Deteriorating Vision in an 82-Year-Old Woman

RONALD N. RUBIN, MD—Series Editor

Dr Rubin is professor of medicine at Temple University School of Medicine and chief of clinical hematology in the department of medicine at Temple University Hospital in Philadelphia.

What’s The “Take Home”?
Pearls From Clinical Cases


An 82-year-old woman reports vision changes in her right eye that have developed gradually over the past several months. She needs significantly brighter light when sewing, reading, and doing other close work. She has also experienced “gaps” in visual images—blank spaces and blind spots in the center of things she looks at; at times she has difficulty in recognizing faces. Her left eye seems unaffected. She fears that she has had a stroke, although she has no speech difficulty, extremity weakness, abnormal sensory sensations (such as numbness or tingling), or any other neurological symptoms.

Her health is good for her age. She has not required hospitalization since a cholecystectomy 12 years earlier. She has mild essential hypertension that is well controlled with a low-dose angiotensin-converting enzyme inhibitor. She also takes a multivitamin supplement daily.

Several random blood glucose levels greater than 120 mg/dL have been documented; however, her hemoglobin A1c level has always been normal, and no treatment other than reduced intake of sweets has been needed. She has no history of congestive heart failure, chronic obstructive pulmonary disease, or cancer, and a review of systems reveals no evidence of these entities.

Heart rate is 80 beats per minute and regular; blood pressure is 115/76 mm Hg. Head, ears, eyes, nose, and throat are normal; no neck bruits are noted. Chest is clear. A soft grade 1/6 ejection murmur is audible along the left sternal border. There is no organomegaly and no abdominal masses. A careful neurological examination reveals cranial nerves II through XII to be grossly intact. The patient has good and equal strength in all 4 extremities. Sensation and cerebellar function are intact, and all reflexes are normal.

A routine hemogram is normal. Results of a chemistry profile are also normal, with a random blood glucose level of 115 mg/dL; the erythrocyte sedimentation rate (ESR) is within normal limits (21 mm/hr). A complete examination by an ophthalmologist has been scheduled for later in the day; a CT scan of the brain has also been scheduled.

Which of the following statements about the cause of this patient’s vision changes is true?

A. She will likely be legally blind in 3 to 6 months.
B. Initial therapy should consist of a course of high-dose corticosteroids.
C. In the developed world, only diabetes mellitus causes more blindness in persons older than 50 years.
D. Therapeutic alternatives include monoclonal antibodies directed against vascular endothelial growth factor (VEGF).

(Answer and discussion on next page.)

What’s The “Take Home”?


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.