Author Response: Hyperreflective Intraretinal Foci as an OCT Biomarker of Retinal Inflammation in Diabetic Macular Edema

Lee, Hyungwoo; Chung, Hyewon

doi:10.1167/iovs.18-25825

Cited by 4 publications

(5 citation statements)

References 3 publications

(2 reference statements)

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“…e distinction between inflammatory HRF and other subtypes of hyperreflective material (i.e., retinal exudates, hemorrhages, and microaneurysms) on OCT B-scans include location within the inner retina, size ≤30 μm, absence of posterior shadowing, and reflectivity similar to the retinal nerve fiber layer (Figure 1) [15,32,33]. Indeed, in a recent international consensus, these morphological characteristics were incorporated as the diagnostic criteria for HRF [17].…”

Section: Origin and Morphometry Of Hyperreflective Focimentioning

confidence: 99%

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

Fragiotta

Abdolrahimzadeh

Dolz-Marco

et al. 2021

Journal of Ophthalmology

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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.

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Section: Origin and Morphometry Of Hyperreflective Focimentioning

confidence: 99%

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

Fragiotta

Abdolrahimzadeh

Dolz-Marco

et al. 2021

Journal of Ophthalmology

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“…The origin of HRF has drawn the interests of numerous teams around the world. Some studies [ 12 , 17 , 18 ] supported that HRF in DME are precursors of hard exudates, representing the exudation of macromolecular substances such as proteins and lipids after BRB destruction; other groups [ 13 , 19 , 21 , 35 ] believed the hyperreflective dots represent an inflammatory response, which originated from microglial cells or white blood cells infiltration. In the current findings, the number of HRF is the lowest in UME, while the associated with hard exudates further supports the hypothesis that HRF are precursors of hard exudates, rather than the product of inflammatory activation.…”

Section: Discussionmentioning

confidence: 99%

“…Noticeably, in studies with positive associations between HRF and inflammatory conditions, the hyperreflective dots observed on SD-OCT images were smaller in size and lower in reflective strength [ 21 ]. The signal intensity of the HRF is reported to be lower than that of the RPE layer and closer to the retinal nerve fiber layer (RNFL) [ 13 , 19 , 35 ]. Vujosevic et al [ 30 ] reported that in DME SD-OCT images, HRF with a larger diameter and signal intensity similar to that of the RPE may be a precursor of hard exudates, while HRF with a smaller diameter and signal intensity similar to that of the RNFL may represent microglia.…”

Section: Discussionmentioning

confidence: 99%

“…In the current study, the signal intensity of HRF was defined as the same as RPE layer, and the minimum diameter of HRF was set to 10 μm to avoid miss counting smaller HRFs. Even though the counting of HRF were done carefully, certain bias is still inevitable as mentioned in other reports [14,19,24,[35][36][37], for example, the selected section of analysis was limited to the central horizontal SD-OCT B-scan. In the future, automatic analysis of SD-OCT microstructural features by new computer algorithms may be an effective method to solve such problems.…”

Section: Discussionmentioning

confidence: 99%

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Comparison of hyperreflective foci in macular edema secondary to multiple etiologies with spectral-domain optical coherence tomography: An observational study

et al. 2022

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Background Hyperreflective foci (HRF) features in macular edema associated with different etiologies may indicate the disease pathogenesis and help to choose proper treatment. The goal of this study is to investigate the retinal microstructural features of macular edema (ME) secondary to multiple etiologies with spectral-domain optical coherence tomography (SD-OCT) and analyze the origin of HRF in ME. Methods This was a retrospective study. SD-OCT images were reviewed to investigate macular microstructural features such as the number and distribution of HRF and hard exudates and the internal reflectivity of the cysts. The differences in microstructural features between groups and the correlations between the number of HRF and other parameters were analyzed. Results A total of 101 eyes with ME from 86 diabetic (diabetic macular edema, DME) patients, 51 eyes from 51 patients with ME secondary to branch retinal vein occlusion (branch retinal vein occlusion-macular edema, BRVO-ME), 59 eyes from 58 central retinal vein occlusion (central retinal vein occlusion-macular edema, CRVO-ME) patients, and 26 eyes from 22 uveitis (uveitic macular edema, UME) patients were included in this study. The number of HRF, the frequency of hard exudates and the enhanced internal reflectivity of the cysts were significantly different among the groups. The number of HRF in the DME group was significantly higher than that in the other groups (all P < 0.05). The frequency of hard exudates and enhanced internal reflectivity of the cysts in the DME group were significantly higher than ME secondary to other etiologies (all P < 0.001). Within the DME group, the number of HRF in the patients with hard exudates was significantly higher than that in the patients without hard exudates (P < 0.001). Conclusion HRF detected with SD-OCT were more frequent in DME patients than in BRVO-ME, CRVO-ME, or UME patients. The occurrence of HRF was correlated with the frequency of hard exudates. HRF may result from the deposition of macromolecular exudates in the retina, which is speculated to be a precursor of hard exudates.

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“…Hyperreflective foci were manually annotated according to the following fundamental features: (i) location within the outer retina; (ii) size ≤30 μm; (iii) absence of a shadow cast by the hyperreflective foci and (iv) reflectivity similar to the retinal nerve fibre layer (RNFL). In the latest international consensus guidelines, these morphological characteristics were incorporated as the diagnostic criteria for hyperreflective foci (Kodjikian et al, 2019; Lee & Chung, 2018; Midena et al, 2018). In total, 391 hyperreflective foci were manually annotated among the 189 B scans originating from nine eyes of seven patients.…”

Section: Methodsmentioning

confidence: 99%

Automated detection of hyperreflective foci in the outer nuclear layer of the retina

Schmidt

Christensen

Dahl

et al. 2022

Acta Ophthalmologica

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Hyperreflective foci are poorly understood transient elements seen on optical coherence tomography (OCT) of the retina in both healthy and diseased eyes. Systematic studies may benefit from the development of automated tools that can map and track such foci. The outer nuclear layer (ONL) of the retina is an attractive layer in which to study hyperreflective foci as it has no fixed hyperreflective elements in healthy eyes. In this study, we intended to evaluate whether automated image analysis can identify, quantify and visualize hyperreflective foci in the ONL of the retina.Methods: This longitudinal exploratory study investigated 14 eyes of seven patients including six patients with optic neuropathy and one with mild non-proliferative diabetic retinopathy. In total, 2596 OCT B-scan were obtained. An image analysis blob detector algorithm was used to detect candidate foci, and a convolutional neural network (CNN) trained on a manually labelled subset of data was then used to select those candidate foci in the ONL that fitted the characteristics of the reference foci best. Results:In the manually labelled data set, the blob detector found 2548 candidate foci, correctly detecting 350 (89%) out of 391 manually labelled reference foci. The accuracy of CNN classifier was assessed by manually splitting the 2548 candidate foci into a training and validation set. On the validation set, the classifier obtained an accuracy of 96.3%, a sensitivity of 88.4% and a specificity of 97.5% (AUC 0.989). Conclusion:This study demonstrated that automated image analysis and machine learning methods can be used to successfully identify, quantify and visualize hyperreflective foci in the ONL of the retina on OCT scans.

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Author Response: Hyperreflective Intraretinal Foci as an OCT Biomarker of Retinal Inflammation in Diabetic Macular Edema

Cited by 4 publications

References 3 publications

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

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

Comparison of hyperreflective foci in macular edema secondary to multiple etiologies with spectral-domain optical coherence tomography: An observational study

Automated detection of hyperreflective foci in the outer nuclear layer of the retina

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