Diagnosis and Associated Risk Factors

Associated Risk Factors and Clinician Roles in Diagnosis

Risk factors associated with Age- Related Macular Degeneration include increasing age, cigarette smoking, and white race. Older age is the most significant risk factor with the prevalence of AMD increasing with age.1,2

Smoking is the environmental factor that is most strongly associated with AMD, and has been demonstrated in many large population studies of white, Latino, and Asian patients. Smoking cigarettes increases the risk of atherosclerosis that can affect the choroidal vessels of the eye. Nicotine also promotes inflammation and angiogenesis through the upregulation of VEGF. Patients who smoke cigarettes are twice as likely to develop AMD as nonsmokers.1-3

Multiple other risk factors also have an association with AMD, with differing levels of evidence to support their impact on the development of disease: genetics, female sex, family history, high body mass index, cardiovascular disease, increased sunlight exposure, systemic inflammation, and low antioxidant levels.1,4

An extended clinician-patient dialogue is needed concerning the importance of smoking reduction and/or cessation and reducing endothelial damage from chronic inflammation, along with cardiovascular physical fitness, reduction of abdominal adiposity, minimizing glycemic load, stress reduction, microbiome and digestive competence, vascular nitric oxide stimulation, and caloric restriction.5

A study published in JAMA Ophthalmology revealed how frequently optometrists and ophthalmologists fail to diagnose Age-Related Macular Degeneration.6,7 The cross-sectional study of primary eye care practices in Birmingham, Alabama, which included 1288 eyes (644 adults) from patients 60 years or older with normal macular health per their medical record based on their most recent dilated comprehensive eye examination by a primary eye care ophthalmologist or optometrist who were enrolled in the Alabama Study on Early Age-Related Macular Degeneration (ALSTAR),6,8,9 revealed that clinicians are not diagnosing AMD about 25% of the time. Each patient in the ALSTAR study had digital color fundus photos taken, which were reviewed by masked, trained graders who determined the presence or absence of AMD findings according to the Clinical Age-Related Maculopathy Staging (CARMS) system.10 The types of AMD-associated lesions also were noted. The results revealed that 1 of 4 eyes studied was not diagnosed with AMD during the dilated fundus examination, despite these eyes having macular characteristics indicative of AMD in the fundus photos. Approximately three-fourths of the 320 undiagnosed eyes had 10 or more small drusen (249 [77.8%]) and/or intermediate drusen (250 [78.1%]), with 96 (30.0%) of undiagnosed eyes having large drusen.7 In addition, the prevalence of undiagnosed AMD in the study was not different for ophthalmologists versus optometrists.6,7 The study authors conclude that reasons for the missed diagnoses remain unclear, but stress that improved AMD detection and diagnosis are needed since many of these patients would have been candidates for therapeutic intervention.

An optometrist or ophthalmologist can perform a slit-lamp examination of the retina to assess for drusen, abnormalities in the RPE, GA, choroidal neovascularization, subretinal fluid, and hemorrhage.1

The diagnosis of Age-Related Macular Degeneration usually is made clinically based on the patient’s history, symptoms, and confirmation with a dilated eye examination using a slit lamp; however, various imaging tests can be used to gain a better understanding of AMD and to monitor progress before and after therapy.1,11,12

  • Optical coherence tomography (OCT) is a noninvasive imaging technique that provides high-resolution, cross sectional images of the retina, retinal nerve fiber layer, and the optic nerve head. OCT has significantly improved the understanding of retinal diseases and can help differentiate AMD from other retinal disorders. Newer-generation OCT, including spectral domain OCT, can determine the presence of subretinal fluid and retinal thickening and is used to monitor progression and therapeutic responses to therapy in patients with wet AMD.
  • Fluorescein angiography (FA) should be performed on patients suspected of having CNV based on symptoms or findings on physical examination. This includes patients complaining of new metamorphopsia or unexplained blurred vision; those with findings of macular edema, subretinal blood, elevation of the RPE on examination; or those with OCT-detected fluid. Patients being considered for treatment with either photodynamic therapy or laser photocoagulation should have angiography to guide therapy and to evaluate recurrences post-treatment. The dye is injected intravenously as a bolus and a sequence of photographs are taken. Newly formed choroidal vessels leak fluorescein; normal retinal vessels do not.
  • Fundus autofluorescence is an imaging technique that can identify areas of GA and can be used to monitor these areas for disease progression. This test also allows for identification of lipofuscin accumulation in the RPE.


  1. Cunningham J. Recognizing age-related macular degeneration in primary care. JAAPA. 2017;30(3):18-22.
  2. Cheung CM, Wong TY. Is age-related macular degeneration a manifestation of systemic disease? New prospects for early intervention and treatment. J Intern Med. 2014;276(2):140-153.
  3. Michalska-Malecka K, Kabiesz A, Nowak M, Spiewak D. Age related macular degeneration—challenge for future: pathogenesis and new perspectives for the treatment. Eur Geriatr Med. 2015;6(1):69-75.
  4. Marra KV, Wagley S, Kuperwaser MC, et al. Care of older adults: role of primary care physicians in the treatment of cataracts and macular degeneration. J Am Geriatr Soc. 2016;64(2):369-377.
  5. Richer S, Ulanski L, Natalia A, Popenko NA, et al. Age-related macular degeneration beyond the Age-related Eye Disease Study II. Adv Ophthalmol Optometry. 2016;1(1):335-369.
  6. Gerson D, Pyfer MF. Peer-Reviewed Study Shows Optometrists and Ophthalmologists Frequently Miss Macular Degeneration. September 2017. https://theophthalmologist.com/subspecialties/peer-reviewed-study-shows-optometrists-and-ophthalmologists-frequently-miss-macular-degeneration. Accessed April 3, 2020.
  7. Neely DC, Bray KJ, Huisingh CE, et al. Prevalence of undiagnosed age-related macular degeneration in primary eye care. JAMA Ophthalmol. 2017;135(6):570-575.
  8. Owsley C, Huisingh C, Jackson GR, et al. Associations between abnormal rod-mediated dark adaptation and health and functioning in older adults with normal macular health. Invest Ophthalmol Vis Sci. 2017;55:4776-4789.
  9. Owsley C, Huisingh C, Clark ME, et al. Comparison of visual function in older eyes in the earliest stages of age-related macular degeneration to those in normal macular health. Curr Eye Res. 2016;41:266-272.
  10. Seddon JM, Sharma S, Adelman RA. Evaluation of the clinical age-related maculopathy staging system. Ophthalmology. 2006;113:260-266 (2006).
  11. American Academy of Ophthalmology. Age-Related Macular Degeneration PPP—2019. https://www.aao.org/preferred-practice-pattern/age-related-macular-degeneration-ppp. Accessed April 3, 2020.
  12. Adhi M, Duker JS. Optical coherence tomography—current and future applications. Curr Opin Ophthalmol. 2013;24(3):213-221.

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Scientific Council

Neil M. Bressler, MD

James P. Gills Professor of Ophthalmology
Professor of Ophthalmology, Johns Hopkins University School of Medicine
Wilmer Eye Institute, Johns Hopkins Medicine
Baltimore, MD

A. Paul Chous, MA, OD, FAAO

Specializing in Diabetes Eye Care & Education, Chous Eye Care Associates
Adjunct Professor of Optometry, Western University of Health Sciences
AOA Representative, National Diabetes Education Program
Tacoma, WA

Steven Ferrucci, OD, FAAO

Chief of Optometry, Sepulveda VA Medical Center
Professor, Southern California College of Optometry at Marshall B. Ketchum University
Sepulveda, CA

Julia A. Haller, MD

Wills Eye Hospital
Philadelphia, PA

Allen C. Ho, MD, FACS

Director, Retina Research
Wills Eye Hospital
Professor and Chair of the Department of Ophthalmology
Thomas Jefferson University Hospitals
Philadelphia, PA

Charles C. Wykoff, MD, PhD

Director of Research, Retina Consultants of Houston
Associate Professor of Clinical Ophthalmology
Blanton Eye Institute & Houston Methodist Hospital
Houston, TX

Clinician Scientific & Educational Resources

The RELIEF Clinical Toolkit is an online tool that aims to provide clinicians with up-to-date information on the presentation, prognosis, pathophysiology, and treatment strategies for age-related macular degeneration (AMD). Click on one of the options below to learn more about AMD.

This activity is provided by Med Learning Group.
This activity is supported by an independent medical education grant from Regeneron Pharmaceuticals, Inc.

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