Link between neovascular eye disease and cardiovascular disease followed by retinal damage

NEW YORK CITY – Subretinal drusenoid deposits (SDD) had a significant association with underlying cardiovascular disease (CVD), adding a missing link between age-related macular degeneration (AMD) and CVD, showed a prospective study.

Among 47 patients with CVD and AMD, 40 (85%) had SDD with or without subretinal drusen. An AI-assisted analysis showed that the combination of SDD and HDL cholesterol ARM2 and underlying CVD predicted the presence of SDD with 94% specificity, reported R. Theodore Smith, MD, PhD, of Mount Sinai Health System in New York.

The data makes a compelling case for evaluating patients with SDD for undiagnosed high-risk cardiovascular disease, he said in a presentation at the meeting of the American Society of Retina Specialists. The results were published simultaneously in Retina.

“In clinical practice, once all of this has been formulated and codified, it’s possible that we could have these fairly inexpensive retinal cameras via[out] the medical world so that patients can be screened by them as part of their routine medical care,” Smith said. MedPage today. “Then they can be told immediately whether or not they have these high-risk features. This means they should have further examination – say an echocardiogram, carotid Doppler – and then be taken to the next level. Find out what may hide.”

Large soft drusen and SDD contribute to the development of neovascular AMD and macular atrophy. However, the lesions differ in their systemic associations, locations, genetics, cholesterol content and prognosis, Smith said. More than a decade ago, research showed an association between SDD and premature mortality, but the precise nature of the relationship remained unclear.

The researchers hypothesized that high-risk cardiovascular diseases – including myocardial infarction (MI), valvular disease and internal carotid artery (ICA) stenosis – are strongly associated with SDD but not with drusen. They further hypothesized that high-risk cardiovascular disease leads to poor choroidal perfusion.

To investigate the hypothesis, Smith and colleagues prospectively identified 97 patients with SDD, with or without drusen, and 103 with drusen only. Data collected included lipid profile and selected genetic evaluation, as well as demographics and medical history.

The 200 patients included 47 people with high-risk cardiovascular disease. The comparison with the SDD status showed the following distribution:

  • MI: 19 (16 with SDD)
  • Valve disease: 17 (14)
  • ICA: 11 (10)

The results translated into an odds ratio for high-risk cardiovascular disease of 9.0 for the association with TDS (95% CI 4.0-22.9, P=0.9-8). Multivariate analysis identified HDL P=0.0002) and ARM2 homozygosity as a predictor of SDD (P=0.01).

Smith showed selected images that reflected the results. An elderly man with myocardial failure had high myopia and confluent DDS without any signs of drusen. A patient with severe aortic stenosis and farsightedness had no atherosclerosis but confluence of SDD and no drusen.

A third example represented what Smith called an “experiment in nature.” The patient’s left internal carotid had a 40% stenosis but a clear right internal carotid. The left eye had “bundles of confluent subretinal deposits” while the right eye had none. Cortical thickness was high on the left and normal on the right.

“If anyone has another explanation other than the infusion, let me know,” Smith said.

The findings are interesting and come from a group of researchers who have been studying the association between SDD and CVD for some time, said Raj Maturi, MD, of the Midwest Retina Institute in Indianapolis. MedPage today by email. The findings involved a fairly modest number of patients and require validation in a larger cohort, noted Maturi, who was not involved in the study.

Maturi asked Smith about the small study population, given the group’s large patient base and long history of investigation. Smith said the size of the study population was limited by the financial resources available to conduct the study.

“We had a few fellows who were doing their best to get patients, and if you want to recruit a patient, it takes a few hours to jump through all the hoops,” Smith said. “We talk a lot about real-world experience; well, that’s real life.”

  • Charles Bankhead is editor for oncology and also covers urology, dermatology and ophthalmology. He joined MedPage Today in 2007. Follow


The study was supported in part by Regeneron.

Smith revealed relationships with MacRegen and Ora.

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