4. It is estimated that by 2020, 196
million individuals worldwide will be
affected by AMD .The yearly
healthcare costs of AMD in the US is
$255 billion, making up almost half of
all costs related to care for vision loss.
14. Key diagnostic factors
• Sudden-onset blurring or distortion of vision
1. Often the first symptom of disease.
2. Can indicate development of choroidal neovascularization with leakage
of fluid in the macula.
• Macular pigmentary changes
• Geographic atrophy
• Choroidal neovascularization
• Pigment epithelial detachment (exudative AMD)
• Progressive loss of vision in 1 or both eyes
• Fibrovascular scar formation
17. Dry AMD with large drusen and hyperpigmentation of the
retinal pigment epithelium at the macula
Advanced dry AMD (geographic atrophy). There is central well-
demarcated geographic atrophy of the retinal pigment
epithelium with visible choroidal vessels and surrounding
22. Choroidal neovascularization in
degeneration. Notes: (A) Fundus
photography of subretinal
neovascularization. (B) Cirrus™
OCT reveals a large subretinal
with subretinal and intraretinal
fluid in the macular area.
43. Age-Related Eye Disease Study Group (AREDS) classification
• No AMD (AREDS category 1) : No or a few small (<63 micrometers in
• Early AMD (AREDS category 2) : Many small drusen or a few intermediate-
sized (63-124 micrometers in diameter) drusen, or macular pigmentary
• Intermediate AMD (AREDS category 3): Extensive intermediate drusen or
at least 1 large (≥125 micrometers) drusen, or geographic atrophy not
involving the foveal center.
• Advanced AMD (AREDS category 4)
1. Geographic atrophy
2. Choroidal neovascularization (wet AMD)
46. AREDS Study
• AREDS1 Study
• The Age Related Eye Disease Study (ARED’s) was a 10 year study sponsored by
the National Institutes of Health (NIH). The study showed that a specific
combination of antioxidants and zinc slowed the progression of advanced age-
related macular degeneration by approximately 25%. The ARED’s formulation
included vitamins A (as beta-carotene), C, E, zinc and copper.
• AREDS2 Study: was designed to:
1. Determine if adding omega-3 fatty acids or lutein and zeaxanthin would make
it more effective.
2. A secondary goal was to determine if eliminating beta-carotene from the
formula would be detrimental (A different study showed a relationship
between beta-carotene and lung cancer in smokers).
3. A third goal of the study was to determine if decreasing the amount of zinc
would be detrimental. The study determined that replacing beta-carotene
with lutein and zeaxanthin was neither better nor worse than the original
AREDS formula O.S.
• Ranibizumab and aflibercept have similar efficacy.
• Bevacizumab is not approved, but recent head-to-head studies
indicate that its efficacy is similar to that of ranibizumab.
• Furthermore, it has been demonstrated that bevacizumab is cost-
effective, whereas ranibizumab is not.
• A systematic review of randomized controlled trials comparing
bevacizumab and ranibizumab could not detect a difference in
systemic safety between the two drugs.
• Another VEGF inhibitor, pegaptanib, is less effective than these drugs
and use has largely been discontinued.
• In practice commonly used protocols include loading doses (typically 3)
and then scheduling as required. Some studies use "treat and extend“
dosing regimens, thereby reducing the number of patient visits and
injections, and lowering direct annual medical costs, compared with
monthly injections. This can be considered as an alternative to monthly
• Long-term follow-up in the Comparison of Age-related Macular
Degeneration Treatments Trials (CATT) study, which compared ranibizumab
and bevacizumab, showed that visual gains over the first 2 years were not
maintained at 5 years, despite continued treatment. However, there was
still a major long-term benefit with 50% of eyes having a visual acuity of
20/40 or better.
51. Cirrus HD-OCT, Carl Zeiss Meditec, Dublin, CA), demonstrating resolution of intraretinal fluid
following treatment with ranibizumab (Lucentis, Genentech, South San Francisco, CA), in a
patient with neovascular AMD. Pretreatment (A), posttreatment
52. Color fundus photographs and (OCT) scans of a right eye before anti-VEGF treatment
[a]; and after anti-VEGF treatment [b]. There is resolution of the macular
haemorrhages and subretinal fluid
• Age-Related Eye Disease Study Group (AREDS) category 2 (early AMD)
• Typically, visual acuity remains unaffected unless progression results.
• Patients have a 1.3% risk over 5 years of progressing to advanced AMD.
• No treatments have been demonstrated to be effective for this category of
• AREDS category 3 (intermediate AMD)
• Typically, visual acuity remains unaffected unless progression results.
• Patients have an 18% risk over 5 years of progressing to advanced AMD.
• Patients receiving antioxidant supplements in the AREDS study had a 25%
reduction in progression to advanced disease and a 19% reduction in visual
loss of ≥3 lines over 5 years.
• AREDS category 4 (advanced AMD)
• Patients with unilateral disease have a 43% chance over 5 years of
developing advanced AMD in the other eye.
• Geographic atrophy (dry) AMD tends to result in less severe visual
impairment than exudative (wet) AMD. In contrast, wet AMD, if
untreated, will result in significant visual loss (doubling of the visual
angle or worse) in over half of patients over the following several
Hinweis der Redaktion
It is characterized by distinct clinical stages including early and intermediate AMD with drusen and macular pigmentary changes,
usually associated with normal or near-normal vision; and late AMD, which is associated with a decrease or
loss of central vision.
Late (or advanced) AMD has 2 forms: geographic atrophy (or “atrophic” or “dry” AMD)
and neovascular AMD (or “wet” or "exudative” AMD).
It is estimated that approximately 7 million people in the US have intermediate AMD and 1.75 million have late AMD.
Although most people (approximately 80%) have geographic atrophy, the neovascular AMD accounts for most of the cases with severe visual loss.
The incidence of disease and its associated features increases with age and is low in people <55 years of age.
Several studies have shown that late AMD is significantly more prevalent in Europeans than in African, Hispanic, or Asian populations.
Epidemiological studies have demonstrated that increasing age, family history, current cigarette smoking,previous cataract surgery are strong risk factors for AMD.
history of cardiovascular disease, high body mass index, hypertension, and low dietary intakes of vitamins (A, C, and E), omega-3 fatty acids, lutein, and zinc.
One study showed that subjects with a Western-type diet had a higher risk of AMD than those with an Oriental-type diet. Another study found that red meat intake was associated with an increased risk of late AMD, whereas fruit intake was found to be protective.
Prevalence of the condition in people ages 75 to 85 years was found to be >3 times that of people ages 43 to 54 years. Subsequent 10-year follow-up revealed incidence rates of 4.2% in the 43 to 54 age group compared with 46.2% in the 75 to 85 age group.
Several studies have shown that smoking is associated with risk of disease development. Cessation of smoking may decrease risk.
FHx of disease
Polymorphisms associated with a number of genes have been shown to modify AMD risk, including the complement factor H locus, ARMS2/HTRA1, and C3.
Pathogenesis is thought to involve a combination of oxidative stress and inflammation, although the precise role of these processes in the initiation and progression of the condition remains unclear. Accumulation of iron, which is a known trigger of oxidative stress, within cells of the retinal pigment epithelium (RPE) could be involved in cellular damage.
Deposition of extracellular material along the inner aspect of Bruch's membrane, plays a central role. This buildup of material alters the permeability of Bruch's membrane, resulting in decreased nutrient delivery to RPE cells and secondary metabolic stress. It is thought that metabolic stress leads to RPE cellular damage and secondary loss of adjacent photoreceptors and choriocapillaris, resulting in geographic atrophy.
Ischemia of the RPE may lead to increased production of vascular endothelial growth factor by RPE cells, which is the major stimulus for neovascularization of the choriocapillaris. Choroidal neovascular vessels break through Bruch's membrane and are prone to leakage, leading to subretinal and intraretinal fluid accumulation.
No AMD: No or a few small (<63 micrometers in diameter) drusen.
Early AMD : Intermediate-sized (63-124 micrometers in diameter) drusen
Intermediate AMD : Intermediate drusen and pigmentary changes, or at least 1 large (≥125 micrometers) drusen.
Choroidal neovascularization with signs including subretinal hemorrhage, serous retinal or retinal pigment epithelium detachments, lipid exudates, or fibrovascular scar.
macular pigmentary changes (common) : Seen in intermediate AMD, along with drusen.
geographic atrophy (common)
A form of late AMD.
Frequently associated with significant visual loss, especially if central macula (fovea) is involved.
choroidal neovascularization (common)
Presents with subretinal or intraretinal fluid, or hemorrhage or lipid deposition.
A form of late AMD. If central macula (fovea) is affected, patient may have severe visual loss
pigment epithelial detachment (exudative AMD) (common)
Presents as dome-shaped, fluid-filled elevation of the neurosensory retina and retinal pigment epithelium.
Commonly occurs as part of the clinical picture of neovascular AMD. Not seen in geographic atrophy.
progressive loss of vision in 1 or both eyes (common) : May occur in patients with choroidal neovascularization or central geographic atrophy.
fibrovascular scar formation (common)
Typically an end-stage finding.
Scars may be disciform.
If foveal center is affected, almost universally results in severe visual loss.
Small drusen-like deposits that form between the photoreceptors and retinal pigment epithelium.
The reticular form has been particularly associated with progression to geographic atrophy, but pseudodrusen are also associated with progression to choroidal neovascularization.
Colour fundus photograph of a patient’s left eye:
olour fundus photograph of a patient’s right eye:
Intermediate AMD (Age-Related Eye Disease Study Group [AREDS] category 3)
Late AMD with central geographic atrophy (Age-Related Eye Disease Study Group [AREDS]
Late AMD with choroidal neovascularization with exudation (Age-Related Eye Disease Study Group
[AREDS] category 4)
Fibrovascular scar from end-stage AMD (Age-Related Eye Disease Study Group [AREDS] category
High resolution optical coherence tomography image showing subretinal and intraretinal fluid
High resolution optical coherence tomography image showing hyperreflective scar
Due to its subretinal location, the neovascular net is delineated with distinct margins. Leakage in late-phase angiography confirms the biologic activity of the lesion
Fluorescein angiogram showing active choroidal neovascularization
Treatment is dependent on the category of disease at presentation, and is aimed at reducing the rate of progression of intermediate AMD to late AMD, and treating choroidal neovascularization (CNV) when present.
Patients with early or intermediate-stage disease have few or no visual symptoms, whereas patients with late AMD (geographic atrophy of neovascular AMD) may have severe visual loss, especially if the condition involves the center of the fovea.
Treatment of patients with CNV is determined by the locations and size of the neovascular disease.
Patients with early AMD
Management involves risk factor modification: smoking cessation, dietary modification, and atherosclerotic risk factor modification.
Patients with intermediate AMD
Management involves risk factor modification: smoking cessation, dietary modification, and atherosclerotic risk factor modification. Antioxidant and mineral supplementation using the formulation of the Age-Related Eye Disease Study Group (AREDS) may be considered for suitable patients.
Patients with advanced AMD: atrophic (dry)
No current treatment has been shown to be effective.
High-dose antioxidant and mineral supplementation can be considered for patients with unilateral advanced disease and with intermediate AMD in the second eye to reduce the risk of the second eye progressing to late AMD.
Repeat eye exam after 6 to 24 months might be considered for patients who remain asymptomatic, and these patients should be seen as soon as possible if they develop symptoms suggestive of CNV.
risk factor modification
» Patients with AMD are encouraged to stop smoking; to eat a balanced diet that has a low glycemic index and is rich in fruits, vegetables, and fish high in omega-3 fatty acids; and to modify cardiovascular risk factors (including lowering cholesterol and saturated fat intake and controlling hypertension). However supplementation with omega-3 long-chain polyunsaturated fatty acids does not influence the risk of progressing to advanced AMD.[
Patients with advanced AMD: exudative (wet)
High-dose antioxidant and mineral supplementation can be considered for patients with unilateral advanced disease and with a second eye at risk of developing disease (i.e., intermediate AMD).
Once a patient has developed CNV, treatment is based on the location and size of the neovascular disease.