Patient Use of Dietary Supplements, Home Monitoring, or Genetic Testing for Nonneovascular Age-Related Macular Degeneration

Abstract

Purpose:

This work evaluated the use and type of dietary supplements and home monitoring for nonneovascular age-related macular degeneration (AMD), as well as the prevalence of genetic testing among patients with AMD.

Methods:

A cross-sectional study was conducted of 129 participants older than 50 years who completed self-administered questionnaires regarding usage and type of dietary supplements and home monitoring, as well as the participants’ use of genetic testing for AMD.

Results:

Of 91 participants with AMD, 83 (91.2%) took vitamins, including 55 (60.4%) who used an Age-Related Eye Disease Study (AREDS) or AREDS2 formulation. Of 38 without AMD, 31 (81.6%) took vitamins (difference from participants with AMD = 9.6% [95% CI, 0%-23.2%]), including 2 on an AREDS formulation. Among 82 participants with AMD who were AREDS candidates (intermediate or advanced AMD in 1 or both eyes), 51 (62.2%; 95% CI, 51.7%-72.7%) took an AREDS or AREDS2 formulation, and 31 (37.8%) did not (5 were unsure). Additionally, 50 (61.0%; 95% CI, 50.4%-71.6%) AREDS candidates did some type of home monitoring. Only 1 (1.2%; 95% CI, 0%-3.6%) underwent genetic testing for AMD. Among 9 with AMD who were not AREDS candidates, 4 (44.4%) used an AREDS formulation, 4 (44.4%) did not, and 1 (11.1%) was unsure; only 1 (11.1%) of these 9 performed home monitoring.

Conclusions:

Despite similar results from past surveys and AREDS2 data supporting supplement use in 2013 and home monitoring in 2014, these findings suggest about one-third of AREDS candidates do not do so, providing further support for improving education regarding appropriate supplement and home monitoring usage. Genetic testing for AMD also appears infrequent.

Introduction

By 2050, more than 5 million people are expected to have age-related macular degeneration (AMD) in the United States, which is a 150% increase from 2010. ¹ Irreversible central vision loss may occur in advanced AMD, and various management approaches exist to minimize disease progression and morbidity among individuals at risk for AMD progression. For example, the Age-Related Eye Disease Study (AREDS) has demonstrated that specific high-dose dietary supplements can reduce progression to advanced AMD, primarily by reducing the risk of developing neovascular AMD among individuals with the intermediate stage (typically unilateral or bilateral large drusen or numerous medium-sized drusen). ² However, past surveys performed between 2003 and 2014 of patients at retinal clinics in the United States and abroad have suggested substantial deficiencies in widespread adoption of treatment recommendations that had been proposed by AREDS investigators. ^{2 -8} Many patients with AMD who were candidates for dietary supplements were either not using them or using them incorrectly.

Furthermore, past reports have identified dietary supplement usage among many individuals for whom no benefit has been shown for their retinal conditions, such as those without AMD, with early AMD, or with advanced AMD and bilateral vision loss. ³ These supplements may be marketed for general eye health. The US Food and Drug Administration does not require dietary supplements to meet the same regulations that apply to drug products, which may contribute to confusion in understanding for what supplements are indicated, for whom, and for what reason.

To further evaluate the role of dietary supplements in AMD management, AREDS2 evaluated the addition of lutein/zeaxanthin, ω-3 long-chain polyunsaturated fatty acids, or both to the original AREDS formulation (or some modification of the original AREDS formulation) for those who risk developing advanced AMD. ⁹ The study also explored omission of beta carotene from the formulation, because there is an increased risk for lung cancer associated with higher doses of beta carotene supplementation than those used in AREDS. ^10,11 For potential enhanced safety, investigators suggested considering the substitution of beta-carotene with lutein/zeaxanthin in the AREDS formulation, an AREDS2 formulation, given that exploratory analyses of secondary outcomes suggested the substitution of lutein/zeaxanthin for beta-carotene remained beneficial. ¹²

A home version of a preferential hyperacuity perimeter (Foresee Home, Notal Vision Ltd) can evaluate central visual field abnormalities and may be recommended for patients with intermediate AMD to facilitate early detection of incident neovascular AMD. ¹³ The device group of the AREDS2-HOME (Home Monitoring of the Eye) study’s participants was more likely to retain vision of 20/40 or better and have smaller lesions at time of choroidal neovascularization diagnosis compared with individuals who did not have the home device. ¹⁴

Surveys on the use of supplements in AMD were last performed prior to the reporting of the AREDS2 study, and to the best of our knowledge no surveys have concentrated on home monitoring techniques. This article describes behaviors several years after the AREDS2 (in 2013) and AREDS2-Home (in 2014) reports to gauge how these studies may have permeated clinical practice. Furthermore, because there also is debate over recommendations on genetic testing for AMD to assess risk of disease progression and whether findings should influence the use of dietary supplements, ^{15 -20} we also explored the prevalence of genetic testing among patients with AMD.

Specifically, this study aimed to address the following potential knowledge gaps. The first purpose was to evaluate the use and type of dietary supplements among patients with AMD, and to determine whether the use was compatible with clinical trial results and preferred practice patterns of the American Academy of Ophthalmology. For comparison, usage of supplements was evaluated in a cohort older than 50 years with retinal disease for which dietary supplements have not been found to be beneficial. The second purpose was to determine the current use of home monitoring in patients with intermediate AMD in at least 1 eye. The third purpose was to explore the prevalence of genetic testing for AMD among patients with a clinical diagnosis of AMD who received care at a tertiary ophthalmic center.

Methods

This study was conducted from March through May 2017. Patients previously diagnosed with AMD and those older than 50 years without AMD but with a diagnosis of retinal vein occlusion or diabetic retinopathy who presented for follow-up care by participating investigators at the Wilmer Eye Institute’s Retina Division were identified through review of medical records as potential study participants.

Individuals who were eligible were asked to complete several self-administered questionnaires (see Supplemental Material) during their visit. A vitamin/dietary supplement use questionnaire, not previously validated but similar to a questionnaire used in a previous publication, ³ asked patients if they were using supplements (Table 1). Those taking supplements were asked about the type, dose, and frequency of supplementation. The questionnaire specifically asked about their use of the original AREDS formulation tablets, original AREDS formulation gel caps, or AREDS2-like formulation. Their understanding of the rationale to use supplements was evaluated with multiple-choice response options. Questions probed the relevant disease that required supplement use and possible benefits of using the supplements. More than 1 response could be selected. For patients not taking supplements, the questionnaire asked whether their eye care provider had ever suggested doing so and if so, why they were not taking any supplements. Finally, patients were asked to identify as a current smoker, former smoker, or never smoker.

Table 1.

Vitamin and Dietary Supplement Usage.

	Group 1: diabetic retinopathy/retinal vein occlusion but no AMD (n = 38)				Group 2: AMD but no evidence to support using AREDS (n = 9)				Group 3: AMD, candidate for AREDS supplementation (n = 82)
	Using		Not using		Using		Not using		Using		Not using
Vitamin usagea	31	81.6%	7	18.4%	7	77.8%	2	22.2%	76	92.7%	5	6.1%
AREDS vitamin usageb	2	5.3%	33	86.8%	4	44.4%	4	44.4%	51	62.2%	26	31.7%

Abbreviations: AMD, age-related macular degeneration; AREDS, Age-Related Eye Disease Study.

^a Group 1: 1 participant was uncertain; group 3: 1 participant was uncertain.

^b Group 1: 3 participants were uncertain; group 2: 1 participant was uncertain; group 3: 5 participants were uncertain.

The home monitoring questionnaire, which was not previously validated, asked about any monitoring that the patients conduct at home and if any, which type(s) they performed and how often monitoring occurs. The genetic testing questionnaire, not previously validated, asked whether genetic testing had been performed, and if so, what the patient’s understanding was for the rationale to pursue genetic tests for AMD.

All patients with AMD were categorized by their AMD severity using a 4-step classification scale, which had been used at entry into AREDS and defined as no AMD (AMD-1), early AMD (AMD-2), intermediate AMD (AMD-3), and advanced AMD (AMD-4). ²¹ The categorization was made by 1 retina specialist (T.Y.A.L.) in a masked fashion. The grading was performed on retinal imaging (30° color fundus photographs, 30° red-free photographs, and/or 30°/60° fluorescein angiography and/or optical coherence tomography) that was obtained as part of routine clinical care the day of the interview. If no retinal imaging was obtained that day, then retinal imaging tests performed closest to the day of the interview were used. About 10% of retinal images were sampled randomly and graded separately in a masked fashion by a second retina specialist (N.M.B.), and a second grading showed 100% agreement between the 2 graders.

Data obtained from medical records included sex, age, race, ethnicity, provider, and visual acuity (VA). Confidence intervals were calculated for a proportion in 1 sample. ²²

Results

A total of 129 participants completed the study, among whom 77 (59.7%) were female, and 115 (89.1%) were White. The mean (±SD) age was 75 (±9) years. Participants were categorized into 1 of 3 groups. Group 1 contained patients who were 50 years and older without AMD but with a history of retinal vein occlusion or diabetic retinopathy (n = 38). Group 2 included patients with AMD who no longer benefited from AREDS supplements (n = 9), and group 3 had patients with AMD who were deemed good candidates for AREDS supplementation (n = 82) based on the AREDS and AREDS2 results.

Group 1 served as the control group. Group 2 participants had bilateral advanced AMD (either neovascular or atrophic) and VA worse than 20/100 in each eye. Group 3 participants had as their most advanced AMD feature intermediate AMD in 1 (n = 4) or both eyes (n = 14), or unilateral advanced AMD with a fellow eye at risk (fellow eye findings spanned small to large drusen, n = 35); individuals with bilateral advanced AMD who retained vision of 20/100 or better in at least 1 eye (n = 29) included 17 with bilateral neovascular AMD, 6 with bilateral geographic atrophy, and 6 with neovascular AMD in 1 eye and geographic atrophy in the other eye. For those without retinal images the day of the study visit, images from the most recent prior clinic visit were graded (median: 2.1 years, interquartile range, 0.7-3.6 years).

Vitamin Usage

Of the 38 control participants in group 1, 31 (81.6%) reported using vitamins (difference from participants with AMD = 9.6% [95% CI, 4.5%-14.7%). Of these 31 participants using vitamins, 28 (90.3%) took vitamins for general health or a specific medical condition that was not eye related, 2 (6.5%) took an AREDS formulation, and 1 (3.2%) was uncertain (see Table 1). Similarly, of the 91 participants with AMD, 83 (91.2%) were taking some type of vitamin, including 55 (60.4%) who used an AREDS formulation. Among the 9 participants in group 2, those for whom there is no established benefit to using supplements for their AMD, 7 (77.8%) reported using vitamins. Of these 7 participants, 3 (42.9%) took vitamins for general health or a specific medical condition that was not eye related and 4 (57.1%) took an AREDS formulation. Among the 4 respondents who were using an AREDS supplement in this group, 2 believed they were reducing the probability of worsening their established neovascular AMD, whereas the other 2 did not know why they were taking the supplements.

In group 3, patients with AMD who were deemed good candidates for specific micronutrient supplements, 76 (92.7%) used vitamins and 51 (62.2%; 95% CI, 51.7%-72.7%) took an AREDS formulation. Of these 76 participants, 24 (31.6%) took vitamins for general health or a specific medical condition that was not eye related and 1 (1.3%) was uncertain. Among the 31 (37.8%) candidates for, but not taking or unsure whether they were taking, an AREDS formulation, 9 had bilateral advanced AMD with 20/100 or better vision in at least 1 eye, 13 had unilateral advanced AMD with intermediate AMD in the contralateral eye (11 participants) or no evidence of the intermediate AMD in the other eye (2 participants), 6 had bilateral intermediate AMD, and 3 had unilateral intermediate AMD.

Among the 51 individuals in the group who were taking AREDS supplements correctly, 20 had bilateral advanced AMD with vision of 20/100 or better in at least 1 eye, 22 had unilateral advanced AMD and intermediate AMD in the fellow eye (18 participants) or no intermediate AMD in the other eye (4 participants), 8 had bilateral intermediate AMD, and 1 had unilateral intermediate AMD.

In the cohort of individuals who took supplements consistent with AREDS recommendations, 23 participants acknowledged the goal was to prevent progression from an earlier stage to a more advanced stage of AMD, 15 believed they were reducing their odds of developing the wet form of AMD, 9 opined the effects would decrease development of dry AMD, 27 thought they were reducing their chance of having their wet AMD get worse, and 16 thought they were reducing the risk of progression of their dry AMD. Three participants did not know why they were taking the AREDS supplements. Thus, a total of 30 (58.8%) chose at least 1 correct response as to what the supplements might accomplish. The responses that were considered correct were: preventing progression from an earlier stage to a more advanced stage of AMD, reducing their odds of developing the wet form of AMD, and reducing their chance of having their wet AMD get worse. However, 6 (11.8%) participants selected only incorrect responses as to what the treatment may offer or offered no understanding of the treatment goals. The responses that were considered incorrect were: decreasing development of dry AMD and reducing the risk of progression of their dry AMD. Finally, 15 (29.4%) chose a combination of correct and incorrect responses.

Recommendations for taking an AREDS formulation among participants came from Johns Hopkins University School of Medicine retina specialists (48 of 63 [76.2%]), retina specialists outside the Wilmer Eye Institute (5 of 63 [7.9%]), ophthalmologists other than retina specialists outside Wilmer (5 of 63 [7.9%]), nonretina ophthalmologists from Wilmer or Johns Hopkins University (3 of 63 [4.8%]), and optometrists or other eye care specialists (non-MD or DO physicians) (2 of 63 [3.2%]).

Home Monitoring

Among the 82 AREDS candidates, 50 (61.0%; 95% CI, 50.4%-71.6%) performed some type of home monitoring, and 32 (39.0%) did not. Use of an Amsler grid (45.5%) or evaluating vision by covering 1 eye at a time and looking at a straight edge (42.4%) were most common. Most participants in this group monitored their vision at home each day, several days a week, each month, or several weeks each month (Table 2). However, about 40% never monitored their vision at home. In the group of patients with AMD but no evidence to support using AREDS, 1 (11.1%) participant monitored vision at home and used the Amsler grid to do so several months a year.

Table 2.

Home Monitoring.^a

	Group 2: AMD but no evidence to support using AREDS (n = 9)				Group 3: AMD, candidate for AREDS supplementation (n = 82)
	Using		Not using		Using		Not using
Home monitoring	1	11.1%	8	88.9%	50	61.0%	32	39.0%
Type
Amsler grid	1	100%	0	0%	30	45.5%	0	0%
PHP	0	0%	0	0%	8	12.1%	0	0%
Cover 1 eye at a time	0	0%	0	0%	28	42.4%	0	0%
Frequency
Each d	0	0%	0	0%	13	15.9%	0	0%
Several d/wk	0	0%	0	0%	14	17.1%	0	0%
Each wk	0	0%	0	0%	6	7.3%	0	0%
Several wks/mo	0	0%	0	0%	11	13.4%	0	0%
Each mo	0	0%	0	0%	4	4.9%	0	0%
Several mo/y	1	11.1%	0	0%	0	0%	0	0%
Less than several mo/y	0	0%	0	0%	2	2.4%	0	0%
Never	8	88.9%	0	0%	32	39.0%	0	0%

Abbreviations: AMD, age-related macular degeneration; AREDS, Age-Related Eye Disease Study; PHP, preferential hyperacuity perimeter.

^a Not applicable to group 1: no AMD, diabetic retinopathy/retinal vein occlusion.

Genetic Testing

Of 91 patients with AMD, only 1 participant (1.2%; 95% CI, 0%-3.6%), who was in group 3, had undergone genetic testing for AMD because of relevant family history.

Conclusions

Among patients older than 50 years with common retinal diseases, vitamin usage was common, but use of a dietary supplement such as that used in AREDS typically was only by those with AMD, not other retinal diseases. As was noted in a previous survey from Wilmer Eye Institute, ³ several patients with AMD for whom a dietary supplement would not be considered still were taking an AREDS formulation. Almost half the patients in the group with no evidence to support using an AREDS formulation and a few participants without AMD still used an AREDS formulation. Although the risk of adverse effects is low, ^{23 -25} there is no known benefit for these patients, and continued education seems warranted to reassure them that such supplements need not be considered.

Overall, use of an AREDS formulation appeared to be similar to a previous study from 2008. ³ There is some evidence of benefit for AREDS supplementation in those with advanced-stage AMD in both eyes with 1 or both eyes at 20/100 or better. ² AREDS had shown a reduced rate of VA loss in the dietary supplement group. Therefore, both in the 2008 study and in this study, participants with the advanced stage in both eyes with 1 or both eyes at 20/100 or better vision were considered to be individuals for whom a dietary supplement such as that used in AREDS might be recommended. In the 2008 study, 61% of candidates for AREDS supplementation were using an AREDS formulation for a scenario in which a benefit was deemed worthy, leaving more than one-third of AREDS candidates not using or incorrectly using AREDS supplementation.

Results from our study were similar, with 62.2% of candidates for AREDS supplementation using them and more than one-third of candidates not. Of the 26 AREDS candidates who did not use AREDS supplementation, 5 responded with reasons for not doing so. Two were not recommended to take them by their eye care provider, and the other 3 provided reasons including questioning the benefits of AREDS supplementation, believing that they did not work, and having gastrointestinal upset while taking them. Of the 4 non-AREDS candidates who did not use AREDS supplementation, 3 were recommended by their eye care provider to do so but chose not to for reasons including having gastrointestinal upset while taking them, forgetting to take them, and the supplements being no longer recommended. Cost may be another potential factor. While understanding the rationale for using supplements among AREDS candidates appeared to be greater in this 2018 study than in the 2008 study, a direct comparison was difficult because of potential confounders not measured, such as patient comprehension of medical information. Furthermore, confidence intervals around the point estimate percentages in each study were relatively large given the relatively small number of individuals surveyed.

The majority of participants in the study with no evidence to support using AREDS supplementation did not conduct any type of home monitoring, whereas most of the candidates for AREDS supplementation did perform some type of home monitoring. In both groups, Amsler grid home monitoring was the most common, followed by vision evaluation by covering 1 eye at a time, followed by use of a preferential hyperacuity perimeter device. Candidates for AREDS supplementation appeared to monitor their AMD more frequently than noncandidates, often each day or several days a week compared with several months a year or never. This difference suggests the need for more physician coaching and education for non-AREDS candidates.

Only 1 patient across all 3 groups had undergone genetic testing. Even after development of the AREDS2 formulation, several post hoc genetic analyses of AREDS patients led to different recommendations regarding genetic testing in the management of AMD. Awh and others ^15,16 recommended genetic testing and suggested a favorable response to AREDS supplementation on single-nucleotide variations in genes strongly associated with AMD. In contrast, Chew et al found AREDS supplements reduced the rate of progression to late AMD regardless of genotype. ^17,18 The American Academy of Ophthalmology Task Force on Genetic Testing recommends avoiding routine genetic testing. ¹⁹ Some believe that clinical examination and imaging allow ophthalmologists to better predict visual outcome than existing genetic tests. ²⁰ Potentially complicating management further, direct-to-consumer advertising of these supplements can be seen in magazines ²⁶ and television commercials. ²⁷

Based on these results, a possible intervention to be considered and evaluated, in addition to physician coaching and education, includes the use of a teach-back method during follow-up visits to check for patient understanding regarding the use of these preventive measures. ²⁸ In addition, performing supplement reconciliation or confirmation of use, for example, pill counts or bottle counts, at these visits may also prompt discussion of vitamin usage and identify incorrect use of AREDS supplementation. Of note, a prospective survey of concordance with the AREDS recommendations showed high patient concordance rates with verbal and written instructions and verbal repetition from staff members at each visit. ²⁹ Providing written and verbal advice relevant to each patient’s stage of AMD in conjunction with continual repetition of instructions may also help reinforce the correct use of AREDS supplementation and home monitoring.

Limitations of this study include the use of information that was self-reported and collected through invalidated surveys, but the surveys were similar to that used in a previous publication. ⁸ Results may have been affected by inaccurate reporting of supplement contents or comprehension of the questions. The number of participants was relatively small, leading to relatively large confidence intervals around reported point estimate percentages. Participants may have been seen by various retina specialists, some who may spend more time on counseling and emphasis of the benefits of AREDS supplementation than others. Different explanations among providers may have been used. Finally, study participants, while recruited among multiple physicians, were from only 1 ophthalmology practice, specifically an academic-based practice specializing in retinal diseases, although a practice that includes authors of AREDS publications on dietary supplements and home monitoring.

This study suggests that the adoption of AREDS supplementation has not changed much in the past decade, with more than one-third of supplement candidates deviating from recommendations that may protect their vision. In addition, some individuals without AMD and some individuals with AMD but not AREDS candidates were still using an AREDS formulation despite little evidence to support such use. More AREDS candidates performed some type of home monitoring and monitored their vision more frequently compared with noncandidates, and the vast majority of participants had not undergone genetic testing for AMD. These findings support the importance of increasing awareness of these preventive measures and improving education regarding monitoring or supplement usage for AMD, such as by inquiring about AREDS usage and ensuring patients meet the criteria for supplementation.