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Cholesterol-inhibiting drugs may be linked to cataracts
KIRKSVILLE, Mo.—"There is concern about the potential for cataracts in patients who use drugs that inhibit cholesterol biosynthesis," said Richard J. Cenedella, PhD, professor and chair of the Department of Biochemistry at Kirksville College of Osteopathic Medicine, here.
"Collectively, the ocular safety studies do not show anything alarming," Cenedella said. "But the clinical trials were usually based on 1- to 2-year follow-ups on patients older than 50. I do not want to raise any red flags, but there may be cause for concern with young people who are taking these drugs."
The drugs, lovastatin (Mevacor, Merck), simvastatin (Zocor, Merck) and pravastatin (Pravachol, Bristol-Myers Squibb) lower elevated blood cholesterol by inhibiting an early enzyme of cholesterol biosynthesis. Collectively, they could be the most prescribed drugs in the United States, according to Cenedella.
Lens needs cholesterol
Lens membrane contains the highest cholesterol content of any known membrane. The lens needs to satisfy a sustained requirement for cholesterol by on-site synthesis. Impairing this synthesis can lead to alteration of lens membrane structure. Because the lens continues to grow throughout life and requires cholesterol, caution should be used in younger patients.
"Anyone younger than 40, and certainly anyone younger than 30, should be monitored with slit lamp examinations," Cenedella said. "These drugs can produce cataracts in animals under certain conditions."
Annual slit-lamp examinations were recommended by lovastatin's manufacturer when the drug was originally approved for general use. Early studies showed no acute ocular toxicity.
Cenedella points out, however, that some statins are potent inhibitors of cholesterol biosynthesis, can block cholesterol accumulation in animal lenses and produce cataracts in dogs.
"One early clinical study using simvastatin showed an increase in cataracts in humans," Cenedella said. "At entry, there were 43 cortical opacities out of 94 lenses. Two years later, there were 63 opacities in these 94 cases. That is an approximate 10% increase per year, whereas 1% is normal due to the consequence of aging."
According to Cenedella, evidence indicates that sustained alteration of lens sterol content and composition due to genetic mutations or exposure to drugs can lead to altered lens clarity. There appears to be no clear relationship between lens cholesterol content and human senile cataracts.
Cholesterol research continues
"We are concerned about cataracts in humans and this is why we are continuing to do research into this, to try to understand more about cholesterol biosynthesis in the lens," Cenedella said.
According to Cenedella, it at least appears possible that therapeutic doses could inhibit lens cholesterol biosynthesis in humans. Doctors should be aware of this and use caution, especially in younger patients.
See the January/February 1996 issue of Survey of Ophthalmology for more information.
Commonly used cholestorol-lowering drugs
- Lovastatin (Mevacor, Merck)
- Simvastatin (Zocor, Merck)
- Pravastatin (Pravachol, Bristol-Myers Squibb)