Age-Related Macular Degeneration Preferred Practice Pattern®

AMERICAN ACADEMY OF OPHTHALMOLOGY® Protecting Sight. Empowering Lives.® © 2019 by the American Academy of Ophthalmology Published by Elsevier Inc. http://dx.doi.org/10.1016/j.ophtha.2019.09.024 ISSN 0161–6420/19 Secretary for Quality of Care: Timothy W. Olsen, MD Academy Staff: Ali Al-Rajhi, PhD, MPH Andre Ambrus, MLIS Meghan Daly Flora C. Lum, MD Medical Editor: Susan Garratt Approved by: Board of Trustees September 7, 2019 © 2019 American Academy of Ophthalmology® All rights reserved AMERICAN ACADEMY OF OPHTHALMOLOGY and PREFERRED PRACTICE PATTERN are registered trademarks of the American Academy of Ophthalmology. All other trademarks are the property of their respective owners. Preferred Practice Pattern® guidelines are developed by the Academy's H. Dunbar Hoskins Jr., MD Center for Quality Eye Care without any external financial support. Authors and reviewers of the guidelines are volunteers and do not receive any financial compensation for their contributions to the documents. The guidelines are externally reviewed by experts and stakeholders before publication. Correspondence: Ali A. Al-Rajhi, PhD, MPH, American Academy of Ophthalmology, P. O. Box 7424, San Francisco, CA 94120–7424. E-mail: . The Retina/Vitreous Preferred Practice Pattern® Panel members wrote the Age-Related Macular Degeneration Preferred Practice Pattern® (PPP) guidelines. The PPP Panel members discussed and reviewed successive drafts of the document, meeting in person twice and conducting other review by e-mail discussion, to develop a consensus over the final version of the document. Retina/Vitreous Preferred Practice Pattern Panel 2018–2019 Ron A. Adelman, MD, MPH, MBA, FACS Gurunadh A. Vemulakonda, MD, American Society of Retina Specialists Representative Steven T. Bailey, MD, Retina Society Representative Amani Fawzi, MD, Macula Society Representative Jennifer I. Lim, MD Gui-shang Ying, MD, PhD, Methodologist Christina J. Flaxel, MD, Chair We thank our partners, the Cochrane Eyes and Vision US Satellite ([email protected]), for identifying reliable systematic reviews that we cite and discuss in support of the PPP recommendations. The Preferred Practice Patterns Committee members reviewed and discussed the document during a meeting in June 2019. The document was edited in response to the discussion and comments. Preferred Practice Patterns Committee 2019 Robert S. Feder, MD, Chair Roy S. Chuck, MD, PhD Steven P. Dunn, MD Christina J. Flaxel, MD Steven J. Gedde, MD Francis S. Mah, MD Randall J. Olson, MD David K. Wallace, MD, MPH David C. Musch, PhD, MPH, Methodologist The Age-Related Macular Degeneration PPP was then sent for review to additional internal and external groups and individuals in July 2019. All those returning comments were required to provide disclosure of relevant relationships with industry to have their comments considered (indicated with an asterisk below). Members of the Retina/Vitreous Preferred Practice Pattern Panel reviewed and discussed these comments and determined revisions to the document. In compliance with the Council of Medical Specialty Societies' Code for Interactions with Companies (available at www.cmss.org/codeforinteractions.aspx), relevant relationships with industry are listed. The Academy has Relationship with Industry Procedures to comply with the Code (available at http://one.aao.org/CE/PracticeGuidelines/PPP.aspx). A majority (88%) of the members of the Retina/Vitreous Preferred Practice Pattern Panel 2018–2019 had no financial relationship to disclose. Retina/Vitreous Preferred Practice Pattern Panel 2018–2019 Christina J. Flaxel, MD: No financial relationships to disclose Ron A. Adelman, MD, MPH, MBA, FACS: No financial relationships to disclose Steven T. Bailey, MD: No financial relationships to disclose Amani Fawzi, MD: No financial relationships to disclose Jennifer I. Lim, MD: Genentech, Alcon Laboratories Inc., Kodiak Sciences, Opthea, Novartis—Consultant/Advisor; Genentech, Novartis Alcon Pharmaceuticals—Lecture Fees Gurunadh A. Vemulakonda, MD: No financial relationships to disclose Gui-shang Ying, MD, PhD: No financial relationships to disclose Preferred Practice Patterns Committee 2019 Robert S. Feder, MD, Chair: No financial relationships to disclose Roy S. Chuck, MD, PhD: No financial relationships to disclose Steven P. Dunn, MD: No financial relationships to disclose Christina J. Flaxel, MD: No financial relationships to disclose Steven J. Gedde, MD: No financial relationships to disclose Francis S. Mah, MD: Alcon Laboratories, Abbott Medical Optics, Bausch + Lomb—Consultant/Advisor; Abbott Medical Optics, Bausch + Lomb—Lecture Fees Randall J. Olson, MD: No financial relationships to disclose David K. Wallace, MD, MPH: No financial relationships to disclose David C. Musch, PhD, MPH, Methodologist: Chengdu Kanghong Biotechnology Opthea, IRIDEX, Notal Vision—Consultant/Advisor Secretary for Quality of Care Timothy W. Olsen, MD: No financial relationships to disclose Academy Staff Ali Al-Rajhi, PhD, MPH: No financial relationships to disclose Andre Ambrus, MLIS: No financial relationships to disclose Meghan Daly: No financial relationships to disclose Flora C. Lum, MD: No financial relationships to disclose The disclosures of relevant relationships to industry of other reviewers of the document from January to October 2019 are available online at www.aao.org/ppp. OBJECTIVES OF PREFERRED PRACTICE PATTERN GUIDELINES P7METHODS AND KEY TO RATINGS P8HIGHLIGHTED FINDINGS AND RECOMMENDATIONS FOR CARE P9INTRODUCTION P10Disease Definition P10Patient Population P11Clinical Objectives P11BACKGROUND P11Incidence and Prevalence P11Risk Factors P13Smoking, Hypertension, and Cardiovascular Disease P13Levels of Antioxidants P13Diet P14Aspirin P14Genetic Factors P14Other Risk Factors P16Natural History P16Early Age-Related Macular Degeneration P16Intermediate Age-Related Macular Degeneration P16Advanced Age-Related Macular Degeneration P17Rationale for Treatment P18Treatment Modalities P19Early Age-Related Macular Degeneration P19Intermediate Age-Related Macular Degeneration P19Neovascular Age-Related Macular Degeneration P22CARE PROCESS P29Patient Outcome Criteria P29Diagnosis P29History P29Examination P29Diagnostic Tests P29Management P31Monitoring and Early Detection P32Indications for Treatment for Choroidal Neovascularization P33Complications of Treatment P36Follow-up Evaluation P39Provider and Setting P40Counseling and Referral P40Socioeconomic Considerations P41APPENDIX 1. QUALITY OF OPHTHALMIC CARE CORE CRITERIA P43APPENDIX 2. INTERNATIONAL STATISTICAL CLASSIFICATION OF DISEASES AND RELATED HEALTH PROBLEMS (ICD) CODES P45GLOSSARY P46LITERATURE SEARCHES FOR THIS PPP P50RELATED ACADEMY MATERIALS P51REFERENCES P52 Background: Age-related macular degeneration is a leading cause of severe, irreversible vision impairment in developed countries. The primary risk factors for the development of advanced AMD include increasing age, northern European ancestry, and genetic factors. Smoking has been shown by numerous studies to be the main modifiable risk factor. This Preferred Practice Pattern (PPP) uses the classification of the Age-Related Eye Disease Study (AREDS) and a more recent clinical classification to define the early and intermediate stages of AMD since current treatment recommendations are based on these classifications. The PPP recommendations are based on Cochrane-identified reliable systematic reviews. Rationale for treatment: Prospective randomized controlled clinical trials support the use of antioxidant vitamins and minerals for slowing the progression to later stages of AMD, intravitreal injection of anti-VEGF agents, photodynamic therapy (PDT), and laser photocoagulation surgery to treat neovascular AMD. It should be noted that intravitreal injection therapy using anti-vascular endothelial growth factor (VEGF) agents (e.g., aflibercept, bevacizumab, and ranibizumab) is the most effective way to manage neovascular AMD and represents the first line of treatment. Care Process: Patient outcome criteria are to reverse or minimize visual loss and improve visual function. The initial evaluation of a patient with signs and symptoms suggestive of AMD includes all features of the comprehensive adult medical eye evaluation, with particular attention to those aspects relevant to AMD. In patients with neovascular AMD, early detection and prompt treatment improves the visual outcome. Symptoms suggestive of postinjection endophthalmitis or retinal detachment require prompt evaluation. Fundus fluorescein angiography and optical coherence tomography (OCT) are useful diagnostic tests in clinical practice to detect new or recurrent neovascular disease activity and guide therapy. Management options for AMD include observation and early detection, antioxidant vitamin and mineral supplements, intravitreal injection of anti-VEGF agents, PDT, laser photocoagulation surgery, and the encouragement of smoking cessation for patients who currently smoke. All patients with AMD should be educated about the prognosis of the disease and the potential value of treatment as appropriate for their visual and functional status. As a service to its members and the public, the American Academy of Ophthalmology has developed a series of Preferred Practice Pattern® guidelines that identify characteristics and components of quality eye care. Appendix 1 describes the core criteria of quality eye care. The Preferred Practice Pattern® guidelines are based on the best available scientific data as interpreted by panels of knowledgeable health professionals. In some instances, such as when results of carefully conducted clinical trials are available, the data are particularly persuasive and provide clear guidance. In other instances, the panels have to rely on their collective judgment and evaluation of available evidence. These documents provide guidance for the pattern of practice, not for the care of a particular individual. While they should generally meet the needs of most patients, they cannot possibly best meet the needs of all patients. Adherence to these PPPs will not ensure a successful outcome in every situation. These practice patterns should not be deemed inclusive of all proper methods of care or exclusive of other methods of care reasonably directed at obtaining the best results. It may be necessary to approach different patients' needs in different ways. The physician must make the ultimate judgment about the propriety of the care of a particular patient in light of all of the circumstances presented by that patient. The American Academy of Ophthalmology is available to assist members in resolving ethical dilemmas that arise in the course of ophthalmic practice. Preferred Practice Pattern® guidelines are not medical standards to be adhered to in all individual situations. The Academy specifically disclaims any and all liability for injury or other damages of any kind, from negligence or otherwise, for any and all claims that may arise out of the use of any recommendations or other information contained herein. References to certain drugs, instruments, and other products are made for illustrative purposes only and are not intended to constitute an endorsement of such. Such material may include information on applications that are not considered community standard, that reflect indications not included in approved U.S. Food and Drug Administration (FDA) labeling, or that are approved for use only in restricted research settings. The FDA has stated that it is the responsibility of the physician to determine the FDA status of each drug or device he or she wishes to use, and to use them with appropriate patient consent in compliance with applicable law. Innovation in medicine is essential to ensure the future health of the American public, and the Academy encourages the development of new diagnostic and therapeutic methods that will improve eye care. It is essential to recognize that true medical excellence is achieved only when the patients' needs are the foremost consideration. All Preferred Practice Pattern® guidelines are reviewed by their parent panel annually or earlier if developments warrant and updated accordingly. To ensure that all PPPs are current, each is valid for 5 years from the approved by date unless superseded by a revision. Preferred Practice Pattern guidelines are funded by the Academy without commercial support. Authors and reviewers of PPPs are volunteers and do not receive any financial compensation for their contributions to the documents. The PPPs are externally reviewed by experts and stakeholders, including consumer representatives, before publication. The PPPs are developed in compliance with the Council of Medical Specialty Societies' Code for Interactions with Companies. The Academy has Relationship with Industry Procedures (available at www.aao.org/about-preferred-practice-patterns) to comply with the Code. Appendix 2 contains the International Statistical Classification of Diseases and Related Health Problems (ICD) codes for the disease entities that this PPP covers. The intended users of the Age-Related Macular Degeneration PPP are ophthalmologists. Preferred Practice Pattern® guidelines should be clinically relevant and specific enough to provide useful information to practitioners. Where evidence exists to support a recommendation for care, the recommendation should be given an explicit rating that shows the strength of evidence. To accomplish these aims, methods from the Scottish Intercollegiate Guideline Network1Bourne RR Sorensen KE Klauber A Foster PJ Johnson GJ Alsbirk PH Glaucoma in East Greenlandic Inuit–a population survey in Ittoqqortoormiit (Scoresbysund).Acta Ophthalmol Scand. 2001; 79: 462-467Crossref PubMed Scopus (24) Google Scholar (SIGN) and the Grading of Recommendations Assessment, Development and Evaluation2Guyatt GH Oxman AD Vist GE et al.GRADE: an emerging consensus on rating quality of evidence and strength of recommendations.Bmj. 2008; 336: 924-926Crossref PubMed Google Scholar (GRADE) group are used. GRADE is a systematic approach to grading the strength of the total body of evidence that is available to support recommendations on a specific clinical management issue. Organizations that have adopted GRADE include SIGN, the World Health Organization, the Agency for Healthcare Research and Policy, and the American College of Physicians.3Bourne RR Sukudom P Foster PJ et al.Prevalence of glaucoma in Thailand: a population based survey in Rom Klao District, Bangkok.Br J Ophthalmol. 2003; 87: 1069-1074Crossref PubMed Scopus (0) Google Scholar ♦All studies used to form a recommendation for care are graded for strength of evidence individually, and that grade is listed with the study citation.♦To rate individual studies, a scale based on SIGN1Bourne RR Sorensen KE Klauber A Foster PJ Johnson GJ Alsbirk PH Glaucoma in East Greenlandic Inuit–a population survey in Ittoqqortoormiit (Scoresbysund).Acta Ophthalmol Scand. 2001; 79: 462-467Crossref PubMed Scopus (24) Google Scholar is used. The definitions and levels of evidence to rate individual studies are as follows: Tabled 1I++High-quality meta-analyses, systematic reviews of randomized controlled trials (RCTs), or RCTs with a very low risk of biasI+Well-conducted meta-analyses, systematic reviews of RCTs, or RCTs with a low risk of biasI-Meta-analyses, systematic reviews of RCTs, or RCTs with a high risk of biasII++High-quality systematic reviews of case-control or cohort studiesHigh-quality case-control or cohort studies with a very low risk of confounding or bias and a high probability that the relationship is causalII+Well-conducted case-control or cohort studies with a low risk of confounding or bias and a moderate probability that the relationship is causalII-Case-control or cohort studies with a high risk of confounding or bias and a significant risk that the relationship is not causalIIINonanalytic studies (e.g., case reports, case series) Open table in a new tab ♦Recommendations for care are formed based on the body of the evidence. The body of evidence quality ratings are defined by GRADE2Guyatt GH Oxman AD Vist GE et al.GRADE: an emerging consensus on rating quality of evidence and strength of recommendations.Bmj. 2008; 336: 924-926Crossref PubMed Google Scholar as follows: Tabled 1Good qualityFurther research is very unlikely to change our confidence in the estimate of effectModerate qualityFurther research is likely to have an important impact on our confidence in the estimate of effect and may change the estimateInsufficient qualityFurther research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate Any estimate of effect is very uncertain Open table in a new tab ♦Key recommendations for care are defined by GRADE2Guyatt GH Oxman AD Vist GE et al.GRADE: an emerging consensus on rating quality of evidence and strength of recommendations.Bmj. 2008; 336: 924-926Crossref PubMed Google Scholar as follows: Tabled 1Strong recommendationUsed when the desirable effects of an intervention clearly outweigh the undesirable effects or clearly do notDiscretionary recommendationUsed when the trade-offs are less certain—either because of low-quality evidence or because evidence suggests that desirable and undesirable effects are closely balanced Open table in a new tab ♦The Highlighted Findings and Recommendations for Care section lists points determined by the PPP Panel to be of particular importance to vision and quality of life outcomes.♦All recommendations for care in this PPP were rated using the system described above. Ratings are embedded throughout the PPP main text in italics.♦Literature searches to update the PPP were undertaken in March 2018 and June 2019 in PubMed and the Cochrane Library. Complete details of the literature searches are available online at www.aao.org/ppp. Although an estimated 80% of age-related macular degeneration (AMD) patients have non-neovascular or atrophic AMD, the neovascular form is responsible for the majority of the severe central visual acuity (VA) loss associated with AMD. The primary risk factors for the development of advanced AMD include increasing age, northern European ancestry, and genetic factors. Cigarette smoking is the main modifiable risk factor that has been consistently identified in numerous studies. Smoking cessation is strongly recommended when advising patients who have AMD or are at risk for AMD. The routine use of genetic testing is not recommended at this time. A meta-analysis of 10 studies found that the use of aspirin was not associated with an increased risk of AMD. Therefore, patients who have been instructed by a physician to use aspirin should continue to use it as prescribed. Antioxidant vitamin and mineral supplementation as per the Age-Related Eye Disease Study (AREDS2) should be considered in patients with intermediate or advanced AMD. There is no evidence to support the use of these supplements for patients who have less than intermediate AMD and no evidence of any prophylactic value for family members without signs of AMD. Fluorescein angiography, optical coherence tomography (OCT), and optical coherence tomography angiography (OCTA) are useful diagnostic tests in clinical practice to detect new or recurrent neovascular disease activity and guide therapy. In patients with neovascular AMD, early detection and prompt treatment improves the visual outcome. Intravitreal injection therapy using anti-vascular endothelial growth factor (VEGF) agents (e.g., aflibercept, bevacizumab, and ranibizumab) is the most effective way to manage neovascular AMD and represents the first line of treatment. Symptoms suggestive of postinjection endophthalmitis or retinal detachment require prompt evaluation. Age-related macular degeneration (AMD) is a disorder of the macula characterized by one or more of the following (for specific terms, see Glossary): ♦Presence of at least intermediate-size drusen (≥63 μm in diameter)♦Retinal pigment epithelium (RPE) abnormalities such as hypopigmentation or hyperpigmentation♦Presence of any of the following features: geographic atrophy of the RPE, choroidal neovascularization ([CNV] exudative, wet), polypoidal choroidal vasculopathy (PCV), reticular pseudodrusen, or retinal angiomatous proliferation This Preferred Practice Pattern uses the classification of the Age-Related Eye Disease Study (AREDS) and a more recent clinical classification4Ferris III, FL Wilkinson CP Bird A et al.Clinical classification of age-related macular degeneration.Ophthalmology. 2013; 120: 844-851Abstract Full Text Full Text PDF PubMed Scopus (478) Google Scholar to define the early and intermediate stages of AMD because current treatment recommendations are based on these classifications. The AREDS was a prospective multicenter randomized clinical trial conducted between 1992 and 2006 designed to assess the natural course and risk factors for age-related cataract and AMD. The effects of antioxidant vitamins and minerals on these two ocular conditions were studied. The classification of AMD from the AREDS is as follows:5Age-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 age-related macular degeneration and vision loss: AREDS report number 8.Arch Ophthalmol. 2001; 119: 1417-1436Crossref PubMed Google Scholar♦No AMD (AREDS category 1) represented the control group; it is characterized by no or few small drusen (<63 μm in diameter).♦Early AMD (AREDS category 2) is characterized by a combination of multiple small drusen, few intermediate drusen (63–124 μm in diameter), or mild RPE abnormalities.♦Intermediate AMD (AREDS category 3) is characterized by any of the following features: ♦Numerous intermediate drusen♦At least one large druse (≥125 μm in diameter)♦Geographic atrophy (a sharply demarcated, usually round or oval, area of atrophy of the RPE not involving the center of the fovea)♦Advanced AMD (AREDS category 4) is characterized by one or more of the following (in the absence of other causes) in one eye: ♦Geographic atrophy of the RPE involving the foveal center♦Neovascular maculopathy that includes the following: ○CNV defined as pathologic angiogenesis originating from the choroidal vasculature that extends through a defect in Bruch's membrane○Serous and/or hemorrhagic detachment of the neurosensory retina or RPE○Retinal hard exudates (a secondary phenomenon resulting from chronic vascular leakage)○Subretinal and sub-RPE fibrovascular proliferation○Disciform scar (subretinal fibrosis) See Glossary for definitions of important terms. Clinical details are available in standard texts.6Gass JDM Stereoscopic Atlas of Macular Diseases: Diagnosis and Treatment.4th ed. CV Mosby, St. Louis, MO1997Google Scholar, 7Ryan SJ Hinton DR Schachat AP Wilkinson CP Retina. 4th ed. CV Mosby, St. Louis, MO2005Google Scholar Patients are typically aged 50 years or older, with or without visual symptoms. Clinicians should consider the possibility of hereditary macular dystrophies in patients under 50 years of age who have clinical features that resemble AMD. ♦Identify patients at risk of visual loss related to AMD♦Educate patients and their families about the disease, risk factors, and preventive measures♦Minimize or reverse visual loss and functional impairment in these patients through appropriate detection, self-assessment, treatment, and follow-up examinations♦Help patients identify expert physicians and resources needed to facilitate improvement in vision Age-related macular degeneration is a leading cause of severe, irreversible vision impairment in developed countries.8Klein R Klein BE Linton KL Prevalence of age-related maculopathy. The Beaver Dam Eye Study.Ophthalmology. 1992; 99: 933-943Abstract Full Text PDF PubMed Google Scholar, 9Kahn HA Leibowitz HM Ganley JP et al.The Framingham Eye Study. I. Outline and major prevalence findings.Am J Epidemiol. 1977; 106: 17-32Crossref PubMed Google Scholar, 10Sommer A Tielsch JM Katz J et al.Racial differences in the cause-specific prevalence of blindness in east Baltimore.N Engl J Med. 1991; 325: 1412-1417Crossref PubMed Google Scholar, 11Klein BE Klein R Cataracts and macular degeneration in older Americans.Arch Ophthalmol. 1982; 100: 571-573Crossref PubMed Google Scholar, 12Friedman DS O'Colmain BJ Munoz B et al.Prevalence of age-related macular degeneration in the United States.Arch Ophthalmol. 2004; 122: 564-572Crossref PubMed Scopus (2043) Google Scholar, 13Congdon N O'Colmain B Klaver CC et al.Causes and prevalence of visual impairment among adults in the United States.Arch Ophthalmol. 2004; 122: 477-485Crossref PubMed Scopus (1812) Google Scholar In 2004, it was estimated that approximately 1.75 million people aged 40 years or older in the United States have advanced AMD, either neovascular AMD or geographic atrophy in at least one eye; and 7.3 million were considered to have high-risk features, such as large drusen (≥125 μm in diameter) in one or both eyes.12Friedman DS O'Colmain BJ Munoz B et al.Prevalence of age-related macular degeneration in the United States.Arch Ophthalmol. 2004; 122: 564-572Crossref PubMed Scopus (2043) Google Scholar The authors projected that the number of individuals affected by advanced AMD in at least one eye will increase to nearly 3 million by year 2020,12Friedman DS O'Colmain BJ Munoz B et al.Prevalence of age-related macular degeneration in the United States.Arch Ophthalmol. 2004; 122: 564-572Crossref PubMed Scopus (2043) Google Scholar based on the aging population demographics in the United States.14Vincent GK Velkoff VA The next four decades, the older population in the United States: 2010 to 2050. 2010; P25-1138.Available at: www.census.gov/prod/2010pubs/p25-1138.pdfDate accessed: September , 2019Google Scholar Aging is the greatest risk factor; therefore, the prevalence of AMD in the United States is anticipated to increase to 22 million by the year 2050, while the global prevalence is expected to increase to 288 million by the year 2040.15Wong WL Su X Li X et al.Global prevalence of age-related macular degeneration and disease burden projection for 2020 and 2040: a systematic review and meta-analysis.Lancet Glob Health. 2014; 2: e106-116Abstract Full Text Full Text PDF PubMed Scopus (986) Google Scholar These predictions are likely to be affected by both more effective treatments for the neovascular forms of AMD using anti-vascular endothelial growth factor (VEGF) agents as well as the slowing of the disease progression using antioxidant vitamins with zinc. The use of anti-VEGF agents will likely reduce the odds of legal blindness from neovascular AMD and could theoretically reduce the rate of legal blindness by up to 70% over 2 years.16Bressler NM Doan QV Varma R et al.Estimated cases of legal blindness and visual impairment avoided using ranibizumab for choroidal neovascularization: non-Hispanic white population in the United States with age-related macular degeneration.Arch Ophthalmol. 2011; 129: 709-717Crossref PubMed Scopus (65) Google Scholar However, longer-term follow-up studies from the population originally treated with regular anti-VEGF agents suggest that these gains in visual acuity (VA) are largely lost in two-thirds of patients followed for over 7 years.17Rofagha S Bhisitkul RB Boyer DS Sadda SR Zhang K Seven-year outcomes in ranibizumab-treated patients in ANCHOR, MARINA, and HORIZON: a multicenter cohort study (SEVEN-UP).Ophthalmology. 2013; 120: 2292-2299Abstract Full Text Full Text PDF PubMed Scopus (451) Google Scholar The use of antioxidant vitamins (i.e., vitamin C, vitamin E), lutein, zeaxanthin, and zinc in an otherwise well-nourished population with intermediate AMD has been demonstrated to reduce the progression toward more advanced stages of AMD by approximately 25% at 5 years.5Age-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 age-related macular degeneration and vision loss: AREDS report number 8.Arch Ophthalmol. 2001; 119: 1417-1436Crossref PubMed Google Scholar, 18Age-Related Eye Disease Study 2 (AREDS2) Research Group Chew EY SanGiovanni JP Ferris FL et al.Lutein/zeaxanthin for the treatment of age-related cataract: AREDS2 randomized trial report number 4.JAMA Ophthalmol. 2013; 131: 843-850Crossref PubMed Scopus (0) Google Scholar A study forecasting the potential impact of treatments in AMD concluded that though the prevalence of AMD will increase substantially by 2050 in the United States, the use of anti-VEGF therapies and vitamin therapies will mitigate these effects.19Rein DB Wittenborn JS Zhang X et al.Forecasting age-related macular degeneration through the year 2050: the potential impact of new treatments.Arch Ophthalmol. 2009; 127: 533-540Crossref PubMed Scopus (198) Google Scholar Overall, AMD is responsible for an estimated 46% of cases of severe visual loss (VA 20/200 or worse) in persons over age 40 in the United States.13Congdon N O'Colmain B Klaver CC et al.Causes and prevalence of visual impairment among adults in the United States.Arch Ophthalmol. 2004; 122: 477-485Crossref PubMed Scopus (1812) Google Scholar While most consider the onset of AMD as occurring in individuals over the age of 50, there are variations in the epidemiologic literature. While relatively few cases of advanced AMD occur between ages 40 an