Age-Related Macular Degeneration: A Marker of CV Disease?

Fran Lowry

July 22, 2022

People with a specific form of age-related macular degeneration (AMD) are at elevated risk for cardiovascular (CV) disease and stroke, suggests new research. In a prospective study, people with the subretinal drusenoid-deposit phenotype of AMD (SDD-AMD) were almost 10 times as likely also to have one or more high-risk vascular or cardiac diseases than people who had soft-drusen AMD, the other major phenotype.

The findings should encourage enhanced screening of at-risk individuals, which might help identify and improve the management of CV disease in more patients, R. Theodore Smith, MD, PhD, professor of ophthalmology, Icahn School of Medicine at Mount Sinai, New York City, told | Medscape Cardiology.

"Now that we have found this very tight connection between SDD-AMD and cardiovascular disease, we can then use this to screen one set of diseases for the other," he said. "If we see eye disease with these particular deposits, then we know this patient is at high risk to have cardiovascular or neurovascular disease that may not as yet have been detected."

Smith is lead author on the study's partial publication in the July issue of Retina and its extension in more patients reported July 16 at the American Society of Retina Specialists 2022 Annual Meeting, held in New York City.

In soft-drusen AMD, small yellow cholesterol deposits form in a layer under the retina. "The deposits can deprive the retina of blood and oxygen, leading to vision loss. But such drusen formation can be slowed by taking appropriate vitamin supplementation," Smith said.

Subretinal drusenoid deposits, in contrast, are not as well recognized and require specialized retinal imaging for detection, he added. "These deposits are also made of fatty lipids and other materials, but form in a different layer beneath the light sensitive retina cells, where they are also associated with vision loss. Currently, there is no known treatment for SDD-AMD."

The 200 study participants, 121 of whom were women, ranged in age from 51 to 100 years and were recruited from two vitreoretinal referral centers in New York City. They underwent optical coherence tomography, autofluorescence, and near-infrared reflectance imaging for identification of their type of AMD, answered health history and status questionnaires, and had their serum lipids measured.

High-risk CV disease in the study was defined as a severe cardiac valve defect, such as aortic valve stenosis; a "myocardial defect," such as myocardial infarction, cardiomyopathy with heart failure, or a history of coronary artery bypass surgery (CABG); or a history of carotid stroke or transient ischemia attack (TIA) with a severe carotid stenosis.

At least one of the high-risk CV diseases was identified in 41.2% of patients with SDD-AMD, but in only 6.8% in the soft-drusen AMD group, for an odds ratio (OR) of 9.62 (95% CI, 4.04 - 22.9; P = .000000009).


Odds Ratio (OR) for High-risk CV Disease in SDD-AMD vs Soft-Drusen AMD
CV Disease Type SDD-AMD, n = 97 Soft-drusen AMD, n = 103 OR (95% CI) P Value
Valve defects 14 3 5.62 (1.56–20.2) 0.0035
Myocardial defects 16 3 6.58 (1.85–23.4) 0.0011
Stroke or TIA 10 1 11.72 (1.50–93.4) 0.0038

A serum high-density-lipoprotein (HDL) cholesterol level of less than 62 mg/dL predicted the presence of a high-risk vascular disease across the entire AMD cohort, regardless of AMD phenotype (P = .0046). Also, 85% of those who had both SDD-AMD and an HDL level of less than 62 mg/dL also had at least one of the high-risk vascular diseases.

"If ophthalmologists diagnose or treat someone with the specific subretinal drusenoid deposits form of AMD, but who otherwise seems well, that patient may have significant undetected heart disease, or possibly carotid artery stenosis that could result in a stroke," Smith said.

"We foresee that in the future, as an improved standard of care, such patients will be considered for early referral to a cardiologist for evaluation and possibly treatment."

The study was funded by Regeneron Pharmaceuticals. Smith discloses consulting for Ora Technologies and holding equity interest in MacRegen. Disclosures for the other authors are in the report.

Retina. 2022;42;1311-1318. Abstract

American Society of Retina Specialists (ASRS) 2022 Annual Meeting. Presented July 16, 2022.

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