History
Patients with age-related macular degeneration (AMD or ARMD) usually report a family history of decreased vision late in life.
They often report difficulty with night vision and with changing light conditions. Specifically, patients report changes in Amsler grid self-evaluation and trouble with reading.
Commonly, AMD patients report visual fluctuation (ie, days when vision is poor and other days when it appears improved).
Patients report difficulty with reading and making out faces.
Metamorphopsia is not a major complaint, but it may be present as the atrophy slowly progresses.
An association between AMD and Alzheimer disease has been reported. [18]
Physical
Funduscopic examination in age-related macular degeneration (AMD or ARMD) is significant for drusen in the early stages of disease. These drusen usually are confluent with significant pigment changes and accumulation of pigment in the posterior pole. RPE often appears atrophic with an easier visualization of the underlying choroidal plexus.
In advanced stages of dry ARD, these focal islands of atrophy coalesce and form large zones of atrophy with severely affected vision.
Signs of choroidal neovascularization include RPE elevation, exudate, or subretinal fluid. The presence of these symptoms may indicate that neovascularization is occurring and that fluorescein angiography may be indicated to evaluate the retina.
The periphery of patients with ARMD often has areas of drusen, as well as RPE mottling and atrophy.
Causes
Oxidative stress is believed to play a major role in the pathogenesis of age-related macular degeneration (AMD or ARMD) because of combined exposures of the retina to light and oxygen. Additionally, AMD is now widely accepted as a genetically inherited disorder with late onset.
Groundbreaking studies in the genetics of AMD have changed the way in which most specialists perceive the disease. Specifically, a majority of the risk of developing AMD is determined by variations in 3 specific genes, as follows:
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CFH gene (chromosome 1)
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BF (complement factor B) gene and C2 (complement component 2) gene (chromosome 6)
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LOC gene (chromosome 10)
Maller and others showed that polymorphisms in the above 3 genes independently raise the risk of AMD. [19] The above genetic factors contribute to approximately 50% of the sibling risk of developing AMD.
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Smoking and a higher body mass index are 2 of the most common other environmental factors that contribute independently to the increase in the risk of developing AMD. Smoking has been clearly identified as increasing the risk of AMD by 2 times.
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Large studies have not shown hypertension or heart disease to increase the odds of developing AMD.
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Serum lipids were extensively studied regarding their relationship with AMD in the National Eye Institute–sponsored AREDS. One report suggests dietary total omega-3 long-chain polyunsaturated fatty acid (LCPUFA) intake was inversely associated with the development of neovascular AMD (although not nonexudative AMD). [20] Similarly, individuals with higher fish consumption had a slightly lower incidence of developing neovascular AMD.
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A study looking at whether the regular consumption of omega-3 fatty acids and fish may affect the onset of AMD in women found that incidence of the disease was significantly decreased among women who ate 1 or more servings of fish per week. [21]
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Studying twins with AMD, Seddon and others arrived at some interesting conclusions. [22] Current cigarette smoking increased the risk of developing AMD by 1.9-fold, and past smoking still increased the risk by 1.7-fold. Increased consumption of fish (>2 servings of fish per week) and a higher intake of omega-3 fatty acids both were protective and reduced the odds of developing AMD by 0.55-fold.
These studies have generally been performed in individuals from the United States of European descent. Thus, the results may not apply to individuals of other races.
Blue light emitted from device screens (eg, smartphones, laptops) also causes vision damage and hastens blindness. Ratnayake et al (2018) found that blue light interacts with retinal, resulting in creation of toxic molecules within photoreceptor and nonphotoreceptor cells, which can cause macular degeneration. [23]
Patients with glaucoma should be asked about cognitive status, since an association between Alzheimer disease and glaucoma has been found. [18]
Complications
The major complication of dry age-related macular degeneration (AMD or ARMD) is the conversion to wet (or exudative/neovascular) AMD.
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A normal-appearing macula of the left eye. Note the even pigmentation of the retinal pigment epithelium and the absence of any yellow excrescences (drusen) in the fovea. The optic nerve has unrelated changes.
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In angiography, fluorescein dye is passed through a peripheral vein and transmits through the vascular system. The dye fluoresces in the vasculature, as seen here. No vascular prominences are seen in the macula or in any areas of dye pooling or staining. The abnormal vessels in the optic nerve, however, do show dye leakage.
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Moderate nonexudative age-related macular degeneration is shown with the presence of drusen (yellow deposits) in the macular region.
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Staining of drusen. Drusen absorb dye and, in the late frames of the angiogram, show hyperfluorescence. This staining is distinguished from the leakage that occurs when the dye spreads outside the boundary of the lesion.
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A more advanced case of nonexudative age-related macular degeneration (ARMD). This image shows drusen that are larger, more confluent, and soft. Soft drusen are defined as drusen that have indistinct borders. Such drusen are more likely to convert to wet ARMD. A few areas of atrophy are noted, where the retinal pigment epithelium (RPE) has lost pigmentation. The retinal cells overlying atrophic RPE are generally nonfunctional and result in a scotoma.
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The atrophic retinal pigment epithelium (RPE) demonstrates staining of the underlying choroidal vasculature. Normally, the intact RPE masks the presence of choroidal fluorescence. However, when the RPE atrophies, the underlying dye appears as an area of hyperfluorescence in the early stages of angiography. In the late stages, the drusen lose fluorescence in concert with (or with a small time lag) the rest of the retinal layers.
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A more advanced case of dry age-related macular degeneration. Several areas of atrophy are present, as are areas of significant pigment mottling in the macula. The large drusen inferior to fixation are poorly distinguished from each other.
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The atrophic areas are easily distinguished by the hyperfluorescence of the retinal pigment epithelium (RPE) in the mid phase of the angiogram. Hypofluorescence of dye, due to masking caused by the increased pigmentation, is seen. No areas of frank dye leakage or exudative age-related macular degeneration (ARMD) are apparent. A "hot cross bun" pattern of dry ARMD-related pigment changes is evident near the fovea.
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High-definition optical coherence tomography scan of a 67-year-old woman showing retinal pigment epithelium mottling and pigment epithelial detachments temporal to fixation consistent with dry macular degeneration.
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Fundus photo showing drusen in a 67-year-old woman with dry age-related macular degeneration.
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Fluorescein angiogram 4 minutes after injection of dye on 67-year-old woman showing pigment epithelial detachments.
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A later frame of the angiogram demonstrating the absence of dye leakage outside the lesion, with staining of the areas of atrophy (window defects) in the macular region.
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High definition optical coherence tomography right eye demonstrating retinal pigment epithelium atrophy and changes in the deeper layers of retina. The absence of intraretinal cysts, subretinal fluid, or sub-retinal pigment epithelium fluid indicates the absence of wet age-related macular degeneration.
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Spectral domain optical coherence tomography (SD-OCT) analysis: OCT B-scans show the presence of pigment epithelial detachment bilaterally in a patient with previously diagnosed dry age-related macular degeneration (AMD), which appeared relatively stable in comparison to previous scans. No subretinal fluid or retinal edema was detected.
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Fluorescein angiography: Fundus angiography in the same patient shows staining of drusen and window defects only in each eye. No active neovascularization was detected in either eye.
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Optical coherence tomography (OCT) shows an active neovascular network in the right eye as opposed to the nonvascularized pigment epithelial detachment found in the left eye. The spectral domain optical coherence tomography (SD-OCT) images in the lower panels confirm pigment epithelial detachment formation in each eye.
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Optical coherence tomography (OCT) shows an active neovascular network in the right eye as opposed to the nonvascularized pigment epithelial detachment found in the left eye. The spectral domain optical coherence tomography (SD-OCT) images in the lower panels confirm pigment epithelial detachment formation in each eye.
