Life After AREDS 2: What Should We Recommend to Patients With or at Risk of AMD?

purposE To establish a consensus on clinical recommendation of oral supplementation for patients with or at risk of developing age-related macular degeneration (AmD), from the perspective of the Age-Related eye Disease Study 2 (AReDS 2) and other studies. MEthods Panel discussion based on a literature review of pertinent articles related to the prevention of AmD with oral supplementation. rEsults on the basis of the findings, patients must first be encouraged to modify their diet and to eliminate modifiable risk factors before being recommended any type of oral supplementation. Then, recommendations must be customized on the basis of a patient’s individual risk profile (i.e., age, gender, heredity, etc.) and severity of disease (i.e., category 1 to 4). essential fatty acids (omega-3s) and vitamins may play a role, in a given clinical population, to prevent the occurrence or the progression of AmD disease. However, there is no single formula that can be applied to all patients with or at risk of AmD. ConClusions This group concluded that the full body of literature must be taken into consideration in order to justify clinical recommendations for patients. A single study such as AReDS 2 cannot, by itself, guide clinical practice. In all cases, recommendations must be individualized and patients should be monitored regularly. KEy words: age-related macular degeneration, poly-unsaturated fatty acids, vitamins, AReDS 2 Life After AReDS 2: What Should We Recommend to Patients With or at Risk of AmD? langis michaud a Julie Brûlé B Jean-Sebastien dufour C pierre Forcier d Guillaume Fortin e Kevin messier F marc-andré rhéaume G yvon rhéaume C patrick Simard C Christina Clark H A : Professor, Université de montréal coordinator of this group Participants : B : Adjunct Professor, Université de montréal C : Clinical Instructor, Université de montréal D : Associate Professor, Université de montréal e : Private Practitioner F : optometristresidency in ocular healthInstitut de l’oeil des Laurentides (oD-mD center) G: m.D. ophthalmologist H: medical writer CLINICAL RESEARCH C C A nA D I A n Jo U R nA L o f o P T o m e T Ry | R ev U e C A nA D I e n n e d ’ o P T o m é T R I e vo L . 76 I S S U e 1 13 C A nA D I A n Jo U R nA L o f o P T o m e T Ry | R ev U e C A nA D I e n n e d ’ o P T o m é T R I e vo L . 76 I S S U e 1 14 Age-related macular degeneration (AmD) is the leading cause of irreversible vision loss in developed countries.1,2 It is estimated that there are 17,000 new cases of neovascular (nv) AmD and 180,000 new cases of geographic atrophy (GA) AmD in Canada every year.3 The disease has a substantial negative impact on patient quality of life and imposes a considerable burden on the economy.3 early and intermediate stages of AmD are prevalent in people older than 65 years of age,4 and without intervention, the condition can evolve to advanced AmD5 and result in significant loss of visual function. Published 12 years ago, the Age-Related eye Disease Study (AReDS) demonstrated that in persons with intermediate to severe AmD, a daily oral supplement containing vitamins and antioxidants reduced the risk of progression to advanced AmD by 25% versus placebo over a period of 5 years.6 This “AReDS formula” consisted of 500 milligrams (mg) vitamin C, 400 international units (IU) of vitamin e, 15 mg beta-carotene, 80 mg zinc oxide, and 2 mg cupric oxide. Since then, observational studies have suggested that dietary intake of other carotenoids, particularly lutein and zeaxanthin, might play a role in protecting against AmD.7,8 moreover, the authors of AReDS9,10 and others8,11-13 highlighted the important role of dietary or supplemental forms of omega-3s, for preventing the development of AmD or its progression. This is the context in which the AReDS 2 was published in may 2013.14 This study, which was initiated in 2006, demonstrated that the addition of lutein, zeaxanthin, and omega-3s to the original AReDS formula, did not further reduce the risk of progression to advanced AmD sommaire but établir des recommandations cliniques consensuelles quant à la gestion clinique des patients atteints ou à risque de développer une dégénérescence maculaire liée à l’âge (DmLA). MÉthodEs Discussion d’un panel d’experts basée sur l’analyse de divers articles scientifiques relatifs à la prise de suppléments vitaminiques et nutritionnels chez des patients atteints ou à risque de DmLA. rÉsultAts Selon le panel, suite à l’analyse des articles, la première intervention devrait être d’inciter le patient à améliorer son hygiène de vie avant de recourir à des suppléments oraux. Par la suite, les recommandations cliniques doivent tenir compte du profil de risque du patient, de sa nutrition, de sa condition systémique ainsi que de l’état de sa santé oculaire. Les omégas 3s et les vitamines peuvent jouer un rôle bénéfique auprès de populations cibles afin de prévenir l’apparition ou l’évolution de la DmLA. Comme il n’existe pas de recettes uniques, le tout doit être personnalisé selon les besoins du patient. ConClusion Le groupe conclut que l’ensemble de la littérature doit être prise en compte afin de justifier le recours à des suppléments oraux (omégas et vitamines) et que les recommandations doivent être personnalisées. Une seule étude, comme AReDS 2, bien que très importante, ne peut déterminer à elle-seule le comportement clinique des professionnels de la vue. L’importance du suivi régulier du patient doit également être comprise par tous. CLINICAL RESEARCH C relative to the original formula.14 However, several secondary and subgroup analyses in this study suggested a benefit to replacing beta-carotene, which is associated with an increased risk of lung cancer in current and former smokers, with other carotenoids such as lutein and zeaxanthin. These conflicting results, notably with regard to omega-3s, have led to confusion among health care professionals about how to counsel patients and their caregivers about dietary strategies to prevent the development and progression of AmD. on november 1, 2013, a group of Quebec experts, consisting of eight optometrists and one ophthalmologist, gathered in montreal to discuss the outcomes of the AReDS 2 from a clinical perspective, with the goal of guiding the optimal management of this disease. In order to consider the AReDS 2 in a more global context, a general critique was undertaken. Then, each participant was assigned to review and present the key findings of a published article related to the use of dietary supplements or dietary factors associated with AmD (see Table 1 for a brief synopsis of the studies and key findings). A facilitated group discussion that ensued focused on synthesizing the data with the eventual goal of developing a clear and practical set of consensusbased, nonbinding clinical recommendations for patients with AmD. gEnErAl CritiquE of thE ArEds 2 First, it is important to recognize that the AReDS 2 was founded on the original AReDS. A socioeconomic analysis of the patients enrolled in this latter study showed that they were, on average, more educated and better nourished at baseline than the average American14 as well as those attending optometry practices in Canada. moreover, a substantial proportion of patients were already taking vitamin and antioxidant supplements,6,14 which suggested that their overall nutrition status was already supported by an external source of these nutrients. In this regard, there was no real placebo group in the AReDS 2. moreover, 14% of patients were additionally taking “nonauthorized” supplements, which further increased their antioxidant intake.14 Furthermore, the dosage and formulation of omega-3 supplements that were used in this study (eicosapentaenoic acid greater than docosahexaenoic acid [ePA>DHA] 1000 mg/day versus 2000 mg/day, as esters or triglycerides) were not optimal, considering the results of earlier studies on this subject. Finally, the AReDS 2 evaluated progression of AmD from moderate to advanced disease (nv and GA forms) without considering the effects of supplementation on the risk of development of the disease or its progression from mild to moderate disease. The conclusions of the AReDS 2 can be applied to patients who were similar to those who were evaluated in the study, that is, patients with moderate to advanced AmD who are well nourished and well educated. Before extrapolating the study results to other patients, evidence derived from other studies must first be considered in order to appreciate the general context from which clinical recommendations can be formulated. General reCommendationS After considering the outcomes of several studies that were presented and keeping a general context in mind, a consensus was reached by this group of experts—that recommendations should be based on the individual patient and their particular risk profile. Health care professionals should assess a patient’s modifiable risk factors at the earliest opportunity to better counsel and categorize their risk of developing AmD or its progression to advanced AmD and to tailor advice about lifestyle, diet, and supplements. Tools are available to assist health care professionals in this regard. The results of the macular Assessment Program (mAP), which aimed at evaluating the perceptions versus the realities of 290 Canadian optometrists, were recently reported and reviewed at this meeting.15 This tool enables optometrists to categorize patients as having low, moderate, or high risk of AmD, on the basis of an evaluation of their modifiable and nonmodifiable risk factors. The literature suggests that the most important modifiable risk factors are smoking, alcohol consumption (>3 standard drinks/day), sun exposure (photostress), poor-quality diet, obesity, cardiovascular risk factors, and adherence to medication, whereas the most important nonmodifiable risk factors include age, gender, family history, ethnicity (Caucasians), and socioeconomic and