Significance of Hyperreflective Foci as an Optical Coherence Tomography Biomarker in Retinal Diseases: Characterization and Clinical Implications

Abstract

Hyperreflective foci (HRF) is a term coined to depict hyperreflective dots or roundish lesions within retinal layers visualized through optical coherence tomography (OCT). Histopathological correlates of HRF are not univocal, spacing from migrating retinal pigment epithelium cells, lipid-laden macrophages, microglial cells, and extravasated proteinaceous or lipid material. Despite this, HRF can be considered OCT biomarkers for disease progression, treatment response, and prognosis in several retinal diseases, including diabetic macular edema, age-related macular degeneration (AMD), retinal vascular occlusions, and inherited retinal dystrophies. The structural features and topographic location of HRF guide the interpretation of their significance in different pathological conditions. The presence of HRF less than 30 μm with reflectivity comparable to the retinal nerve fiber layer in the absence of posterior shadowing in diabetic macular edema indicates an inflammatory phenotype with a better response to steroidal treatment. In AMD, HRF overlying drusen are associated with the development of macular neovascularization, while parafoveal drusen and HRF predispose to macular atrophy. Thus, HRF can be considered a key biomarker in several common retinal diseases. Their recognition and critical interpretation via multimodal imaging are vital to support clinical strategies and management.

OCT-Based Biomarkers are Associated with Systemic Inflammation in Patients with Treatment-Naïve Diabetic Macular Edema

“…As a major OCT feature discussed in the current paper, retinal HRF can be seen in multiple retinal diseases, and serves as a promising but controversial OCT biomarker in DME treatment Theories have been expounded upon the pathophysiology of HRF, including lipoprotein extravasation [18], inflammationinduced microglial cell activation [19], migrating retinal pigment epithelium (RPE) cells [58], and degenerated photoreceptor cells [59], etc. It is accepted that HRF is related to retinal inflammation in DME [57], and HRF is a potential biomarker for DME treatment management. Compared to anti-VEGF, corticosteroid treatment caused more HRF reduction in DME eyes [60].…”

The Presence of Hyperreflective Foci Reflects Vascular, Morphologic and Metabolic Alterations in Retinitis Pigmentosa

“…There are several hypotheses explaining the origin of HRF in general. Some studies suppose that the HRF represents an inflammatory component like microglia or migrated RPE and/or the extravasation of lipoproteins following the breakdown of the blood-retinal barrier [ 53 , 54 ]. It has been shown that HRF foci are also a predictive marker of the final visual outcome in diseases like retinal vein occlusion [ 50 ], diabetic retinopathy [ 46 ], polypoidal choroidal vasculopathy [ 55 ], neovascular age-related macular degeneration [ 55 ], but also in degenerative diseases like RP [ 38 , 39 , 40 , 41 ].…”

Characteristics of intermediate age-related macular degeneration with hyperreflective foci

“…Hyperreflective foci (HRF) are visualized at any retinal layer through spectral-domain/swept-source optical coherence tomography (SD/SS-OCT) in several retinal diseases and are defined as well-demarcated lesions with equal reflectivity to the RPE bands. They are sometimes detected as hyperpigmentation on color fundus photography 2 . They are believed to migrate toward the vitreous side of the retina from the RPE in eyes with early/intermediate AMD.…”