Search Results (42)

Background/Objectives: Hyperreflective foci (HRF) are supportive optical coherence tomography (OCT) imaging biomarkers that have been examined for their association with disease progression and severity in various retinal disorders. The accurate identification and segmentation of these tiny structures of lipid extravasation remain complicated because of their small size, class imbalance, similarity in the reflectivity patterns with the surrounding structures and imaging artifacts. While U-Net-based models have promised exceptional results for medical image segmentation, optimal architectural settings and suitable preprocessing methods for HRF detection remain unclear. Methods: This research assessed optimal settings for U-Net-based models for HRF segmentation by evaluating standard U-Net and attention U-Net under different preprocessing regimes. Attention U-Net employed Z-score normalization and contrast-limited adaptive histogram equalization (CLAHE) enhancement with soft dice loss. The standard U-Net was trained on OCT images with CLAHE using focal Tversky loss. A total of 435 fovea-centered OCT B scans with the corresponding, consensus-annotated HRF masks were utilized for this research. Results: The standard U-Net outperformed attention U-Net with a dice score of 0.5207, an AUC of 0.8411, and a recall of 0.6439 on raw OCT images. The attention U-Net with preprocessing (dice: 0.5033, AUC: 0.6987, recall: 0.5391) demonstrated satisfactory performance. The results showed that the U-Net model with CLAHE and focal Tversky loss improved recall by 19.4% relative to the attention U-Net, and this corresponds roughly to a 23% relative decline in false negatives. This indicates increased sensitivity in identifying HRF regions. Conclusions: The best-performing configuration using U-Net-based architectures for segmentation of HRFs combines the standard U-Net model with CLAHE and focal Tversky loss for handling class imbalance. This approach yields relatively higher sensitivity, indicating that the standard U-Net model delivers a simple and robust framework for automated HRF segmentation on the evaluated dataset, promising further validation in broader clinical datasets. Full article

Background/Objectives: To analyze the agreement between two swept-source optical coherence tomography (SS-OCT) devices in assessing glistening on intraocular lenses (IOL). Methods: Patients who had previously undergone cataract surgery were included. They were sequentially examined using two SS-OCT devices: Anterion (Heidelberg Engineering Inc., Heidelberg, Germany) and Triton (Topcon, Inc., Tokyo, Japan). Six corresponding scans from both devices were compared, and glistening, observed as hyperreflective foci (HRF), was manually counted. The total number of HRF and the degree of glistening were measured and categorized into four groups. The agreement between the two devices was analyzed using the intraclass correlation coefficient (ICC). Results: A total of 333 eyes from 285 patients were evaluated. The mean age was 76.5 ± 8.0 years (range: 45–95). The median number of HRF detected in a single scan was 1.1 (IQR 0.0–10.2, range 0–176) using Triton and 2.7 (IQR 0.2–20.1, range 0–250) using Anterion. The ICC across different scans ranged from 0.8 to 0.9, indicating strong agreement between the two devices. Bland–Altman plots showed better concordance in lenses with low glistening grades, while higher grades revealed greater discrepancies, with Anterion detecting significantly more HRF than Triton. Among all factors studied, only postsurgical time was associated with glistening. Conclusions: Two different SS-OCT devices can detect and quantify glistening in IOLs. The concordance between them was high, particularly for lower glistening grades. However, in higher grades, Anterion detected significantly more HRF than Triton. Full article

Background: Inflammatory hyperreflective retinal foci (I-HRF) have been recognized as an optical coherence tomography (OCT) biomarker of aggregates of activated microglial cells. Microglia, the principal resident immune cells, are key players in geographic atrophy (GA) development and progression. Objective: To quantify I-HRF distribution across inner (IR) and outer (OR) retinal layers in GA compared with healthy controls. Methods: Retrospective observational study including patients aged ≥50 years with GA lesion area >1.25 mm² and age-matched healthy subjects. GA eyes were classified as bilateral GA (B-GA) or unilateral GA (U-GA; fellow eye with macular neovascularization). Using Spectralis OCT, I-HRF (≤30 μm; RNFL-like reflectivity; no posterior shadowing) were identified and counted across IR and OR. Results: Sixty-eight eyes from 46 patients with GA (B-GA: 49 eyes; U-GA: 19 eyes) and 19 control eyes were studied. I-HRF were higher in IR than in OR in all groups (p < 0.001). I-HRF were higher in GA eyes in both layers compared with controls (p < 0.05). U-GA exhibited higher I-HRF than B-GA in IR (44.32 ± 8.47 vs. 30.10 ± 7.62; p < 0.001), while I-HRF were not significantly different in OR (9.58 ± 3.04 vs. 8.02 ± 3.33; p = 0.081). Conclusions: I-HRF are increased in GA. They are more numerous in IR, consistent with their proposed inflammatory origin. These findings further support the role microglia may play in GA pathology. I-HRF may become an OCT biomarker to track GA-associated neuroinflammation in different GA phenotypes. Longitudinal studies are needed to clarify I-HRF significance in GA progression. Full article

Background/Objectives: Pigment migration is a key biomarker of progression in age-related macular degeneration (AMD). This study assessed the diagnostic performance of ring aperture Retro mode (RAR) imaging for detecting pigment migration and compared its performance with established multimodal imaging techniques. Methods: This retrospective study included 80 eyes from 61 consecutive patients with AMD who underwent multimodal imaging with color fundus images (CFIs), fundus autofluorescence (FAF), RAR imaging (Mirante, NIDEK), and en face optical coherence tomography (OCT) with B-scans (Cirrus HD-OCT 5000, Zeiss). Two independent retina specialists graded the AMD stage and the presence of pigment migration across modalities. Sensitivity and positive predictive value (PPV) of RAR were calculated using en face OCT as the reference standard. Results: RAR demonstrated high diagnostic performance, with a sensitivity of 94.7% and a PPV of 93.4% relative to en face OCT. RAR frequently identified pigment migration that was not visible on CFI or FAF, particularly in early AMD and in eyes with media opacity. Distinct morphologic patterns—including hyperreflective foci, thickened retinal pigment epithelium, refractile drusen, and cuticular drusen—were consistently identifiable on RAR. In four eyes with geographic atrophy, RAR detected perifoveal pigment redistribution at least six months before foveal involvement was confirmed by OCT and FAF. Conclusions: RAR imaging is a rapid, sensitive, and clinically practical technique for detecting pigment migration in AMD. By complementing en face OCT and enhancing visualization in cases where standard imaging is limited, RAR may strengthen early disease surveillance, support prognostic assessment, and improve multimodal diagnostic workflows in routine practice. Full article

Purpose: To characterize, using clustering analysis, the OCT morphological and clinical phenotypes of diabetic macular edema (DME) in a very large population (>2000 DME eyes) using standardized and validated OCT-based biomarkers. Methods: A cross-sectional study was conducted on OCT scans collected from 2355 eyes of 1688 patients with DME and performed during real-world clinical practice. OCT scans were automatically analyzed by a software able to automatically quantify OCT key biomarkers: intraretinal fluid (IRF), subretinal fluid (SRF), hyperreflective retinal foci (I-HRF), and external limiting membrane (ELM) and ellipsoid zone (EZ) interruption. Clustering analysis was performed using the above-mentioned biomarkers, including the distribution of IRF across the three ETDRS rings. Results: The overall population was predominantly composed of type 2 diabetes patients (89%), with a mean diabetes duration of 15.6 ± 10.7 years and mean best corrected visual acuity (BCVA) of 63 ± 18 ETDRS letters. Multivariate clustering identified four morphological phenotypes with distinct patterns of fluid distribution associated with different I-HRF counts, SRF volume, and percentages of ELM/EZ integrity (p < 0.0001). Conclusions: This large OCT analysis identified distinct morphological subtypes of DME, confirming the clinical relevance of key imaging biomarkers. The distribution and severity of DME features differ among clusters, supporting the importance of OCT-based phenotyping in tailoring treatment strategies and understanding disease evolution. Full article

Background: Radiation maculopathy (RM) is a delayed, sight-threatening complication of ocular radiotherapy. Traditionally regarded as a pure microvascular disease, emerging evidence points to the central role played by retinal neuroinflammation, driven by microglial activation and cytokine dysregulation affecting both the retina and the choroid. Hyperreflective retinal foci, neuroinflammatory in origin (I-HRF), visualized through advanced imaging modalities such as spectral domain optical coherence tomography (OCT), have been identified as early and critical biomarkers of both preclinical and clinical retinal neuroinflammation. Materials and Methods: This review synthesizes findings from experimental and clinical studies to explore the pathophysiology of neuroinflammation and the associated imaging parameters in RM. Results: The integration of experimental and clinical evidence specifically underscores the significance of I-HRF as an early indicator of neuroinflammation in RM. OCT enables the identification and quantification of these biomarkers, which are linked to microglial activation and cytokine dysregulation. Conclusions: The pathophysiology of RM has evolved from a predominantly vascular condition to one strongly secondary to neuroinflammatory mechanisms involving the retina and choroid. In particular, I-HRF, as early biomarkers, offers the potential for preclinical diagnosis and therapeutic intervention, paving the way for improved management of this sight-threatening complication. Full article

Background: Secondary epiretinal membrane (ERM) is a common complication of diabetic retinopathy, but data on surgical outcome is limited. The aim of this study was to evaluate anatomical and functional outcomes after pars plana vitrectomy with ERM peeling in eyes with diabetic retinopathy. Methods: A retrospective analysis was conducted on 87 eyes of 87 consecutive patients with diabetic retinopathy who underwent ERM peeling over a ten-year period (04/2013–11/2022). Collected data included demographics, best-corrected visual acuity (BCVA), stage of diabetic retinopathy, and optical coherence tomography parameters such as central subfield retinal thickness (CSRT), macular volume (MV), and presence of hyperreflective foci, subretinal fluid, and intraretinal fluid. Statistical analyses were performed using a paired t-test and the Wilcoxon test. Results: The majority of patients had type 2 diabetes (96.6%), and 69.0% presented with diabetic macular edema (DME). The mean follow-up was 2.2 ± 2.0 years. Significant postoperative reductions were observed in CSRT (from 377.20 ± 99.28 µm to 337.99 ± 113.834 µm; p = 0.008) and MV (from 10.11 ± 1.46 mm³ to 99.28 ± 1.07 mm³; p < 0.001). No significant changes in BCVA were observed across the entire study cohort. ERM recurrence was rare (2.3%), and no major complications occurred. Conclusions: ERM peeling in diabetic eyes leads to significant anatomical improvement, especially in advanced diabetic retinopathy and DME, but with limited functional gains. The surgical indication should be carefully considered. Full article

Background: Diabetic macular edema (DME) is the most common cause of vision loss among diabetic patients. The first-line treatments for DME are anti-vascular endothelial growth factor (VEGF)-drugs, while intravitreal steroids are generally reserved for second-line treatment. Limited data exist on the role of optical coherence tomography (OCT) biomarkers as predictors of success in non-responders to anti-VEGF treatment undergoing simultaneous cataract surgery and dexamethasone intravitreal implant (DEX-I). Methods: This study was designed as a retrospective analysis of patients with DME who were refractory to anti-VEGF treatment but underwent cataract surgery and received a DEX-I at the time of surgery. All procedures were performed between May 2021 and February 2024. The best-corrected visual acuity (BCVA) and central subfoveal thickness (CST) were recorded at baseline and at 1 week, 1 month, and 3 months. The following OCT-based biomarkers were also collected: ellipsoid zone (EZ) integrity, disorganization of the retinal inner layers (DRIL), CST, and hyperreflective foci (HRF). Correlations between the baseline biomarkers and the anatomical outcome were analyzed using linear mixed models (LMMs). Results: Eleven patients (eighteen eyes) met the inclusion criteria. The mean CST decreased significantly from 469.4 ± 53.8 µm at baseline, to 373.1 ± 34.7 µm at 1 week (p = 0.002) and 354.4 ± 24.1 µm at 1 month (p = 0.011). The mean BCVA improved significantly from 0.47 LogMAR to 0.33 LogMAR at 1 week (p = 0.001), 0.23 LogMAR at 1 month (p < 0.001), and 0.25 LogMAR at 3 months (p < 0.001). Baseline predictors significantly influencing CST included the presence of DRIL, a disrupted/absent EZ, and a higher CST. Conclusions: The administration of DEX-I for DME refractory to anti-VEGF treatment in patients undergoing cataract surgery promoted functional improvements persisting longer than the anatomical ones. Patients presenting with DRIL, disrupted EZ, and higher CST at baseline may be better candidates for the combination of DEX-I and cataract surgery. Full article

Background: Hyperreflective retinal foci (HRF) are small, discrete, hyperreflective elements observed in the retina using optical coherence tomography (OCT). They appear in many retinal diseases and have been linked to disease progression, treatment response, and prognosis. However, their definition and clinical use vary widely, not just between different diseases, but also within a single disorder. Methods: This perspective is based on a review of peer-reviewed studies examining HRF across different retinal diseases. The studies included analyzed HRF morphology, distribution, and clinical relevance using OCT. Particular attention was given to histopathological correlations, disease-specific patterns, and advancements in automated quantification methods. Results: HRF distribution and features vary with disease type and even within the same disease. A variety of descriptions have been proposed with different characteristics in terms of dimensions, reflectivity, location, and association with back shadowing. Automated OCT analysis has enhanced HRF detection, enabling quantitative analysis that may expand their use in clinical practice. However, differences in software and methods can lead to inconsistent results between studies. HRF have been linked to microglial cells and may be defined as neuro-inflammatory cells (Inflammatory, I-HRF), migrating retinal pigment epithelium cells (Pigmentary, P-HRF), blood vessels (Vascular, V-HRF), and deposits of proteinaceous or lipid elements leaking from vessels (Exudative, E-HRF). Conclusions: HRF are emerging as valuable imaging biomarkers in retinal diseases. Four main types have been identified, with different morphological features, pathophysiological origin, and, therefore, different implications in the management of retinal diseases. Advances in imaging and computational analysis are promising for their incorporation into personalized treatment strategies. Full article

Optical coherence tomography (OCT) has emerged as a pivotal imaging modality in elucidating the pathogenic, clinical, and prognostic implications of age-related macular degeneration (AMD). This review examines the utility of OCT in providing high-resolution, cross-sectional imaging of retinal structures comparable to an in vivo histopathology. Recent histopathological correlations with OCT have enabled the precise characterization of AMD extracellular lesions, improving the interpretation of several OCT signatures. By correlating OCT findings with clinicopathological features, a deeper understanding of the underlying pathophysiology of AMD is achieved, facilitating early detection, risk stratification, and therapeutic decision making. Furthermore, OCT-derived biomarkers offer valuable insights into disease severity, response to treatment, and prognostic outcomes, thereby enhancing patient care and optimizing visual outcomes. Full article

Background/Purpose: This study compared the effects of three induction doses of anti-vascular endothelial growth factor (anti-VEGF) on diabetic macular edema (DME) with that of long-term treatment using biomarkers to find out the predictability potential of early response to anti-VEGF treatment for the long-term restorative effect. Methods: We retrospectively reviewed the clinical and optical coherence tomography (OCT) data of 71 DME eyes treated with three monthly anti-VEGF doses and followed for 1 year. BCVA, central subfield thickness (CST), subretinal fluid (SRF), intraretinal cysts, hyperreflective foci (HF), disorganization of inner retinal layers (DRILs), ellipsoid zone/external limiting membrane (EZ/ELM) integrity, and vitreoretinal relationships were assessed at baseline, 3, 6, and 12 months. Results: Patients (50.7% male) had a mean follow-up of 12 months. After three anti-VEGF doses, 19 eyes required no additional injections, 25 continued anti-VEGF, 20 switched to dexamethasone implants, and seven received combination therapy. Best corrected visual acuity (BCVA) improved from 0.52 to 0.40 logMAR at 3 months, 0.30 at 6 months, and stabilized at 0.40 at 12 months. CST decreased from 406 µm to 317 µm at 3 months and 307 µm at 12 months. Significant early improvements in BCVA, CST, SRF, and intraretinal cysts were sustained in the long-term follow-up. HF reduction became significant after 6 months, while DRIL and EZ/ELM integrity remained unchanged. Conclusions: The improvement of OCT biomarkers in DME patients supported that intravitreal anti-VEGF significantly restored the retinal microstructure, which was already evident at 3 months in the control after anti-VEGF induction. Full article

Background: In this study, we evaluated the incidence of cystoid macular edema (CME) after pars plana vitrectomy (PPV) for different retinal pathologies and assessed the role of optical coherence tomography (OCT) biomarkers in guiding treatment decisions in post-surgical CME patients who were refractory to medical therapy over a follow-up period of 12 months. Methods: Medical records of consecutive pseudophakic patients, who underwent PPV for different retinal pathologies, were retrospectively evaluated in this single-center, uncontrolled study. The incidence of post-PPV CME was assessed. Eyes with post-PPV CME in the first 2 months after surgery, with available clinical and OCT data for 12 months after surgery, were included in the evaluation. The mean best-corrected visual acuity (BCVA; logMAR), mean central macular thickness (CMT; μm) change, and response to different treatments [medical therapy and intravitreal dexamethasone (DEX) implant] were evaluated 1, 3, 6, 9, and 12 months after PPV. The impact of OCT biomarkers on the exposure to DEX implants was assessed. Adverse events, potentially related to the treatment, were investigated as well. Results: Of the 346 pseudophakic patients (352 eyes) who participated in this study, 54 (54 eyes) developed CME within the first 2 months after PPV (incidence of 15.3%). Among them, 48 patients were deemed eligible for the 12-month analysis. Preoperative mean BCVA (1.44 ± 0.99 logMAR) significantly improved to 0.32 ± 0.37 logMAR after 12 months (p < 0.001). The mean baseline CMT of 347 (±123.5) μm significantly decreased to 290 μm (±80.4; p = 0.003) by the end of the follow-up. Twenty-five eyes (52%) required one or more DEX implants for CME, due to being refractory to topical therapy. Significant correlations were found between the mean CMT values at various time points. Additionally, patients who required DEX implants at months 3 and 9 were more likely to present intraretinal fluid (IRF), disorganization of inner retinal layers (DRIL), disorganization of outer retinal layers (DROL), and hyper-reflective foci (HRF) at 1-month OCT. Five patients experienced a slight increase in intraocular pressure (IOP), which was successfully managed with topical medication. Conclusions: Topical therapy alone can be a valuable option for post-PPV CME in approximately 50% of patients. Significant visual recovery and macular thickness reduction at 12 months demonstrated that DEX implants can be a safe and effective second-line treatment for pseudophakic patients with post-PPV CME and who are refractory to medical therapy. Early post-surgical OCT biomarkers may indicate a more severe CME that might benefit from the steroid implant. Full article

Objective: Lesions characterized as complete retinal pigment epithelium and outer retinal atrophy (cRORA) are linked to the progression of intermediate age-related macular degeneration (iAMD). However, the extent of functional impairment of such precursor lesions remains uncertain. Methods: In this cross-sectional study, 4 participants (mean age ± standard deviation: 71.5 ± 2.1 years) underwent extensive multimodal imaging and psychophysical testing of cRORA lesions secondary to iAMD. Lesion-specific functional testing was performed using patient individualized testing grids with clinical conventional available (Stimulus size: 0.43°, ~125 µm) and experimental adaptive optics scanning light ophthalmoscope (AOSLO, stimulus size 0.07°, ~20 µm) based microperimetry (MP). One cRORA lesion site and one in-eye control region were tested per patient, respectively. Results: AOSLO imaging revealed an overall decrease in photoreceptor reflectivity, areas of hyporeflectivity over drusen, interspersed with hyperreflective foci, and disrupted photoreceptor mosaic in regions of cRORA. Localized retinal sensitivity assessment with clinical conventional MP yielded an average loss of −14.0 ± 3.3 dB at cRORA lesions compared to the in-eye control regions. In contrast, localized visual impairment assessed by high-resolution AOSLO-MP with smaller test stimuli (20 µm) revealed a sensitivity loss of −15.1 ± 5.1 dB at cRORA lesions (p < 0.01). Notably, also the area surrounding cRORA lesions can be impacted. Conclusions: We demonstrated that cRORA lesions are associated with severe localized functional impairment. cRORA precursor lesions may thus be considered as a surrogate outcome measure in future interventional iAMD trials. Full article

Objectives: To examine the effects of glucagon-like-peptide-1 receptor agonists (GLP1-RAs) on diabetic retinopathy (DR) progression, visual acuity (VA), central subfield thickness (CST), and response to intravitreal injections (IVIs) in the Hadassah ophthalmological cohort. Methods: Of 4500 Hadassah patients with DR, 146 had a documented first course of GLP1-RA treatment lasting at least a year along with ophthalmological follow-up. Of these, 35 underwent at least two optical coherence tomography (OCT) exams with a one-year interval. These 35 GLP1-RA–naïve patients were compared to a control group of 31 patients with DR who did not receive GLP1-RA treatment. We compared demographics, medical records, ocular data, and OCT characteristics between the two study groups. Results: At baseline, patients who received GLP1-RA treatment had a significantly higher prevalence of retinal detachment and vitreous hemorrhage, as well as a higher (though not statistically significant) prevalence of cardiovascular comorbidities compared to the control group. At the end of the follow-up period, the GLP1-RA group had a higher prevalence of DR progression compared to controls (3/19 vs. 0/20, respectively; p = 0.106, Fisher’s exact test), but also showed a better response to IVIs (27/35 vs. 17/31, respectively; unadjusted OR: 2.78, p = 0.058; 95% CI: [0.963, 8.020], Pearson’s chi-square test). However, vitreous hemorrhage and hyperreflective retinal foci were confounding factors (adjusted IVI response OR: 1.76, p = 0.229, 95% CI: [0.553, 5.650], logistic regression). No significant differences were observed between the two groups in terms of change in visual acuity (−0.135 vs. −0.063 logMAR, respectively; p = 0.664, Student’s t-test) or CST (−13.49 vs. −30.13 μm; p = 0.464, Student’s t-test). Conclusions: This study presents preliminary findings showing no significant differences in DR progression, visual acuity, and CST between patients treated with GLP1-RA and control patients. Moreover, GLP1-RA therapy was not significantly associated with improved IVI response, with ocular parameters acting as confounding factors. Full article

Retinal vein occlusion (RVO) is a significant cause of vision loss, characterized by the occlusion of retinal veins, leading to conditions such as central retinal vein occlusion (CRVO) and branch retinal vein occlusion (BRVO). Macular edema (ME), a prevalent consequence of RVO, is the primary cause of vision impairment in affected patients. Anti-VEGF agents have become the standard treatment, showing efficacy in improving visual acuity (VA) and reducing ME. However, a subset of patients exhibit a suboptimal response to anti-VEGF therapy, necessitating alternative treatments. Corticosteroids, which address inflammatory pathways implicated in ME, have shown promise, particularly in cases resistant to anti-VEGF. This review aims to identify biomarkers that predict treatment response to corticosteroids in RVO-associated ME, utilizing multimodal imaging and cytokine assessments. Baseline imaging, including SD-OCT and OCT-A, is essential for evaluating biomarkers like hyperreflective foci (HRF), serous retinal detachment (SRF), and central retinal thickness (CRT). Elevated cytokine levels, such as IL-6 and MCP-1, correlate with ME severity and poor anti-VEGF response. Early identification of these biomarkers can guide timely transitions to corticosteroid therapy, potentially enhancing treatment outcomes. The practical conclusion of this review is that integrating biomarker assessment into clinical practice enables personalized treatment decisions, allowing for earlier and more effective management of RVO-associated ME by transitioning patients to corticosteroid therapy when anti-VEGF agents are insufficient. Advanced diagnostics and machine learning may further refine personalized treatment strategies, improving the management of RVO-associated ME. Full article