. Am J Epidemiol. 2004;160:339-49.
Reprint of: Survey of patients with age-related macular degeneration: knowledge and adherence to recommendations Sanket U. Shah, MD, Suman Pilli, MD, David G. Telander, MD, PhD, Lawrence S. Morse, MD, PhD, Susanna S. Park, MD, PhD ABSTRACT ● RÉSUMÉ Objective: To evaluate the patient’s understanding of the importance and adherence to the various lifestyle and Age-Related Eye Disease Study (AREDS) supplement recommendations for age-related macular degeneration (AMD). Design: Cross-sectional study. Participants: Patients with AMD treated at the vitreoretinal service clinic. Methods: Telephone questionnaire survey was administered to assess knowledge and adherence to various recommendations made to patients with AMD about lifestyle and AREDS supplements in this single-institution study. Results: Among 92 patients with AMD contacted, dietary modification, exercise and weight reduction, smoking cessation, and AREDS supplementation recommendations were recalled by 47 (51%), 21 (23%), 5 (5%), and 90 (98%) patients, respectively. The necessity of making these interventions was believed by 29 (62%), 16 (76%), 4 (80%), and 67 (74%) patients, respectively. Patient adherence to dietary modification was 81%, to exercise and weight reduction was 76%, to smoking cessation was 0%, and to AREDS supplementation was 88% (71% on correct dose). Financially, 29% of the patients noted a mean increase of $88 per month in expenditure because of making dietary modifications, but most reported such as justified; 61% noted a mean increase of $25 per month in expenditure from consumption of AREDS supplements, and most (96%) believed this was justified. Conclusions: Patients with AMD recalled recommendations for AREDS supplementation more often than other lifestyle changes but generally felt recommendations were necessary and affordable. Adherence to smoking cessation recommendation was poor (0%), but to other recommendations was good. Objet : Évaluation de la compréhension par les patients de l'importance et de l'adhésion aux divers modes de vie et des recommandations supplémentaires de l'étude sur les maladies oculaires liées à l'âge (AREDS) (en anglais seulement) pour la dégénérescence maculaire liée à l'âge (DMLA). Nature : Étude transversale. Participants : Des patients atteints de DMLA examinés dans une clinique vitro-rétinienne. Méthodes : Administration d'un questionnaire d'enquête par téléphone pour évaluer la connaissance et l'adhésion à diverses recommandations faites aux patients de DMLA quant au mode de vie et aux suppléments AREDS dans une seule étude institutionnelle. Résultats : Parmi les 92 patients atteints de DMA contactés, 47 (51 %), 21 (23 %), 5 (5 %) et 90 (98 %) se sont souvenus respectivement des modifications alimentaires, des exercices et de la réduction du poids, de l'abandon du tabagisme et des recommandations supplémentaires d'AREDS. Par ailleurs, 29 (62 %), 16 (76 %), 4 (80 %) et 67 (74 %) patients ont ressenti respectivement la nécessité de faire ces interventions. En outre, 81 % des patients adhéraient aux modifications alimentaires, 76 % à l'exercice et à la réduction du poids, 0 % à l'abandon du tabagisme et 88% aux suppléments d'AREDS (71 % à la dose appropriée). Financièrement, 29 % des patients ont noté une hausse moyenne de 88 $ par mois des dépenses visant à modifier l'alimentation mais la plupart ont trouvé cela justifié; 61 % ont noté une hausse moyenne de 25 $ par mois des dépenses de consommation des suppléments d'AREDS et la plupart (96 %) ont trouvé cela justifié. Conclusions : Les patients atteints de DMLA ont rappelé les recommandations concernant les suppléments d'AREDS plus souvent que les autres modifications du mode de vie, mais ils ont généralement estimé que les recommandations étaient nécessaires et abordables. L'adhésion à la recommandation de l'abandon du tabagisme était nulle, mais l'adhésion aux autres recommandations était bonne.
Age-related macular degeneration (AMD) affects more than 1.75 million individuals in the United States and accounted for 54% of the blindness among white Americans in the year 2000.1,2 Smoking and body mass index are modifiable risk factors associated with progression to advanced AMD in patients with intermediate AMD.3 Healthy lifestyles such as nutritious diet, physical activity,
and not smoking were found to be associated with 71% lower odds of development of AMD.4 Advanced AMD has been significantly related with overall diet quality, and factors such as fish intake have been suggested to be protective against it.5,6 In addition, the Age-Related Eye Disease Study (AREDS) showed that a specifically formulated vitamin supplement consisting of antioxidants
This article is a reprint of a previously published article. For citation purposes, please use the original publication details; Sanket U. Shah, Suman Pilli, David G. Telander, et al., Survey of patients with age-related macular degeneration: knowledge and adherence to recommendations. Can J Ophthalmol 2013;48:204–209. **DOI of original item: http://dx. doi.org/10.1016/j.jcjo.2013.01.013
Correspondence to Susanna S. Park, MD PhD, Department of Ophthalmology and Vision Science, University of California Davis Eye Center, 4860 Y Street, Suite 2400, Sacramento, CA 95817; susanna. [email protected]
From the Vitreoretinal Service, Department of Ophthalmology and Vision Science, University of California Davis Eye Center, Sacramento, Calif
Can J Ophthalmol 2015;50:S23–S28 0008-4182/15/$-see front matter & 2015 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.jcjo.2015.04.005
Originally received Oct. 2, 2012. Final revision Jan. 16, 2013. Accepted Jan. 24, 2013 CAN J OPHTHALMOL — VOL. 50, NO. S1, JUNE 2015
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Survey of patients with age-related macular degeneration—Shah et al. Table 1—Contents of various Age-Related Eye Disease Study supplements
β-Carotene Vitamin C Vitamin E Zinc oxide Cupric oxide No. of pills daily
Ocuvite PreserVision (daily dose)
ICaps AREDS Formula (daily dose)
Ocu-Plus Formula (daily dose)
RetinaVites (daily dose)
VisiVite original AREDS formula (daily dose)
Vitalux AREDS (daily dose)
28 640 IU/17.2 mg 452 mg 400 IU 69.6 mg 1.6 mg 2 or 4‡
28 640 IU/17.2 mg 452 mg 400 IU 69.6 mg 1.6 mg 2 or 4‡
25 000 IU/15 mg 1000 mg 400 IU 50 mgn 2 mgn 2
25 000 IU/15 mg 500 mg 400 IU 80 mg 2 mg 2
25 000 IU/15 mg 500 mg 400 IU 80 mg 2 mg 2
9548 IU/5.73 mg 500 mg 400 IU 80 mg† 2 mg† 2
AREDS, Age-Related Eye Disease Study. n Zinc gluconate and copper gluconate (not oxide); additional ingredients in Ocu-Plus Formula include selenium, chromium, citrus bioflavonoid complex, N-acetylcysteine, quercetin, rutin, bilberry extract, eyebright, α-lipoic acid, ginkgo biloba, L-glutathione, lutein, and zeaxanthin. † Zinc gluconate and copper hydrolyzed vegetable protein chelate (not oxide); additional ingredients in Vitalux AREDS include lutein and zeaxanthin. ‡ Two soft gels daily or 4 tablets daily.
and zinc (15 mg β-carotene, 500 mg vitamin C, 400 IU vitamin E, 80 mg zinc oxide, and 2 mg cupric oxide) reduced the risk for progression to advanced AMD in patients with extensive intermediate-size drusen, at least 1 large druse, noncentral geographic atrophy in 1 or both eyes, or advanced AMD or vision loss caused by AMD in 1 eye.7 Based on these criteria, recommendations of lifestyle modification and AREDS supplementation are made to patients with AMD. In spite of the potential for considerable public health impact, low adherence to use of AREDS supplements in patients with AMD has been reported.8–10 The purpose of this study was to assess from the patient’s perspective the necessity to follow these recommendations, the patient adherence, and the financial difficulty faced by the patients in following various recommendations.
METHODS A questionnaire was designed (S.U.S., S.P.) and approved (S.S.P., L.S.M., D.G.T.) by the authors to assess the necessity of, the adherence to, and the financial difficulty regarding the various recommendations in AMD from the patient’s perspective. No previously validated questionnaires to specifically address this study’s objective could be identified. The recommendations included lifestyle changes (increase in the intake of fruits, vegetables, and fish; decrease in the intake of processed food, sugar, and red meat; exercise and weight reduction; smoking cessation) and supplementation with AREDS formula products. The study protocol including the questionnaire was prospectively approved by the Institutional Review Board of University of California (UC) Davis Medical Center, Sacramento, Calif. The electronic medical records were reviewed to generate a database of patients with the diagnosis of AMD treated in the Vitreo-retinal service at UC Davis Eye Center from January 1, 2007, to May 30, 2009. Telephone interview was used to obtain and record response of the patients to the questionnaire in this single-centre study. If the patient could not be contacted the 1st time, 2 additional attempts were made at different times of the day after work hours.
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Patients were explained the purpose of the study, and their consent was obtained verbally before proceeding with the interview. Demographic information including medical record number, age, sex, diagnosis, and best corrected visual acuity were recorded from the most recent eye clinic encounter documented in the medical record. The various recommendations made to the patients were recorded, and the qualification of the person who made those recommendations (vitreoretinal specialist, comprehensive ophthalmologist, optometrist, other) was noted. Questions directed to judge patient awareness and knowledge included whether the patients knew about having the condition of AMD and whether they think it was necessary to modify their lifestyle and to consume AREDS supplements as recommended to prevent the progression of AMD. Questions directed to assess patient adherence included whether the patients made any changes after being given the recommendations. The quantification of changes such as the number of servings of fruits, vegetables, fish, processed food, sugar, and red meat before and after obtaining recommendations, the amount of weight loss (if any), and the number of days in the week that patients adhered to the recommendation of diet and exercise were used to record patients’ adherence. Financial difficulty in terms of additional expenditure incurred because of following of any of the recommendations was noted. Comfort level associated with following of each of the recommendations was noted on a scale from 1 to 10, with 1 meaning “uncomfortable” and 10 meaning “totally comfortable” with following the recommendation. Questions regarding smoking included whether currently smoking, whether smoked in the past, the number of years smoked for, the number of years since cessation (where applicable), and the average number of packs of cigarettes smoked per day. Questions regarding AREDS supplements included the commercial brand of product used, number of pills consumed daily, regularity, adverse effects such as yellowing of skin, dysgeusia, headache, gastritis, fatigue, thyroid dysfunction, easy bruisability, urinary tract infections, or cognitive changes and use of other vitamins or dietary supplements at present or in the past. The definition of “AREDS supplement” in this study was slightly liberal in terms of exact dose of contents.
Survey of patients with age-related macular degeneration—Shah et al. Table 2—Recommendations and adherence regarding lifestyle and Age-Related Eye Disease Study recommendations in patients with age-related macular degeneration
Recommendations Increased intake of fruits and vegetables Increased intake of fish Decreased intake of processed food Decreased sugar intake Decreased red meat intake Exercise Weight reduction Smoking cessation AREDS vitamin supplements
Patients recommended, n (% of total)
Patients adherent to recommendations, n (% of those recommended)
37 (40)
33 (89)
30 18 17 18 20 17 6 90
23 16 16 15 14 4 0 79
(33) (20) (18) (20) (22) (18) (7) (98)
(77) (89) (94) (83) (70) (24) (0) (88)
AREDS, Age-Related Eye Disease Study.
The contents of various AREDS supplements in this study are summarized in Table 1. For comparing patient adherence in dry versus wet AMD, patients with wet AMD in at least 1 eye were considered to have wet AMD. Statistical analysis was performed with SPSS software version 16.0 (SPSS Inc, Chicago, Ill.) using χ2 test, unpaired t test, and 1-way ANOVA test as appropriate to evaluate associations of factors.
RESULTS Of 157 consecutive patients with AMD who were contacted by telephone, 65 (41%) were excluded because of hearing loss, dementia, debilitating comorbidities, or refusal to participate in the study. Ninety-two (59%) patients qualified for and consented to participating in the questionnaire survey. Of these 92 patients, 26 (28%) were male and 66 (72%) were female. The mean patient age was 79 years (SD, 9 years; range, 51–95 years). The patients had last seen the retina specialist, on average, 3 months (SD, 3 months; range, 1–12 months) before the time of the phone interview. Most patients (n ¼ 91, 99%) were aware of their diagnosis of AMD. The diagnosis included intermediate to advanced dry AMD in 1 or both eyes (n ¼ 124 eyes, 67%) and wet AMD in at least 1 eye (n ¼ 60 eyes, 33%). Recommendations about dietary modification and exercise, AREDS supplements, and smoking cessation were made by a retinal specialist (n ¼ 69, 75%),
a comprehensive ophthalmologist (n ¼ 22, 24%), and an optometrist or a primary care physician (n ¼ 1, 1%). The various recommendations made and the number of patients adherent to them are summarized in Table 2. Patient knowledge and perceived need to adhere to recommendations are summarized in Table 3. Of 47 patients given dietary recommendations, 38 (81%) modified their diet with a comfort level of 8.4 on a scale of 1 to 10. The specific dietary recommendations are summarized in Table 2. Adherence to the recommended diet was for less than 3 days per week in 6 (16%), 3 to 5 days per week in 10 (26%), and more than 5 days per week in 22 (58%) patients. Financial difficulty caused by following dietary recommendation was reported by 11 (29%) patients. A mean increase of $88 per month in their expenditure was reported, and most patients (91%) believed that such an increase was justified. Of 21 patients given recommendations on weight reduction and exercise, 16 (76%) adhered to the recommendation with a comfort level of 9.4 on a scale of 1 to 10. Of 90 patients given AREDS supplement recommendations, 79 (88%) adhered to the recommendation with a comfort level of 9.4 on a scale of 1 to 10. Among these patients, 28% were taking 1 pill daily, 56% were taking 2 pills daily, 1% were taking 3 pills daily, 9% were taking 4 pills daily, 5% were taking 5 pills daily, and 1% were taking 6 pills daily. The correct number of pills includes 2 Ocu-Plus Formula tablets (Rebuild Your Vision LLC, Woodinville, WA) daily, 2 RetinaVites tablets (American Vitamin Supply LLC, Southfield, MI) daily, 2 Ocuvite PreserVision soft gels (Bausch & Lomb) daily, 2 ICaps AREDS Formula soft gels (Alcon Laboratories Inc, Fort Worth, TX) daily, 4 Ocuvite PreserVision tablets (Bausch & Lomb) daily, or 4 ICaps AREDS Formula tablets (Alcon Laboratories) daily as noted in Table 1. Patients quantified adherence as being regular (n ¼ 68, 86%), mostly regular (n ¼ 9, 11%), or irregular (n ¼ 2, 3%) with taking the AREDS supplements. After accounting for the total number and type of pills consumed and the reported adherence, the effective daily dose of vitamins A, C, and E, zinc, and copper was inadequate to meet AREDS criteria in 29% of patients. The formulations used by the patients included tablet or soft gel formulation of Ocuvite PreserVision (78%), tablet or soft gel formulation of ICaps AREDS Formula (8%), and others (3%) including Ocu Plus Formula (n ¼ 1) and
Table 3—Patients’ knowledge and perceived need regarding lifestyle and AREDS supplementation recommendations for agerelated macular degeneration Recommendations Diet Weight reduction or exercise Smoking cessation AREDS supplements
Patients recommended, n (%) 47 21 5 90
(51) (23) (5) (98)
Recommendation felt necessary, n (%) 29 15 4/5 67
(62) (71) (80) (74)
Recommendation felt unnecessary, n (%) 5 1 1/5 6
(11) (5) (20) (7)
Uncertain about recommendation, n (%) 13 5 0 17
(28) (24) (0) (19)
AREDS, Age-Related Eye Disease Study.
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Survey of patients with age-related macular degeneration—Shah et al. Table 4—Consumption of additional vitamins and/or dietary supplements besides Age-Related Eye Disease Study supplements in patients with age-related macular degeneration Additional vitamins/dietary supplements Multivitamin Calcium Fish oil Omega-3-fatty acid Other herbal/nutritional supplementsn Total
Patients, n (%) 50 29 20 6 4 66
(63) (37) (25) (8) (5) (84)
*Soy lecithin, bilberry, garlic, ginseng, flax seeds, lysin, and forskohlii.
RetinaVites (n ¼ 1). Some of the patients (9%) were on AREDS II study supplements. Few patients (3%) used non-AREDS supplements. Few patients used lutein (29%) and zeaxanthin (4%) separately in addition to Ocuvite PreserVision or ICaps AREDS Formula. Financial difficulty caused by AREDS supplements was reported by 48 (61%) of the patients, with a mean increase of $25 per month in their expenditure because of AREDS supplements, but most (96%) felt that such an increase was justified. None of the patients reported any adverse effects from taking AREDS supplements. Other vitamins and/or dietary supplements besides AREDS supplements were consumed by 66 (84%) of 79 patients who were on AREDS supplements and are summarized in Table 4. We compared the adherence to AREDS supplementation in patients with dry AMD in both eyes (n ¼ 46 patients, 85%) with patients with wet AMD in at least 1 eye (n ¼ 44 patients, 91%) among the 90 patients who recalled receiving AREDS supplementation recommendation. No statistically significant difference (p40.05) between the 2 groups was observed. Based on history, 5 (5%) patients were currently smoking an average of 1 pack a day for the past 41 months. They were recommended to quit smoking. A positive smoking history was present in 46 (50%) patients who smoked an average of 1 pack a day in the past for 24 months and had quit, on average, 31 months ago. Forty-one patients (45%) had never smoked. None of the patients adhered to the recommendation of smoking cessation. Among the patients who followed any of the lifestyle or AREDS supplementation recommendations, 42 (49%) patients reported subjective improvement in vision, whereas 43 (51%) reported no such effect. Statistical analysis showed significant associations between multivitamin use and perceived need for adherence to AREDS supplementation (p ¼ 0.037, χ2 test), multivitamin use and adherence to weight reduction and exercise (p ¼ 0.007, Fisher’s exact test), and multivitamin use and adherence to AREDS supplements (p ¼ 0.009, Fisher’s exact test). Other factors such as sex, mean age, person making the recommendation (vitreoretinal specialist versus others), and smoking status (current or past smoker versus nonsmoker) were not associated with perceived need or with adherence to any recommendations.
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DISCUSSION The adherence to recommendations of lifestyle modifications in AMD has not been well studied previously. Smoking is one of the most important risk factors, and its cessation is an important recommendation with the potential to alter AMD progression.11 In our study, although very few patients warranted smoking counseling, the adherence to smoking cessation was 0%. This indicates that alternative measures of patient education about smoking cessation may need to be explored. Behavioral interventions and pharmacologic treatments with nicotine replacement therapy, bupropion, and varenicline may be appropriate alternatives to consider given the possible addictive nature of smoking. Other lifestyle modifications such as diet and physical activity were well received by most patients. Although most patients recalled recommendations for AREDS supplementation in our study, fewer patients recalled being given lifestyle recommendations. It is unclear whether the physician decided that the lifestyle recommendations were not necessary for some of the patients based on history and physical examination, or the patients did not recall dietary and exercise recommendations considering that a pill would be easier to take and may seem to be more effective from the patient’s point of view. Because the recommendations may not have been uniform, it is also possible that in a typical busy retinal practice with limited time for each patient, the ophthalmologist may find it easier to recommend a pill and omit lifestyle changes. Nevertheless, vitreoretinal specialists and ophthalmologists should remember to provide recommendations on lifestyle modification, together with AREDS supplements. The adherence to AREDS supplements has been reported to be low in previous studies (36–43%).9,10 However, the adherence was higher (88%) in our study. This may be because most of the patients had more advanced disease and were recruited from the retina subspecialty clinic. Our patients might have been more concerned about their retinal condition and prospects of going blind than a patient with milder disease seen in a general ophthalmology setting; however, statistical analysis in our study showed no correlation between adherence to AREDS supplement and the type of specialist making the recommendation. In addition, there was no difference in rate of adherence to AREDS supplementation recommendation among patients with dry versus wet AMD. Multivitamin users were more likely to feel the need to be adherent to AREDS supplements in our study because these patients are likely to be more health conscious. Multivitamin or multimineral use was reported in 35% of U.S. adults because of expectation to improve their health with these supplements.12 Concomitant multivitamin use may be an indicator of health-conscious attitude, and the finding of our study may be related to such an attitude.
Survey of patients with age-related macular degeneration—Shah et al.
Fig. 1 — Sample of patient handout summarizing Age-Related Eye Disease Study and lifestyle recommendations given to patients with age-related macular degeneration treated in the retinal clinic.
Whether regional differences in the United States in terms of lifestyle and multivitamin use would explain our study results is unknown. In evaluating patients taking AREDS supplements, it is important to find out the specific brand and formulation that the patient chooses to use because some patients may take non-AREDS formulations inadvertently. Our study shows that although a high percentage of patients were on true AREDS supplements, a wide range of doses was being
consumed. As noted in our study, 29% of the patients who were adherent to AREDS supplements did not consume adequate daily dose. Different formulations such as tablet and soft gel available for the same brand of AREDS supplements may further complicate this issue. Certain formulations available exclusively in Canada, such as Vitalux and Macula 2, are noteworthy with regard to dosage of individual ingredients. Although Vitalux resembles the AREDS formula (Table 1), Macula 2 is a distinct CAN J OPHTHALMOL — VOL. 50, NO. S1, JUNE 2015
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Survey of patients with age-related macular degeneration—Shah et al. vitamin–mineral formulation that does not meet AREDS criteria. Therefore, it is crucial to stress to the patient the exact dose and frequency based on the formulation and the brand that the patient agrees to use. This is important not only to realize the full effect of these supplements (by preventing underusage), but also to prevent potential adverse effects (by preventing overusage). Although written take-home instructions are commonly dispensed in our clinic (Fig. 1), such a strategy seems inadequate. Poor patient adherence seems to be multifactorial in origin. Some of the factors include patient failure to comprehend the importance of AMD-related recommendations, little understanding among general internists regarding significance of lifestyle modifications in AMD, inadequate nursing involvement, inadequate explanation and reinforcement from ophthalmologists, and lack of nutritionist support and referral. Welldesigned, prospective studies may shed light on some of these hitherto unknown factors. Some of the shortcomings of this study include a relatively small sample size (especially the size of patients with history of smoking), problems inherent to a questionnaire survey, and outcomes based on subjective patient responses. The primary purpose of this study was to investigate how the patient perceived and implemented the lifestyle and AREDS supplement recommendations for AMD. Although several epidemiologic studies have focused on the objective risk factors for AMD progression and suggested specific recommendations to minimize the risk for progression of AMD, our study suggests that there remains a significant gap between the recommendations made by the ophthalmologist and the recommendations actually practiced by the patients with AMD. This study highlights the importance of proper patient education of the recommendations and regular follow-up to the recommendations to ensure that the recommendations are being implemented correctly.
Disclosure: The authors have made the following disclosures: Dr. Telander has received research funds from Genentech via UC Davis. Dr. Morse has received compensation for lecture from Genentech and for consulting from Genentech and Allergan; he has also received research funds for university from Genentech, EMMES, Allergan, Iridex, and Bausch & Lomb. Dr. Park has
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received compensation for lecture from Allergan and for consulting from Regeneron, Healthnet, Genentech, Oraya, and Allergan; she has also received research funds for university from Allergan and Genentech. Drs. Shah and Pilli declare no potential conflict of interest. Supported by: This study was supported by Research to Prevent Blindness, Unrestricted Departmental Grant, New York, N.Y. REFERENCES 1. Friedman DS, O’Colmain BJ, Muñoz B, et al. Eye Diseases Prevalence Research Group. Prevalence of age-related macular degeneration in the United States. Arch Ophthalmol. 2004;122: 564-72. 2. Congdon N, O’Colmain B, Klaver CC, et al. Eye Diseases Prevalence Research Group. Causes and prevalence of visual impairment among adults in the United States. Arch Ophthalmol. 2004;122:477-85. 3. Clemons TE, Milton RC, Klein R, Seddon JM, Ferris FL 3rd. AgeRelated Eye Disease Study Research Group. Risk factors for the incidence of advanced age-related macular degeneration in the AgeRelated Eye Disease Study (AREDS). AREDS report. Ophthalmology. 2005;112:533-9. 4. Mares JA, Voland RP, Sondel SA, et al. Healthy lifestyles related to subsequent prevalence of age-related macular degeneration. Arch Ophthalmol. 2011;129:470-80. 5. Montgomery MP, Kamel F, Pericak-Vance MA, et al. Overall diet quality and age-related macular degeneration. Ophthalmic Epidemiol. 2010;17:58-65. 6. Swenor BK, Bressler S, Caulfield L, West SK. The impact of fish and shellfish consumption on age-related macular degeneration. Ophthalmology. 2010;117:2395-401. 7. Age-Related Eye Disease Study Research Group. A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E, beta carotene, and zinc for advanced age-related macular degeneration and vision loss: AREDS report no. 8. Arch Ophthalmol. 2001;119:1417-36. 8. Bressler NM, Bressler SB, Congdon NG, et al. Age-Related Eye Disease Study Research Group. Potential public health impact of Age-Related Eye Disease Study results: AREDS report no. 11. Arch Ophthalmol. 2003;121:1621-4. 9. Ng WT, Goggin M. Awareness of and compliance with recommended dietary supplement among age-related macular degeneration patients. Clin Exp Ophthalmol. 2006;34:9-14. 10. Hochstetler BS, Scott IU, Kunselman AR, Thompson K, Zerfoss E. Adherence to recommendations of the age-related eye disease study in patients with age-related macular degeneration. Retina. 2010;30: 1166-70. 11. Age-Related Eye Disease Study Research Group. Risk factors associated with age-related macular degeneration. A case-control study in the age-related eye disease study: Age-Related Eye Disease Study Report Number 3. Ophthalmology. 2000;107:2224-32. 12. Radimer K, Bindewald B, Hughes J, Ervin B, Swanson C, Picciano MF. Dietary supplement use by US adults: data from the National Health and Nutrition Examination Survey, 1999-2000. Am J Epidemiol. 2004;160:339-49.