MACULAR DEGENERATION

 

I. Pathophysiology

  1. Deterioration of central part of the retina, corresponding to the center of the visual field
  2. Cause gradual, but irreversible visual loss--often not noticed by pt in the early stages
  3. Late-stage macular degeneration has 2 recognized forms
    1. Atrophic ("dry"--Characterized by sub-retinal deposits ("drusen") and loss of retinal pigment epithelium ("geographic atrophy") 
    2. Neovascular/exudative ("wet")--Results in detachment of retinal pigment epithelium and choroidal neovascularization, leading to scarring and, in some cases, hemorrhage with sudden loss or distortion of vision

II. Risk factors

  1. Prevalence increases with age
  2. Family history
  3. Cigarette smoking
  4. Low dietary intake of antioxidant vitamins and zinc (JAMA 294:3101, 2005--JW)
  5. European ancestry (for "wet" macular degeneration)
  6. Prevention
    1. HMG-CoA Reductase Inhibitors ("Statins") were associated with sig. reduced risk of MD in one case-control study (OR 0.14) (BMJ 323:375, 2001--JW)
    2. In a study in 5,442 women > 40yo with CAD or CAD risk factors randomized to a combination of (folate 2.5mg, vit. b6 50mg, and vit. b12 1mg) QD vs. placebo, after mean 7y f/u, the vitamin recipients had sig. lower incidence of age-related macular degeneration (2% vs. 3%) ("Women's Antioxidant and Folic Acid Cardiovascular Study" ("WAFACS") trial; Arch. Int. Med. 169:335, 2009-JW)

III. Tx

  1. Laser photocoagulation--50% of tx'd pts have some initial reduction in central vision due to reactive neovascularization after treatment
  2. "Photodynamic therapy" (has largerly replaced laser photocvoagulation for "wet" MD as of 2006
  3. Antioxidants & Zinc
    1. In a randomized study of 3640 pts 55-80yo with age-related macular degeneration (at various stages) randomized to ZnO 80mg, Antioxidants (vit. C 500mg, Vit. E 400IU, beta-carotene 15mg), both, or placebo, over avg. 6.3y f/u, incidence of progression to advanced AMD was sig. lower in combined therapy group than placebo (20% vs. 28%); other comparisons showed no sig. diff. ("AREDS" trial; Arch. Ophth. 119:1417, 2001--JW, Med. Lett.)
  4. Vascular Endothelial Growth Factor antagonists
    1. Pegaptanib (Macugen)
    2. Ranibizumab (Lucentis) (a monoclonal Ab that neutralizes VEGF) injected intravitreally--Better than both placebo (NEJM 355:1419, 2006--JW) and photodynamic therapy  (NEJM 355:1432, 2006--JW) in randomized trials
    3. Bevacizumab (Avastin)
    4. In a study in pts with neovascular age-related macular degeneration randomized to intravitreal bevacizumab vs. ranibizumab, 1y changes in visual acuity were not sig. diff. between the two groups though bevacizumab was associated with sig. more frequent serious systemic adverse events (24% vs. 19%) (NEJM 364:1897, 2011-JW) In a retrospective cohort study in > 30,000 pts > 65yo with COPD initially treated with long-acting beta agonists or tiotropium, all-cause mortality was sig. higher (RR 1.14) among pts initially prescribed tiotropium (Ann. Int. Med. 154:583, 2011-JW)
  5. Experimental tx's as of 2000--Submacular surgery, external-beam radiation therapy, thalidomide, retinal transplantation