Subretinal drusenoid deposits: Marker for unrecognized cardiac disease

(Image credit: ©H_Ko/AdobeStock)

Subretinal drusenoid deposits (SDDs) may be a newly recognized marker for serious, undiagnosed heart disease, an issue for the underserved populations and for women, according to R. Theodore Smith, MD, PhD, who is from the Icahn School of Medicine at Mount Sinai, Department of Ophthalmology, and the New York Eye and Ear Infirmary of Mount Sinai, both in New York.

He reported this finding at the Association for Research in Vision and Ophthalmology 2025 annual meeting, May 4-8, Salt Lake City.

Ophthalmologists are in a prime position to recognize patients who are at high risk of life-threatening cardiac disease. The key to this recognition is knowing the differences between drusen and subretinal drusenoid deposits (SDDs), which, Smith emphasized, are two distinct diseases within age-related macular degeneration (AMD).

The factors that differentiate drusen and SDDs are location on optical coherence tomography (OCT):below the retinal pigment epithelium for drusen, and above itfor SDDs; genetic risk: mutations in the CFH gene and ARMS2 gene, respectively; and cholesterols: esterified and non-esterified. Conversion to late AMD, both exudative and atrophic,can occur with both lesions, and itdevelops sooner with SDDs.

Importantly, patients with SDDs die sooner than those with drusen, as reported in 2007 by Ron Klein.¹ However, the question of why remained unsolved for 15 years. Then, in 2022,SDDs, but not drusen, were found to be associated strongly (p=0.000000009) with vascular diseases that pose a high risk for death in a study² by Ledesma-Gil and colleagues; Smith was the senior author. The investigators reported that SDDs may be related to downstream inadequate ocular perfusion resulting from the systemic vasculopathies.

The investigators’ hypothesis was that patients with these high risk for death vascular diseases suffer low choroidal blood flow, hypoxic damage to the photoreceptors, and then SDDs; cardiac disease results in low flow to the entire body; and carotid artery disease results in low flow to the ipsilateral eye.

Smith explained that in patients with damaged hearts from heart attack,poor cardiac output causes low systemic flow to the eye and choroid, then SDDs. Severe mitral valve regurgitation, with turbid retrograde blood flow into the left atrium, likewise causes low cardiac output leading to SDDs. Cardiac arrhythmias, e.g., atrial fibrillation and atrial flutter, cause irregular ventricular filling and heart failure.³ The result is poor ocular perfusion downstream and SDDs, as shown in this recent study reported at ARVO 2025.

Mount Sinai Cardiac Ward Arrhythmia Study

Smith described a study conducted at Mount Sinai that included 107 subjects with cardiac disease who were assessed for arrhythmias. The patients had no known retinal disease. The investigators analyzed patient age, sex, blood pressure, presence of diabetes, lipid levels, and findings on electrocardiography. The risk variables studied were cardiac output and cardiac index and the type and severity of arrhythmias. The outcome variable was the presence or absence of SDDs in either eye.

The results showed that among the patients with cardiac disease, SDDs occurred in 48.4% (15 of 31) of patients who had had an arrhythmia over the long term; this was in contrast to 31.3% of patients without arrhythmias (21/67, p =0.01527). In addition, in 21 patients with atrial fibrillation, 11 (52.4%) had SDDs, Smith reported.

The analysis also showed that among the patients with arrhythmias that had resolved as the result of anti-arrhythmic intervention, such as implantation of a pacemaker or ablation, very few (1 of 9 or 11.1%) of patients had SDDs.

“This prevalence is significantly lower than in patients with unresolved long-term arrhythmias (p = 0.04448, two-proportion z-test),” Smith reported. “This shows that restoration of circulation to the eye can be therapeutic for the SDD form of AMD.”

The take-home message is that ophthalmologists should be aware of these findings aboutSDDs, which can be detected on routine OCT retinal imaging.Such patients can then be referred for cardiovascular testing and possibly increaseddiagnosis of undetected heart disease and prevention of adverse cardiovascular events.Patients with high-risk vascular disease should also be referred to an ophthalmologist for vision-saving screening.

“Cardiac diseases compromise blood flow to the eyes downstream. Cardiac arrhythmias, including atrial fibrillation, are associated with SDDs in the retina; they decrease cardiac output, then cause SDDs by inadequate ocular perfusion. SDDs may be a marker for serious, undiagnosed heart disease, an issue for the underserved and women,” Smith concluded.

Smith conducted this study with members of a multidisciplinary team that included Research Fellows, Anisha Kasi, Ryan Yang Fei, and Adriana Kaganovski; Retina specialists Gareth Lema, MD, and Richard Rosen, MD; and Cardiology specialist Vikran Agarwal, MD, all from New York Eye and Ear Infirmary of Mount Sinai.

References

1. Klein R, Meuer SM, Knudtson MD, Iyengar SK, Klein BEK. The epidemiology of retinal reticular drusen. Am J Ophthalmol.2008;145:317-326.e1

2. Ledesma-Gil G, Otero-MarquezO, AlauddinS, etal. Subretinaldrusenoiddeposits are stronglyassociatedwithcoexistent high-risk vascular diseases. BMJ Open Ophthalmol. 2022;7:e001154. doi:10.1136/ bmjophth-2022-001154

3. Xiao YF. Cardiac arrhythmia and heart failure: From bench to bedside. J GeriatrCardiol. 2011;8:131-132.

Theodore Smith, MD, PhD

Email: RTS1MD@gmail.com

Dr. Smith is Professor of Ophthalmology at the Icahn School of Medicine at Mount Sinai, New York. He is a consultant to Roche.