Table 1. Recommendation Grading
|I++||High-quality meta-analyses, systematic reviews of randomized controlled trials (RCTs), or RCTs with a very low risk of bias|
|I+||Well-conducted meta-analyses, systematic reviews of RCTs, or RCTs with a low risk of bias|
|I-||Meta-analyses, systematic reviews of RCTs, or RCTs with a high risk of bias|
|II++||High-quality systematic reviews of case-control or cohort studies|
High-quality case-control or cohort studies with a very low risk of confounding or bias and a high probability that the relationship is causal
|II+||Well-conducted case-control or cohort studies with a low risk of confounding or bias and a moderate probability that the relationship is causal|
|II-||Case-control or cohort studies with a high risk of confounding or bias and a significant risk that the relationship is not causal|
Nonanalytic studies (e.g., case reports, case series)
|G - Good quality||Further research is very unlikely to change our confidence in the estimate of effect|
|M - Moderate quality||Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate|
|In - Insufficient quality||Further 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
|S - Strong recommendation||Used when the desirable effects of an intervention clearly outweigh the undesirable effects or clearly do not|
|D- Discretionary recommendation||Used 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|
1. To rate individual studies, a scale based on Scottish Intercollegiate Guideline Network (SIGN) is used.
2. The body of evidence quality ratings is defined by Grading of Recommendations Assessment, Development and Evaluation (GRADE). 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.
3. Key recommendations for care are defined by GRADE.
- Although an estimated 80% of age-related macular degeneration (AMD) patients have non-neovascular or atrophic AMD, the neovascular form is responsible for nearly 90% of the severe central visual acuity loss associated with AMD.
- The primary risk factors for the development of advanced AMD include increasing age, ethnicity, 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.
- A meta-analysis of 10 studies found that the use of aspirin may not be 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 original Age-Related Eye Disease Study (AREDS) and AREDS2 trials 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.
- Replacement of the beta-carotene from the original AREDS formulation with lutein/zeaxanthin in the AREDS2 supplements may decrease the risk of lung cancer in smokers.
- In patients with neovascular AMD, early detection and prompt treatment improves the visual outcome. Treatment with AREDS2 supplements reduces the progression to advanced AMD in the fellow eye.
- Fundus angiography and optical coherence tomography (OCT) are useful diagnostic tests in clinical practice to detect new or recurrent neovascular disease activity and guide therapy.
- 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.
- Intravitreal anti-VEGF therapy is generally well tolerated and rarely associated with serious adverse events such as infectious endophthalmitis or retinal detachment. Symptoms suggestive of postinjection endophthalmitis or retinal detachment require prompt evaluation.
- Smoking cessation is strongly recommended when advising patients. (I++, G, S)
- In light of all the available information on the subject of aspirin use and age-related macular degeneration (AMD), current recommendations are for those patients who have been instructed to use aspirin by a physician to continue their aspirin therapy as prescribed. (II++, G, S)
- Routine genetic testing for risk alleles is not currently recommended for patients with AMD. (III, In, D)
- Age-related macular degeneration (AMD) is a disorder of the macula characterized by one or more of the following:
- Presence of at least intermediate-size drusen (≥63 μm in diameter)
- Retinal pigment epithelium (RPE) abnormalities such as hypopigmentation or hyperpigmentation
- Reticular pseudodrusen
- Presence of any of the following features: geographic atrophy of the RPE, choroidal neovascularization (exudative, wet), polypoidal choroidal vasculopathy, or retinal angiomatous proliferation
Table 2. Classification of AMD from the AREDSa
|1||No AMD||No or few small drusen (<63 μm in diameter)|
|2||Early AMD||A combination of multiple small drusen, few intermediate drusen (63–124 μm in diameter), or mild RPE abnormalities|
|3||Intermediate AMD||Any of the following features:|
|4||Advanced AMD||One or more of the following (in the absence of other causes) in one eye:|
AMD, age-related macular degeneration; AREDS, Age-Related Eye Disease Study; CNV, choroidal neovascularization; RPE, retinal pigment epithelium
- 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. (II++, G, S)
- An initial history should consider symptoms of metamorphosia, decreased vision, scotoma, photopsia. (II-, G, S)
- An initial history should consider medication and nutritional supplement use. (III, G, S)
- An initial history should consider ocular history, medical history, and family history. (II+, G, S)
- An initial history should consider social history. (III, G, S)
- A physical examination should include a comprehensive eye exam. (II++, G, S)
- A physical examination should include stereoscopic biomicroscopic examination of the macula. (III, G, S)
- Binocular slit-lamp biomicroscopy of the ocular fundus is often necessary to detect subtle clinical signs of CNV. (III, G, S)
- Optical coherence tomography (OCT) is important in diagnosing and managing AMD, particularly with respect to determining the presence of subretinal fluid and in documenting the degree of retinal thickening. (III, G, S)
- OCT also assists in evaluating the response of the retina and RPE to therapy by allowing structural changes to be followed accurately. (II+, G, S)
- Newer-generation OCT modalities, including spectral domain OCT (SD-OCT), are preferred technologies. (III, In, D)
- Intravenous fundus fluorescein angiography is indicated when the patient complains of new metamorphopsia or has unexplained blurred vision, and/or when clinical examination reveals elevation of the RPE or retina, macular edema, subretinal blood, hard exudates, or subretinal fibrosis. (II-, G, S)
- Intravenous fundus fluorescein angiography is helpful to detect the presence of and determine the extent, type, size, and location of CNV. (III, In, D)
- If verteporfin photodynamic therapy (PDT) or laser photocoagulation is being considered, the angiogram is also used as a guide to direct treatment. (III, In, D)
- Intravenous fundus fluorescein angiography is helpful to detect persistent or recurrent CNV or other retinal diseases following treatment. (III, In, D)
- Intravenous fundus fluorescein angiography is helpful to assist in determining the cause of visual loss that is not explained by the clinical examination. (III, In, D)
- If CNV is suspected on the basis of new symptoms or ocular findings, fluorescein angiography should be performed and interpreted expeditiously by an individual experienced in managing patients with neovascular AMD. (III, G, S)
- If fluorescein angiography is performed, the physician must be aware of potential risks associated with this procedure. (II-, G, S)
- Each angiographic facility should have a care plan in place for an emergency situation, as well as a clear protocol to minimize the risks and to manage complications. (III, G, S)
- Color fundus photographs may be obtained when angiography is performed, because they are useful in finding landmarks, evaluating serous detachments of the neurosensory retina and RPE, and determining the etiology of blocked fluorescence. (III, G, D)
- Fundus photographs may also be used as a baseline reference for selected patients with advanced non-neovascular AMD and for follow-up of treated patients. (III, G, D)
- Indocyanine green (ICG) angiography has been shown to be useful in evaluating specific forms of AMD, such as pigment epithelial detachment, poorly defined CNV, occult CNV, and lesions including retinal angiomatous proliferation or idiopathic polypoidal choroidal vasculopathy. (II-, M, D)
- When ICG angiography is performed, the physician must be aware of potential risks associated with this procedure: severe medical complications, allergic reactions, and even death. (III, G, S)
- Several other tests including fundus autofluorescence, microperimetry and adaptive optics have been used for evaluation of patients with AMD. However, their role in clinical practice is poorly defined at this time. (III, In, D)
- Patients with early AMD and/or a family history of AMD should be encouraged to assess their own visual acuity using monocular vision testing (i.e., Amsler grid), and have scheduled dilated eye examinations for detecting the intermediate stage of AMD. (III, G, S)