Deteriorating Vision in an 82-Year-Old Woman
What’s The “Take Home”?
CORRECT ANSWER: D
The findings presented here are almost certainly the result of age-related macular degeneration, a potentially blinding disease that affects—to at least some degree—as many as 1 in 3 persons older than 75 years.1 This insidious disease develops gradually and painlessly. However, macular degeneration is the leading cause of blindness in people older than 50 years.2 Thus, choice C is false.
Dry versus wet macular degeneration. There are 2 clinical variants of age-related macular degeneration. The wet form is the more rapidly progressive of the 2 and causes visual distortions, such as straight lines appearing wavy (metamorphopsia). Wet macular degeneration develops in the second eye in 15% of affected patients per year; if left untreated, it can cause legal blindness within months.3 Dry macular degeneration, on the other hand, takes years to complete its progression, and its typical presenting symptoms are gaps in image and increasing need for illumination.
The definitive diagnosis of macular degeneration requires the demonstration of abnormalities in the macula (eg, a sharply demarcated round or oval hypopigmented juxtafoveal spot and the presence of drusen crystals/dots).3 Other macular abnormalities (eg, geographical atrophy in the dry form, and neovascularization in the wet form) serve to differentiate the 2 variants.4 However, this patient’s clinical presentation clearly seems consistent with dry macular degeneration. Thus, choice A (blindness within months) is false.
Risk factors. The epidemiology of macular degeneration is somewhat ill defined, and both genetic and environmental factors appear to be important in its development. Risk is increased in first-degree relatives (odds ratio, 2.4 to 4.2).3 However, similar risk ratios have also been demonstrated for smokers and for persons with a history of lifelong exposure to bright light. These clinical observations have been buttressed by a variety of in vitro and animal studies that have demonstrated toxic effects of components of smoke and effects of light on the choroid retina.3
Treatment. Therapy for macular degeneration has until now been suboptimal. Classic photocoagulation with laser therapy was found to be little or no better than no treatment. Use of lower-intensity lasers with photosensitizing agents (to prevent collateral damage to the overlying
retina) has efficacy and can slow progression of vision loss but does not seem to improve visual acuity.2
Therefore, attempts were made to suppress the cytokine-induced increase in vascular permeability and angiogenesis in the retina through treatment with recombinant humanized monoclonal antibody to vascular endothelial growth factor (anti-VEGF).2,5 Several large clinical trials demonstrated the efficacy of this therapy—specifically, it prevented vision loss and improved visual acuity at 2 years with low incidence of serious adverse effects.2,5,6 A brace of editorials accompanying publication of the trial results underscored their breakthrough nature.7
The anti-VEGF agents ranibizumab and bevacizumab have both demonstrated clinical efficacy for the treatment of age-related macular degeneration.8 Efficacy in this dreaded blindness-inducing disease has been nothing short of outstanding, with the achievement of acuity improvements of 8 to 8.5 letters (equal to 3 lines on an eye chart) in a significant majority of patients. A recent trial compared these two agents with each other and also compared the usual fixed schedule of monthly intraocular injections with an “as needed” schedule. “As needed” was determined by ophthalmologic techniques measuring neovascularization, fluid or hemorrhage under the fovea, dye leakage, or increased lesion size compared with previous evaluation on a monthly basis.8
This trial demonstrated essential equivalence between the two drugs and between the schedules; the results have the potential to markedly lower therapy cost as a result of fewer injections and the significantly lower price of bevacizumab. The author will let the drug company, FDA, and insurance companies wrestle with that issue. What is categorically true and exciting is that there exist a variety of drug and schedule options to effectively treat age-related macular degeneration. Thus, choice D is true.
Choice B, corticosteroid therapy, refers to the treatment of another geriatric disease that threatens sight, temporal arteritis. This patient does not manifest any other features of this disorder (proximal shoulder or hip pain and weakness, headache, etc), and her ESR (a key finding in polymyalgia rheumatica) is normal, which makes this diagnosis highly unlikely. Thus, choice B is not the best answer here.
Outcome of this case. An ophthalmological examination confirmed retinal changes diagnostic of macular degeneration. The patient currently is receiving an anti-VEGF agent on a monthly regimen with significant improvement in visual acuity. ■
1. Stone EM. A very effective treatment for neovascular macular degeneration. N Engl J Med. 2006;355:1493-1495.
2. Bressler NM. Age-related macular degeneration is the leading cause of blindness. JAMA. 2004;291:1900-1901.
3. de Jong PT. Age-related macular degeneration. N Engl J Med. 2006;355:1474-1485.
4. Jager RD, Mieler WF, Miller JW. Age-related macular degeneration. N Engl J Med.2008;358:2606-2617.
5. Rosenfeld PJ, Brown DM, Heier JS, et al. Ranibizumab for neovascular agerelated macular degeneration. N Engl J Med. 2006;355:1419-1431.
6. Brown DM, Kaiser PK, Michels M, et al. Ranibizumab versus verteporfin for neovascular age-related macular degeneration. N Engl J Med. 2006;355:1432-1444.
7. Steinbrook R. The price of sight—ranibizumab, bevacizumab, and the treatment of macular degeneration. N Engl J Med. 2006;355:1409-1412.
8. CATT Research Group. Ranibizumab and bevacizumab for neovascular age-related macular degeneration. N Engl J Med. 2011;364:1897-1908.