CARDIO MEDS AND AMD

Patients receiving common vasodilator and anti-hypertensive agents could be at increased risk for macular disease, suggests the latest report from the Beaver Dam Eye Study, a long-term survey of age-related eye disease including cataract, macular degeneration and diabetic retinopathy.

The latest findings, reported in the journal Ophthalmology (in press) indicate that use of vasodilator anti-hypertensive medications, including hydralazine (Apresoline) and minoxidil (Loniten) was associated with a 72 per cent increase in the risk for developing early stage age-related macular degeneration (AMD). Oral nitroglycerine was also associated with the development of early AMD.

Some 19 per cent of study participants who were receiving vasodilators during the study developed signs of early AMD compared with only eight per cent of those not receiving vasodilators. The difference was statistically significant after adjusting for age, sex and other potential confounding factors.

Moreover, the study found that patients receiving the much more commonly prescribed oral beta-blocker antihypertensive agents also appeared to be at increased risk. One half of one per cent of patients not receiving oral beta-blockers showed signs of neovascular AMD, compared with 1.2 per cent of those taking beta-blockers. However, no significant association between vasodilators or antihypertensive medications was observed with late AMD, pure geographic atrophy or the progression of AMD.

Further research needed

The researchers cautioned that the current study was not able to discern effects of the medications themselves and the conditions for which participants were taking those medications. In addition the association may be due to uncontrolled confounding, that is not adjusting for factors related to the endpoint AMD and the use of these medications. The relationship may be due to chance.

“As significant as these results may be, it’s important that they be replicated first, and if possible tested in a clinical trials setting before changing anyone’s medication regimens. Further research is needed to determine the cause of these increased risks,” said Ronald Klein MD, MPH, professor of ophthalmology, University of Wisconsin, and lead researcher of the study.

In particular, the researchers note that they do not know the reasons for this association of vasodilators with AMD. Interestingly, they note that in the past, systemic vasodilators were used in the treatment of AMD. At one time it was hypothesised that vasoconstriction of the retinal and choroidal vessels were involved in the pathogenesis of AMD. At the same time, vasodilators were not recommended by some in the treatment of exudative AMD because they were thought to increase the risk of haemorrhage.

The researchers caution that the association between coronary vasodilators with early AMD seen in the study could be the result of bias by indication. This means that it might not be the result of the use of the vasodilator drugs themselves, but rather of the condition for which the drugs were used. However, they note that the association remains even after excluding patients who had had a myocardial infarction, arguing against this.

Widely prescribed treatments

In addition to the treatment of hypertension, vasodilators are often prescribed for the treatment of angina pectoris. More recently they have become a widely prescribed treatment for erectile dysfunction. These conditions are all common in those patients who are considered at risk for macular disease.

Hydralazine is currently not used as a first-line treatment for hypertension. Rather it is reserved for severe, refractory disease, typically in combination with beta-blockers and diuretics. Hydralazine elicits the baroreceptor reflex, which can increase heart rate and cardiac output. This can produce angina pectoris and even myocardial infarction.

Minoxidil is another vasodilator that is reserved for hypertension patients who do not respond to standard treatment with diuretics and other antihypertensive agents. It is probably best known for its effects on hair growth. It is available in topical form for the treatment of baldness.

The new findings are just the latest contribution to the understanding of eye disease and the elderly provided by the Beaver Dam Eye Study. Conducted under the auspices of the US National Eye Institute, the study has produced more than 300 journal publications on the prevalence and incidence of vision loss, cataract and macular disease.

The Beaver Dam Eye Study produced a better understanding of risk factors associated with cataract and macular disease, particularly cigarette smoking. The study also showed the association of retinal drusen and retinal pigment and progression to late stages of AMD. This in turn has helped researchers to design clinical trials in this area.

Another recent publication from the Beaver Dam Study Group, also in the journal Ophthalmology, reviewed the effects of lifestyle on vision and visual impairment over the 20-year study period. Cigarette smoking was confirmed as a significant risk factor for vision impairment. People who did consume alcoholic beverages appeared to be at increased risk for visual impairment compared with moderate drinkers. People who were sedentary appeared to be at higher risk for vision impairment compared to those with more active lifestyles.

Ronald Klein: kleinr@epi.ophth.wisc.edu