Macular Degeneration Flashcards
The cause of AMD is unknown
• There is no ideal animal model of AMD
Classification – Disease Process
lighter coloured eyes more affected
- Dry: (85-90% of cases) (common interferes least)
- The cells of the retinal pigment epithelium (RPE) become less efficient
- The retina accumulates waste material which deposits
- The retinal pigment membrane degenerates and atrophies
- Wet: (10-15% of cases; more severe type)
- Integrity of Bruch’s membrane broken
- Neovascular complexes from the choroid grow
- New vessels are leaky, leading to edema
- Fibrovascular scar involving macular area
AMD - Types
Dry
• Generally milder
• Formation of drusen
• No approved treatments
Drusen are yellow deposits under the retina. Drusen are made up of lipids and protein
Wet
• Aggressive
• Neovascularization
• Approved treatment available
againg greatest risk
Etiology
- oxidative stress-mediated
- dysregulated antioxidant mechanisms
- inflammation
- dysregulated lipid metabolism
- dysregulated angiogenesis
breakdown of lips, proteins
drusen
Diagnosis
Self-monitoring with Amsler grid
• Dilated eye exam
wet - distorted with new vessels in back
Risk Factors
- Non-modifiable
- Age
- Genetics
- Lighter eye colour
- Modifiable
- Smoking
- Free radicals (overexposure to sunlight)
- Vascular insufficiency
- High intake of saturated fats
- Low omega-3 fatty acid intake
- Heavy ethanol intake
- Elevated BMI
- HTN, CV disease
Non-pharmacologic Treatment
- Lifestyle
- Smoking
- cessation
- Fat consumption
- Reduce saturated fats
- Increase omega-3 fatty acids
- Increase nut, fruit, fish intake
- Exercise
- Sunglasses - UV protection
Diet – Observational Studies
People who eat balanced diets rich in nutrients, fruit,
and fish may have lower rates of AMD.
- Dietary studies found decreased AMD with:
- 3+ fruit servings per day
- Weekly fish consumption
- Zinc consumption
- High overall intake of antioxidants
AMD – Rationale for Zinc
- Zinc is highly concentrated in the retinal pigment epithelium
- Acts as a cofactor for antioxidant enzymes
- Involved in DNA synthesis, RNA transcription, and cell division
Zinc ◼ Meat ◼ Poultry ◼ Fish ◼ Dairy
Toxicity of Zinc ◼ Acute: gastric pain, nausea, dizziness ◼ Chronic: low copper (low HDL, anemia), low iron (anemia) ◼ Concern with patient with low HDL, anemia ◼ Animal studies ◼ Glucose homeostasis; neoplasms ◼ Concern with patient with diabetes? ◼ Long term data?
AMD - Rationale for Antioxidants
• Oxidative stress in the retina and lens contribute to degenerative changes
Sources of Nutrients ◼ Vitamin E ◼ Whole grains ◼ Nuts ◼ Legumes ◼ Polyunsaturated oils ◼ (vegetable oil) ◼ Monounsaturated oils ◼ (olive oil)
- Vitamin C
- Citrus
- Melons
- Broccoli
AMD - Rationale for Lutein
• Lutein and zeaxanthin are the only carotenoids found in the eye Lutein ◼ Kale ◼ Spinach ◼ Lettuce ◼ Broccoli ◼ Corn ◼ Peas ◼ Brussel sprouts ◼ Cabbage
supplements - Prevention
Results:
• Vit E supplements preventing development of AMD
• Risk ratio (RR) 0.97 (CI95 0.90 - 1.06)
• Beta‐carotene supplements preventing any AMD
• RR 1.00 (CI95, 0.88 - 1.14)
For a patient with no maculopathy, what
should we recommend?
◼ Lifestyle (smoking, sun exposure, etc.)
◼ Balanced diet (consider consulting dietitian)
◼ Do NOT recommend ophtho-vitamin supplements
for prevention of AMD
AREDS - Safety
◼ No differences in ◼ Mortality ◼ Hematocrit ◼ Cholesterol ◼ Lipid lowering medications ◼ Antioxidant arms ◼ Yellow skin 8.3% vs 6.0% (p=0.008) ◼ Hospitalization for infection (1.6% vs 0.8%) ◼ Zn arms ◼ Self-reported anemia 13.2% vs 10.2% (p=0.004) ◼ Hct = NS ◼ Genitourinary hospitalization 7.5% vs 4.9% ◼ Circulatory AE 0.9% vs 0.3%
Considerations with Antioxidants
◼ Multiple studies of beta-carotene have found
increased rates of mortality in smokers.
◼ This result was not found in AREDS or AREDS2.
◼ Lung cancer was increased in AREDS2
◼ Application: Do not recommend antioxidant
supplements for a patient who smokes.
Summary - Supplements
• Evidence that AMD progression may be delayed - benefit with
combination therapy.
• No evidence for individual vitamins or minerals.
• The original AREDS formulation is supported
• These supplements have safety risks
Wet AMD – VEGF-I
• Vascular system delivers O2, nutrients; removes waste
• Uncontrolled permeability can lead to edema, tissue injury, thrombi, ischemic
consequences, and elevated pressure
• The end result can be vision loss
• Ocular AE
- Ocular inflammation
- 7% vs 2% control
- Increased intraocular pressure (IOP)
- 15-20% vs 4% control
- Endophthalmitis
- <1% of treated patients vs 0% in controls
- Extra-ocular AE
- Hemorrhage
- 9% vs 5%
