[Use of artificial intelligence for recognition of biomarkers in intermediate age-related macular degeneration]. / Einsatz von künstlicher Intelligenz zur Erkennung von Biomarkern bei der intermediären altersabhängigen Makuladegeneration.

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.

[OCT biomarkers in diabetic maculopathy and artificial intelligence]. / OCT-Biomarker bei diabetischer Makulopathie und künstliche Intelligenz.

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).

Application and progress of artificial intelligence technology in the segmentation of hyperreflective foci in OCT images for ophthalmic disease research.

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.

Fingerprint sign of the Henle fibre layer in epiretinal membrane: a cross-sectional and longitudinal study.

PURPOSE: To investigate the incidence and distribution of fingerprint-like microwaves in the Henle fibre layer (HFL) of the eyes with epiretinal membrane (ERM). METHODS: Patients with idiopathic ERM were included. The fingerprint sign was defined using en-face optical coherence tomography images of the HFL, and its extent was classified into three grades. RESULTS: At baseline, fingerprint sign was found in 70 of 83 (84.3%) eyes with ERM and was more frequently observed in eyes with a higher ERM stage (P < 0.001). Its extent increased (P < 0.001) with an increase in ERM stage or the central macular thickness (P < 0.001). Best corrected visual acuity (BCVA) was worse in eyes with a fingerprint sign than in those without (P = 0.024). Metamorphopsia was more common in eyes with a greater extent of fingerprint-like microwaves (P = 0.048). The fingerprint sign persisted over a mean follow-up period of 18.0 ± 23.3 without surgery. In 45 eyes that underwent surgery, the extent of fingerprint-like microwaves decreased at 1.2 months (P = 0.001), and further decreased at 13.7 months postoperatively (P = 0.019). However, the proportion of eyes with a fingerprint sign after surgery was similar to that observed preoperatively (P = 0.912). CONCLUSIONS: Fingerprint-like microwaves were commonly found in eyes with ERM and were associated with ERM severity and BCVA. The microwaves remained long after surgery, although their extent may have decreased after the ERM was resolved. These results suggest that ERM traction may cause long-lasting changes in the HFL.

Prognostic impact of hyperreflective foci in nonsyndromic retinitis pigmentosa.

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.

Aflibercept combined with triamcinolone acetonide in the treatment of diabetic macular edema: optical coherence tomography and optical coherence tomography angiography.

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<0.05). The difference in CMT between the two groups was statistically significant after the first two injections (P<0.01), but not after the third injection (P=0.875). The number of HRF (1mo: 7.41±8.25 vs 10.86±7.22, P=0.027; 2mo: 5.33±6.13 vs 9.12±8.61, P=0.034; 3mo: 3.58±3.00 vs 6.37±5.97, P=0.007) and height of SRF (1mo: 82.39±39.12 vs 105.77±42.26 µm, P=0.011; 2mo: 36.84±10.02 vs 83.59±37.78 µm, P<0.01; 3mo: 11.57±3.29 vs 45.43±12.60 µm, P<0.01) in combined group were statistically significant less than aflibercept group after each injection, while the area of FAZ showed no significant change before and after treatment in both groups. CONCLUSION: The combination therapy of aflibercept and TA shows more significant effects on DME eyes with decreased HRF and SRF. However, both aflibercept and combination therapy show no significant change in the area of FAZ.

Optical coherence tomography biomarkers as outcome predictors to guide dexamethasone implant use in patients with iERM: a randomized controlled trial.

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.

Acquired Vitelliform Lesions in Intermediate Age-Related Macular Degeneration: A Cross Sectional Study.

PURPOSE: This study aims to define the characteristics of acquired vitelliform lesions (AVLs) in patients with intermediate age-related macular degeneration (iAMD). DESIGN: Retrospective, observational, cross sectional study. SUBJECTS: This study included 217 eyes with AVLs associated with iAMD, and an equivalent number of control patients. METHODS: OCT scans were evaluated for qualitative and quantitative parameters at both the eye and lesion level. Eye-level parameters included the presence of: hyporeflective core drusen, intraretinal hyperreflective foci (IHRF), subretinal drusenoid deposits, macular pachyvessels, central retinal thickness, and central choroidal thickness. Lesion-level qualitative parameters included the presence of ellipsoid zone (EZ) and external limiting membrane disruption overlying the AVL, IHRF overlying the AVL, AVL overlying drusen, pachyvessels under the AVL, a solid core within AVL, and AVL location. Lesion-level quantitative characteristics included AVL height and width, AVL distance from the fovea, and sub-AVL choroidal thickness. MAIN OUTCOME MEASURES: The primary outcomes assessed included the frequency of IHRF, the presence of macular pachyvessels, central choroidal thickness, and the dimensions (both height and width) of AVLs. RESULTS: Comparing the AVL and control groups, the frequency of IHRF (AVL: 49.3% vs. control: 26.3%) and macular pachyvessels (37.3% vs. 6.9%) was significantly higher in the AVL case group, and the central choroidal thickness (256.8 ± 88 µm vs. 207.1± 45 µm) was thicker in the AVL group. Acquired vitelliform lesions located over drusen, with overlying IHRF, or situated subfoveally, and AVL lesions with EZ disruption were found to have a greater lesion height and width compared with AVL lesions lacking these characteristics (P value < 0.001 for all). Additionally, a significant negative correlation was observed between the distance from the fovea and AVL height (Spearman rho: -0.19, P = 0.002) and width (Spearman rho: -0.30, P = 0.001). CONCLUSIONS: This study represents the largest reported cohort of AVL lesions associated with iAMD. Novel findings include the higher frequency of pachyvessels in addition to the presence of a thicker choroid in these eyes, as well as the greater height and width of AVL closer to the foveal center. These findings may offer insights into pathophysiologic mechanisms underlying the development of AVL. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Efficacity and Safety of the Fluocinolone Acetonide Implant in Uveitic Macular Edema: A Real-Life Study from the French Uveitis Network.

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.

Does dexamethasone implant combination with aflibercept monotherapy affect one-year outcomes in treatment-naive diabetic macular edema with inflammatory biomarkers?

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.

Optical Coherence Tomography Features of Macular Hyperpigmented Lesions without Intraretinal Hyperreflective Foci in Age-Related Macular Degeneration.

PURPOSE: To evaluate the optical coherence tomography (OCT) features of hyperpigmented lesions in the absence of intraretinal hyperreflective foci (IHRF) on OCT in eyes with age-related macular degeneration (AMD). METHODS: We retrospectively analyzed OCT images of eyes with intermediate AMD (iAMD) and macular hyperpigmentation (HP) on color fundus photograph (CFP) but without IHRF on OCT in the corresponding location. The most prominent or definite HP was selected for analysis. The infrared reflectance (IR) image registered with the CFP, and the location corresponding to the HP lesion were defined on the IR image. The location of the HP on the corresponding OCT B-scan was assessed for retinal pigment epithelium (RPE) elevation, acquired vitelliform lesion (AVL), abnormal retinal pigment epithelium + basal lamina (RPE + BL) band reflectivity, RPE + BL band thickening, as well as interdigitation zone (IZ), ellipsoid zone (EZ) and external limiting membrane (ELM) disruption. RESULTS: 49 eyes (39 patients) were included in this study. Forty-six (94%) of the hyperpigmented lesions showed a thickened RPE + BL band. RPE + BL band reflectivity was increased in 37 (76%) of the lesions. RPE + BL band thickening, however, was not correlated with RPE + BL band reflectivity (p-value = 0.31). Either thickening or hyperreflectivity of the RPE + BL band was present in all cases. Twenty (41%) lesions had evidence of ELM disruption, 42 (86%) demonstrated EZ disruption and 48 (98%) had IZ disruption. Five (10%) HPs demonstrated AVL. Among cases with RPE elevation (15 cases, 31%), 10 were classified as drusen, 2 as drusenoid PEDs, and 3 as fibrovascular PEDs. CONCLUSIONS: Thickening and/or hyperreflectivity of the RPE + BL band commonly correspond to regions of macular hyperpigmentation without IHRF in eyes with iAMD.

Assessment of intraretinal hyperreflective foci using multimodal imaging in eyes with age-related macular degeneration.

PURPOSE: This study aimed to investigate the correspondence between intraretinal hyperreflective foci (IHRF) identified on optical coherence tomography (OCT) B-scans with hyperpigmentation on colour fundus photography (CFP) or hyperreflectivity on infrared reflectance (IR) images in eyes with age-related macular degeneration (AMD). METHODS: Flash CFP, IR images and OCT B-scans obtained at the same visit were evaluated. Individual IHRF identified on OCT B-scans were assessed for the qualitative presence or absence of a hypotransmission tail into the choroid. The corresponding IR image obtained at the time of OCT acquisition was analysed for the presence or absence of hyperreflectivity in this region. The IR images were manually registered to the CFP image, and CFP images were inspected for the presence or absence of hyperpigmentation at the location of IHRF. RESULTS: From 122 eyes, a total of 494 IHRF were evaluated. For the primary analysis of qualitative presence or absence of hyperpigmentation on CFP and hyperreflectivity on IR at the locations corresponding to IHRF on OCT, 301 (61.0%) of the IHRFs demonstrated evidence of hyperpigmentation on CFP, while only 115 (23.3%) showed evidence of hyperreflectivity on IR. The qualitative determination of the presence or absence of an abnormality on CFP or IR were significantly different (p < 0.0001). 327 (66.2%) of the IHRF showed hypotransmission, and 80.4% of these IHRF showed hyperpigmentation on CFP, though only 23.9% (p < 0.0001) demonstrated hyperreflectivity on IR. CONCLUSIONS: Less than two-thirds of IHRF evident on OCT manifest as hyperpigmentation on colour photos, though IHRF with posterior shadowing are more likely to be evident as pigment. IR imaging appears to be even more poorly sensitive for visualizing IHRF.

Plasma Metabolites Associated with OCT Features of Age-Related Macular Degeneration.

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 Disclosures: Proprietary or commercial disclosure may be found after the references.

Macular dynamics and visual acuity prognosis in retinal vein occlusions - ways to connect.

Background and Objectives: This study aimed to establish possible connections between macular dynamics, various macular features, and visual acuity prognosis among patients with retinal vein occlusions. Materials and Methods: This study included 85 patients with central retinal vein occlusions (CRVO) and 26 with branch retinal vein occlusions (BRVO). We assessed macular features such as central macular thickness (CMT), foveal intraretinal hemorrhage (IRH), the presence and distribution of hyperreflective foci (HF), ellipsoid zone (EZ) disruption, inner retinal layer disorganization (DRIL), and posterior vitreous detachment (PVD), as well as their dynamics over one year of observation and their impact on final visual acuity prognosis, depending on the type of occlusion. Results: Best corrected visual acuity (BCVA) evolution is statistically significant regarding groups of age and type of occlusion and insignificant regarding gender. The best response to intravitreal treatment, quantified as a decrease in CMT, was registered after the first intravitreal injection. Connecting a decrease in CMT with BCVA improvement, we did not register a statistically significant correlation in the CRVO group, only in BRVO cases. The study results showed that complete PVD plays a significant positive role in decreasing CMT and BCVA improvement in cases of CRVO. Our study revealed that no matter the type of occlusion, the presence of foveal IRH will have a negative impact on the BCVA outcome. Statistically significant differences have been noted only for the evolution of visual acuity in non-ischemic CRVO cases, in correlation with the presence of EZ disruption. Outer retinal layer HF has proved to be a predictive factor for poor visual acuity outcomes. Conclusions: The most important non-imaging predicting factors regarding BCVA after retinal vein occlusions are age and baseline BCVA. CMT's dynamics still establish a weak connection with visual acuity fluctuations. The presence of foveal IRH, outer retinal layer HF, and foveal EZ disruption has a negative impact on visual acuity outcomes. Abbreviations: CRVO = central retinal vein occlusions, BRVO = branch retinal vein occlusions, CMT = central macular thickness, IRH = foveal intraretinal hemorrhage, HF = hyperreflective foci, EZ = ellipsoid zone disruption, DRIL = inner retinal layer disorganization, PVD = posterior vitreous detachment, BCVA = best corrected visual acuity, OCT = optical coherence tomography, BCVA Ti = best corrected visual acuity at first, BCVA Tf = best corrected visual acuity after one year, NR of IVI = number of intravitreal injections, SD = standard deviation, M = male, F = female, CMT Ti = central macular thickness at first, CMT T1 = central macular thickness after first injection, CMT T3 = central macular thickness after 3 injections, CMT Tf = central macular thickness after one year.

Automated evaluation of retinal hyperreflective foci changes in diabetic macular edema patients before and after intravitreal injection.

Purpose: Fast 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). Methods: Unlike 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. Results: Results 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. Conclusion: Our 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.

Analysis of Cytokine Levels Based on Optical Coherence Tomography Findings in Acute and Chronic Central Serous Chorioretinopathy.

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.

Changes of optical coherence tomographic hyperreflective foci in rhegmatogenous retinal detachment patients after successful surgery.

PURPOSE: To assess the changes of hyperreflective foci (HRF) in rhegmatogenous retinal detachment (RRD) patients after successful reattachment surgery. METHODS: Twenty-nine macula-off RRD eyes with successful reattachment surgery were retrospectively analyzed. Optical coherence tomography (OCT) was used to image macular regions and measure HRF in outer retina and inner retina at 0.5, 1, 3, 6, 12 months after surgery. The relationships between HRF and photoreceptor layer status, visual outcomes were evaluated. RESULTS: After retinal reattachment, HRF mainly distributed at the location where external limiting membrane (ELM) or inner and outer segment (IS/OS) line was disrupted. The HRF numbers in outer and inner retina were greater in eyes with discontinuous IS/OS line than eyes with continuous IS/OS line (all p<0.05). In the outer retina,  HRF increased in the initial three months after retinal reattachment, and then decreased gradually after 3 months (p<0.05). The HRF number in the outer retina at postoperative 0.5 months was associated with favorable visual outcomes at 6 and 12 months (r=-0.487,  p =0.025; r=-0.626,  p=0.005, respectively), nevertheless, the HRF number at 3 months was correlated with poor visual results at 6 and 12 months (r=0.441,  p =0.017; r=0.477,  p=0.019, respectively). CONCLUSION: HRF mainly occurred near the site where ELM or IS/OS line was injured after retinal reattachment. In the outer retina, the number of HRF gradually increased in the first 3 months and then gradually decreased. The early appearance of HRF in the outer retina was associated with a good visual prognosis, while the late appearance may suggest a less favorable visual outcome.

Semi-automated quantification of vitreal hyperreflective foci in SD-OCT and their relevance in patients with peripheral retinal breaks.

BACKGROUND: Retinal breaks (RB) are emergencies that require treatment to prevent progression of rhegmatogenous retinal detachment. Vitreal hyperreflective foci (VHF) representing migration of RPE cell clusters or interphotoreceptor matrix from the RB are potential biomarkers. The aim of this study is to investigate VHF in RB-patients using SD-OCT. METHODS: The retrospective cross-sectional study included RB patients from our Department of Ophthalmology, HSK Wiesbaden who underwent macular SD-OCT (SPECTRALIS®, Heidelberg Engineering, Germany) on both eyes. VHF, defined and quantified as foci that differ markedly in size and reflectivity from the background speckle pattern, were assessed for presence and frequency. The RB-affected eyes were the study group (G1), the partner eyes the control group (G2). RESULTS: 160 consecutive patients with RB were included. Age was 60 ± 10.2 years (52% female). 89.4% of G1 and 87.5% of G2 were phakic (p = 0.73). 94.4% (n = 151) were symptomatic. Symptom duration was 8.0 ± 10.1 days in G1, 94.4% (n = 151) showed VHF versus 5.6% (p < 0.0001) in G2, of which 75% (n = 6) showed asymptomatic lattice degenerations. Detectable VHF showed a strong association of OR = 320 (95% CI, 110-788, p < 0.0001)) with respect to symptomatic RB. Sensitivity and specificity were 94.7% and 94.7%, respectively. CONCLUSIONS: Most eyes with symptomatic RB show vitreal VHF in SD-OCT. Detected VHF are strongly associated with RB, and our semi-automated greyscale reflectivity analysis indicates that VHF likely originate from photoreceptor complexes torn out of the RB area that migrate into the vitreous cavity. The presence of VHF may indicate RB and should lead to a thorough fundus examination in both symptomatic and asymptomatic cases.

Evaluation of the efficacy of anti-vascular endothelial growth factors in diabetic macular edema with retinal inner and outer layers disorganization.

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.

Hyperreflective material in patients with non-neovascular pachychoroid disease.

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.