Retinal Findings and Cardiovascular Risk: Prognostic Conditions, Novel Biomarkers, and Emerging Image Analysis Techniques

Abstract

Many retinal diseases and imaging findings have pathophysiologic underpinnings in the function of the cardiovascular system. Myriad retinal conditions, new imaging biomarkers, and novel image analysis techniques have been investigated for their association with future cardiovascular risk or utility in cardiovascular risk prognostication. An intensive literature search was performed to identify relevant articles indexed in PubMed, Scopus, and Google Scholar for a targeted narrative review. This review investigates the literature on specific retinal disease states, such as retinal arterial and venous occlusions and cotton wool spots, that portend significantly increased risk of future cardiovascular events, such as stroke or myocardial infarction, and the implications for personalized patient counseling. Furthermore, conditions diagnosed primarily through retinal bioimaging, such as paracentral acute middle maculopathy and the newly discovered entity known as a retinal ischemic perivascular lesion, may be associated with future incident cardiovascular morbidity and are also discussed. As ever-more-sophisticated imaging biomarkers and analysis techniques are developed, the review concludes with a focused analysis of optical coherence tomography and optical coherence tomography angiography biomarkers under investigation for potential value in prognostication and personalized therapy in cardiovascular disease.

Keywords: cardiovascular risk; myocardial infarction; optical coherence tomography; optical coherence tomography angiography; retinal ischemic perivascular lesions; retinal vascular occlusions; stroke; subretinal drusenoid deposits.

Figure 1

Color fundus photo of a central retinal vein occlusion with optic disc edema (box), venous dilation and tortuosity (arrowheads), intraretinal hemorrhages (one of many, star), and exudates (one group of many, circle).

Figure 2

(A) Fundus photography demonstrating reticular pseudodrusen/subretinal drusenoid deposits in a dot pattern. (B) Fundus autofluoresence imaging with pinpoint hypoautofluorescent lesions with surrounding hyperautofluoresence. (C) Ocular coherence tomography imaging with hyperreflective deposits between the RPE and ellipsoid zone with some lesions puncturing through the ellipsoid zone into the outer retina, consistent with subretinal drusenoid deposits (arrows).

Figure 3

(A) Multicolor image demonstrating multiple wedge-shaped lesions pointed towards the fovea consistent with acute macular neuroretinopathy. (B) Ocular coherence tomography through several lesions demonstrating hyperreflectivity in the outer plexiform layer with ellipsoid zone hyporeflectivity (box).

Figure 4

(A) Ocular coherence tomography demonstrating hyperreflectivity perifoveally in the inner nuclear layer consistent with paracentral acute middle maculopathy. (B) Ocular coherence tomography angiography demonstrating decreased flow signal superior and superotemporal to the fovea in the superficial vascular plexus corresponding to the PAMM lesion in Figure 4A (box). (C) Ocular coherence tomography angiography demonstrating decreased flow signal in the deep capillary plexus corresponding to the PAMM lesion in Figure 4A (oval).

Figure 5

Ocular coherence tomography demonstrating several areas of focal atrophy of the inner nuclear layer (INL) with underlying expansion of the outer nuclear layer consistent with retinal ischemic perivascular lesions (RIPLs) (arrows).

Figure 6

(TOP): Widefield ocular coherence tomography angiography of a patient with type 2 diabetes demonstrating an enlarged foveal avascular zone (box), microaneurysms (one of many, arrow), capillary nonperfusion (one area of many, circle), and venous looping (one of many, inside triangle). (BOTTOM): Normal retinal vasculature as demonstrated on widefield ocular coherence tomography angiography as a comparison.

Figure 6

(TOP): Widefield ocular coherence tomography angiography of a patient with type 2 diabetes demonstrating an enlarged foveal avascular zone (box), microaneurysms (one of many, arrow), capillary nonperfusion (one area of many, circle), and venous looping (one of many, inside triangle). (BOTTOM): Normal retinal vasculature as demonstrated on widefield ocular coherence tomography angiography as a comparison.