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Age-related Macular Degeneration (AMD)

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General Information

Description

  • progressive chronic retinal disease affecting the aging eye, characterized by drusen (focal yellowish deposits of acellular, polymorphous debris), geographic atrophy of retinal pigment epithelium, and neovascularization that can lead to visual impairment1,2,3,4
  • AMD is a leading cause of vision loss globally1

Also called

  • age-related maculopathy (ARM), also called early AMD
  • macular syndrome
  • macular degeneration

Definitions

  • choroidal neovascularization (CNV) - pathologic angiogenesis originating from choroidal vasculature that extends through a defect in Bruch's membrane1

Types

  • Age-related Eye Disease Study (AREDS) classification of AMD1,3,4
    • Category 1
      • none or a few small drusen (< 63 micrometers in diameter)
    • Category 2 (early AMD) requires any or all of the following
      • multiple small drusen
      • few intermediate drusen (63-124 micrometers in diameter)
      • retinal pigment epithelium abnormalities
    • Category 3 (intermediate AMD) requires any or all of the following
      • extensive intermediate drusen
      • at least 1 large drusen (≥ 125 micrometers in diameter, approximately equivalent to size of retinal vein at rim of optic disc)
      • geographic atrophy not involving foveal center
    • Category 4 (advanced or "late" AMD)
      • geographic atrophy involving foveal center (progressive atrophy of retinal pigment epithelium, choriocapillaris, and photoreceptors)
      • any features of neovascular age-related macular degeneration
        • choroidal neovascularization (CNV) and any of its potential sequelae, including
          • subretinal fluid
          • lipid deposition
          • subretinal hemorrhage
          • retinal pigment epithelium detachment
          • fibrotic scar
      • visual loss presumed to be due to age-related macular degeneration
      • not part of this classification, but might also include involutional, atrophic stage of neovascular age-related macular degeneration not amenable to further treatment
  • "early" and "late" classification is preferred over "wet" and "dry" classification2,4
    • "dry" referred to presence of drusen, pigmentary irregularities, or both
    • "wet" referred to presence of exudates and hemorrhages, which are neovascular manifestations
    • "late" macular degeneration may have either nonneovascular or neovascular signs
  • Macular Photocoagulation Study (MPS) classification of CNV AMD
    • based on fluorescein angiography
  • variants include3
    • polypoidal choroidal vasculopathy
      • can account for 50% of neovascular age-related macular degeneration cases in persons of Asian descent, compared to 8%-13% in persons of white race
      • difficult to distinguish clinically from choroidal neovascularization
      • more commonly presents with recurrent serous and hemorrhagic retinal pigment epithelium detachment
      • may have subretinal orange, bulging dilatations
    • retinal angiomatous proliferation
      • reported to account for 12%-15% of neovascular age-related macular degeneration
      • characterized by hemorrhage, edema, and exudates within retinal layers in addition to other typical signs of choroidal neovascularization
      • may have visible anastomoses between retinal and subretinal new vessels

References

General references used

  1. American Academy of Ophthalmology (AAO). Preferred Practice Pattern guidelines on age-related macular degeneration. AAO 2015 JanOpenInNew
  2. Chakravarthy U, Evans J, Rosenfeld PJ. Age related macular degeneration. BMJ. 2010 Feb 26;340:c981OpenInNew, commentary can be found in BMJ 2010 Mar 24;340:c1611OpenInNew
  3. Lim LS, Mitchell P, Seddon JM, Holz FG, Wong TY. Age-related macular degeneration. Lancet. 2012 May 5;379(9827):1728-38OpenInNew
  4. Jager RD, Mieler WF, Miller JW. Age-related macular degeneration. N Engl J Med. 2008 Jun 12;358(24):2606-17OpenInNew, correction can be found in N Engl J Med. 2008 Oct 16;359(16): 1736, commentary can be found in N Engl J Med 2008 Oct 16;359(16):1735OpenInNew

Recommendation grading systems used

  • American Academy of Ophthalmology (AAO) grading system for recommendations (based on Scottish Intercollegiate Guideline Network [SIGN] and Grading of Recommendations Assessment, Development and Evaluation [GRADE] grading systems)
    • levels of evidence
      • I++ - high-quality meta-analyses, systematic reviews of RCTs, or RCTs with very low risk of bias
      • I+ - well-conducted meta-analyses, systematic reviews of RCTs, or RCTs with low risk of bias
      • I- - meta-analyses, systematic reviews of RCTs, or RCTs with high risk of bias
      • II++
        • high-quality systematic reviews of case-control or cohort studies
        • high-quality case-control or cohort studies with very low risk of confounding or bias and high probability that relationship is causal
      • II+ - well-conducted case-control or cohort studies with low risk of confounding or bias and moderate probability that relationship is causal
      • II- - case-control or cohort studies with high risk of confounding or bias and significant risk that relationship is not causal
      • III - nonanalytical studies (for example, case reports, case series)
    • quality of evidence
      • Good - further research very unlikely to change confidence in estimate of effect
      • Moderate - further research likely to have important impact on confidence in estimate of effect; estimate may change
      • Insufficient - further research very likely to have important impact on confidence in estimate of effect; estimate likely to change; any estimate of effect very uncertain
    • strength of recommendation
      • Strong recommendation - desirable effects of intervention clearly outweigh undesirable effects (or vice versa)
      • Discretionary recommendation - unclear whether desirable effects outweigh undesirable effects (or vice versa); uncertainty due to low-quality evidence or evidence suggests that desirable and undesirable effects are closely balanced
    • Reference - AAO preferred practice pattern guideline on age-related macular degeneration (AAO 2015 JanOpenInNew)
  • American Society for Apheresis (ASFA) recommendation grading system
    • categories of indications for therapeutic apheresis
      • Category I - disorders for which apheresis is accepted as first-line therapy, either as primary stand-alone treatment or in conjunction with other modes of treatment
      • Category II - disorders for which apheresis is accepted as second-line therapy, either as stand-alone treatment or in conjunction with other modes of treatment
      • Category III - optimum role of apheresis therapy is not established and decision-making should be individualized
      • Category IV - disorders in which published evidence demonstrates or suggests apheresis to be ineffective or harmful; Institutional Review Board (IRB) approval is desirable if apheresis treatment is undertaken in these circumstances
    • grades of recommendations
      • Grade 1A - strong recommendation, high-quality evidence
        • can apply to most patients in most circumstances without reservation
        • supported by randomized controlled trials (RCTs) without important limitations or overwhelming evidence from observational studies
      • Grade 1B - strong recommendation, moderate-quality evidence
        • can apply to most patients in most circumstances without reservation
        • supported by RCTs with important limitations (inconsistent results, methodological flaws, indirect, or imprecise) or exceptionally strong evidence from observational studies
      • Grade 1C - strong recommendation, low- or very low-quality evidence
        • recommendation may change when higher quality evidence becomes available
        • supported by observational studies or case series
      • Grade 2A - weak recommendation, high-quality evidence
        • best action may differ depending on circumstances of patients' or societal values
        • supported by RCTs without important limitations or overwhelming evidence from observational studies
      • Grade 2B - weak recommendation, moderate-quality evidence
        • best action may differ depending on circumstances of patients' or societal values
        • supported by RCTs with important limitations (inconsistent results, methodological flaws, indirect, or imprecise) or exceptionally strong evidence from observational studies
      • Grade 2C - weak recommendation, low- or very low-quality evidence
        • very weak recommendation; other alternatives may be equally reasonable
        • supported by observational studies or case series
    • Reference - ASFA guideline on use of therapeutic apheresis in clinical practice (27322218J Clin Apher 2016 Jun;31(3):149OpenInNew)
  • United States Preventive Services Task Force (USPSTF) grades of recommendation (after July 2012)
    • Grade A - USPSTF recommends the service with high certainty of substantial net benefit
    • Grade B - USPSTF recommends the service with high certainty of moderate net benefit or moderate certainty of moderate-to-substantial net benefit
    • Grade C - USPSTF recommends selectively offering or providing the service (based on professional judgment and patient preference) with at least moderate certainty of small net benefit
    • Grade D - USPSTF recommends against providing the service with moderate-to-high certainty of no net benefit or harms outweighing benefits
    • Grade I - insufficient evidence to assess balance of benefits and harms
    • Reference - USPSTF Grade DefinitionsOpenInNew

Synthesized Recommendation Grading System for DynaMed

  • DynaMed systematically monitors clinical evidence to continuously provide a synthesis of the most valid relevant evidence to support clinical decision-making (see 7-Step Evidence-Based MethodologyOpenInNew).
  • Guideline recommendations summarized in the body of a DynaMed topic are provided with the recommendation grading system used in the original guideline(s), and allow DynaMed users to quickly see where guidelines agree and where guidelines differ from each other and from the current evidence.
  • In DynaMed (DM), we synthesize the current evidence, current guidelines from leading authorities, and clinical expertise to provide recommendations to support clinical decision-making in the Overview & Recommendations section.
  • We use the Grading of Recommendations Assessment, Development and Evaluation (GRADE)OpenInNew to classify synthesized recommendations as Strong or Weak.
    • Strong recommendations are used when, based on the available evidence, clinicians (without conflicts of interest) consistently have a high degree of confidence that the desirable consequences (health benefits, decreased costs and burdens) outweigh the undesirable consequences (harms, costs, burdens).
    • Weak recommendations are used when, based on the available evidence, clinicians believe that desirable and undesirable consequences are finely balanced, or appreciable uncertainty exists about the magnitude of expected consequences (benefits and harms). Weak recommendations are used when clinicians disagree in judgments of relative benefit and harm, or have limited confidence in their judgments. Weak recommendations are also used when the range of patient values and preferences suggests that informed patients are likely to make different choices.
  • DynaMed (DM) synthesized recommendations (in the Overview & Recommendations section) are determined with a systematic methodology:
    • Recommendations are initially drafted by clinical editors (including ≥ 1 with methodological expertise and ≥ 1 with content domain expertise) aware of the best current evidence for benefits and harms, and the recommendations from guidelines.
    • Recommendations are phrased to match the strength of recommendation. Strong recommendations use "should do" phrasing, or phrasing implying an expectation to perform the recommended action for most patients. Weak recommendations use "consider" or "suggested" phrasing.
    • Recommendations are explicitly labeled as Strong recommendations or Weak recommendations when a qualified group has explicitly deliberated on making such a recommendation. Group deliberation may occur during guideline development. When group deliberation occurs through DynaMed-initiated groups:
      • Clinical questions will be formulated using the PICO (Population, Intervention, Comparison, Outcome) framework for all outcomes of interest specific to the recommendation to be developed.
      • Systematic searches will be conducted for any clinical questions where systematic searches were not already completed through DynaMed content development.
      • Evidence will be summarized for recommendation panel review including for each outcome, the relative importance of the outcome, the estimated effects comparing intervention and comparison, the sample size, and the overall quality rating for the body of evidence.
      • Recommendation panel members will be selected to include at least 3 members that together have sufficient clinical expertise for the subject(s) pertinent to the recommendation, methodological expertise for the evidence being considered, and experience with guideline development.
      • All recommendation panel members must disclose any potential conflicts of interest (professional, intellectual, and financial), and will not be included for the specific panel if a significant conflict exists for the recommendation in question.
      • Panel members will make Strong recommendations if and only if there is consistent agreement in a high confidence in the likelihood that desirable consequences outweigh undesirable consequences across the majority of expected patient values and preferences. Panel members will make Weak recommendations if there is limited confidence (or inconsistent assessment or dissenting opinions) that desirable consequences outweigh undesirable consequences across the majority of expected patient values and preferences. No recommendation will be made if there is insufficient confidence to make a recommendation.
      • All steps in this process (including evidence summaries which were shared with the panel, and identification of panel members) will be transparent and accessible in support of the recommendation.
    • Recommendations are verified by ≥ 1 editor with methodological expertise, not involved in recommendation drafting or development, with explicit confirmation that Strong recommendations are adequately supported.
    • Recommendations are published only after consensus is established with agreement in phrasing and strength of recommendation by all editors.
    • If consensus cannot be reached then the recommendation can be published with a notation of "dissenting commentary" and the dissenting commentary is included in the topic details.
    • If recommendations are questioned during peer review or post publication by a qualified individual, or reevaluation is warranted based on new information detected through systematic literature surveillance, the recommendation is subject to additional internal review.

DynaMed Editorial Process

Special acknowledgements

  • Adam T. Lipman, MD (Fellow of Vitreoretinal Surgery, Lahey Hospital and Medical Center; Massachusetts, United States)
  • Dr. Lipman has declared that he has no financial conflicts of interest.
  • Esther Jolanda van Zuuren, MD (Head of Allergy, Dermatology, and Venereology, Leiden University Medical Centre; Netherlands)
  • Dr. van Zuuren declares no relevant financial conflicts of interest.
  • Alan Ehrlich, MD, FAAFP (Executive Editor; Associate Professor of Family Medicine, University of Massachusetts Medical School; Massachusetts, United States)
  • Dr. Ehrlich declares no relevant financial conflicts of interest.
  • DynaMed topics are written and edited through the collaborative efforts of the above individuals. Deputy Editors, Section Editors, and Topic Editors are active in clinical or academic medical practice. Recommendations Editors are actively involved in development and/or evaluation of guidelines.
  • Editorial Team role definitions
    Topic Editors define the scope and focus of each topic by formulating a set of clinical questions and suggesting important guidelines, clinical trials, and other data to be addressed within each topic. Topic Editors also serve as consultants for the internal DynaMed Editorial Team during the writing and editing process, and review the final topic drafts prior to publication.
    Section Editors have similar responsibilities to Topic Editors but have a broader role that includes the review of multiple topics, oversight of Topic Editors, and systematic surveillance of the medical literature.
    Recommendations Editors provide explicit review of DynaMed Overview and Recommendations sections to ensure that all recommendations are sound, supported, and evidence-based. This process is described in "Synthesized Recommendation Grading."
    Deputy Editors are employees of DynaMed and oversee DynaMed internal publishing groups. Each is responsible for all content published within that group, including supervising topic development at all stages of the writing and editing process, final review of all topics prior to publication, and direction of an internal team.

How to cite

National Library of Medicine, or "Vancouver style" (International Committee of Medical Journal Editors):

  • DynaMed [Internet]. Ipswich (MA): EBSCO Information Services. 1995 - . Record No. T114486, Age-related Macular Degeneration (AMD); [updated 2018 Nov 30, cited place cited date here]. Available from https://www.dynamed.com/topics/dmp~AN~T114486. Registration and login required.
  • KeyboardArrowRight

    Overview and Recommendations

    • Background

    • Evaluation

    • Management

  • Related Summaries

  • KeyboardArrowRight

    General Information

    • Description

    • Also called

    • Definitions

    • Types

  • KeyboardArrowRight

    Epidemiology

    • Who is most affected

    • Incidence/Prevalence

    • Likely risk factors

    • Possible risk factors

    • Factors not associated with increased risk

  • KeyboardArrowRight

    Etiology and Pathogenesis

    • Causes

    • Pathogenesis

  • KeyboardArrowRight

    History and Physical

    • KeyboardArrowRight

      History

      • Chief concern (CC)

      • Medication history

      • Past medical history (PMH)

      • Family history (FH)

      • Social history (SH)

    • KeyboardArrowRight

      Physical

      • HEENT

  • KeyboardArrowRight

    Diagnosis

    • Making the diagnosis

    • Differential diagnosis

    • Testing overview

    • KeyboardArrowRight

      Imaging studies

      • Optical coherence tomography

      • Intravenous fundus angiography

      • Other imaging

  • KeyboardArrowRight

    Management

    • Management overview

    • Treatment setting

    • Counseling

    • KeyboardArrowRight

      Medications

      • KeyboardArrowRight

        Antivascular endothelial growth factor (anti-VEGF) antibodies

        • Bevacizumab

        • Ranibizumab

        • Aflibercept

        • Conbercept

        • Pegaptanib

      • Antioxidants

      • Intravitreal steroids

      • Other medical therapies

      • Therapies without evidence for effectiveness

    • Surgery and procedures

    • Radiation therapy

    • Consultation and referral

    • KeyboardArrowRight

      Other management

      • Photodynamic therapy (PDT)

      • Laser photocoagulation

      • Self-monitoring and other therapies

      • Rheopheresis

      • Autologous stem cell injections

    • Follow-up

  • KeyboardArrowRight

    Complications and Prognosis

    • Complications

    • Prognosis

  • KeyboardArrowRight

    Prevention and Screening

    • KeyboardArrowRight

      Prevention

      • Vitamin supplements

      • Dietary factors

      • Statins

      • Additional preventive measures or factors

    • Screening

  • KeyboardArrowRight

    Quality Improvement

    • Physician Quality Reporting System Quality Measures

    • Choosing Wisely

    • Choosing Wisely Australia

  • KeyboardArrowRight

    Guidelines and Resources

    • KeyboardArrowRight

      Guidelines

      • United States guidelines

      • United Kingdom guidelines

      • Canadian guidelines

      • European guidelines

    • Review articles

    • MEDLINE search

  • Patient Information

  • KeyboardArrowRight

    ICD Codes

    • ICD-10 codes

  • KeyboardArrowRight

    References

    • General references used

    • Recommendation grading systems used

    • Synthesized Recommendation Grading System for DynaMed

    • DynaMed Editorial Process

    • Special acknowledgements

    • How to cite

Topic Editor
Adam T. Lipman MD
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Affiliations

Fellow of Vitreoretinal Surgery, Lahey Hospital and Medical Center; Massachusetts, United States

Conflicts of Interest

Dr. Lipman has declared that he has no financial conflicts of interest.

Recommendations Editor
Esther Jolanda van Zuuren MD
KeyboardArrowDown
Affiliations

Head of Allergy, Dermatology, and Venereology, Leiden University Medical Centre; Netherlands

Conflicts of Interest

Dr. van Zuuren declares no relevant financial conflicts of interest.

Deputy Editor
Alan Ehrlich MD, FAAFP
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Affiliations

Executive Editor, DynaMed; Associate Professor of Family Medicine, University of Massachusetts Medical School; Massachusetts, United States

Conflicts of Interest

Dr. Ehrlich declares no relevant financial conflicts of interest.

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