Mark L. Nelson



• Dry age-related macular degeneration (AMD) is a leading cause of severe vision loss in elderly populations of European descent. Dry AMD causes approximately half of permanent vision loss in older Caucasian patients in the US.

• Retinal findings include drusen, pigmentary changes, and geographic atrophy.

• AMD is a degenerative condition which affects the outer retina, as well as the retinal pigment epithelium (RPE), Bruch’s membrane, and the choriocapillaris.

Geriatric Considerations

This is a disease that predominantly affects patients over the age of 65 years. While non-neovascular AMD is less likely to cause severe vision loss than neovascular macular degeneration, it is still a significant cause of legal blindness in patients over 65 years old.



• The 5-year incidence of large drusen or pigmentary changes average 8.7% (ranging from 3.2% in people less than 60 years, and 18.3% in people in their 70s).

• Population studies showed the 5-year incidence of advanced AMD to be 1.1% with 0% in ages less than 60 years, and 5.4% in those older than 80 years.

• Progression of disease from drusen and pigmentary changes to advanced AMD including neovascular AMD increases with age.


Over 8 million people in the US have early AMD of whom 1 million will develop advanced AMD in the next 5 years.


• Age is the most important risk factor

• Family history

• Caucasian ancestry

• Smoking is an important modifiable risk factor

• Studies have been inconsistent about the role of body-mass-index, cardiovascular disease, hypertension, HDL, and total cholesterol.

• Very light pigmentation and blue irides may increase risk.


• Population studies with twins and family members have shown a familial component

• Complement Factor H (CFH), complement factor B, HTRA1 on chr. 10q26 all predispose to AMD with CFH being most important.


• AREDS (Age-Related Eye Disease Study) showed antioxidant vitamin supplementation can decrease progression of moderate to severe AMD.

– Patients with a higher intake of dark, green leafy vegetables and omega-3 fatty acids have a lower risk of developing AMD.

– Smoking cessation is critical.


• Degenerative changes involving outer portions of the retina, RPE, and Bruch’s membrane, and less severely, the choriocapillaris

• The earliest signs may be basal deposits in the RPE and between the RPE and Bruch’s membrane.

• Drusen develop because of these deposits and changes in the RPE.

• Hard drusen are PAS-positive nodules between the RPE and Bruch’s membrane.

• Soft drusen are eosinophilic deposits adjacent to Bruch’s membrane.

• Whether photoreceptor atrophy occurs primarily or secondarily to changes in Bruch’s membrane and the RPE, is not known.

• Recent evidence cites A2E, a component of lipofuscin, as a possible pathologic link leading to RPE apoptosis


The nexus of a high photic and oxygen environment in highly metabolic tissue, creates a milieu rife for free radical formation and oxidative damage. Pathologic changes and deposits in Bruch’s membrane and the RPE lead to structural changes that lead to AMD. Despite the prevalence of AMD, the etiology is not well understood.



• Many times patients are asymptomatic and are diagnosed on a routine eye examination.

• Symptoms suggest more advanced disease and include metamorphopsia and gradual impairment of vision over months to years.

• AMD is bilateral but may be asymmetric.

• Sudden visual changes or metamorphopsia in patients with dry AMD may signify progression to exudative AMD.


• Signs of AMD include drusen, RPE changes, incipient and geographic atrophy, and, in cases of exudative AMD, fluid, hard exudates, hemorrhage, and choroidal neovascular membrane (CNV).

• Drusen are classified as small (<64 μm), medium (64–124 μm), and large (>124 μm) or as hard (discrete well demarcated), soft (poorly demarcated), and confluent (contiguous boundaries).

• The RPE shows geographic or non-geographic atrophy and focal hyperpigmentation.

• Geographic atrophy is described as well demarcated areas of RPE loss. Non-geographic atrophy is less well defined and has a more mottled appearance. Focal hyperpigmentation occurs at the outer retina.

• Early AMD is defined as multiple small or intermediate drusen with no evidence of advanced AMD.

• Intermediate AMD is defined as extensive intermediate drusen or 1 large drusen.

• Advanced AMD is defined as presence of geographic atrophy or signs of wet AMD.



Initial approach

• Optical coherence tomography (OCT), color photographs, and fluorescein angiography (FA) can be used to document and follow progression of AMD.

• FA can show both hyper- and hypofluorescent areas. Hyperfluorescent lesions include RPE atrophy, RPE tears, CNV, pigment epithelial detachments (PED), and subretinal fibrosis. Hypofluorescent lesions are seen with hemorrhage, lipid deposits, and focal hyperpigmentation. Hemorrhage, fluid, and CNV are hallmarks of exudative (wet) AMD.

• FA can be used when acute visual changes occur to assess for possible progression to exudative AMD.

• OCT can show CNV, edema, subretinal fluid, PED, and drusen as well as delineate areas of RPE atrophy.

• Fundus autofluorescence photography shows areas of RPE loss and surrounding damaged RPE. It is an evolving method of imaging patients with dry AMD.

Follow-up & special considerations

• Risk of progression to wet AMD can be calculated using the AREDS simplified severity score. The score is calculated for each eye

– Large Drusen – 1 point

– Pigment abnormalities – 1 point

– Bilateral intermediate drusen – 1 point

– Advanced AMD in one eye – 2 points

• 0 factors – 1.5%, 1 factor – 3%, 2 factors – 12%, 3 factors – 25%, 4 factors – 50%


Central serous chorioretinopathy, pattern dystrophy of the RPE, Best’s disease, idiopathic juxtafoveal telangiectasia, and central areolar dystrophy



First Line

The AREDS study showed vitamins can slow progression of disease. The AREDS formulation is daily administration of 500 mg Vitamin C, 400 IU Vitamin E, 15 mg beta carotene, 80 mg zinc oxide, and 2 mg cupric oxide (to prevent zinc induced anemia).


• Use of beta carotene is not recommended in smokers or lung cancer survivors as it may increase risk of lung cancer.

• AREDS showed that patients with intermediate or advanced AMD benefited from vitamin supplementation. There is no data to support a beneficial effect of vitamins in those with no or early AMD.

• Reductions in modifiable risk factors are encouraged, especially smoking cessation. Reducing BMI and controlling cholesterol and cardiovascular risk factors may help reduce the progression of AMD.

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Nov 9, 2016 | Posted by in OPHTHALMOLOGY | Comments Off on AMD-DRY
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