Macular Degeneration Disease

BASICS

DESCRIPTION

One definition of ARMD is pigmentary changes in the macula or typical drusen associated with visual loss to the 20/30 level or worse, not caused by cataract or other eye disease in individuals over 50 years of age. Other definitions do not include age or visual acuity criteria. ARMD is the leading cause of irreversible, severe visual loss in persons over 65 years of age.

Stages:
- Atrophic/nonexudative: drusen and/or pigmentary changes in the macula
- Neovascular/exudative: growth of blood vessels underneath the retina
System(s) affected: Nervous
Genetics:
- The neovascular/exudative form is rare in blacks and more common in whites
- Genetic susceptibility may be a factor in senile macular degeneration, with approximately 1/4 of all senile cases being genetically determined
Incidence/Prevalence in USA:
- In the Framingham Eye Study (FES) drusen were noted in 25% of all participants who were ≥52 years of age. ARMD-associated visual loss was noted in 5.7%.
- Prevalence increases with age. Over 75 years, one quarter of men and one third of women will have evidence of ARMD.
- The prevalence of severe visual loss from ARMD increases with age. 2.2% of patients over 65 years of age are blind in one or both eyes from ARMD.
- The atrophic/nonexudative stage accounts for 20% of cases of severe visual loss.
- The neovascular/exudative stage accounts for 80% of cases of severe visual loss.
Predominant age: FES prevalence rates:
- 1.6% of those individuals who were 52–64 years old
- 11% of those who were 65–74 years old
- 27.9% of those who were > 75 years
Predominant sex: Female > Male

SIGNS AND SYMPTOMS

Atrophic/nonexudative stage
- Drusen
  - Small yellowish-white lesions
  - Can be subdivided into types such as hard drusen and soft drusen
- Atrophy of the retinal pigment epithelium (RPE), a pigment layer underneath the retina
Neovascular/exudative stage
- Blood vessels growing underneath the retina from the choroid are called choroidal neovascular membranes (CNVMs) or subretinal neovascularization (SRN). The choroid is the vascular layer underneath the RPE.
  - Subretinal fluid
  - Exudates
  - Subretinal hemorrhage
  - Patients frequently notice distortion of central vision. On Amsler grid testing the horizontal or vertical lines may become broken, distorted, or missing. Patients may notice straight lines appear crooked, e.g., telephone poles.
- Disciform scar: An advanced stage resulting in a fibrovascular scar

CAUSES

Visible light can result in the formation and accumulation of metabolic byproducts in the RPE, which normally helps remove metabolic byproducts from the retina. Excess accumulation interferes with normal RPE metabolic activity and can lead to the formation of drusen.
The neovascular stage generally arises from the atrophic stage.
Most patients do not progress beyond the atrophic/nonexudative stage; however, those who do are at greater risk of developing severe visual loss.

RISK FACTORS

Excess sunlight exposure
Blue or light iris color
Hyperopia
History of cardiovascular disease (hypertension, circulatory problems)
Short height
History of lung infection
Cigarette smoking
Low dietary intake of antioxidant nutrients
Family history

DIAGNOSIS

LABORATORY

N/A

Drugs that may alter lab results: N/A
Disorders that may alter lab results: N/A

PATHOLOGICAL FINDINGS

Drusen: deposits of hyaline material between the retinal pigment epithelium (RPE) and Bruch's membrane (the limiting membrane between the RPE and the choroid)
Breaks in Bruch's membrane allow CNVMs to invade the RPE and grow into the subretinal space

SPECIAL TESTS

Fluorescein angiography: Can detect CNVMs. This test helps to differentiate between atrophic and neovascular ARMD.
Indocyanine green videoangiography: May be useful in identifying occult or hidden CNVMs.

IMAGING

N/A

DIAGNOSTIC PROCEDURES

Daily Amsler grid testing
Eye examination with detailed fundus examination
Fluorescein angiography

TREATMENT

APPROPRIATE HEALTH CARE

Outpatient for laser treatment. Inpatient or outpatient for vitrectomy surgery.

GENERAL MEASURES

Atrophic/nonexudative macular degeneration
- No specific treatment alters the course
- Free radical formation in the retina, induced by visible light, may play a role in cellular damage that results in ARMD
- Vitamin A, E, C, and beta-carotene may be useful in preventing cellular damage
- Oral zinc may retard visual loss
- Laser photocoagulation to treat drusen is unwarranted
Neovascular/exudative macular degeneration
- The Macular Photocoagulation Study (MPS) demonstrated a treatment benefit for laser treatment of CNVMs which were 200 microns (0.2 mm) or greater from the center of the macula
  - The MPS showed that the benefits of argon laser photocoagulation were greatest one year after treatment. At that time the proportion of eyes with severe visual loss was reduced 51% by treatment, from 43% in untreated eyes to 21% in treated eyes. The deterioration in treatment effect in the MPS is primarily due to recurrent CNVMs growing towards the center of the macula
  - Fluorescein angiogram usually can determine whether a CNVM is present, if it is well defined, and if it is in a treatable position
  - Recurrent CNVMs, after laser treatment, were seen in 59% of patients with ARMD. 73% of the recurrences occurred within the first year of treatment, usually within the first 6 months
Treatment of CNVMs from 1 to 199 microns from the center of the macula has been studied by the Age-Related Macular Degeneration Study-Krypton Laser (ARMDS-K)
- The benefit of laser treatment was greatest among patients without evidence of hypertension. No benefit was observed among patients who had highly elevated blood pressure and/or used antihypertensive medication
- Because patients in the ARMDS-K treatment group had CNVMs closer to the center of vision, the magnitude of treatment benefit after laser photocoagulation is smaller in the ARMDS-K treatment group than in the argon laser trial for CNVMs further away from the center of the macula
- Laser treatment can be applied to CNVMs directly underneath the center of vision; however, this can result in immediate worsening of vision. The long-term benefits of laser treatment for these lesions make this form of laser treatment an option
Vitrectomy has been used to remove CNVMs, but the benefits of this procedure are being studied
- CNVMs can bleed spontaneously leaving blood underneath the retina. Vitrectomy to remove subretinal blood may be of benefit and should be performed within 7 days of the bleed. Tissue plasminogen activator (tPA), instilled into the eye, may help remove a subretinal hemorrhage
Macular translocation involves intentionally creating a retinal detachment and attempting to shift the macula away from the CNVM. Laser is then applied to the CNVM after the retina is translocated. This procedure is currently being refined and is associated with potential serious surgical risks
Patients need to be monitored (usually with fluorescein angiography) after laser treatment for recurrent CNVMs. After treatment, patients should report changes in the Amsler grid or their vision
Photodynamic therapy (PDT) with verteporfin reduces vision loss in patients with greater than 50% "classic" subfoveal CNVMs. Verteporfin is administered intravenously and diode laser at 689 nm is applied to the CNVM
Low vision aids may be helpful
Investigation/experimental treatments: transplanting of fetal RPE cells, laser treatment to drusen, low dose radiation therapy, transpupillary thermotherapy via a diode laser at 810 nm for occult subfoveal CNVMs

SURGICAL MEASURES

See General Measures

ACTIVITY

Patients with the neovascular form of ARMD should avoid straining and anticoagulants if possible prior to laser treatment

DIET

A diet high in vitamins A, E, C, and beta-carotene along with zinc may be of benefit
Eating dark green, leafy vegetables (spinach or collard greens) which are rich in carotenoids may decrease the risk of developing the neovascular/exudative stage

PATIENT EDUCATION

American Academy of Ophthalmology, 655 Beach Street, San Francisco, CA 94109-1336
Visually impaired patients should check with their local low vision center for aids

FOLLOW UP

PREVENTION/AVOIDANCE

Ultraviolet protection for eyes
Well balanced diet which includes zinc, vitamins A, E, C, and beta-carotene
Routine ophthalmologic visits; q2-4 years for patients 40-64 and q1-2 years after age 65
Daily Amsler grid testing

POSSIBLE COMPLICATIONS

Blindness

EXPECTED COURSE AND PROGNOSIS

Patients with bilateral soft drusen, and pigmentary changes in the macula, but no evidence of exudation, have an increased likelihood of developing CNVMs and subsequent visual loss
Patients with bilateral drusen carry a cumulative risk of 14.7% over five years of suffering significant visual loss in one eye from the neovascular stage of ARMD
Patients with neovascular stage in one eye and drusen in the opposite eye are at a risk of 5-14% annually of developing the neovascular stage in the opposite eye with drusen
High incidence of recurrence after laser treatment for CNVMs

MISCELLANEOUS

ASSOCIATED CONDITIONS

Presumed ocular histoplasmosis syndrome
Exudative retinal detachment
Vitreous hemorrhage
Other causes of CNVMs

AGE-RELATED FACTORS

Pediatric: N/A
Geriatric: Prevalence will increase as population ages.
Others: N/A

PREGNANCY

N/A

OTHER NOTES

N/A

ABBREVIATIONS

ARMD = age-related macular degeneration
SMD = senile macular degeneration
SRN = subretinal neovascularization
CNVM = choroidal neovascular membrane
RPE = retinal pigment epithelium
MPS = macular photocoagulation study
ARMDS-K = Age-related macular degeneration study-Krypton Laser
PDT = photodynamic therapy

Clinical Investigations

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