Automatic Identification and Severity Classification of Retinal Biomarkers in SD-OCT Using Dilated Depthwise Separable Convolution ResNet with SVM Classifier

Macular oedema is a common complication and vision-limiting factor in uveitis. The aim of this study was to compare retinal thickness as measured by optical coherence tomography and photoreceptor function as measured by fundus-related microperimetry with respect to their correlation with visual acuity. Prospective observational monocentre study. Thirty-one patients (53 eyes) with endogenous uveitis and fluorescein angiographically confirmed macular oedema were evaluated. Foveal thickness was analysed using spectral-domain (Spectralis(TM) ; Heidelberg Engineering, Heidelberg, Germany) OCT and retinal sensitivity was assessed using fundus-related microperimetry (MP1; Nidek Technologies, Padova, Italy). All findings were correlated with best-corrected visual acuity (BCVA). Foveal thickness was correlated with BCVA [p = 0.005, r = 0.38, 95% confidence interval (CI) 0.12-0.59]. For microperimetry measurements, a negative correlation with logMAR visual acuity was found. Fixation abnormalities were not associated with poor visual acuity, increased foveal thickness or retinal sensitivity. In eyes with cystoid changes in the outer plexiform and inner nuclear layer, foveal thickness was increased (p < 0.0001). Epiretinal membrane formation was present in 70%. In these eyes, foveal thickness was significantly increased (p = 0.003) and visual acuity was worse (p = 0.08). Foveal thickness and fundus-related microperimetry were correlated with visual acuity. Cystoid changes in the outer plexiform and inner nuclear layer and the presence of epiretinal membrane were associated with poor visual acuity. Fixation abnormalities were not associated with poor visual acuity.

Comparison between Spectral-domain and Swept-source OCT Angiography Scans for the Measurement of Hyperreflective Foci in Age-related Macular Degeneration

Diabetic macular edema (DME) is a leading cause of vision impairment in diabetes mellitus. Spectral-domain optical coherence tomography (SD-OCT) provides valuable biomarkers for assessing disease severity and treatment response. This study evaluates the visual outcomes and SD-OCT biomarker changes in patients treated with intravitreal ranibizumab at a tertiary hospital. A prospective cohort study was conducted on 50 Type 2 diabetes mellitus patients with center-involving DME at Employees' State Insurance Corporation (ESIC) Medical College and Hospital, Hyderabad, from July 2022 to December 2023. Inclusion criteria were best-corrected visual acuity (BCVA) <6/9 and central retinal thickness (CRT) ≥280 µm. Exclusion criteria included other retinal diseases, vision-impairing cataracts, or glaucoma. Patients received three monthly intravitreal ranibizumab injections and were followed up at one, two, three, and six months. BCVA, CRT, and SD-OCT biomarkers such as hyperreflective foci (HRF), subretinal neuroretinal detachment (SND), intraretinal cyst (IRC) size, disorganization of retinal inner layers (DRIL), ellipsoid zone (EZ) disruption, and external limiting membrane (ELM) disruption were assessed. Statistical analysis was performed using SPSS software, version 26 (IBM Corp., Armonk, NY). BCVA improved from 0.76±0.39 at baseline to 0.37±0.29 at six months (p<0.00001). CRT reduced from 473.66±111.65 µm to 326.64±71.37 µm (p<0.00001). HRF, SND, and IRC size showed significant regression. DRIL, EZ, and ELM disruption improved significantly (p<0.00001). There was no statistically significant association between OCT biomarker features and BCVA improvement of more than three lines. Intravitreal ranibizumab significantly improves visual acuity and reduces retinal thickness in DME patients. SD-OCT biomarkers are valuable in monitoring treatment response and disease progression.

Local Anatomic Precursors to New-Onset Geographic Atrophy in Age-Related Macular Degeneration as Defined on OCT

PurposeTo investigate sex-based differences in inflammation-related biomarkers on Spectral-Domain Optical Coherence Tomography (SD-OCT). DesignCross-sectional study. ParticipantsPatients with diabetic macular edema (DME) between February 1, 2019, and March 31, 2023, without intravitreal anti–vascular endothelial growth factor (anti-VEGF) injection within the prior six months. MethodsWe reviewed each patient’s medical record for age, biological sex, race and ethnicity, most recent glycated hemoglobin level (HbA1c), visual acuity (VA), and central macular thickness (CMT). OCT biomarkers that have been found in literature to be associated with inflammation, including disorganization of retinal inner layers (DRIL), retinal hyperreflective foci (HRF), hyperreflective choroidal foci (HCF), subfoveal neuroretinal detachment (SND), and perturbation in retinal nerve fiber layer (RNFL) thickness, ganglion cell layer (GCL) thickness, and inner nuclear layer (INL) thickness were evaluated by graders masked to the clinical characteristics of the patients. We performed multivariable regression analyses with the OCT biomarkers as the outcome variables and sex, age, HbA1c, and CMT as independent variables. Main Outcome MeasuresOCT inflammation-related biomarkers as listed above ResultsFemale patients were on average two years older than male patients (P = 0.041). There were no significant differences in race and ethnicity, HbA1c, VA, or CMT between male and female patients. After controlling for age, HbA1c, and CMT, we found male sex to be associated with more HRF (incidence rate ratio [IRR] = 1.19, 95% confidence interval [CI] = 1.10 – 1.29), more HCF (odds ratio = 2.01, 95% CI = 1.12 – 3.64), and thicker INL (7 μm thicker in males, 95% CI = 2 – 12). Sex was not a significant predictor for either DRIL or SND in the multivariable regression models. Patients with higher HbA1c were more likely to have more HRF (IRR = 1.02 per 1 point increase, 95% CI = 1.00 – 1.04) after controlling for other factors. ConclusionsMale sex was correlated with more inflammation-related biomarkers on OCT including more HRF, more HCF, and thicker INL, after accounting for age, glycemic control, and amount of DME. Further studies are needed to evaluate the potential implications of these sex-based differences for individualized treatment.

The presence of choroidal hyperreflective foci in Stargardt disease is, to our knowledge, a potentially new finding. Evaluation of these foci may aid in better understanding of the disease process. To report the presence of choroidal hyperreflective foci in spectral-domain optical coherence tomography (SD-OCT) images from eyes with Stargardt disease and investigate the relationship between the number of hyperreflective foci and disease severity. Twenty-six eyes of 13 patients with a clinical diagnosis of Stargardt disease were evaluated in a retrospective case series. Patient data were collected between January 1, 2009, and August 31, 2014. The number of choroidal hyperreflective foci in Stargardt disease as well as correlation with visual acuity, central macular thickness (CMT), and disease duration were the main outcomes. A total of 707 macular SD-OCT scans of 13 patients with Stargardt disease were reviewed and evaluated for the presence and number of retinal/choroidal hyperreflective foci, central macular thickness, visual acuity, and disease duration. Enhanced depth imaging with OCT (EDI-OCT) scans available for 2 patients were compared with SD-OCT scans. A PubMed/Google search was performed to identify SD-OCT images in Stargardt disease; these findings were reviewed for the presence of choroidal hyperreflective foci. The mean (SD) numbers of hyperreflective foci in each retinal/choroidal layer in decreasing frequency were as follows: Bruch membrane/retinal pigment epithelial (RPE) complex, 78.22 (24.39); choriocapillaris, 25.77 (17.57); Sattler layer, 18.59 (12.89); outer retina, 16.64 (6.96); inner retina, 0.95 (1.58); and Haller layer, 0.73 (0.87). The number of hyperreflective foci in the Bruch membrane/RPE complex increased exponentially with decreasing CMT (R2 = 0.99; P = .008). The number of hyperreflective foci in the Bruch membrane/RPE complex, choriocapillaris, and Sattler layer increased proportionally with decreasing visual acuity (R2 = 0.97, R2 = 0.95, and R2 = 0.99, respectively; and P = .007, P = .006, and P = .008, respectively). Direct correlation existed between the number of hyperreflective foci in the choriocapillaris and the Sattler layer and disease duration (R2 = 0.98 and R2 = 0.99, respectively; and P = .006 and P =.009, respectively). In the 10 studies on Stargardt disease, choroidal hyperreflective foci were present in 51 of 54 SD-OCT images (94%). Based on the findings of the present study, choroidal hyperreflective foci in Stargardt disease, prominent at the Bruch membrane/RPE complex, choriocapillaris, and Sattler layer, correlate with disease severity in terms of retinal atrophy, decline in vision, and disease duration. Further studies are necessary to assess whether these findings are unique to Stargardt disease.

The aim of this study is to correlate small dot hyper‐reflective foci (HRF) observed in spectral domain optical coherence tomography (SD‐OCT) scans of an animal model of hyperglycaemia with focal electroretinography (fERG) response and immunolabelling of retinal markers. The eyes of an animal model of hyperglycaemia showing signs of diabetic retinopathy (DR) were imaged using SD‐OCT. Areas showing dot HRF were further evaluated using fERG. Retinal areas enclosing the HRF were dissected and serially sectioned, stained and labelled for glial fibrillary acidic protein (GFAP) and a microglial marker (Iba‐1). Small dot HRF were frequently seen in OCT scans in all retinal quadrants in the inner nuclear layer or outer nuclear layer in the DR rat model. Retinal function in the HRF and adjacent areas was reduced compared with normal control rats. Microglial activation was detected by Iba‐1 labelling and retinal stress identified by GFAP expression in Müller cells observed in discrete areas around small dot HRF. Small dot HRF seen in OCT images of the retina are associated with a local microglial response. This study provides the first evidence of dot HRF correlating with microglial activation, which may allow clinicians to better evaluate the microglia‐mediated inflammatory component of progressive diseases showing HRF.

BackgroundFabry disease (FD) is an X-linked inherited storage disorder caused by deficiency of lysosomal alpha-Galactosidase A. Here we describe new retinal findings in patients with FD assessed by Spectral domain optical coherence tomography (SD-OCT) and their possible clinical relevance.Methods54 eyes of 27 FD patients and 54 eyes of 27 control subjects were included. The ophthalmic examination included visual acuity testing, tonometry, slit lamp and fundus examination. SD-OCT imaging of the macula was performed in all subjects. Central retinal thickness and retinal nerve fiber layer analysis were quantified. Vessel tortuosity was obtained by a subjective scoring and mathematically calculated. Inner retinal hyperreflective foci (HRF) were quantified, clinically graded and correlated with a biomarker of Fabry disease (lyso-Gb3).ResultsIn comparison to an age-matched control group, a significant amount of HRF was identified in macular SD-OCT images in FD patients. These HRF were localized within the inner retinal layers. Furthermore, lyso-Gb3 levels correlated significantly with the quantitative evaluation of HRF (p < 0,001). In addition, the vessel tortuosity was remarkably increased in FD patients compared to control persons and correlated significantly with lyso-G3 levels (p = 0.005). A further subanalysis revealed significantly higher HRF and vessel tortuosity scores in male patients with the classic FD phenotype.ConclusionsThe observational, cross sectional, comparative study describes novel intraretinal findings in patients with FD. We were able to identify suspicious HRF within the inner retinal layers. These findings were not accompanied by functional limitations, as visual acuity remained unchanged. However, HRF correlated well with lyso-Gb3, a degradation product of the accumulating protein Gb3 and might potentially indicate Gb3 accumulation within the highly metabolic and densely vascularized macula.

Subretinal Fluid in Uveitic Macular Edema: Effect on Vision and Response to Therapy

Background: Choroidal neovascular membrane (CNVM) is common problems and causes loss of central sight in the geriatric population. This is essential to comprehend the morphological characteristics of CNVM and baseline visual acuity (VA) in age-related macular degeneration (AMD). Objective: To examine the correlation between new patients with untreated AMD and their baseline VA, demographic, angiographic, and spectral-domain OCT (SD-OCT) CNVM features. Methods: A study was conducted at a tertiary eye hospital on 50 eyes belonging to consecutive individuals with newly diagnosed and untreated AMD from June 2022 to May 2023. Snellen baseline visual acuity (VA) was converted to the LogMAR scale. SD-OCT biomarkers were meticulously study for intraretinal fluid (IRF), subretinal fluid (SRF), sub-RPE fluid (SRPE), hyperreflective material (HRM), photoreceptor disruption, hyperreflective foci (HRF), and Outer retinal tubulation (ORT). OCT angiography helped to find choroidal neovascular membrane type and location. Results: In this study, 28 (56%) of the participants in this study were male, and the mean age was 73.3 ± 8.7 years. The baseline visual acuity VA) score in this study was 1.06±0.38 Log MAR. Visual acuity was observed to be considerably lower when SRF (p=0.01) and SRPE (p=0.03) were present. Age, sex, CNVM types, lesion pattern, and the presence of IRF, HRM, photoreceptor disruption, ORT, or HRF did not significantly correlate with BCVA. Conclusion: In the untreated AMD, the presence of SRF and SRPE fluid on SD-OCT were significant biomarkers for worse baseline visual function. In contrast, CNVM type and other OCT biomarkers showed no significant association with initial visual acuity.

Association Between Hyperreflective Foci in the Outer Retina, Status of Photoreceptor Layer, and Visual Acuity in Diabetic Macular Edema

We propose an automated segmentation method to detect, segment, and quantify hyperreflective foci (HFs) in three-dimensional (3-D) spectral domain optical coherence tomography (SD-OCT). The algorithm is divided into three stages: preprocessing, layer segmentation, and HF segmentation. In this paper, a supervised classifier (random forest) was used to produce the set of boundary probabilities in which an optimal graph search method was then applied to identify and produce the layer segmentation using the Sobel edge algorithm. An automated grow-cut algorithm was applied to segment the HFs. The proposed algorithm was tested on 20 3-D SD-OCT volumes from 20 patients diagnosed with proliferative diabetic retinopathy (PDR) and diabetic macular edema (DME). The average dice similarity coefficient and correlation coefficient ([Formula: see text]) are 62.30%, 96.90% for PDR, and 63.80%, 97.50% for DME, respectively. The proposed algorithm can provide clinicians with accurate quantitative information, such as the size and volume of the HFs. This can assist in clinical diagnosis, treatment, disease monitoring, and progression.

Intraretinal Hyperreflective Foci in Acquired Vitelliform Lesions of the Macula: Clinical and Histologic Study

AimsWe aimed to investigate predictive factors for visual and anatomic outcomes in patients with macular edema secondary to non-infectious uveitis.Material and methodsWe conducted a multicenter, prospective, observational, 12-month follow-up study. Participants included in the study were adults with non-infectious uveitic macular edema (UME), defined as central subfoveal thickness (CST) of >300 μm as measured by spectral domain optical coherence tomography (SD-OCT) and fluid in the macula. Demographic, clinical and tomographic data was recorded at baseline, 1, 3, 6 and 12 months. Foveal-centered SD-OCT exploration was set as the gold-standard determination of UME using a standard Macular Cube 512x128 A-scan, within a 6 x 6 mm2 area, and the Enhanced High Definition Single-Line Raster. To assess favorable prognosis, the main outcomes analyzed were the best-corrected visual acuity (BCVA) and the CST. Favorable prognosis was defined as sustained improvement of BCVA (2 lines of gain of the Snellen scale) and CST (decrease of 20% of the initial value or <300 μm) within a 12 month period.ResultsFifty-six eyes were analyzed. The number of eyes with sustained improvement in the CST was 48 (86.2%), against 23 (41.1%) eyes with sustained improvement in BCVA. Favorable prognosis, as defined above, was observed in 18 (32.1%) eyes. UME prognosis was negatively correlated with baseline foveal thickening, alteration in the vitreo-macular interface and cystoid macular edema. In contrast, bilaterally, systemic disease and the presence of anterior chamber cells were predictive of favorable prognosis.ConclusionAvailable treatment modalities in UME may avoid chronic UME and improve anatomic outcome. However, the proportion of functional amelioration observed during 12 months of follow-up is lower. Thicker CST, alteration in the vitreo-macular interface and cystoid macular edema may denote less favorable prognosis. Conversely, bilaterally, systemic disease and anterior chamber cells may be associated with favorable prognosis in UME.

Purpose:Choroidal hyperreflective foci (HCF) are novel spectral-domain optical coherence tomography (SDOCT) biomarkers in diabetic macular edema (DME). The present study intended to validate HCF and assess their role in the treatment outcome.Methods:It was a retrospective, longitudinal, records-based pilot study recruiting consecutive patients of nonproliferative diabetic retinopathy with treatment naïve DME. Patients were treated with three intravitreal anti-vascular endothelial growth factor injections and followed by a pro re nata regimen.Results:A total of 43 eyes of 28 patients were included in the study. Eyes were divided into two groups. Group A (n = 19) comprised eyes with retinal hyperreflective foci (HRF) and group B (n = 24) had eyes with both HRF and HCF. The mean age of patients in group A and B was 58.5 ± 2.1 years and 55.2 ± 8.8 years, respectively. Mean best-corrected visual acuity at presentation was 0.38 ± 0.25 in group A and 0.59 ± 0.29 in group B (P = 0.01). Final BCVA was 0.35 ± 0.39 in group A and 0.47 ± 0.34 in group B (P = 0.3). External limiting membrane was intact in 19 out of 19 eyes in group A and two (8.3%) eyes in group B (P = 0).Conclusion:Presence of HCF meant significantly worse initial BCVA compared to the eye that had HRF alone. The final BCVA was also worse in eyes with HCF compared to those with HRF and without HCF; however, the difference did not reach a significance level, probably pointing toward the fact that HCF and HRF are pathophysiologically identical. Further studies with a larger sample size and prospective design are needed to take these findings forward.