OCT biomarkers related to subthreshold micropulse laser treatment effect in central serous chorioretinopathy.

BACKGROUND: To identify the OCT biomarkers related to the anatomical outcomes in eyes with central serous chorioretinopathy (CSCR) after subthreshold micropulse laser (SML) treatment. METHODS: Patients with CSCR underwent SML were enrolled in this retrospective study. Only patients who underwent enhanced depth imaging optical coherence tomography (EDI-OCT) examination before and after SML were selected. Patients were divided into two groups based on whether subretinal fluid (SRF) absorbed or not after SML. Group 1 was the SRF resolved group, and Group 2 was the SRF non-resolved group. Factors including age and gender, duration of symptoms, CSCR history, the height of SRF at baseline, retinal pigment epithelium (RPE) /inner choroid alterations, as well as subfoveal choroidal thickness (SFCT) of the affected eye and the fellow eye before and after SML were recorded and compared between two groups. Longitudinal change of SFCT of a subgroup of patients were analyzed. RESULTS: A total of 58 eyes of 58 patients were involved in this study. SRF of 31 eyes got completely absorbed, and SRF of 27 eyes was retained after SML. Logistic regression analysis revealed baseline SFCT of the affected eye (OR = 1.007, 95% CI: 1.001-1.012, P = 0.019) and RPE/inner choroid alterations (OR = 25.229, 95% CI: 2.890-220.281, P = 0.004) were correlated with SML efficacy. Thirty-three eyes of 33 patients were enrolled in the subgroup analysis. A significant difference of SFCT changes between two groups were demonstrated (P = 0.001). The difference of SFCT between baseline and three months after SML was also related to SRF resolution (OR = 0.952, 95% CI: 0.915-0.990, P = 0.014). CONCLUSION: Baseline SFCT, change of SFCT at 3-month after treatment, and RPE/inner choroid alterations were the OCT biomarkers related to SRF resolution after SML treatment.

Correlating the patterns of diabetic macular edema, optical coherence tomography biomarkers and grade of diabetic retinopathy with stage of renal disease.

PURPOSE: To correlate optical coherence tomography (OCT)-based morphological patterns of diabetic macular edema (DME), biomarkers and grade of diabetic retinopathy (DR) in patients with various stages of chronic kidney disease (CKD) secondary to diabetes. DESIGN: Multicentric retrospective cross-sectional study was conducted at seven centers across India. METHODS: Data from medical records of patients with DME and CKD were entered in a common excel sheet across all seven centers. Staging of CKD was based on estimated glomerular filtration rate (eGFR). RESULTS: The most common morphological pattern of DME was cystoid pattern (42%) followed by the mixed pattern (31%). The proportion of different morphological patterns did not significantly vary across various CKD stages (p = 0.836). The presence of external limiting membrane-ellipsoid zone (ELM-EZ) defects (p < 0.001) and foveal sub-field thickness (p = 0.024) showed a direct correlation with the stage of CKD which was statistically significant. The presence of hyperreflective dots (HRD) and disorganization of inner retinal layers (DRIL) showed no significant correlation with the stage of CKD. Sight threatening DR was found to increase from 70% in CKD stage 3 to 82% in stages 4 and 5 of CKD, and this was statistically significant (p = 0.03). CONCLUSION: Cystoid morphological pattern followed by mixed type was the most common pattern of DME on OCT found in patients suffering from stage 3 to 5 of CKD. However, the morphological patterns of DME did not significantly vary across various CKD stages. ELM-EZ defects may be considered as an important OCT biomarker for advanced stage of CKD.

Intravitreal Dexamethasone Implant in the Treatment of Diabetic Macular Edema Focusing on the Role of OCT Biomarkers

OBJECTIVE: The aim of this study was to evaluate the outcomes of Ozurdex® (DEX) implant in patients with diabetic macular edema (DME) in real-world clinical practice, and to determine the correlation between known OCT biomarkers and the effect of treatment. MATERIAL AND METHODS: This retrospective study included 42 eyes of 33 patients (16 women, 17 men) treated with DEX at the Department of Ophthalmology, Faculty of Medicine and Dentistry of Palacký University and University Hospital Olomouc for DME indication between 2020 and 2023. Follow-up examinations were conducted at 1, 3, and 6 months after the first DEX application. The main assessed parameters were: best-corrected visual acuity (BCVA), intraocular pressure (IOP), central retinal thickness (CRT), OCT biomarkers. The results were subsequently statistically evaluated. RESULTS: At the first follow-up after DEX application, there was an average decrease in CRT of 186 ±146µm and a gain of 3 ±7 letters. Positive morphological and functional responses were observed in 39 eyes (92.9%) and 23 eyes (54.8%) respectively. The disorganization of retinal inner layers (DRIL) biomarker was initially present in 41 eyes (97.6%), with reduction or disappearance observed in 13 eyes (31%) post-application. Eyes with ellipsoid zone disruption (EZ disruption) had an average initial BCVA of 49.6 letters, compared to 57.8 letters in the group without this biomarker. The mean gain in BCVA was +8.7 letters in treatment-naive eyes and +2.1 letters in previously treated eyes. Chronic DME was less frequent in treatment-naive (n = 1, 14.3%) compared to previously treated eyes (n = 28, 84.8%). All these results were statistically significant (p < 0.05). An increase in IOP post-DEX application occurred in 9 patients (21.4%). CONCLUSION: Our results confirm DEX as a safe and effective treatment option for DME. Treatment-naive patients achieved better functional outcomes. We confirmed ellipsoid zone disruption (EZ disruption) as a negative biomarker. Additionally, we demonstrated the capacity of DEX to reduce disorganization of the retinal inner layers (DRIL).

Enhancing Diabetic Macular Edema Treatment Outcomes: Exploring the ESASO Classification and Structural OCT Biomarkers.

INTRODUCTION: This study assessed the European School of Advanced Studies in Ophthalmology (ESASO) classification's prognostic value for diabetic macular edema (DME) in predicting intravitreal therapy outcomes. METHODS: In this retrospective, multicenter study, patients aged > 50 years with type 1 or 2 diabetes and DME received intravitreal antivascular endothelial growth factor (anti-VEGF) agents (ranibizumab, bevacizumab, and aflibercept) or steroids (dexamethasone). The primary outcome was visual acuity (VA) change post-treatment, termed as functional response, measured 4-6 weeks post-third anti-VEGF or 12-16 weeks post-steroid injection, stratified by initial DME stage. RESULTS: Of the 560 eyes studied (62% male, mean age 66.7 years), 31% were classified as stage 1 (early), 50% stage 2 (advanced), 17% stage 3 (severe), and 2% stage 4 (atrophic). Visual acuity (VA; decimal) improved by 0.12-0.15 decimals in stages 1-2 but only 0.03 decimal in stage 3 (all p < 0.0001) and 0.01 in stage 4 (p = 0.38). Even in eyes with low baseline VA ≤ 0.3, improvements were significant only in stages 1 and 2 (0.12 and 0.17 decimals, respectively). Central subfield thickness (CST) improvement was greatest in stage 3 (-229 µm, 37.6%, p < 0.0001), but uncorrelated with VA gains, unlike stages 1 and 2 (respectively: -142 µm, 27.4%; - 5 µm, 12%; both p < 0.0001). Stage 4 showed no significant CST change. Baseline disorganization of retinal inner layers and focal damage of the ellipsoid zone/external limiting membrane did not influence VA improvement in stages 1 and 2. Treatment patterns varied, with 61% receiving anti-VEGF and 39% dexamethasone, influenced by DME stage, with no significant differences between therapeutic agents. CONCLUSION: The ESASO classification, which views the retina as a neurovascular unit and integrates multiple biomarkers, surpasses single biomarkers in predicting visual outcomes. Significant functional improvement occurred only in stages 1 and 2, suggesting reversible damage, whereas stages 3 and 4 likely reflect irreversible damage.

Visual acuity prediction on real-life patient data using a machine learning based multistage system.

In ophthalmology, intravitreal operative medication therapy (IVOM) is a widespread treatment for diseases related to the age-related macular degeneration (AMD), the diabetic macular edema, as well as the retinal vein occlusion. However, in real-world settings, patients often suffer from loss of vision on time scales of years despite therapy, whereas the prediction of the visual acuity (VA) and the earliest possible detection of deterioration under real-life conditions is challenging due to heterogeneous and incomplete data. In this contribution, we present a workflow for the development of a research-compatible data corpus fusing different IT systems of the department of ophthalmology of a German maximum care hospital. The extensive data corpus allows predictive statements of the expected progression of a patient and his or her VA in each of the three diseases. For the disease AMD, we found out a significant deterioration of the visual acuity over time. Within our proposed multistage system, we subsequently classify the VA progression into the three groups of therapy "winners", "stabilizers", and "losers" (WSL classification scheme). Our OCT biomarker classification using an ensemble of deep neural networks results in a classification accuracy (F1-score) of over 98%, enabling us to complete incomplete OCT documentations while allowing us to exploit them for a more precise VA modelling process. Our VA prediction requires at least four VA examinations and optionally OCT biomarkers from the same time period to predict the VA progression within a forecasted time frame, whereas our prediction is currently restricted to IVOM/no therapy. We achieve a final prediction accuracy of 69% in macro average F1-score, while being in the same range as the ophthalmologists with 57.8 and 50 ± 10.7 % F1-score.

Association between resistivity index of central retinal artery and severity of diabetic retinopathy.

Purpose: Diabetic retinopathy (DR) is a leading cause of ocular morbidity. Its progression depends mainly on retinal vasculature and ocular blood flow. Color Doppler imaging (CDI) is a noninvasive imaging technique that measures blood flow velocity. The resistivity index (RI), calculated by the CDI, reflects the vascular resistance distal to the measuring location. RI is independent of the doppler angle and position of the patient, making it a reliable and reproducible parameter. To the best of our knowledge, there is only one study in literature studying the association between resistivity index (RI) of the central retinal artery (CRA) and severity of DR. Aim: To determine the association between RI of CRA and severity of DR. To determine the association between RI of CRA and spectral-domain optical coherence tomography (SD-OCT) biomarkers for DR. Methods: Type II diabetics visiting our OPD underwent DR screening and were graded into three categories according to ETDRS classification which include Group A-No diabetic retinopathy (No DR), Group B-Nonproliferative diabetic retinopathy (Moderate-Severe-Very Severe NPDR), and Group C-Proliferative diabetic retinopathy (PDR). SD-OCT was performed. Ultrasonic color doppler imaging was done. RI of the CRA was noted. It was compared between the three groups and its association with severity of DR and OCT biomarkers (central subfield thickness, cube average thickness and ellipsoid zone disruption) was studied. Results: 56 eyes of 28 patients were included in our study with 20 in Group A,14 in Group B, and 22 in Group C. RI of CRA compared within groups showed statistically significant association with severity of DR (P < 0.001). The presenting BCVA (LogMar) showed positive correlation with RI in all groups. OCT biomarker central subfield thickness showed a positive correlation with RI in Groups A (P < 0.001) and B. Ellipsoid zone (EZ) disruption showed a statistically significant association with RI in Group C (P < 0.001). Conclusion: The RI of CRA is a reliable biomarker for the assessment of the severity of DR. Patients with high RI of CRA had higher chances of EZ disruption and presented with poor visual acuity.

Improving OCT Image Segmentation of Retinal Layers by Utilizing a Machine Learning Based Multistage System of Stacked Multiscale Encoders and Decoders.

Optical coherence tomography (OCT)-based retinal imagery is often utilized to determine influential factors in patient progression and treatment, for which the retinal layers of the human eye are investigated to assess a patient's health status and eyesight. In this contribution, we propose a machine learning (ML)-based multistage system of stacked multiscale encoders and decoders for the image segmentation of OCT imagery of the retinal layers to enable the following evaluation regarding the physiological and pathological states. Our proposed system's results highlight its benefits compared to currently investigated approaches by combining commonly deployed methods from deep learning (DL) while utilizing deep neural networks (DNN). We conclude that by stacking multiple multiscale encoders and decoders, improved scores for the image segmentation task can be achieved. Our retinal-layer-based segmentation results in a final segmentation performance of up to 82.25±0.74% for the Sørensen-Dice coefficient, outperforming the current best single-stage model by 1.55% with a score of 80.70±0.20%, given the evaluated peripapillary OCT data set. Additionally, we provide results on the data sets Duke SD-OCT, Heidelberg, and UMN to illustrate our model's performance on especially noisy data sets.

Biomarkers to Predict the Success of Treatment with the Intravitreal 0.19 mg Fluocinolone Acetonide Implant in Uveitic Macular Edema.

To predict the need for additional local corticosteroids after receiving the 0.19 mg fluocinolone acetonide (FAc) implant in patients with macular edema secondary to non-infectious uveitis previously treated with local peribulbar corticosteroids. The number of corticosteroids required prior FAc, visual acuity, central retinal thickness, ellipsoid zone reflectivity ratio (EZR), and choroidal vascularity index (CVI) were compared between patients who did and did not require additional corticosteroids after FAc implantation. Pearson's correlation coefficient (R) between putative predictors and the number of adjunctive corticosteroids after FAc implantation were measured; significant candidates were included in a generalized regression model. Patients who required additional corticosteroids after FAc had higher CVI and central retinal thickness as well as worse EZR at subsequent visits (p < 0.05). The number of corticosteroids required prior to FAc implantation (R: 0.49), CVI change from baseline to 6 months (R: −0.41), and central retinal thickness at baseline (R: −0.36) correlated to the number of additional corticosteroids (all p < 0.05). A higher number of corticosteroids per year before FAc implantation was predictive for an increase in corticosteroids required after FAc (odds ratio = 2.65), while a decrease in CVI from baseline to 6 months was inversely correlated (odds ratio = 0.82). Our results suggest that the more corticosteroids prior to FAc and the greater the short-term CVI reducing effect, the less is the chance to get additional corticosteroids after FAc.

Retinal structural changes in mood disorders: The optical coherence tomography to better understand physiopathology?

BACKGROUND: Mood disorders are particularly common, disabling conditions. Diagnosis can be difficult as it may involve different pathophysiological assumptions. This could explain why such disorders are resistant to treatment. The retina is part of the central nervous system and shares a common embryonic origin with the brain. Optical coherence tomography (OCT) is an imaging technique for analysing the different layers of the retina. We reviewed studies that examined the retina with OCT in mood disorders. METHODS: We conducted Pubmed search and additional manual research based on the bibliography in each of selected articles. We found and analysed 11 articles relevant to our subject. RESULTS: This literature review confirms that it is possible to use OCT to detect neurodegeneration and neuroinflammation in mood disorders. Their impact is thought to depend on the duration and severity of the disease, and whether it is in acute or chronic stage. The differences seen in studies dealing with depression and those looking at bipolar disorder may reflect the particular characteristics of each disorder. A number of OCT parameters can be proposed as biomarkers of active or chronic inflammation and neurodegeneration. Markers of predisposition to an at-risk mental state are also suggested. LIMITATIONS: The main limitation is selection bias, studies including more varied population would help to confirm and precise these results. CONCLUSION: OCT is thus a particularly promising tool for evaluating some of the etiopathogenetic mechanisms involved in mood disorders. The combination with other approaches could help to find more specific biomarkers.

Predicting Incremental and Future Visual Change in Neovascular Age-Related Macular Degeneration Using Deep Learning.

PURPOSE: To evaluate the predictive usefulness of quantitative imaging biomarkers, acquired automatically from OCT scans, of cross-sectional and future visual outcomes of patients with neovascular age-related macular degeneration (AMD) starting anti-vascular endothelial growth factor (VEGF) therapy. DESIGN: Retrospective cohort study. PARTICIPANTS: Treatment-naive, first-treated eyes of patients with neovascular AMD between 2007 and 2017 at Moorfields Eye Hospital (a large, United Kingdom single center) undergoing anti-VEGF therapy. METHODS: Automatic segmentation was carried out by applying a deep learning segmentation algorithm to 137 379 OCT scans from 6467 eyes of 3261 patients with neovascular AMD. After applying selection criteria, 926 eyes of 926 patients were analyzed. MAIN OUTCOME MEASURES: Correlation coefficients (R2 values) and mean absolute error (MAE) between quantitative OCT (qOCT) parameters and cross-sectional visual function, as well as the predictive value of these parameters for short-term visual change, that is, incremental visual acuity (VA) resulting from an individual injection, as well as VA at distant time points (up to 12 months after baseline). RESULTS: Visual acuity at distant time points could be predicted: R2 = 0.80 (MAE, 5.0 Early Treatment Diabetic Retinopathy Study [ETDRS] letters) and R2 = 0.7 (MAE, 7.2 ETDRS letters) after injection at 3 and at 12 months after baseline (P < 0.001 for both), respectively. Best performing models included both baseline qOCT parameters and treatment response. Furthermore, we present proof-of-principle evidence that the incremental change in VA from an injection can be predicted: R2 = 0.14 (MAE, 5.6 ETDRS letters) for injection 2 and R2 = 0.11 (MAE, 5.0 ETDRS letters) for injection 3 (P < 0.001 for both). CONCLUSIONS: Automatic segmentation enables rapid acquisition of quantitative and reproducible OCT biomarkers with potential to inform treatment decisions in the care of neovascular AMD. This furthers development of point-of-care decision-aid systems for personalized medicine.

Age, Initial Central Retinal Thickness, and OCT Biomarkers Have an Influence on the Outcome of Diabetic Macular Edema Treated With Ranibizumab- Tri-center 12-Month Treat-and-Extend Study.

Objective: We report the tri-center 1-year outcomes of a treat-and-extend (T&E) regimen in four-week intervals with ranibizumab for diabetic macular edema (DME). Methods: In this retrospective study, all eyes received 3 monthly loading injections of 0.5 mg ranibizumab, followed by a T&E regimen for DME. Regression models were used to evaluate the associating factors for visual and anatomical outcomes. Results: Ninety one eyes from 64 patients were enrolled. Mean LogMAR best-corrected visual acuity (BCVA) improved from 0.58 at baseline to 0.36 at month 12 and mean central retinal thickness (CRT) decreased from 411 µm at baseline to 290 µm at month 12. Younger age and eyes having thinner baseline CRT, with ellipsoid zone disruption (EZD), and without epiretinal membrane (ERM) were associated with better final CRT. Moreover, eyes with thicker baseline CRT tend to receive more injections. Among the parameters, only having ERM or EZD was associated with significant BCVA recovery. Conclusions: A T&E regimen with ranibizumab by 4-week intervals is effective in improving BCVA and reducing CRT with efficacy notable starting from the third month. Clinical parameters including age, initial CRT, and presence of ERM or EZD significantly influenced therapeutic outcomes. Moreover, the presence of ERM should not preclude DME patients from receiving anti-VEGF therapy. Future studies with larger cohorts are warranted.