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Background/Objectives: Retinal hyperreflective foci, 25–50 µm in diameter, that can be imaged by noninvasive optical coherence tomography (OCT) may represent microglial activity related to inflammation. This study aimed to detect hyperreflective foci in the OCT-hyporeflective avascular outer nuclear layer of the retina in relapsing–remitting MS (RRMS) patients without ongoing eye or optic nerve disease. Methods: A cohort of 13 RRMS patients (8 eyes with and 18 eyes without prior optic neuritis) underwent retinal OCT at baseline, after 1 month, after 6 months, and then every 6 months for 3 years. The data were compared with single-examination data from 106 eyes in 53 age-matched healthy subjects. Results: The prevalence of hyperreflective foci at baseline was higher in RRMS patients than in healthy subjects (46.2% vs. 1.8%, p < 0.005). Patients with optic neuritis had much more foci than those without (p < 0.001). Hyperreflective foci recurred in 23.1% of RRMS patients, bilaterally in one with prior optic neuritis and unilaterally in two without. Conclusions: Patients with RRMS, notably those with prior optic neuritis, had elevated rates of retinal infiltration in the absence of retinal disease, suggesting that the phenomenon may represent elevated activity of an immune surveillance or housekeeping mechanism rather than retinal disease. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the prognostic impact of hyperreflective foci (HRF) on spectral-domain optical coherence tomography (SD-OCT) in nonsyndromic retinitis pigmentosa (RP). Methods: Retrospective, single-center cohort study including genetically-tested RP patients with a minimum follow-up of 24 months. Clinical data including demographics, genetic results and best-corrected visual acuity (BCVA) at baseline and follow-up were collected. Horizontal and vertical SD-OCT scans were analyzed by 2 independent graders. Outer nuclear layer (ONL) thickness and ellipsoid zone (EZ) width were manually measured in horizontal and vertical scans. HRF were classified according to location: outer retinal layers within the central 3mm (central-HRF), outer retinal layers beyond the central 3mm (perifoveal-HRF), and choroid (choroidal-HRF). Central macular thickness (CMT), central point thickness (CPT) and choroidal thickness (CT) at baseline and follow-up were also recorded. Results: A total of 175 eyes from 94 RP patients (47.9% female, mean age 50.7±15.5 years) were included, with a mean follow-up of 29.24±7.17 months. Mean ETDRS (early treatment diabetic retinopathy study) BCVA decreased from 61.09±23.54 to 56.09±26.65 (p=0.082). At baseline, 72 eyes (41.1%) showed central-HRF, 110 eyes (62.9%) had perifoveal-HRF and 149 eyes (85.1%) exhibited choroidal-HRF. Central-HRF and perifoveal-HRF were associated with worse final BCVA, as well as greater BCVA deterioration (all p<0.0029). Only central-HRF were associated with a worse final CMT (p<0.001). Shorter EZ widths were associated with all types of HRF (p<0.05). Perifoveal and choroidal-HRF predicted smaller final EZ areas (p<0.01). Conclusion: HRF are highly prevalent in RP patients and appear to have a negative prognostic impact in visual function and EZ area. [ABSTRACT FROM AUTHOR]

Hyperreflective foci (HRF) are biomarkers in detection of diabetic retinopathy (DR). Presence of HRF on spectral domain optical coherence tomography (SD-OCT) can give a correlation with visual acuity change and grades of DR. Purpose of this study is to determine the presence, location, and role of HRF in the retina of DM patients with and without retinopathy. A total of 192 eyes of patients suffering from type II DM were evaluated. Patients were divided into 2 groups, with Group A having diabetes without retinopathy (20 patients) and group B (76 patients) having diabetes and various grades of retinopathy. SD-OCT was performed in all patients, passing through the center of fovea. On OCT, presence and absence of HRF were noted. Characteristics of the hyper-reflective spots were evaluated: location, shape, size, back shadowing and association with central macular thickness (CMT), visual acuity, and grades of retinopathy. HRF were present in 169 eyes (88%) out of 192 eyes. The shape and location of HRF tend to change with disease progression. HRF were significantly associated with increasing grades of retinopathy (χ2 = 57.586, p < 0.01) Association of macular edema was significant with both retinopathy (χ2 = 8.895, p < 0.05) and HRF (χ2 = 34.720, p < 0.01). Association of best-corrected visual acuity with HRF (χ2 = 21.232, p < 0.01), macular edema (χ2 = 86.960, p < 0.01), and CMT (χ2 = 47.959, p< 0.01) was significant. HRF is a great indicator for early diagnosis of subclinical retinopathy and can be used to monitor the progression of disease and development of macular edema. Significant difference is present in HRF distribution and morphology. [ABSTRACT FROM AUTHOR]

Copyright of Die Ophthalmologie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Die Ophthalmologie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Purpose: to identify the intraretinal hyperreflective foci (HRF), their specific characteristics, localization features and correlations with the duration of the disease, type of course and previous episodes of optic neuritis (ON) in multiple sclerosis (MS) patients using a high-resolution OCT scanning protocol. Materials and methods. The study included 160 patients (318 eyes) divided into 8 groups, i.e. Group 1: 44 eyes (13.84 %) — MS onset without a history of ON; Group 2: 30 eyes (9.43 %) — debut of MS with ON; Group 3: 56 eyes (17.61 %) — relapsing-remitting MS (RRMS) lasting ≤ 10 years without ON; Group 4: 38 eyes (11.95 %) — RRMS lasting ≤ 10 years with ON; Group 5: 49 eyes (15.41 %) — RRMS lasting ˃ 10 years without ON; Group 6: 37 eyes (11.63 %) — RRMS lasting ˃ 10 years with ON; Group 7: 34 eyes (10.69 %) — secondary progressive MS (SPMS) without ON; Group 8: 30 eyes (9.43 %) — SPMS with ON. Results. HRF were identified in all groups, at the levels of both the outer nuclear layer (ONL) and the inner nuclear layer (INL). Their number increased depending on the duration, type of course, and the presence of ON history. The thickness of the inner layers of the retina corresponded to the average normative indicators in the group with the onset of MS without ON. In the SPMS group after ON, a decrease in the total thickness of ganglions retinal cells layer (GCL) and the inner plexiform layer (IPL) was noted, showing minimal values of both avGCL + IPL (65.83 ± 8.27 μm) and avRNFL (76.37 ± 6.94 μm). High inverse correlations were revealed between avGCL + IPL and the amount of GRF at the levels of ONL and INL (-0.82 and -0.85, respectively, p = 0.01). Conclusions. The presence and quantity of HRF can be considered as a prognostic non-invasive biomarker associated with the duration of MS and the history of ON, allowing one to visualize the penetration of microglia activated by immune cells into the unmyelinated part of the central nervous system, helpful in elucidating their role in the pathogenesis and progression of the disease.

With the advancement of retinal imaging, hyperreflective foci (HRF) on optical coherence tomography (OCT) images have gained significant attention as potential biological biomarkers for retinal neuroinflammation. However, these biomarkers, represented by HRF, present pose challenges in terms of localization, quantification, and require substantial time and resources. In recent years, the progress and utilization of artificial intelligence (AI) have provided powerful tools for the analysis of biological markers. AI technology enables use machine learning (ML), deep learning (DL) and other technologies to precise characterization of changes in biological biomarkers during disease progression and facilitates quantitative assessments. Based on ophthalmic images, AI has significant implications for early screening, diagnostic grading, treatment efficacy evaluation, treatment recommendations, and prognosis development in common ophthalmic diseases. Moreover, it will help reduce the reliance of the healthcare system on human labor, which has the potential to simplify and expedite clinical trials, enhance the reliability and professionalism of disease management, and improve the prediction of adverse events. This article offers a comprehensive review of the application of AI in combination with HRF on OCT images in ophthalmic diseases including age-related macular degeneration (AMD), diabetic macular edema (DME), retinal vein occlusion (RVO) and other retinal diseases and presents prospects for their utilization.

Abstract Background We aimed to investigate the anatomical features of optical coherence tomography (OCT) and vitreous cytokine levels as predictors of outcomes of combined phacovitrectomy with intravitreal dexamethasone (DEX) implants for idiopathic epiretinal membrane (iERM) treatment. Methods A prospective, single-masked, randomized, controlled clinical trial included 48 eyes. They were randomly assigned in a 1:1 ratio to undergo the DEX group (combined phacovitrectomy with ERM peeling and Ozurdex implantation) and control group (phacovitrectomy only). Best-corrected visual acuity (BCVA) and central macular thickness (CMT) were assessed at 1 d, 1 week, 1 month, and 3 months. The structural features of OCT before surgery were analysed for stratified analysis. Baseline soluble CD14 (sCD14) and sCD163 levels in the vitreous fluid were measured using ELISA. Results BCVA and CMT were not significantly different in the DEX and control groups. Eyes with hyperreflective foci (HRF) at baseline achieved better BCVA (P time*group=0.746; P group=0.043, Wald χ²=7.869) and lower CMT (Ptime*group = 0.079; Pgroup = 0.001, Wald χ²=6.774) responses to DEX during follow-up. In all patients, the mean vitreous level of sCD163 in eyes with HRF was significantly higher than that in eyes without HRF (P = 0.036, Z=-2.093) at baseline. In the DEX group, higher sCD163 predicted greater reduction in CMT from baseline to 1 month (r = 0.470, P = 0.049). Conclusions We found that intraoperative DEX implantation did not have beneficial effects on BCVA and CMT over a 3-month period in all patients with iERM, implying that the use of DEX for all iERM is not recommended. In contrast, for those with HRF on OCT responded better to DEX implants at the 3-month follow-up and thier vitreous fluid expressed higher levels of sCD163 at baseline. These data support the hypothesis that DEX implants may be particularly effective in treating cases where ERM is secondary to inflammation. Trial registration The trail has been registered at Chinese Clinical Trail Registry( https://www.chictr.org.cn ) on 2021/03/12 (ChiCTR2100044228). And all patients in the article were enrolled after registration.

AIM: To analyze the relationship between optical coherence tomography (OCT) and OCT angiography (OCTA) imaging in patients with diabetic macular edema (DME) who are treated with a combination of aflibercept and triamcinolone acetonide (TA). METHODS: A total of 76 eyes newly diagnosed DME were included in this study. They were randomly assigned to receive either aflibercept or a combination of aflibercept and TA. Injections once a month for a total of three injections. Central macular thickness (CMT), number of hyperreflective foci (HRF), height of subretinal fluid (SRF), and area of foveal avascular zone (FAZ) were evaluated using OCT and OCTA at baseline and after each monthly treatment. RESULTS: Both groups showed improvement in best corrected visual acuity (BCVA) and reduction in macular edema after treatment, and the difference in BCVA between the two groups was statistically significant after each treatment (P

Background: We aimed to investigate the anatomical features of optical coherence tomography (OCT) and vitreous cytokine levels as predictors of outcomes of combined phacovitrectomy with intravitreal dexamethasone (DEX) implants for idiopathic epiretinal membrane (iERM) treatment. Methods: A prospective, single-masked, randomized, controlled clinical trial included 48 eyes. They were randomly assigned in a 1:1 ratio to undergo the DEX group (combined phacovitrectomy with ERM peeling and Ozurdex implantation) and control group (phacovitrectomy only). Best-corrected visual acuity (BCVA) and central macular thickness (CMT) were assessed at 1 d, 1 week, 1 month, and 3 months. The structural features of OCT before surgery were analysed for stratified analysis. Baseline soluble CD14 (sCD14) and sCD163 levels in the vitreous fluid were measured using ELISA. Results: BCVA and CMT were not significantly different in the DEX and control groups. Eyes with hyperreflective foci (HRF) at baseline achieved better BCVA (Ptime*group=0.746; Pgroup=0.043, Wald χ²=7.869) and lower CMT (Ptime*group = 0.079; Pgroup = 0.001, Wald χ²=6.774) responses to DEX during follow-up. In all patients, the mean vitreous level of sCD163 in eyes with HRF was significantly higher than that in eyes without HRF (P = 0.036, Z=-2.093) at baseline. In the DEX group, higher sCD163 predicted greater reduction in CMT from baseline to 1 month (r = 0.470, P = 0.049). Conclusions: We found that intraoperative DEX implantation did not have beneficial effects on BCVA and CMT over a 3-month period in all patients with iERM, implying that the use of DEX for all iERM is not recommended. In contrast, for those with HRF on OCT responded better to DEX implants at the 3-month follow-up and thier vitreous fluid expressed higher levels of sCD163 at baseline. These data support the hypothesis that DEX implants may be particularly effective in treating cases where ERM is secondary to inflammation. Trial registration: The trail has been registered at Chinese Clinical Trail Registry(https://www.chictr.org.cn) on 2021/03/12 (ChiCTR2100044228). And all patients in the article were enrolled after registration. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the safety and efficacy of the fluocinolone acetonide implant (FAi, Iluvien® Horus pharma, Nice, France) in non-infectious uveitic macular edema (UME) and to approach the predictive factors of treatment response. Methods: This retrospective, multicenter real-life study included patients with chronic non-infectious UME who received intravitreal FAi after at least two dexamethasone implants (DEXi). Results: Twenty-six eyes from 22 patients (73.1% of females) were included. The mean age was 60.4 ± 16 years. The mean follow-up was 11.4 ± 2 months. The mean baseline best-corrected visual acuity (BCVA) was 0.43 ± 0.36 LogMAR, improving significantly after 1, 3, 6 and 12 months (all p < 0.05 vs. baseline). The mean baseline central macular thickness (CMT) was 429 ± 110 μm, improving significantly after 1, 3, 6 and 12 months (all p < 0.05 vs. baseline). Five eyes (19.2%) developed ocular hypertension during the follow-up, requiring initiation or strengthening of intraocular pressure lowering medication. The majority of eyes (77%) did not require any rescue DEXi during the available 12-month follow-up. The resolution of UME after DEXi seemed to predict the anatomical response after FAi. The baseline presence of a disorganization of the inner retinal layers (DRIL) and hyperreflective foci (HRF) were both associated with a higher likelihood of requiring rescue DEXi injections. Conclusion: FAi implantation led to a significant BCVA and CMT improvement with a good safety profile over the 12-month follow-up. Predictive factors of treatment outcomes seem to include the anatomical response to DEXi and the presence of DRIL and HRF at baseline. [ABSTRACT FROM AUTHOR]

Background and Objectives: Hyperreflective foci (HRF) are a morphological sign of accumulation of lipid extravasation, proteinaceous material, and inflammatory cells in the layers of retina. The purpose of this study is to determine the presence, location, and characteristics of hyperreflective foci in the retina of normolipemic patients with xanthelasma palpebrarum. Methods: A total of 50 test subjects with xanthelasma were evaluated and compared with 50 control subjects. SD-OCT was performed in all patients passing through the center of fovea. On OCT, presence and absence of hyperreflective foci were noted. Following characteristics of the hyperreflective spots were evaluated and compared: location (inner retina or outer retina), shape, size, and back shadowing. Results: Hyperreflective foci were present in 87 out of 100 eyes of test subjects (87%) and none in control group (P-value < 0.001, significant). Shape of hyperreflective foci was predominantly round (54.2%), and location of hyperreflective foci was predominantly in outer nuclear and outer plexiform layer (30.1%). Back shadowing was present with frequency of 58 (80.6%). Conclusion: Hyperreflective foci are a great indicator for lipid extravasation and have been significantly associated with patients of xanthelasma having normal lipid levels. This signifies a defect in vascular integrity in patients of xanthelasma with normal lipid levels. Hence, these patients are at increased risk of atherosclerotic plaque formation and systemic complications.

Purpose: To compare the anatomical and functional outcomes of the combination of aflibercept and dexamethasone implant (CT) against aflibercept monotherapy (AM) in treatment-naive diabetic macular edema (DME) patients with serous macular detachment and hyperreflective foci. Methods: This study included 82 eyes of 82 patients with treatment-naive DME who completed the follow-up period of 12 months. All patients had optical coherence tomography biomarkers of an inflammatory DME phenotype. Patients were consecutively selected and classified into two groups: The CT group consisted of 39 eyes treated with aflibercept therapy and initially combined with a single-dose dexamethasone implant. The AM group consisted of 43 eyes treated with aflibercept alone. The primary outcome measures of the study were the mean reduction of the central macular thickness (CMT) and total macular volume parameters (TMV) and improvement in best-corrected visual acuity. Results: In both groups, the patient characteristics, including age, gender, duration of diabetes, HbA1c levels, phakic percentage, and diabetic retinopathy status were similar (P > 0.05). The mean reduction in CMT and TMV was significantly higher in the CT group compared to the AM group (P < 0.001 and P = 0.002, respectively). In contrast, mean letter gains were not significantly higher (P = 0.240) at the end of the study. In the CT group, 20.5% of patients showed a transient IOP increase, and 18% developed cataracts. In subgroup analysis, the mean letter gain in pseudophakic eyes was significantly higher (12.5 in the CT vs. 9.3 in the AM group, P = 0.027). Conclusion: The CT, where inflammation is prominent, can provide faster recovery. The pseudophakic eyes seem to be the ideal patient group for CT. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the characteristics of optical coherence tomography (OCT) and aqueous humor cytokine differences between acute and chronic central serous chorioretinopathy (CSC) and to evaluate the relevance of these findings. Methods: This was a cross-sectional, observational study. Patients with CSC were divided into acute and chronic groups based on the symptom duration and were compared with normal controls. Best-corrected visual acuity (BCVA), central macular thickness (CMT), subfoveal choroidal thickness (CT), hyperreflective foci (HF), and cytokines including vascular endothelial growth factor (VEGF), interleukin (IL)-6, IL-8, IL-10, interferon-inducible protein-10 (IP-10), and monocyte chemoattractant protein-1 (MCP-1) were used as comparison metrics. Results: A total of 62 patients (62 eyes) with CSC (22 with acute CSC and 40 with chronic CSC) and 35 patients as controls were included in this study. The chronic CSC group had significantly older average ages and worse BCVA than the acute CSC group (both p < 0.05). Both CSC groups showed significant increases in CMT and CT (both p < 0.05). In chronic CSC, the CMT was thinner, with more HF in the neuroretina (p = 0.034). VEGF levels were significantly higher in patients with chronic CSC than in those with acute CSC and controls (p < 0.05). The levels of inflammatory cytokines showed no significant difference between the CSC and control groups. Spearman's correlation analysis showed that the number of HF was positively correlated with disease duration (r = 0.311, p = 0.014), logMAR BCVA (r = 0.487, P < 0.001) and MCP-1 levels (r = 0.256, p = 0.045). Conclusions: Chronicity of CSC could lead to upregulation of VEGF. HF was associated with a more severe visual impairment in CSC patients and had relations with the levels of MCP-1. [ABSTRACT FROM AUTHOR]

INTRODUCTION: We aimed to investigate the monocyte/high-density lipoprotein cholesterol (HDL-C) ratio (MHR) in diabetic macular edema (DME) patients with hyperreflective foci (HF) on optical coherence tomography (OCT) and compare them with the results of patients without HF. METHODS: The data were obtained by retrospectively reviewing the data of patients followed up with a diagnosis of diabetes mellitus in the internal medicine clinic and with a diagnosis of DME in our clinic. DME patients who have blood monocyte and HDL-C levels before the treatment of DME in the laboratory archive were included in the study. DME and HF were detected by OCT. The patients with DME were divided into two groups according to the presence of HF observed on OCT. Thirty-five DME patients with HF were included in the study group. Thirty-five DME patients without HF were determined as the control group. RESULTS: The mean MHR was significantly higher in DME patients with HF (p=0.002). The optimal cutoff value of MHR for HF was 9.72. The area under the receiver operating characteristics curve was 0.681. DISCUSSION AND CONCLUSION: The MHR described as a potential biomarker of inflammation was significantly higher in DME patients with HF, suggesting that elevated MHR might be associated with severity of inflammation in DME patients.

Abstract Background This study aimed to report eleven cases of non-neovascular pachychoroid disease with hyperreflective material (HRM) that occurred in Japanese patients. Methods A retrospective review of data from eleven patients who had non-neovascular retinal pigment epithelium (RPE) protrusion with HRM in the neurosensory retina between March 2017 and June 2022 was conducted. Clinical examination, color fundus photography, fluorescein angiography, spectral-domain optical coherence tomography (SD-OCT), and OCT angiography data were analyzed. Main outcome measures were patient characteristics, changes in SD-OCT findings, and symptom outcomes. Results All cases had RPE protrusion and HRM with dilated choroidal veins, which were characteristic of pachychoroid disease. However, none of the cases had macular neovascularization (MNV). In 9 eyes (81.8%), HRM improved spontaneously without intervention and resulted in alterations in RPE, referred to as pachychoroid pigment epitheliopathy (PPE) or focal choroidal excavation (FCE). In these cases, symptoms such as metamorphopsia and distortion improved without treatment. In the remaining two cases (18.2%), HRM still persisted during the follow-up period. Conclusion There are some cases of non-neovascular pachychoroid disorder with HRM, which might be a new entity of pachychoroid spectrum disease or an early stage of PPE or FCE. These cases should not be misdiagnosed as MNV, and careful observation is necessary.

Purpose: The most widely used classifications of age-related macular degeneration (AMD) and its severity stages still rely on color fundus photographs (CFPs). However, AMD has a wide phenotypic variability that remains poorly understood and is better characterized by OCT. We and others have shown that patients with AMD have a distinct plasma metabolomic profile compared with controls. However, all studies to date have been performed solely based on CFP classifications. This study aimed to assess if plasma metabolomic profiles are associated with OCT features commonly seen in AMD. Design: Prospectively designed, cross-sectional study. Participants: Subjects with a diagnosis of AMD and a control group (> 50 years old) from Boston, United States, and Coimbra, Portugal. Methods: All participants were imaged with CFP, used for AMD staging (Age-Related Eye Disease Study 2 classification scheme), and with spectral domain OCT (Spectralis, Heidelberg). OCT images were graded by 2 independent graders for the presence of characteristic AMD features, according to a predefined protocol. Fasting blood samples were collected for metabolomic profiling (using nontargeted high-resolution mass spectrometry by Metabolon Inc). Analyses were conducted using logistic regression models including the worst eye of each patient (AREDS2 classification) and adjusting for confounding factors. Each cohort (United States and Portugal) was analyzed separately and then results were combined by meta-analyses. False discovery rate (FDR) was used to account for multiple comparisons. Main Outcome Measures: Plasma metabolite levels associated with OCT features. Results: We included data on 468 patients, 374 with AMD and 94 controls, and on 725 named endogenous metabolites. Meta-analysis identified significant associations (FDR < 0.05) between plasma metabolites and 3 OCT features: hyperreflective foci (6), atrophy (6), and ellipsoid zone disruption (3). Most associations were seen with amino acids, and all but 1 metabolite presented specific associations with the OCT features assessed. Conclusions: To our knowledge, we show for the first time that plasma metabolites have associations with specific OCT features seen in AMD. Our results support that the wide spectrum of presentations of AMD likely include different pathophysiologic mechanisms by identifying specific pathways associated with each OCT feature. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references.

Aims: This study aims to compare the effectiveness of treatment between anti-vascular endothelial growth factor (anti-VEGF) agents in diabetic macular edema (DME) patients with disorganization of retinal inner layers (DRIL). Epiretinal membrane, serous macular detachment, ellipsoid zone (EZ) disorder, external limiting membrane (ELM) disorder, and hyperreflective foci were also examined. Methods: Patients treated for DME and also had DRIL were included in the study. The study design was retrospective and cross-sectional. The complete ophthalmologic records and imaging were scanned at the beginning, 3rd-month, 6th-month, and 12th-month follow-up, and the treatments administered were recorded. Anti-VEGF agents administered to the patients were examined in three groups: bevacizumab, ranibizumab, and aflibercept. Result: A total of 141 eyes of 100 patients were included in our study. One hundred and fifteen eyes (81.6%) had a BCVA of 0, 5, or less at the beginning. There was no statistically significant difference between the three groups regarding initial BCVA and CMT and the change in BCVA and CMT at the beginning and the 12th month (p > 0.05). There was a negative correlation between EZ and ELM disorders in patients and the change in BCVA at 12 months (r: 0.45 p < 0.001, r: 0.32 p < 0.001, respectively). The number of injections over five was positively correlated with the change in CMT but not with BCVA (r: − 2.35 p = 0.005 and r: 0.147 p = 0.082, respectively). Conclusions: No statistically significant difference was found between anti-VEGF agents when treating DME patients with DRIL. In addition, we have shown that anatomically better results were obtained in those who had five or more injections, although not in terms of BCVA. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the distribution of hyperreflective foci (HRF) in eyes with dry age-related macular degeneration (AMD). Methods: We retrospectively reviewed optical coherence tomography (OCT) images of 58 dry AMD eyes presenting HRF. The distribution of HRF according to the early treatment diabetic retinopathy study area was analyzed according to the presence of subretinal drusenoid deposits (SDDs). Results: We classified 32 eyes and 26 eyes into the dry AMD with SDD group (SDD group) and dry AMD without SDD group (non-SDD group), respectively. The non-SDD group had higher prevalence and density of HRF at the fovea (65.4% and 1.71 ± 1.48) than the SDD group (37.5% and 0.48 ± 0.63, P = 0.035 and P < 0.001, respectively). However, the prevalence and density of HRF in the outer circle area of the SDD group (81.3% and 0.11 ± 0.09) were greater than those of the non-SDD group (53.8% and 0.05 ± 0.06, p = 0.025 and p = 0.004, respectively). The SDD group showed higher prevalence and mean densities of HRF in the superior and temporal area than in the non-SDD group (all, p < 0.05). Conclusion: HRF distributions in dry AMD varied according to the presence of SDDs. This might support that the degenerative features may be different between dry AMD eyes with and without SDDs. [ABSTRACT FROM AUTHOR]

Copyright of Bosphorus Medical Journal / Boğaziçi Tıp Dergisi is the property of KARE Publishing and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Abstract Background To investigate the relationship between intraretinal hyperreflective foci (HRF) and visual function in intermediate age-related macular degeneration (iAMD). Methods Retrospective, cross-sectional study. iAMD patients underwent spectral domain optical coherence tomography (SD-OCT) imaging and vision function testing: normal luminance best corrected visual acuity (VA), low luminance VA (LLVA), quantitative contrast sensitivity function (qCSF), low luminance qCSF (LLqCSF), and mesopic microperimetry. Each OCT volume was graded for the presence and number of HRF. Each HRF was graded for: separation from the retinal pigment epithelium (RPE), above drusen, and shadowing. Central drusen volume was calculated by the built-in functionality of the commercial OCT software after manual segmentation of the RPE and Bruch’s membrane. Results HRF group: 11 eyes; 9 patients; mean age 75.7 years. No-HRF group: 11 eyes; 10 patients; mean age 74.8 years. In linear mixed effect model adjusting for cube-root transformed drusen volume, HRF group showed statistically significant worse VA, LLVA, LLqCSF, and microperimetry. HRF group showed worse cone function, as measured by our pre-defined multicomponent endpoint, incorporating LLVA, LLqCSF and microperimetry (p = 0.018). For eyes with HRF, # of HRF did not correlate with any functional measures; however, % of HRF separated from RPE and # of HRF that created shadowing were statistically associated with low luminance deficit (LLD). Conclusions The association between the presence of HRF and worse cone visual function supports the hypothesis that eyes with HRF have more advanced disease.

PurposeFast and automated reconstruction of retinal hyperreflective foci (HRF) is of great importance for many eye-related disease understanding. In this paper, we introduced a new automated framework, driven by recent advances in deep learning to automatically extract 12 three-dimensional parameters from the segmented hyperreflective foci in optical coherence tomography (OCT).MethodsUnlike traditional convolutional neural networks, which struggle with long-range feature correlations, we introduce a spatial and channel attention module within the bottleneck layer, integrated into the nnU-Net architecture. Spatial Attention Block aggregates features across spatial locations to capture related features, while Channel Attention Block heightens channel feature contrasts. The proposed model was trained and tested on 162 retinal OCT volumes of patients with diabetic macular edema (DME), yielding robust segmentation outcomes. We further investigate HRF’s potential as a biomarker of DME.ResultsResults unveil notable discrepancies in the amount and volume of HRF subtypes. In the whole retinal layer (WR), the mean distance from HRF to the retinal pigmented epithelium was significantly reduced after treatment. In WR, the improvement in central macular thickness resulting from intravitreal injection treatment was positively correlated with the mean distance from HRF subtypes to the fovea.ConclusionOur study demonstrates the applicability of OCT for automated quantification of retinal HRF in DME patients, offering an objective, quantitative approach for clinical and research applications.

In this study, we described multimodal imaging findings occurring before the onset of macular neovascularization in angioid streaks. Our imaging findings suggest that intraretinal hyperreflective foci concentration and migration may represent the early alterations preceding macular neovascularization complication. Purpose: To describe the steps leading to the development and progression of macular neovascularization (MNV) in angioid streaks. Methods: The study was designed as retrospective, longitudinal case series. Patients with angioid streaks were investigated by means of multimodal imaging, including fundus autofluorescence and structural optical coherence tomography. Main outcome measures were hyperreflective foci and MNV progression steps. Results: Overall, 40 eyes (20 patients) affected by angioid streaks were evaluated. Over the follow-up, five eyes of five patients developed MNV. The mean follow-up was of 1.6 years. The mean number of anti–vascular endothelial growth factor injections was 4.35 ± 1.4. Mean best-corrected visual acuity was 0.53 ± 0.38 LogMAR at the MNV onset, improving to 0.42 ± 0.40 LogMAR at the end of the follow-up (P > 0.05). Intraretinal hyperreflective foci onset and coalescence represented the first alterations occurring before the onset of the MNV. Anti–vascular endothelial growth factor treatment was associated with exudation relapsing and remitting, with still present intraretinal hyperreflective foci and pigment accumulation. The longitudinal analysis of our cohort of eyes outlined the event timeline: 1.2 months to find concentrated hyperreflective foci, 4.5 months to observe pigment organization through the outer nuclear layer, and 1.5 years to detect MNV. Conclusion: Hyperreflective foci formation, concentration, and migration represent early alterations occurring before the onset of the MNV in angioid streaks. [ABSTRACT FROM AUTHOR]

Background: This study aimed to report eleven cases of non-neovascular pachychoroid disease with hyperreflective material (HRM) that occurred in Japanese patients. Methods: A retrospective review of data from eleven patients who had non-neovascular retinal pigment epithelium (RPE) protrusion with HRM in the neurosensory retina between March 2017 and June 2022 was conducted. Clinical examination, color fundus photography, fluorescein angiography, spectral-domain optical coherence tomography (SD-OCT), and OCT angiography data were analyzed. Main outcome measures were patient characteristics, changes in SD-OCT findings, and symptom outcomes. Results: All cases had RPE protrusion and HRM with dilated choroidal veins, which were characteristic of pachychoroid disease. However, none of the cases had macular neovascularization (MNV). In 9 eyes (81.8%), HRM improved spontaneously without intervention and resulted in alterations in RPE, referred to as pachychoroid pigment epitheliopathy (PPE) or focal choroidal excavation (FCE). In these cases, symptoms such as metamorphopsia and distortion improved without treatment. In the remaining two cases (18.2%), HRM still persisted during the follow-up period. Conclusion: There are some cases of non-neovascular pachychoroid disorder with HRM, which might be a new entity of pachychoroid spectrum disease or an early stage of PPE or FCE. These cases should not be misdiagnosed as MNV, and careful observation is necessary. [ABSTRACT FROM AUTHOR]

Hyperreflective foci (HF) reflects inflammatory responses for fundus diseases such as diabetic macular edema (DME), retina vein occlusion (RVO), and central serous chorioretinopathy (CSC). Shown as high contrast and reflectivity in optical coherence tomography (OCT) images, automatic segmentation of HF in OCT images is helpful for the prognosis of fundus diseases. Previous traditional methods were time-consuming and required high computing power. Hence, we proposed a lightweight network to segment HF (with a speed of 57 ms per OCT image, at least 150 ms faster than other methods). Our framework consists of two stages: an NLM filter and patch-based split to preprocess images and a lightweight DBR neural network to segment HF automatically. Experimental results from 3000 OCT images of 300 patients (100 DME,100 RVO, and 100 CSC) revealed that our method achieved HF segmentation successfully. The DBR network had the area under curves dice similarity coefficient (DSC) of 83.65%, 76.43%, and 82.20% in segmenting HF in DME, RVO, and CSC on the test cohort respectively. Our DBR network achieves at least 5% higher DSC than previous methods. HF in DME was more easily segmented compared with the other two types. In addition, our DBR network is universally applicable to clinical practice with the ability to segment HF in a wide range of fundus diseases. [ABSTRACT FROM AUTHOR]

Diabetic retinopathy is a form of diabetic microangiopathy, and vascular hyperpermeability in the macula leads to retinal thickening and concomitant reduction of visual acuity in diabetic macular edema (DME). In this review, we discuss multimodal fundus imaging, comparing the pathogenesis and interventions. Clinicians diagnose DME using two major criteria, clinically significant macular edema by fundus examination and center-involving diabetic macular edema using optical coherence tomography (OCT), to determine the appropriate treatment. In addition to fundus photography, fluorescein angiography (FA) is a classical modality to evaluate morphological and functional changes in retinal capillaries, e.g., microaneurysms, capillary nonperfusion, and fluorescein leakage. Recently, optical coherence tomography angiography (OCTA) has allowed us to evaluate the three-dimensional structure of the retinal vasculature and newly demonstrated that lamellar capillary nonperfusion in the deep layer is associated with retinal edema. The clinical application of OCT has accelerated our understanding of various neuronal damages in DME. Retinal thickness measured by OCT enables us to quantitatively assess therapeutic effects. Sectional OCT images depict the deformation of neural tissues, e.g., cystoid macular edema, serous retinal detachment, and sponge-like retinal swelling. The disorganization of retinal inner layers (DRIL) and foveal photoreceptor damage, biomarkers of neurodegeneration, are associated with visual impairment. Fundus autofluorescence derives from the retinal pigment epithelium (RPE) and its qualitative and quantitative changes suggest that the RPE damage contributes to the neuronal changes in DME. These clinical findings on multimodal imaging help to elucidate the pathology in the neurovascular units and lead to the next generation of clinical and translational research in DME. [ABSTRACT FROM AUTHOR]

AIM: To investigate the anti-inflammatory effect of intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) in patients with macular edema secondary to retinal vein occlusion (RVO-ME). METHODS: Twenty-eight eyes from twenty-eight treatment-naïve patients (14 males and 14 females) with RVO-ME were included in this retrospective study. The retinal vein occlusion (RVO) was comprised of both central retinal vein occlusion (CRVO, n=14) and branch retinal vein occlusion (BRVO, n=14). Intravitreal injection of anti-VEGF reagents were administered monthly for three consecutive months, in which 18 patients were injected with ranibizumab and 10 patients were injected with conbercept. All eyes were imaged with optical coherence tomography angiography (OCTA) at baseline and 1wk after monthly intravitreal anti-VEGF injection. The visual acuity (VA), central macular thickness (CMT), the number of hyperreflective foci (HRF) recognized as an inflammatory sign in OCT images, and non-perfusion area (NPA), were compared before and after anti-VEGF treatments. RESULTS: The mean interval between baseline and follow-up was 29.4±0.79 (range, 27-48)d. Compared with the baseline, the VA improved (logMAR 1.5±0.1 vs 0.8±0.1, P

Abstract 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

Background: To investigate the relationship between intraretinal hyperreflective foci (HRF) and visual function in intermediate age-related macular degeneration (iAMD). Methods: Retrospective, cross-sectional study. iAMD patients underwent spectral domain optical coherence tomography (SD-OCT) imaging and vision function testing: normal luminance best corrected visual acuity (VA), low luminance VA (LLVA), quantitative contrast sensitivity function (qCSF), low luminance qCSF (LLqCSF), and mesopic microperimetry. Each OCT volume was graded for the presence and number of HRF. Each HRF was graded for: separation from the retinal pigment epithelium (RPE), above drusen, and shadowing. Central drusen volume was calculated by the built-in functionality of the commercial OCT software after manual segmentation of the RPE and Bruch's membrane. Results: HRF group: 11 eyes; 9 patients; mean age 75.7 years. No-HRF group: 11 eyes; 10 patients; mean age 74.8 years. In linear mixed effect model adjusting for cube-root transformed drusen volume, HRF group showed statistically significant worse VA, LLVA, LLqCSF, and microperimetry. HRF group showed worse cone function, as measured by our pre-defined multicomponent endpoint, incorporating LLVA, LLqCSF and microperimetry (p = 0.018). For eyes with HRF, # of HRF did not correlate with any functional measures; however, % of HRF separated from RPE and # of HRF that created shadowing were statistically associated with low luminance deficit (LLD). Conclusions: The association between the presence of HRF and worse cone visual function supports the hypothesis that eyes with HRF have more advanced disease. [ABSTRACT FROM AUTHOR]

Background: The photoreceptor outer segment (PROS) layer demonstrates focal thinning above the fluorescein leakage in acute central serous chorioretinopathy (CSC); however, the nature of this phenomenon is not known. Objectives: To study the relationship between the PROS layer and thickness of the outer retinal layers above the fluorescein leakage in newly diagnosed acute CSC. Design: Single-center retrospective study. Methods: All participants received multimodal imaging, including fluorescein angiography and optical coherence tomography. Thickness of PROS, outer nuclear layer (ONL), and ONL-outer plexiform layer (OPL) complex was measured above the leakage and outside the leakage within the area of neurosensory detachment. The number of intraretinal hyperreflective foci of the outer retina was counted. The correlation between PROS thickness and ONL, OPL-ONL complex thickness, and the number of intraretinal hyperreflective foci was calculated. Results: Fifty eyes of 48 patients (38 males and 10 females, 43.8 ± 10.6 years) with a mean symptom duration of 1.4 ± 1.3 months were included. PROS thickness above the fluorescein leakage showed a statistically significant correlation with ONL thickness, OPL-ONL complex thickness, and the number of hyperreflective foci in the outer retina, 0.57, 0.60, and −0.46, respectively (p < 0.001). Measuring the extent of PROS thinning above the leakage in newly diagnosed CSC allowed to predict self-resolution of subretinal fluid. The greatest linear dimension of PROS thinning showed an area under the receiver operating curve (ROC) curve of 0.98. The cases without PROS thinning had the fastest resolution of subretinal fluid. Conclusion: PROS thinning above the fluorescein leakage in acute CSC is associated with thinning of the outer retinal layers and reveals mild outer retinal atrophy. The absence of PROS thinning predicts faster resolution of CSC. [ABSTRACT FROM AUTHOR]

Purpose: 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. [ABSTRACT FROM AUTHOR]

Background and Objectives: The identification of possible biomarkers that can predict treatment response among DME eyes is important for the individualization of treatment plans. We investigated optical coherence tomography (OCT)-based biomarkers that may predict the one-year real-life outcomes among diabetic macular edema (DME) eyes following treatment by intravitreal ranibizumab (IVR) injections. Materials and Methods: A total of 65 eyes from 35 treatment-naïve patients with DME treated with ranibizumab injection were recruited. Best-corrected visual acuity (BCVA), central retinal thickness (CRT), intraocular pressure (IOP), and OCT scans were retrospectively recorded at baseline before treatment and at 3 months, 6 months, and 12 months after treatment. The OCT scans were evaluated for biomarkers of interest, which included central retinal thickness (CRT), amount and locations of hyperreflective foci (HRF), subretinal fluid (SRF), intraretinal cysts (IRC), large outer nuclear layer cyst (LONLC), ellipsoid zone disruption (EZD), disorganization of retinal inner layers (DRIL), hard exudates (HE), epiretinal membrane (ERM), and vitreomacular interface (VMI). Correlations between these OCT biomarkers and outcome measures (visual and structural) were statistically analyzed. Results: A total of 65 eyes from 35 patients with DME were enrolled. The mean age was 64.2 ± 10.9 years old. Significant improvement in terms of mean BCVA (p < 0.005) and mean CRT was seen at final follow-up compared to baseline. The biomarkers of DRIL, LONLC, and SRF were found to be predictive for at least 50 μm CRT reduction after treatment (with odds ratio of 8.69, 8.5, and 17.58, respectively). The biomarkers of IRC, LONLC, and SRF were predictive for significant improvement in terms of BCVA and CRT after treatment. Finally, the number of HRF was predictive for both BCVA improvement and a CRT reduction of less than 100 μm after treatment. No serious complications were reported during the study. Conclusion: Our study demonstrated the utility of OCT biomarkers as therapeutic predictors of ranibizumab treatment among DME eyes. [ABSTRACT FROM AUTHOR]

Quantitative autofluorescence (qAF8) level is a presumed surrogate marker of lipofuscin content in the retina. We investigated the changes in the qAF8 levels in non-neovascular AMD. In this prospective cohort study, Caucasians aged ≥50 years with varying severity of non-neovascular AMD in at least one eye and Snellen visual acuity ≥6/18 were recruited. The qAF8 levels were analysed in the middle eight segments of the Delori pattern (HEYEX software, Heidelberg, Germany). The AMD categories were graded using both the Beckman classification and multimodal imaging (MMI) to include the presence of subretinal drusenoid deposits (SDD). A total of 353 eyes from 231 participants were analyzed. Compared with the age-matched controls, the qAF8 values decreased in the eyes with AMD (adjusted % difference = −19.7% [95% CI −28.8%, −10.4%]; p < 0.001) and across the AMD categories, (adjusted % differences; Early, −13.1% (−24.4%, −1%), p = 0.04; intermediate AMD (iAMD), −22.9% (−32.3%, −13.1%), p < 0.001; geographic atrophy −25.2% (−38.1%, −10.4%), p = 0.002). On MMI, the qAF8 was reduced in the AMD subgroups relative to the controls, (adjusted % differences; Early, −5.8% (−18.9%, 8.3%); p = 0.40; iAMD, −26.7% (−36.2%, −15.6%); p < 0.001; SDD, −23.7% (−33.6%, −12.2%); p < 0.001; atrophy, −26.7% (−39.3%, −11.3%), p = 0.001). The qAF8 levels declined early in AMD and were not significantly different between the severity levels of non-neovascular AMD, suggesting the early and sustained loss of function of the retinal pigment epithelium in AMD. [ABSTRACT FROM AUTHOR]

Introduction: Objectives of the study were to describe the hyperreflective foci (HRF) on optical coherence tomography angiography in diabetic macular edema (DME) with subretinal fluid (SRF) and explore the association of HRF in the outer retina with photoreceptor integrity and visual outcomes after anti-vascular endothelial growth factor (anti-VEGF) treatment. Methods: We retrospectively reviewed 46 eyes (36 patients) with DME treated with anti-VEGF drugs. The following parameters, including best-corrected visual acuity (BCVA), central macular thickness (CMT), the height of SRF, the number of HRF in the superficial capillary plexus, deep capillary plexus, and the outer retina, as well as the integrity of external limiting membrane (ELM) and ellipsoid zone (EZ), were evaluated and compared between the baseline and after 2 monthly injections of anti-VEGF drugs. The relationship between the HRF in the outer retina and the integrity of ELM and EZ, as well as BCVA, was analyzed. Results: BCVA was significantly improved in DME after anti-VEGF treatment; however, for the subgroup of DME patients with SRF, visual acuity remained unchanged after anti-VEGF treatment (p < 0.05 vs. p = 0.375). The number of HRF (p < 0.05), CMT (p < 0.001), and SRF height (p < 0.001) were significantly reduced, accompanied with partial restoration of ELM and EZ integrity after anti-VEGF injection. The HRF in the outer retina was correlated with the final ELM (p = 0.036) and EZ (p = 0.004) status. The final BCVA was significantly better in eyes with intact ELM (p = 0.002) and EZ at final visit (p < 0.001). Conclusion: The number of HRF in outer retina was negatively associated with the microstructural restoration of ELM and EZ, as well as the visual outcome in DME patients with SRF after anti-VEGF treatment. [ABSTRACT FROM AUTHOR]

Hyperreflective foci (HRF) have been associated with retinal disease progression and demonstrated as a negative prognostic biomarker for visual function. Automated segmentation of HRF in retinal optical coherence tomography (OCT) scans can be beneficial to identify the formation and movement of the HRF biomarker as a retinal disease progresses and can serve as the first step in understanding the nature and severity of the disease. In this paper, we propose a fully automated deep neural network based HRF segmentation model in OCT images. We enhance the model's performance by using a patch-based strategy that increases the model's compute on the HRF pixels. The patch-based strategy is evaluated against state of the art HRF segmentation pipelines on clinical retinal image data. Our results shows that the patch-based approach demonstrates a high precision score and intersection over union (IOU) using a ResNet34 segmentation model with Binary Cross Entropy loss function. The HRF segmentation pipeline can be used for analyzing HRF biomarkers for different retinopathies. [ABSTRACT FROM AUTHOR]

Background: The presence of hyperreflective foci (HRF) in retinitis pigmentosa (RP) is a potentially new finding. We investigated the presence of HRF in SD-OCT images in eyes with RP and its relation to vascular, morphologic and metabolic findings in RP. Methods: The study was performed on 42 RP patients and 24 controls. Using SD-OCT, we calculated the amount of HRF within the entire retina (HRF-ER) and the outer nuclear layer (HRF-ONL). Retinal vessel diameters (μm) and oxygen saturation (%) values were measured using Oxymap T1. We evaluated the mean diameter in retinal arterioles (D-A) and venules (D-V), the corresponding oxygen saturation values (A-SO2, V-SO2) and the oxygen saturation difference (A-V SO2). Results: RP differed from controls by HRF-ER, HRF-ON and EZ-length (p < 0.001). D-A and D-V were narrower and A-SO2 and V-SO2 were higher in RP (p ≤ 0.001). Within RP, significant interactions were found between the HRF-ER* group and: BCVA, EZ length, D-A, A-SO2 and A-V SO2 (p ≤ 0.018). The HRF-ONL* group interactions were significant for: BCVA, EZ length, D-A, A-SO2 and A-V SO2 (p ≤ 0.014). Conclusion: The present study highlights the presence of HRF to reflect the vascular, morphologic and metabolic alterations in RP. These biomarkers seem to be associated with remodeling and apoptosis that occur with the progression of degeneration. [ABSTRACT FROM AUTHOR]

Microglial activation is one of the main pathogenic factors to cause retinal neuroinflammation. Recently, with the advancement of retinal imaging technologies, hyperreflective foci(HRF), as a novel biomarker in optical coherence tomography(OCT)imaging, have received more attention in retinal neuroinflammation. Current research demonstrated that HRF are the aggregates mainly derived from the activated microglia in retina or mononuclear phagocyte-macrophage from the blood. HRF were defined as discrete and well-circumscribed hyperreflective dot-shaped lesions with the maximum diameter between 20-50μm in retina and choroid imaged with OCT. Under pathological conditions, the number of HRF increases significantly. Under pathological condations, the number of HRF was obviously increased, which might be related to the severity of some retinal diseases. However, the research on the source and function of HRF is still in its infancy. This review is aimed to describe the basic characteristics of HRF and their roles in both retinal inflammatory diseases and neurodegenerative diseases of the central nervous system. HRF are expected to be a potential and novel biomarker of inflammation for early diagnosis and prognosis of neuroinflammation in both retinal and central nervous system diseases.

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. [ABSTRACT FROM AUTHOR]

Advances in imaging and artificial intelligence (AI) have revolutionized the detection, quantification and monitoring for the clinical assessment of intermediate age-related macular degeneration (iAMD). The iAMD incorporates a broad spectrum of manifestations, which range from individual small drusen, hyperpigmentation, hypopigmentation up to early stages of geographical atrophy. Current high-resolution imaging technologies enable an accurate detection and description of anatomical features, such as drusen volumes, hyperreflexive foci and photoreceptor degeneration, which are risk factors that are decisive for prediction of the course of the disease; however, the manual annotation of these features in complex optical coherence tomography (OCT) scans is impractical for the routine clinical practice and research. In this context AI provides a solution by fully automatic segmentation and therefore delivers exact, reproducible and quantitative analyses of AMD-related biomarkers. Furthermore, the application of AI in iAMD facilitates the risk assessment and the development of structural endpoints for new forms of treatment. For example, the quantitative analysis of drusen volume and hyperreflective foci with AI algorithms has shown a correlation with the progression of the disease. These technological advances therefore improve not only the diagnostic precision but also support future targeted treatment strategies and contribute to the prioritized target of personalized medicine in the diagnostics and treatment of AMD., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Diabetes mellitus is a chronic disease the microvascular complications of which include diabetic retinopathy and maculopathy. Diabetic macular edema, proliferative diabetic retinopathy, and diabetic macular ischemia pose a threat to visual acuity. Artificial intelligence can play an increasingly more important role in making the diagnosis and the treatment regimen of maculopathies in everyday clinical practice in the future. It can be used to automatically detect and quantify pathological parameters of the retina. The aim is to improve patient care in the clinical routine using so-called clinical decision support systems with personalized treatment algorithms. This review article outlines the current research regarding new biomarkers in diabetic maculopathy using optical coherence tomography (OCT) and OCT angiography (OCT-A)., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

PurposeTo investigate the associations between cytokine levels in the aqueous humor (AH) and hyperreflective foci (HF) on spectral-domain optical coherence tomography (SD-OCT) in neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV).MethodsThe prospective study included 63 eyes with nAMD, 44 with PCV, and 43 with cataracts (Controls). AH samples were obtained before anti-vascular endothelial growth factor (VEGF) therapy or cataract surgery. Cytokines interleukin 6 (IL-6), IL-8, IL-10, interferon-inducible protein 10 (IP-10), monocyte chemotactic protein 1 (MCP-1), and VEGF were measured by multiplex bead assay. Best-corrected visual acuity (BCVA), central macular thickness (CMT), and the number of HF were evaluated at baseline and 1 month after anti-VEGF treatment.ResultsNo significances difference in IL-6 and IL-8 levels were noted among the three groups (P = 0.370 and P = 0.067). VEGF, IP-10, and IL-10 levels were significantly higher in nAMD and PCV groups than in Controls (all P < 0.05). In nAMD, HF was positively correlated with VEGF (rs = 0.300, P = 0.025) and in eyes with HF group, VEGF and IL-10 were significantly higher than those without HF (P = 0.008 and P = 0.022). In PCV, no correlation was observed between HF and cytokines (all P > 0.05). After anti-VEGF treatment, patients with HF in nAMD and PCV were predisposed to worse visual outcomes (P = 0.022 and P = 0.015) and a significantly greater reduction in CMT (P = 0.001 and P = 0.057). And nAMD patients with HF were more sensitive to anti-VEGF treatment than those without HF (P = 0.029).ConclusionsIn the nAMD group, HF was positively correlated with VEGF. Patients in nAMD with HF had elevated levels of VEGF and IL-10 and responded favorably to anti-VEGF. HF might serve as an inflammatory biomarker and a predictive factor for therapeutic efficacy in patients with nAMD.

PurposeTo identify optical coherence tomography (OCT) biomarkers that may predict functional and anatomical outcomes in diabetic macular edema (DME) patients treated with intravitreal dexamethasone (DEX) implant.Materials and MethodsSixty-four eyes from 50 patients with DME were enrolled. Best-corrected visual acuity (BCVA) and OCT biomarkers including central retinal thickness (CRT), subretinal fluid (SRF), intraretinal cysts (IRC), ellipsoid zone disruption (EZD), disorganization of retinal inner layers (DRIL), hard exudate (HE), hyperreflective foci (HRF), epiretinal membrane (ERM), and vitreomacular interface (VMI) changes were evaluated at baseline and at 3, 6, and 12 months after treatment. Multiple logistic analysis was performed to evaluate each OCT biomarker as a predictive factor for functional and anatomical improvement at the end of treatment.ResultsThe presence of SRF at baseline was associated with a favorable outcome, with CRT improving by more than 100 μm after treatment from multivariate logistic regression analysis [odds ratio 6.16 (1.75–21.6)]. In addition, baseline SRF predicted a greater CRT improvement from multiple regression analysis (model R-square 0.11, p = 0.006). The reduction of DRIL, SRF, LONLC, IRC, and EZD were correlated with better CRT improvement (more than 100 μm) (P < 0.05). SRF and EZD recovery can also predict better visual prognosis (P < 0.05).ConclusionOCT biomarkers can be used to predict who may benefit the most after DEX treatment. We suggest that the DEX implant should be considered as a first line treatment in DME patients with SRF.

Purpose: Multimodal imaging was used to identify and characterize the cause of hyperpigmentation seen on color fundus images (CFIs) of eyes with intermediate age-related macular degeneration (iAMD). Design: Retrospective review of a prospective study. Participants: Patients with iAMD. Methods: Color fundus images with macular hyperpigmentation were compared with same-day images obtained using fundus autofluorescence (FAF), near infrared reflectance (NIR), and swept-source (SS) OCT imaging. Two SS OCT en face slabs were generated: a retinal slab to identify hyperreflective foci within the retina and a slab from beneath the retinal pigment epithelium (RPE; the sub-RPE slab) that was used to detect regions that cause decreased light transmission into the choroid, also known as hypotransmission defects. All images were registered to allow for qualitative comparisons by 2 independent graders. Main Outcome Measures: Comparison between foci of macular hyperpigmentation seen on CFIs with the detection of these regions on FAF, NIR, and SS OCT en face images. Results: Compared with CFIs, FAF imaging seemed to be the least sensitive method for the detection of hyperpigmentation, whereas NIR and SS OCT imaging reliably detected these hyperpigmented areas. Although NIR imaging detected most of the hyperpigmentation seen in CFIs, SS OCT imaging detected all the areas of hyperpigmentation and anatomically localized these areas by using both en face and B-scan images. En face OCT slabs of the retina and sub-RPE region were registered to the CFIs, and areas of hyperpigmentation were shown to correspond to hyperreflective foci in the retina and regions of thickened RPE seen on OCT B-scans. Although both hyperpigmentation and early atrophic lesions appeared bright on NIR imaging, en face SS OCT imaging was able to distinguish these lesions because hyperpigmentary changes appeared dark and early atrophic lesions appeared bright on the sub-RPE slab. Conclusions: En face OCT imaging in conjunction with OCT B-scans were able to identify and localize the hyperpigmentation seen in CFIs reliably. This hyperpigmentation was not only associated with intraretinal hyperreflective foci, but also corresponded to areas with a thickened RPE.

Background and Objectives: The identification of possible biomarkers that can predict treatment response among DME eyes is important for the individualization of treatment plans. We investigated optical coherence tomography (OCT)-based biomarkers that may predict the one-year real-life outcomes among diabetic macular edema (DME) eyes following treatment by intravitreal ranibizumab (IVR) injections. Materials and Methods: A total of 65 eyes from 35 treatment-naïve patients with DME treated with ranibizumab injection were recruited. Best-corrected visual acuity (BCVA), central retinal thickness (CRT), intraocular pressure (IOP), and OCT scans were retrospectively recorded at baseline before treatment and at 3 months, 6 months, and 12 months after treatment. The OCT scans were evaluated for biomarkers of interest, which included central retinal thickness (CRT), amount and locations of hyperreflective foci (HRF), subretinal fluid (SRF), intraretinal cysts (IRC), large outer nuclear layer cyst (LONLC), ellipsoid zone disruption (EZD), disorganization of retinal inner layers (DRIL), hard exudates (HE), epiretinal membrane (ERM), and vitreomacular interface (VMI). Correlations between these OCT biomarkers and outcome measures (visual and structural) were statistically analyzed. Results: A total of 65 eyes from 35 patients with DME were enrolled. The mean age was 64.2 ± 10.9 years old. Significant improvement in terms of mean BCVA (p < 0.005) and mean CRT was seen at final follow-up compared to baseline. The biomarkers of DRIL, LONLC, and SRF were found to be predictive for at least 50 μm CRT reduction after treatment (with odds ratio of 8.69, 8.5, and 17.58, respectively). The biomarkers of IRC, LONLC, and SRF were predictive for significant improvement in terms of BCVA and CRT after treatment. Finally, the number of HRF was predictive for both BCVA improvement and a CRT reduction of less than 100 μm after treatment. No serious complications were reported during the study. Conclusion: Our study demonstrated the utility of OCT biomarkers as therapeutic predictors of ranibizumab treatment among DME eyes.

Quantitative autofluorescence (qAF8) level is a presumed surrogate marker of lipofuscin content in the retina. We investigated the changes in the qAF8 levels in non-neovascular AMD. In this prospective cohort study, Caucasians aged ≥50 years with varying severity of non-neovascular AMD in at least one eye and Snellen visual acuity ≥6/18 were recruited. The qAF8 levels were analysed in the middle eight segments of the Delori pattern (HEYEX software, Heidelberg, Germany). The AMD categories were graded using both the Beckman classification and multimodal imaging (MMI) to include the presence of subretinal drusenoid deposits (SDD). A total of 353 eyes from 231 participants were analyzed. Compared with the age-matched controls, the qAF8 values decreased in the eyes with AMD (adjusted % difference = −19.7% [95% CI −28.8%, −10.4%]; p < 0.001) and across the AMD categories, (adjusted % differences; Early, −13.1% (−24.4%, −1%), p = 0.04; intermediate AMD (iAMD), −22.9% (−32.3%, −13.1%), p < 0.001; geographic atrophy −25.2% (−38.1%, −10.4%), p = 0.002). On MMI, the qAF8 was reduced in the AMD subgroups relative to the controls, (adjusted % differences; Early, −5.8% (−18.9%, 8.3%); p = 0.40; iAMD, −26.7% (−36.2%, −15.6%); p < 0.001; SDD, −23.7% (−33.6%, −12.2%); p < 0.001; atrophy, −26.7% (−39.3%, −11.3%), p = 0.001). The qAF8 levels declined early in AMD and were not significantly different between the severity levels of non-neovascular AMD, suggesting the early and sustained loss of function of the retinal pigment epithelium in AMD.

Purpose: To investigate hyperreflective choroidal foci (HCF) using en face swept-source optical coherence tomography (SS-OCT) and determine the factors that contribute to the distribution of HCF in normal eyes. Methods: In this retrospective study, we included healthy eyes with a normal fundus. HCF were defined as hyperreflective spots on en face SS-OCT images. The number, mean area, total area, and circularity of the HCF were compared with various choroid measurements obtained using SS-OCT, SS-OCT angiography, and fundus photography. Results: We investigated 51 eyes from 51 patients. The mean patient age was 56.0 ± 14.7 years, and 32 (62.7%) were female. The number and total area of HCF did not differ between the female and male patients and the right and left eyes. The number of HCF was correlated with the stromal area of the choroid (r = 0.291, P = 0.040) and subfoveal choroidal vascularity index (r = − 0.364, P = 0.009). The total area of HCF was correlated with the stromal area of the choroid (r = 0.283, P = 0.045). However, the number and total area of HCF were not correlated with age, degree of macular tessellation, subfoveal choroidal thickness, and choriocapillaris vascular density and flow void area. Conclusion: HCF were observed in normal eyes, and their distribution was associated with the underlying stromal component of the choroid. The results of this study can be used as a reference for determining abnormal hyperreflective foci in the choroid of the eyes with various diseases. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to analyze the factors associated with hyperreflective foci (HRF) in diabetic macular edema (DME) in treatment naïve eyes. Methods: This retrospective observational study included 131 eyes of 91 treatment naïve patients with DME. Details of ophthalmological examination with duration of vision loss and systemic parameters were noted. The spectral-domain optical coherence tomography (SD-OCT) images were analyzed for number and location of HRF and the associated imaging biomarkers. Results: Inner retinal (IR) HRF were seen in 88 eyes (67%), outer retinal (OR) in 28 (21%), and subretinal (SR) in 12 (9%). The IR had (7.1 ± 7) HRF, the OR (6.5 ± 4.8), and SR (3.9 ± 2.9). A greater proportion of eyes with HRF also had subretinal fluid (SRF), significantly higher blood pressure and lower serum triglycerides. Univariate linear regression analysis showed women (3 HRF greater vs. men, P = 0.04), eyes with cystoid spaces (2.95 more HRF vs. no cystoid spaces, P = 0.02), and SRF (2.96 more HRF vs. no SRF, P = 0.007) had more HRF, whereas higher triglycerides (1 HRF lesser per 50 mg lower TGL, P = 0.03) had lesser. Conclusion: Our study highlights the importance of HRF as an imaging biomarker in DME suggesting an inflammatory origin. Long-term observations of large cohorts with automated analysis can give more insights.