Age-Related Macular Degeneration

Aka: Age-Related Macular Degeneration, Macular Degeneration, ARMD, Vascular Endothelial Growth Factor Inhibitor Intravitreal Injection, VEGF Inhibitor Intravitreal Injection, VEGF Inhibitor Intraocular Implant

1. Epidemiology
   1. Leading cause of central Vision Loss over age 65 years
   2. Age-related changes
      1. Onset after age 50 years (mean onset: 75 years old)
      2. Prevalence
         1. Sixth decade: 1%
         2. Ninth decade: 15%
2. Risk Factors
   1. Advancing age (see epidemiology above)
   2. Female sex
   3. White race
   4. Tobacco Abuse (increases risk 3 fold)
   5. Diet low in caretenoids
   6. Increased sunlight exposure
   7. Cardiovascular disease
   8. Aspirin (weak evidence only by observation study)
      1. Neovascular Macular Degeneration (wet AMD) was observed more with Aspirin use for >10 years
      2. Klein (2012) JAMA 308(23):2469-78 [PubMed]
3. Pathophysiology
   1. Idiopathic
   2. Retinal photoreceptor dysfunction
      1. Results from atrophy or Choroidal neovascularization
      2. Mediators
         1. Subretinal Hemorrhage
         2. Subretinal Fibrosis (disciform scarring)
         3. Subretinal Fluid and lipid accumulation
      3. Outcome: Decreased Visual Acuity to blindness
4. Types
   1. Non-neovascular, dry, non-exudative ARMD
      1. Accounts for 80% of all diagnosed cases
      2. Geographic atrophy and drusen (yellow lipid deposits) predominate
   2. Neovascular, wet, exudative ARMD
      1. Accounts for 80% of significant visual Disability
      2. Choroidal neovascularization (CNV)
      3. Complicated by Macular Hemorrhage
5. Symptoms
   1. Slow, insidious central Vision Loss
   2. Decreased dark adaptation
6. Exam
   1. Amsler Grid
      1. Identifies central visual defects
      2. While staring at a central black dot, patients report missing or distorted grid lines
7. Signs: Bilateral eye involvement
   1. Drusen
      1. Yellow lipid deposits, debris within Retinal pigment basement membrane
      2. Appear with ophthalmoscope as yellow spots on Retina
      3. Small drusen <63 microns are seen on aging Macula
      4. Numerous, large drusen are consistent with ARMD
   2. Geographic atrophy
   3. Serous Retinal pigment epithelial detachment
   4. Choroidal neovascularization
8. Management: Vascular Endothelial Growth Factor Inhibitors (VEGF Inhibitors)
   1. See Prevention and Nutritional Supplements and Antioxidants as below
   2. Indications
      1. Neovascular ARMD
   3. Vascular Endothelial Growth Factor Inhibitors (VEGF Inhibitors) Intravitreal Injection
      1. Intravitreal injection monthly for 4 months (or until stable), then every 3 months
      2. Monoclonal antibodies available for intravitreal injection
         1. Bevacizumab (Avastin)
            1. Not FDA approved, but $150/dose compared to >$1500 for other agents
         2. Ranibizumab (Lucentis)
            1. Also available as an ocular implant (Susvimo, see below)
         3. Pagaptanib (Macugen)
         4. Aflibercept (Eylea)
         5. Faricimab (Vabysmo)
            1. Combined VEGF Inhibitor and Angiopoietin-2 Inhibitor
   4. VEGF Inhibitor Ocular Implant containing Ranibizumab (Susvimo)
      1. Ocular implant with Ranibizumab (Susvimo) is inserted via a small incision in pars plana and Sclera
      2. Requires reservoir refill via needle every 24 months
      3. As effective as intravitreal injection
      4. Conjunctival Hemorrhage, hyperemia ad Iritis are common adverse effects in the first month
      5. Endophthalmitis risk (1.7%) is higher with implants than with injection (0.5%)
      6. (2022) Med Lett Drugs Ther 64(1649) 71-2
      7. Holekamp (2022) Ophthalmology 129:125 [PubMed]
9. Management: Slow progression of CNV-related Vision Loss
   1. Laser photocoagulation of subretinal blood vessels
   2. Photodynamic therapy
      1. Give IV photosensitive drug (wavelength specific)
      2. Expose eye to targeted wavelength to activate drug
   3. Experimental
      1. External beam Radiotherapy
      2. Vitreoretinal microsurgery
10. Management: Visual aids
    1. Magnifiers
    2. Increased light sources in home environment
11. Prevention: General measures
    1. Tobacco Cessation is key
    2. Control Hypertension
    3. Decrease UV Light exposure (Sunglasses)
    4. Nutrition
       1. See Nutritional Supplements below
       2. Decrease Dietary Fat intake
       3. Increase grean leafy vegetable intake
12. Prevention: Nutritional Supplements and Antioxidants
    1. Vitamin C, Vitamin E, Beta Carotene, and Zinc
       1. Indications
          1. Intermediate or advanced ARMD
       2. Efficacy
          1. May reduce progression from intermediate to advanced ARMD (NNT 22 over 5 years)
          2. May protect the other eye when ARMD is present in one eye
          3. Does not prevent development of ARMD
       3. Components (based on AREDS Study)
          1. Vitamin C 500 mg
          2. Vitamin E 400 IU
          3. Zinc 80 mg (25 mg in AREDS2)
          4. Copper 2 mg
          5. Beta Carotene 15 mg (removed in new formulations and replaced by Lutein and Zeaxanthin)
             1. No benefit per AREDS 2 study (and increased Lung Cancer risk in smokers)
       4. Components (based on AREDS2 Study)
          1. Includes components of the original AREDS Study without Beta Carotene
          2. Lutein 10 mg daily
             1. Improves Vision in men with Macular Degeneration
             2. Richer (2004) Optometry 75:216-30 [PubMed]
          3. Zeaxanthin 2 mg
          4. Zinc 25 mg (reduced from 80 mg in AREDS formulation)
       5. References
          1. (2013) Presc Lett 20(8):45
          2. (2001) Arch Ophthalmol 119:1417-36 [PubMed]
    2. Components not found useful in ARMD prevention
       1. Beta Carotene (and Lung Cancer risk in smokers)
       2. Omega-3 Fatty Acids
13. Screening
    1. Initiate at age 45 years with dilated exam
14. References
    1. Martidis in Yanoff (2004) Ophthalmology p. 925-33
    2. (2013) Presc Lett 20(3): 16
    3. Pelletier (2016) Am Fam Physician 94(3):219-26 [PubMed]
    4. Lim (2012) Lancet 379(9827): 1728-38 [PubMed]
    5. Weir (2004) CMAJ 170:463-4 [PubMed]