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Diabetic macular edema (DME), defined as retinal thickening near, or involving the fovea caused by fluid accumulation in the retina, can lead to vision impairment and blindness in patients with diabetes. Current knowledge of retina anatomy and function and DME pathophysiology has taken great advantage of the availability of several techniques for visualizing the retina. Combining these techniques in a multimodal imaging approach to DME is recommended to improve diagnosis and to guide treatment decisions. We review the recent literature about the following retinal imaging technologies: optical coherence tomography (OCT), OCT angiography (OCTA), wide-field and ultrawide-field techniques applied to fundus photography, fluorescein angiography, and OCTA. The emphasis will be on characteristic DME features identified by these imaging technologies and their potential or established role as diagnostic, prognostic, or predictive biomarkers. The role of artificial intelligence in the assessment and interpretation of retina images is also discussed. • Diabetic macular edema (DME) leads diabetic patients to vision loss and blindness. • Multimodal imaging combines various techniques. • Multimodal imaging aids DME diagnosis and guides treatment. • Imaging has potential as diagnostic, prognostic, or predictive biomarkers. • Artificial intelligence can assess and interpret retina images. [ABSTRACT FROM AUTHOR]

Abstract Age-related macular degeneration (AMD) and diabetic macular edema (DME) are significant causes of blindness worldwide. The prevalence of these diseases is steadily increasing due to population aging. Therefore, early diagnosis and prevention are crucial for effective treatment. Classification of Macular Degeneration OCT Images is a widely used method for assessing retinal lesions. However, there are two main challenges in OCT image classification: incomplete image feature extraction and lack of prominence in important positional features. To address these challenges, we proposed a deep learning neural network model called MSA-Net, which incorporates our proposed multi-scale architecture and spatial attention mechanism. Our multi-scale architecture is based on depthwise separable convolution, which ensures comprehensive feature extraction from multiple scales while minimizing the growth of model parameters. The spatial attention mechanism is aim to highlight the important positional features in the images, which emphasizes the representation of macular region features in OCT images. We test MSA-NET on the NEH dataset and the UCSD dataset, performing three-class (CNV, DURSEN, and NORMAL) and four-class (CNV, DURSEN, DME, and NORMAL) classification tasks. On the NEH dataset, the accuracy, sensitivity, and specificity are 98.1%, 97.9%, and 98.0%, respectively. After fine-tuning on the UCSD dataset, the accuracy, sensitivity, and specificity are 96.7%, 96.7%, and 98.9%, respectively. Experimental results demonstrate the excellent classification performance and generalization ability of our model compared to previous models and recent well-known OCT classification models, establishing it as a highly competitive intelligence classification approach in the field of macular degeneration.

Abstract Introduction The aims of this work were to evaluate the real-world efficacy and safety of a loading dose of intravitreal faricimab in eyes with active neovascular age-related macular degeneration (n-AMD) or diabetic macular edema (DME) and to analyze the treatment outcome in relation to specific biomarkers. Methods Patients with active n-AMD or DME, treated with four monthly intravitreal injections of faricimab, were enrolled in this retrospective, uncontrolled study. Best-corrected visual acuity (BCVA), central subfield thickness (CST), presence of retinal fluid (RF) on optical coherence tomography (OCT), and adverse events were assessed at baseline and at weeks 4, 8, 12, and 16. Predefined biomarkers were evaluated at baseline (BL) and at last visit. Results Sixteen eyes of 15 patients with n-AMD (n-AMD group) and 15 eyes of 12 patients with DME (DME group) were included. Mean (± standard deviation) logarithm of minimum angle of resolution (logMAR) BL BCVA changed from 0.68 (± 0.43) to 0.53 (± 0.36; P = 0.13) and from 0.51 (± 0.34) to 0.32 (± 0.24; P: 0.048) at week 16 in n-AMD and DME group, respectively. A statistically significant mean CST reduction was reported in both groups at last visit (n-AMD: − 166.5 μm; P = 0.0009/DME: − 110.8 μm; P = 0.0086). Seventy-five and 33% of eyes with n-AMD and DME respectively achieved complete RF resolution at last visit. Subfoveal inner and outer retinal damage correlated with a lower final BCVA in n-AMD group. The presence of large (> 100 μm) juxtafoveal microaneurysms (MAs) was significantly correlated with a higher chance of residual fluid in eyes with DME. Conclusions Both n-AMD and DME groups achieved satisfactory anatomical results after a loading-dose of intravitreal faricimab. BCVA improvement might be hampered by pre-existing retinal damage in eyes with n-AMD. Large, juxtafoveal MAs might represent a hallmark of a slower anatomical response to the treatment in eyes with DME.

Diabetic macular edema (DME) poses a significant threat to vision. It is characterized by the enlargement of the macula due to the accumulation of plasma in the extracellular space of the retina. Detection of DME, crucial for timely intervention, traditionally relies on manual inspection of images, which is time-consuming and prone to human error. Leveraging advancements in computer-assisted diagnostics, this study proposes a novel approach utilizing the DenseUNet+ architecture tailored for precise segmentation across diverse image modalities. The proposed method integrates data from four modalities within dense block structures, followed by linear operations and concatenation to enhance feature representation. Evaluation using ResNet101V2 and DenseNet201 demonstrates superior performance, with accuracy exceeding 95% and 99%, respectively, showcasing their efficacy in screening retinal optical coherence tomography (OCT) images for DME. This research highlights the potential of deep learning techniques to enhance ophthalmologists' abilities to efficiently screen, diagnose, and manage DME, thus reducing the risk of irreversible vision loss. [ABSTRACT FROM AUTHOR]

Introduction: The aims of this work were to evaluate the real-world efficacy and safety of a loading dose of intravitreal faricimab in eyes with active neovascular age-related macular degeneration (n-AMD) or diabetic macular edema (DME) and to analyze the treatment outcome in relation to specific biomarkers. Methods: Patients with active n-AMD or DME, treated with four monthly intravitreal injections of faricimab, were enrolled in this retrospective, uncontrolled study. Best-corrected visual acuity (BCVA), central subfield thickness (CST), presence of retinal fluid (RF) on optical coherence tomography (OCT), and adverse events were assessed at baseline and at weeks 4, 8, 12, and 16. Predefined biomarkers were evaluated at baseline (BL) and at last visit. Results: Sixteen eyes of 15 patients with n-AMD (n-AMD group) and 15 eyes of 12 patients with DME (DME group) were included. Mean (± standard deviation) logarithm of minimum angle of resolution (logMAR) BL BCVA changed from 0.68 (± 0.43) to 0.53 (± 0.36; P = 0.13) and from 0.51 (± 0.34) to 0.32 (± 0.24; P: 0.048) at week 16 in n-AMD and DME group, respectively. A statistically significant mean CST reduction was reported in both groups at last visit (n-AMD: − 166.5 μm; P = 0.0009/DME: − 110.8 μm; P = 0.0086). Seventy-five and 33% of eyes with n-AMD and DME respectively achieved complete RF resolution at last visit. Subfoveal inner and outer retinal damage correlated with a lower final BCVA in n-AMD group. The presence of large (> 100 μm) juxtafoveal microaneurysms (MAs) was significantly correlated with a higher chance of residual fluid in eyes with DME. Conclusions: Both n-AMD and DME groups achieved satisfactory anatomical results after a loading-dose of intravitreal faricimab. BCVA improvement might be hampered by pre-existing retinal damage in eyes with n-AMD. Large, juxtafoveal MAs might represent a hallmark of a slower anatomical response to the treatment in eyes with DME. [ABSTRACT FROM AUTHOR]

Gene therapy holds promise as a transformative approach in the treatment landscape of age-related macular degeneration (AMD), diabetic retinopathy (DR), and diabetic macular edema (DME), aiming to address the challenges of frequent intravitreal anti-vascular endothelial growth factor (VEGF) injections. This manuscript reviews ongoing gene therapy clinical trials for these disorders, including ABBV-RGX-314, ixoberogene soroparvovec (ixo-vec), and 4D-150. ABBV-RGX-314 utilizes an adeno-associated virus (AAV) vector to deliver a transgene encoding a ranibizumab-like anti-VEGF antibody fragment, demonstrating promising results in Phase 1/2a and ongoing Phase 2b/3 trials. Ixo-vec employs an AAV2.7m8 capsid for intravitreal delivery of a transgene expressing aflibercept, showing encouraging outcomes in Phase 1 and ongoing Phase 2 trials. 4D-150 utilizes an evolved vector to express both aflibercept and a VEGF-C inhibitory RNAi, exhibiting positive interim results in Phase 1/2 studies. Other therapies reviewed include EXG102-031, FT-003, KH631, OLX10212, JNJ-1887, 4D-175, and OCU410. These therapies offer potential advantages of reduced treatment frequency and enhanced safety profiles, representing a paradigm shift in management towards durable and efficacious cellular-based biofactories. These advancements in gene therapy hold promise for improving outcomes in AMD and addressing the complex challenges of DME and DR, providing new avenues for the treatment of diabetic eye diseases. [ABSTRACT FROM AUTHOR]

Purpose: This study aims to establish DROL (disruption of retinal outer layers), PROS (photoreceptor outer segment length), SND (subfoveal neuroretinal detachment), and hyperreflective walls of foveal cystoid spaces (HRW) as optical coherence tomography (OCT) biomarkers and predictors of central macular thickness (CMT) and visual acuity in diabetic macular edema (DME) treated with intravitreal ranibizumab (IVR). Methods: In this prospective, interventional study performed at a tertiary care center over a span of 1 year from December 2021 to December 2022, 50 eyes of 46 patients of DME were included. Visual acuity and spectral domain OCT imaging were performed at baseline. Using inbuilt calipers on SD-OCT, the horizontal extent of DROL and the vertical extent of PROS were measured manually. SND and HRW were assessed qualitatively. IVR was administered and patients were followed up at 4, 8, and 12 weeks. Results: The eyes without DROL had statistically significant (P < 0.05) lesser CMT and better BCVA (best-corrected visual acuity) (P < 0.05) after pro re nata injection of IVR. There was a positive correlation between the extent of baseline DROL with final CMT (P < 0.05) and final logMAR BCVA (P > 0.05), whereas negative correlation with the extent of baseline PROS with final CMT (P < 0.05) and final logMAR BCVA (P > 0.05). The presence of HRW and SND predicted non-resolution of CMT and worse visual acuity after treatment with IVR in DME . Conclusion: DROL, PROS, SND, and hyperreflective walls of foveal cystoid spaces may be utilized as qualitative as well as quantitative biomarkers to predict the post-treatment CMT and visual acuity in DME.

The aim of this study was to establish whether multiple blood parameters might predict an early treatment response to intravitreal bevacizumab injections in patients with diabetic macular edema (DME). Seventy-eight patients with non-proliferative diabetic retinopathy (NPDR) and DME were included. The treatment response was evaluated with central macular thickness decrease and best corrected visual acuity increase one month after the last bevacizumab injection. Parameters of interest were the neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), vitamin D, and apolipoprotein B to A-I ratio (ApoB/ApoA-I). The NLR (2.03 ± 0.70 vs. 2.80 ± 1.08; p < 0.001), MLR (0.23 ± 0.06 vs. 0.28 ± 0.10; p = 0.011), PLR (107.4 ± 37.3 vs. 135.8 ± 58.0; p = 0.013), and SII (445.3 ± 166.3 vs. 675.3 ± 334.0; p < 0.001) were significantly different between responder and non-responder groups. Receiver operator characteristics analysis showed the NLR (AUC 0.778; 95% CI 0.669–0.864), PLR (AUC 0.628; 95% CI 0.511–0.735), MLR (AUC 0.653; 95% CI 0.536–0.757), and SII (AUC 0.709; 95% CI 0.595–0.806) could be predictors of response to bevacizumab in patients with DME and NPDR. Patients with severe NPDR had a significantly higher ApoB/ApoA-I ratio (0.70 (0.57–0.87) vs. 0.61 (0.49–0.72), p = 0.049) and lower vitamin D (52.45 (43.10–70.60) ng/mL vs. 40.05 (25.95–55.30) ng/mL, p = 0.025). Alterations in the NLR, PLR, MLR, and SII seem to provide prognostic information regarding the response to bevacizumab in patients with DME, whilst vitamin D deficiency and the ApoB/ApoA-I ratio could contribute to better staging. [ABSTRACT FROM AUTHOR]

Purpose: This study aims to establish DROL (disruption of retinal outer layers), PROS (photoreceptor outer segment length), SND (subfoveal neuroretinal detachment), and hyperreflective walls of foveal cystoid spaces (HRW) as optical coherence tomography (OCT) biomarkers and predictors of central macular thickness (CMT) and visual acuity in diabetic macular edema (DME) treated with intravitreal ranibizumab (IVR). Methods: In this prospective, interventional study performed at a tertiary care center over a span of 1 year from December 2021 to December 2022, 50 eyes of 46 patients of DME were included. Visual acuity and spectral domain OCT imaging were performed at baseline. Using inbuilt calipers on SD-OCT, the horizontal extent of DROL and the vertical extent of PROS were measured manually. SND and HRW were assessed qualitatively. IVR was administered and patients were followed up at 4, 8, and 12 weeks. Results: The eyes without DROL had statistically significant (P < 0.05) lesser CMT and better BCVA (best-corrected visual acuity) (P < 0.05) after pro re nata injection of IVR. There was a positive correlation between the extent of baseline DROL with final CMT (P < 0.05) and final logMAR BCVA (P > 0.05), whereas negative correlation with the extent of baseline PROS with final CMT (P < 0.05) and final logMAR BCVA (P > 0.05). The presence of HRW and SND predicted non-resolution of CMT and worse visual acuity after treatment with IVR in DME. Conclusion: DROL, PROS, SND, and hyperreflective walls of foveal cystoid spaces may be utilized as qualitative as well as quantitative biomarkers to predict the post-treatment CMT and visual acuity in DME. [ABSTRACT FROM AUTHOR]

Purpose: Our aim was to identify recent research trends on diabetic macular edema (DME) and focus on publications from different countries, institutions, and authors. Methods: We retrieved and analyzed data from January 1, 2003 to December 31, 2022 on the DME research field from the Web of Science Core Collection (WoSCC) database. Microsoft Excel and VOSviewer were applied to perform visualization analysis and evaluate the trends. Results: A total of 4482 publications were identified, and the annual global publications increased steadily, from 36 to 390, during this period. The United States (1339 publications, 71,754 citations), Johns Hopkins University (176 publications, 17,015 citations), and Bressler NM (76 publications, 9621 citations) were the most influential and productive countries, institutions, and authors, respectively. The top 100 keywords were classified into five clusters: (1) therapy and adverse effects of DME; (2) clinical biomarkers of DME; (3) mechanistic research on DME; (4) improving bioavailability and efficacy; and (5) early diagnosis of diabetic complications. “Diabetic macular edema,” “retinopathy,” “ranibizumab,” and “optical coherence tomography angiography” were the most frequent keywords. Regarding the average appearing years (AAYs) of the keywords, “deep learning” (AAY:2020.83), “optical coherence tomography angiography” (AAY:2019.59), “intravitreal Aflibercept” (AAY:2019.29), and “dexamethasone implant” (AAY:2019.20) were recognized as the hotspots of the DME research area in the short run. Conclusion: In the past two decades, the United States was in master status in DME research. Although intravitreal drug injection has been the mainstream therapy for a long time, the effectiveness of different drugs, such as dexamethasone, new solutions for drug delivery, such as intravitreal implantation, and more accurate tools for the classification and follow-up of DME patients, such as deep learning systems, are still research hotspots.

This study investigates the anatomical changes at the macula in patients with diabetic macular edema (DME) using Spectral Domain-Ocular Coherence Tomography (SD-OCT), highlighting the significance of SD-OCT in diagnosing and managing DME. The research encompasses the pathophysiological aspects of DME, the role of OCT in its evaluation, and the impact of various risk factors on macular changes. Background: Diabetic Macular Edema (DME) is a leading cause of vision impairment among patients with diabetic retinopathy, characterized by the accumulation of fluid in the macula due to the breakdown of the blood-retinal barrier. The study outlines the clinical and pathophysiological features of DME and emphasizes the importance of early detection and management to prevent vision loss. Spectral Domain-Ocular Coherence Tomography (SD-OCT) offers detailed imaging of retinal layers, making it an indispensable tool in the assessment of DME. Materials and Methods: The study was conducted at the Department of Anatomy along with Dept of Ophthalmology, S.M.S Hospital and Medical College, Jaipur, with a sample size of 100 eyes from treatment-naive patients with DME. Inclusion criteria were clearly defined to ensure the study's integrity. SD-OCT (Topcon 3D OCT 2000) was used to measure central macular thickness, the presence of intra-retinal cystoid spaces, and the integrity of the outer retinal layer at the fovea, among other parameters. Results: The study found significant anatomical changes in the macula among patients with DME, including increased central macular thickness and the presence of intra-retinal cystoid spaces. The average central macular thickness was found to be significantly higher in patients with DME, indicating the severity of macular edema. The integrity of the outer retinal layer at the fovea was compromised in a significant number of cases, correlating with decreased visual acuity. Conclusion: The findings underscore the utility of SD-OCT in the comprehensive assessment of DME, providing essential insights into the anatomical alterations at the macula. Early detection and accurate evaluation of macular changes using SDOCT can guide the management and treatment of DME, potentially improving visual outcomes for patients. The study also suggests the need for further research to explore the implications of these anatomical changes on the prognosis of DME. [ABSTRACT FROM AUTHOR]

Purpose: Our aim was to identify recent research trends on diabetic macular edema (DME) and focus on publications from different countries, institutions, and authors. Methods: We retrieved and analyzed data from January 1, 2003 to December 31, 2022 on the DME research field from the Web of Science Core Collection (WoSCC) database. Microsoft Excel and VOSviewer were applied to perform visualization analysis and evaluate the trends. Results: A total of 4482 publications were identified, and the annual global publications increased steadily, from 36 to 390, during this period. The United States (1339 publications, 71,754 citations), Johns Hopkins University (176 publications, 17,015 citations), and Bressler NM (76 publications, 9621 citations) were the most influential and productive countries, institutions, and authors, respectively. The top 100 keywords were classified into five clusters: (1) therapy and adverse effects of DME; (2) clinical biomarkers of DME; (3) mechanistic research on DME; (4) improving bioavailability and efficacy; and (5) early diagnosis of diabetic complications. "Diabetic macular edema," "retinopathy," "ranibizumab," and "optical coherence tomography angiography" were the most frequent keywords. Regarding the average appearing years (AAYs) of the keywords, "deep learning" (AAY:2020.83), "optical coherence tomography angiography" (AAY:2019.59), "intravitreal Aflibercept" (AAY:2019.29), and "dexamethasone implant" (AAY:2019.20) were recognized as the hotspots of the DME research area in the short run. Conclusion: In the past two decades, the United States was in master status in DME research. Although intravitreal drug injection has been the mainstream therapy for a long time, the effectiveness of different drugs, such as dexamethasone, new solutions for drug delivery, such as intravitreal implantation, and more accurate tools for the classification and follow-up of DME patients, such as deep learning systems, are still research hotspots. [ABSTRACT FROM AUTHOR]

Purpose: This study aims to compare posterior subtenon triamcinolone acetonide injection either formulated or alone versus suprachoroidal triamcinolone in the management of diabetic macular edema. Methods: This study is a prospective interventional study that included 75 patients, divided into three groups, each group with 25 patients. Group I received a combination of triamcinolone acetonide (TA) (40 mg) and VISCOAT, which is a combination of sodium chondroitin sulfate (20 mg) and sodium hyaluronate (15 mg). The injection was done in the posterior subtenon space using the NAGATA cannula. Group II received TA (40 mg) in the posterior subtenon space. Group III underwent an injection of 4 mg/100µl of TA in the supra choroidal space. Results: We found a statistically significant difference between the three studied groups regarding BCVA (P = 0.001) and CMT at six months postoperative (P = 0.001) with the highest median BCVA and lowest median CMT observed in the formulated TA group. Conclusion: We concluded that early treatment of DME by formulated TA is better than TA alone, and suprachoroidal TA in the form of increasing the BCVA and decreasing the CMT without any elevation of IOP. Trial registration number NCT05464953. Date of registration 17/7/2022 (retrospectively registered). [ABSTRACT FROM AUTHOR]

Early detection of diabetic retinopathy (DR) and diabetic macular edema (DME) is difficult due to the presence of abnormalities like micro-aneurysms in the fundus images which causes vision loss for diabetic patients. In this paper, we detect DR and DME in an earlier stage by performing preprocessing to enhance the quality of the input image, which includes three steps: noise filtering, artefact removal and contrast enhancement. Second, blood vessel segmentation is performed, using Improved Mask-Regional Convolutional Neural Networks (Mask RCNN), which increases the accuracy and precision rate of DR and DME detection. Finally, feature extraction and classification using VGG-16 is performed, which extracts structural features, colour and orientation features. Based on the extracted features, the proposed VGG-16 classifies the image into three classes: normal, DR and DME. After detecting DR and DME, we calculate the severity level of the disease using conditional entropy which classifies the severity into mild, moderate and severe. The proposed work is evaluated by two different datasets: IDRiD and MESSIDOR. The performance of the DR and DME detection is evaluated in terms of accuracy (80.7%), sensitivity (93.67%), specificity (93.67%), F1 score (94.61%), ROC curve and AUC curve compared to existing works. [ABSTRACT FROM AUTHOR]

The aim of this study was to establish whether multiple blood parameters might predict an early treatment response to intravitreal bevacizumab injections in patients with diabetic macular edema (DME). Seventy-eight patients with non-proliferative diabetic retinopathy (NPDR) and DME were included. The treatment response was evaluated with central macular thickness decrease and best corrected visual acuity increase one month after the last bevacizumab injection. Parameters of interest were the neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), vitamin D, and apolipoprotein B to A-I ratio (ApoB/ApoA-I). The NLR (2.03 ± 0.70 vs. 2.80 ± 1.08; p < 0.001), MLR (0.23 ± 0.06 vs. 0.28 ± 0.10; p = 0.011), PLR (107.4 ± 37.3 vs. 135.8 ± 58.0; p = 0.013), and SII (445.3 ± 166.3 vs. 675.3 ± 334.0; p < 0.001) were significantly different between responder and non-responder groups. Receiver operator characteristics analysis showed the NLR (AUC 0.778; 95% CI 0.669–0.864), PLR (AUC 0.628; 95% CI 0.511–0.735), MLR (AUC 0.653; 95% CI 0.536–0.757), and SII (AUC 0.709; 95% CI 0.595–0.806) could be predictors of response to bevacizumab in patients with DME and NPDR. Patients with severe NPDR had a significantly higher ApoB/ApoA-I ratio (0.70 (0.57–0.87) vs. 0.61 (0.49–0.72), p = 0.049) and lower vitamin D (52.45 (43.10–70.60) ng/mL vs. 40.05 (25.95–55.30) ng/mL, p = 0.025). Alterations in the NLR, PLR, MLR, and SII seem to provide prognostic information regarding the response to bevacizumab in patients with DME, whilst vitamin D deficiency and the ApoB/ApoA-I ratio could contribute to better staging.

Abstract Anti-vascular endothelial growth factor (anti-VEGF) therapies have become the standard of care in the treatment of neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME), resulting in a remarkable decrease in disease-related vision loss. However, the need for regular injections places a significant burden on patients, caregivers, and the healthcare system and improvements in vision may not be maintained long term. As a result of its drying potency and duration of action, brolucizumab, an intravitreal anti-VEGF therapy approved for the treatment of nAMD and DME, could decrease injection frequency for patients and provide an efficacious treatment; however, balancing its benefits and risks can be challenging. There have been reports of intraocular inflammation (IOI) in patients treated with brolucizumab, which, if left untreated, may result in severe vision loss. Recent evidence, however, indicates that early recognition of IOI and prompt and aggressive systemic corticosteroid treatment in response to posterior segment involvement can lead to favorable outcomes in these relatively rare but severe cases. A series of consensus meetings were conducted in 2022 between Swiss medical retina experts and diabetologists, discussing the current data for brolucizumab and exploring various challenges to its use, including the associated risk of IOI. The outcome is a collation of practical insights and guidance for ophthalmologists on the use of brolucizumab in patients with nAMD and DME, including patient selection and assessment, treatment regimen and monitoring, and the recognition and management of adverse events.

Abstract Background To assess the cost-effectiveness of the delayed-release device of dexamethasone compared with aflibercept in the treatment of patients with naïve diabetic macular edema (DME) from a societal perspective in the healthcare sector Zaragoza III in Spain. Methods A Markov model with five states defined by visual acuity (VA) in the better-seeing eye (Snellen scale) and an additional death state were constructed. Two cohorts of patients were distributed along the VA states and treated during a year with either dexamethasone or aflibercept. One-year follow-up on each group was performed. Medical costs related to the DME treatment and follow-up, medical costs related to the DME comorbidities, and non-medical-related costs were taken into account. Costs (2020 €), health outcomes (Quality-Adjusted Life Years-QALYs), both discounted at a 3.5% annual rate, and incremental cost-effectiveness ratios (ICER: €/QALY) were determined for a lifetime horizon in the base case analysis. Results Patients treated with dexamethasone were €77,349 more costly and provided 2.667 additional QALYs (€29,002/QALY) than those treated with aflibercept. The variable efficiency per patient was calculated dividing the improvement in quality of life (on the VFQ-25 scale) by the cost of the treatment. With the obtained results it can be concluded that the efficiency of treating the patients with dexamethasone is significantly superior than the efficiency of treating them with aflibercept. Conclusions The cost per QALY gained with the delayed-release device of dexamethasone compared with the one obtained by aflibercept in the naïve DME population is just below the €30,000 threshold, below which, new drugs are sometimes regarded as cost-effective strategies in Spain. In this model, the key variables with greater impact on the cost-effectiveness results were the selected time horizon, the chosen extrapolation method and the number of aflibercept and dexamethasone injections.

Anti-vascular endothelial growth factor (anti-VEGF) therapies have become the standard of care in the treatment of neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME), resulting in a remarkable decrease in disease-related vision loss. However, the need for regular injections places a significant burden on patients, caregivers, and the healthcare system and improvements in vision may not be maintained long term. As a result of its drying potency and duration of action, brolucizumab, an intravitreal anti-VEGF therapy approved for the treatment of nAMD and DME, could decrease injection frequency for patients and provide an efficacious treatment; however, balancing its benefits and risks can be challenging. There have been reports of intraocular inflammation (IOI) in patients treated with brolucizumab, which, if left untreated, may result in severe vision loss. Recent evidence, however, indicates that early recognition of IOI and prompt and aggressive systemic corticosteroid treatment in response to posterior segment involvement can lead to favorable outcomes in these relatively rare but severe cases. A series of consensus meetings were conducted in 2022 between Swiss medical retina experts and diabetologists, discussing the current data for brolucizumab and exploring various challenges to its use, including the associated risk of IOI. The outcome is a collation of practical insights and guidance for ophthalmologists on the use of brolucizumab in patients with nAMD and DME, including patient selection and assessment, treatment regimen and monitoring, and the recognition and management of adverse events. [ABSTRACT FROM AUTHOR]

Diabetic Macular Edema (DME) represents a significant visual impairment among individuals with diabetes, leading to a dramatic reduction in visual acuity and potentially resulting in irreversible vision loss. Optical Coherence Tomography (OCT), a technique that produces high-resolution retinal images, plays a vital role in the clinical assessment of this condition. Physicians typically rely on OCT B-Scan images to evaluate DME severity. However, manual interpretation of these images is susceptible to errors, which can lead to detrimental consequences, such as misdiagnosis and improper treatment strategies. Hence, there is a critical need for more reliable diagnostic methods. This study aims to address this gap by proposing an automated model based on Generative Adversarial Networks (GANs) to generate OCT B-Scan images of DME. The model synthesizes images from patients' baseline OCT B-Scan images, which could potentially enhance the robustness of DME detection systems. We employ five distinct GANs in this study: Deep Convolutional GAN, Conditional GAN, CycleGAN, StyleGAN2, and StyleGAN3, drawing comparisons across their performance. Subsequently, the hyperparameters of the best-performing GAN are fine-tuned using Particle Swarm Optimization (PSO) to produce more realistic OCT images. This comparative analysis not only serves to improve the detection of DME severity using OCT images but also provides insights into the appropriate choice of GANs for the effective generation of realistic OCT images from the baseline OCT datasets.

Background: Diabetic retinopathy (DR) afflicts more than 93 million people worldwide and is a leading cause of vision loss in working adults. While DR therapies are available, early DR development may go undetected without treatment due to the lack of sufficiently sensitive tools. Therefore, early detection is critically important to enable efficient treatment before progression to vision-threatening complications. A major clinical manifestation of early DR is retinal vascular leakage that may progress from diffuse to more localized focal leakage, leading to increased retinal thickness and diabetic macular edema (DME). In preclinical research, a hallmark of DR in mouse models is diffuse retinal leakage without increased thickness or DME, which limits the utility of optical coherence tomography and fluorescein angiography (FA) for early detection. The Evans blue assay detects diffuse leakage but requires euthanasia, which precludes longitudinal studies in the same animals. Methods: We developed a new modality of ratiometric fluorescence angiography with dual fluorescence (FA-DF) to reliably detect and longitudinally quantify diffuse retinal vascular leakage in mouse models of induced and spontaneous DR. Results: These studies demonstrated the feasibility and sensitivity of FA-DF in detecting and quantifying retinal vascular leakage in the same mice over time during DR progression in association with chronic hyperglycemia and age. Conclusions: These proof-of-concept studies demonstrated the promise of FA-DF as a minimally invasive method to quantify DR leakage in preclinical mouse models longitudinally. [ABSTRACT FROM AUTHOR]

Diabetic macular edema (DME) causes visual impairment in diabetic retinopathy (DR). Diabetes mellitus is a global epidemic and diabetic individuals are at risk of developing DR. Approximately 1 in 10 diabetic patients suffers from DME, which is the commonest cause of vision-threatening DR at primary-care screening. Furthermore, diabetes predisposes to a higher frequency and a younger onset of cataract, which further threatens vision in DME patients. Although cataract extraction is an effective cure, vision may still deteriorate following cataract surgery due to DME progression or recurrence, of which the risks are significantly higher than for patients without concurrent or previous history of DME at the time of operation. The management of pre-existing DME with visually significant cataract is a clinical conundrum. Deferring cataract surgery until DME is adequately treated is not ideal because of prolonged visual impairment and maturation of cataract jeopardizing surgical safety and monitoring of DR. On the other hand, the progression or recurrence of DME following prompt cataract surgery is a profound disappointment for patients and ophthalmic surgeons who had high expectations for postoperative visual improvement. Prescription of perioperative anti-inflammatory eye drops is effective in lowering the risk of new-onset DME after cataract surgery. However, management of concurrent DME at the time of cataract surgery is much more challenging because DME is unlikely to resolve spontaneously even with the aid of anti-inflammatory non-steroidal or steroid eye drops. A number of clinical trials using intravitreal injection of corticosteroids and anti-vascular endothelial growth factor (anti-VEGF) as first-line therapy have demonstrated safety and efficacy to treat DME. These drugs have also been administered perioperatively for the prevention of DME worsening in patients undergoing cataract surgery. This article reviews the scientific evidence to guide ophthalmologists on the efficacy and safety of various therapies for managing patients with DME who are particularly vulnerable to cataract surgery-induced inflammation, which disintegrates the blood-retinal barrier and egression of fluid in macular edema. [ABSTRACT FROM AUTHOR]

Purpose: The present study aims to determine the macular and choroidal optical coherence tomography angiography (OCTA) biomarkers in the assessment and monitoring of diabetic macular edema (DME) and diabetic macular ischemia (DMI) in patients with non-proliferative diabetic retinopathy (NPDR). Methods: In this cohort study, a total of 176 eyes of 110 patients with NPDR were investigated at our institute over a period of 10 months. Eyes were divided into four groups based on the severity of NPDR. Each eye was subjected to OCTA (Topcon 3D OCT-1 Maestro2) macula 6 × 6 mm2 en face. It features IMAGEnet 6 software for dynamic viewing of OCTA and imaging data. Four OCTA biomarkers for the macula were identified: foveal avascular zone area (FAZ area), foveal avascular zone contour irregularity (FAZ-CI), capillary dropout areas (CDA), and perifoveal intercapillary areas (PICA). The choroidal OCTA biomarker was the number of choroidal circulation flow voids (CCFV). For all analyses, P < 0.05 was considered statistically significant. Results: Increase in FAZ area and number of CDA were statistically significant (p < 0.0001) with an increase in central foveal thickness, suggesting a correlation of ischemic changes with an increase in DME. FAZ-CI, enlarged PICA, and CCFV were significantly associated with more severe NPDR patients. Conclusion: A correlation between DME and DMI in a patient of NPDR and its progression can be evaluated in a single visit. A unique feature of our study is it revealed novel diagnostic biomarkers of OCTA for DMI and DME. [ABSTRACT FROM AUTHOR]

Background: To assess the cost-effectiveness of the delayed-release device of dexamethasone compared with aflibercept in the treatment of patients with naïve diabetic macular edema (DME) from a societal perspective in the healthcare sector Zaragoza III in Spain. Methods: A Markov model with five states defined by visual acuity (VA) in the better-seeing eye (Snellen scale) and an additional death state were constructed. Two cohorts of patients were distributed along the VA states and treated during a year with either dexamethasone or aflibercept. One-year follow-up on each group was performed. Medical costs related to the DME treatment and follow-up, medical costs related to the DME comorbidities, and non-medical-related costs were taken into account. Costs (2020 €), health outcomes (Quality-Adjusted Life Years-QALYs), both discounted at a 3.5% annual rate, and incremental cost-effectiveness ratios (ICER: €/QALY) were determined for a lifetime horizon in the base case analysis. Results: Patients treated with dexamethasone were €77,349 more costly and provided 2.667 additional QALYs (€29,002/QALY) than those treated with aflibercept. The variable efficiency per patient was calculated dividing the improvement in quality of life (on the VFQ-25 scale) by the cost of the treatment. With the obtained results it can be concluded that the efficiency of treating the patients with dexamethasone is significantly superior than the efficiency of treating them with aflibercept. Conclusions: The cost per QALY gained with the delayed-release device of dexamethasone compared with the one obtained by aflibercept in the naïve DME population is just below the €30,000 threshold, below which, new drugs are sometimes regarded as cost-effective strategies in Spain. In this model, the key variables with greater impact on the cost-effectiveness results were the selected time horizon, the chosen extrapolation method and the number of aflibercept and dexamethasone injections. [ABSTRACT FROM AUTHOR]

Artificial intelligent (AI) systems for clinical-decision support are an important tool in clinical routine. It has become a crucial diagnostic tool with adequate reliability and interpretability in disease diagnosis and monitoring. Undoubtedly, these models are faced with insufficient data challenges for training, which often directly determines the model's performance. In order word, insufficient data for model training leads to inefficiency in the model built. To overcome this problem, we propose an AI-driven model by transfer learning in accurate diagnosis for medical decision support. Our approach leverages the shortage of data with a pretrained model by training the neural network with a fraction of the new dataset. For this purpose, we utilized the VGG19 network as the backbone network to support our model in integrating known features with the newly learned features for accurate diagnosis and decision making. Integrating this trained model speeds up the training phase and improve the performance of the proposed model. Experimental results show that the proposed model is effective and efficient in diagnosing different medical diseases. As such, we anticipated that this diagnosis tool will ultimately aid in facilitating early treatment of these treatable diseases, which will improve clinical out-comes. [ABSTRACT FROM AUTHOR]

The long-term effect of intravitreal Fluocinolone acetonide (FAc) on retinal morphology and function in diabetic macular edema (DME) was investigated. Seventeen eyes of twelve consecutive DME patients, treated by intravitreal FAc, were retrospectively evaluated. Retinal morphology was assessed with central macular thickness (CMT). Retinal function was assessed by best-corrected visual acuity (BCVA) and cone b-wave and photopic negative response (PhNR). The main outcome was a mean change in CMT at month 24. The secondary outcomes were changes in cone b-wave and PhNR at month 24. The incidence of adverse events was also recorded. Mean CMT decreased from 406.52 µm (±138.74) at baseline to 310 µm (±130.39) at 24 months (p = 0.008). No significant changes in the other parameters were found. At baseline, BCVA and PhNR amplitude were negatively correlated (r = −0.55) with CMT. At the end of follow-up, the change in CMT was negatively correlated with baseline CMT (r = −0.53, p = 0.03) and positively correlated with baseline PhNR amplitude (r = 0.58, p < 0.01). A significant, long-term reduction in CMT was observed in DME patients after FAc implant. The anti-edema effect tended to be stronger in patients with the poorest baseline retinal morphology (CMT) and function (PhNR). Structure/function correlations might help to characterize the patients who may benefit from this treatment. [ABSTRACT FROM AUTHOR]

Introduction Diabetic macular edema (DME) is the most common and vision-threatening complication in diabetic patients with diabetic retinopathy (DR), especially in those with Type 2 diabetes mellitus. Optical coherence tomography (OCT) is a reliable tool most commonly used for assessing macular morphology and provides quantitative information on the macula. OCT also examines the outer retinal layers, which can predict visual outcomes. Thus, our study aims to identify the association of various OCT-detected DME morphological patterns with central subfield thickness (CST) and visual acuity. Materials and methods This is a cross-sectional observational study of 50 patients with DME detected on OCT who visited the Ophthalmology Department of Saveetha Medical College and Hospitals for a period of six months, from November 2023 to April 2024. A complete ocular examination, including best corrected visual acuity, scored with the logMAR scale, anterior segment examination, and fundus biomicroscopy using 90D and 78D lenses, was performed. Early Treatment of Diabetic Retinopathy Study (ETDRS) grading of DR into mild to very severe non-proliferative diabetic retinopathy (NPDR) and proliferative diabetic retinopathy (PDR) was noted. Spectral-domain OCT was used to diagnose DME. The CST was measured, and DME was classified into four patterns: sponge-like retinal swelling (SLRS), cystoid macular edema (CME), subretinal fluid (SRF), and posterior hyaloid traction (PHT). Results In the present study, males represented 60%, and females represented 40%. The mean age of the patients was 58.07 ± 6.80 years, with a mean duration of diabetes of 11.91 ± 5.14 years. Of the 50 patients with 100 eyes, only 60 eyes showed DME on OCT. CME was the most common morphological pattern (37%), while the least common pattern was PHT (10%). No significant association was found between a specific morphological pattern and control of diabetes. The most common pattern observed was SLRS in moderate NPDR, CME in severe NPDR, SRF in very severe NPDR, and PHT in PDR. Very severe NPDR patients showed all patterns of DME, and the PHT pattern was observed only in very severe NPDR and PDR. The highest mean CST was observed in the very severe NPDR stage, and the least was in the moderate NPDR stage. The mean CST was highest in SRF patterns and lowest in SLRS patterns. The best mean visual acuity was observed in the SLRS pattern, while the worst mean visual acuity was observed in the SRF pattern, followed by the PHT pattern. Conclusion Our study highlights the importance of OCT in patients with diabetes, as OCT patterns of DME are critical for predicting visual outcomes in DR. Severe grades of DR are usually associated with SRF and PHT patterns. Since patients with SRF and PHT patterns have the worst visual outcomes, these patients, upon identification, need to be counseled about their poor visual prognosis. Those with less severe DR should be closely monitored and advised on effective diabetes control to prevent progression and protect their vision., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Institutional Ethics Committee, Saveetha Medical College and Hospitals issued approval 114/06/2023/IEC/SMCH. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Ramakrishnan et al.)

PurposeDiabetic macular edema (DME) is one of the leading causes of visual impairment in diabetic retinopathy (DR). Physicians rely on optical coherence tomography (OCT) and baseline visual acuity (VA) to tailor therapeutic regimen. However, best-corrected visual acuity (BCVA) from chart-based examinations may not wholly reflect DME status. Chart-based examinations are subjected findings dependent on the patient’s recognition functions and are often confounded by concurrent corneal, lens, retinal, optic nerve, or extraocular disorders. The ability to infer VA from objective optical coherence tomography (OCT) images provides the predicted VA from objective macular structures directly and a better understanding of diabetic macular health. Deviations from chart-based and artificial intelligence (AI) image-based VA will prompt physicians to assess other ocular abnormalities affecting the patients VA and whether pursuing anti-VEGF treatment will likely yield increment in VA.Materials and methodsWe enrolled a retrospective cohort of 251 DME patients from Big Data Center (BDC) of Taipei Veteran General Hospital (TVGH) from February 2011 and August 2019. A total of 3,920 OCT images, labeled as “visually impaired” or “adequate” according to baseline VA, were grouped into training (2,826), validation (779), and testing cohort (315). We applied confusion matrix and receiver operating characteristic (ROC) curve to evaluate the performance.ResultsWe developed an OCT-based convolutional neuronal network (CNN) model that could classify two VA classes by the threshold of 0.50 (decimal notation) with an accuracy of 75.9%, a sensitivity of 78.9%, and an area under the ROC curve of 80.1% on the testing cohort.ConclusionThis study demonstrated the feasibility of inferring VA from routine objective retinal images.Translational relevanceServes as a pilot study to encourage further use of deep learning in deriving functional outcomes and secondary surrogate endpoints for retinal diseases.

Abstract Objective To develop and validate a questionnaire for the investigation of non-adherence (NA) barriers in patients receiving intravitreal injection (IVT). Design Questionnaire development and cross-sectional patient survey combined with a retrospective medical chart review. Participants German patients with neovascular age-related macular degeneration (nAMD) or diabetic macular edema (DME) receiving anti-vascular endothelial growth factor (anti-VEGF) treatment via IVT. Methods The previously validated (indications: atrial fibrillation, human immunodeficiency virus, chronic inflammatory lung disease) Adherence Barriers Questionnaire (ABQ) was revised according to specifications of IVT, within the framework of an expert panel. The ABQ-IVT, which initially consisted of 24 items formulated as statements (4-point-Likert-scale ranging from “strongly agree” to “strongly disagree”), was applied in a cross-sectional survey. Evaluation of the questionnaire included an assessment of internal consistency and factor analysis. The occurrence of potential barriers in the patient sample was evaluated using descriptive statistics. To identify patient subpopulations, hierarchical cluster analysis was performed using ABQ-IVT answers as predictors. Due to difficulties in capturing NA as an external criterion, the evaluation of the questionnaire was limited to its internal validity and reliability. Main outcome measures Patients’ answers to the ABQ-IVT questionnaire and interviews. Results Of 253 patients, 234 (92%) were able to complete the ABQ-IVT questionnaire. Within the reliability analysis, the ABQ-IVT was reduced to 17 items. The condensed questionnaire demonstrated good internal consistency (Cronbach’s alpha = 0.78), and factor analysis showed no evidence for subscales of the questionnaire. Nearly half of the patients (49%) reported being affected by at least three different barriers. On average, a patient was affected by 3.1 barriers. The most frequently reported barriers were “Challenge due to time commitment of physician visits” (45% of the patients), “Depression” (29%) and “Travel and opportunity costs” (27%). Cluster analysis identified six patient subpopulations, each affected by different sets of barriers and differed regarding their patient characteristics. Conclusions The ABQ-IVT is a practical and reliable instrument for identifying patient-specific barriers to IVT treatment adherence. In practice, the questionnaire may be useful in assessing whether individual patients are at higher risk of NA due to specific adherence barriers. Aside from better awareness, this allows earlier interventions, though these still need to be validated. Patient subpopulations face different barriers and may, therefore, need distinct preventative care.

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

The diversified ocular disorders in which cystoid macular edema (CME) occurs, are strongly associated with the vision loss. Optical coherence tomography (OCT) scans that allow screening of the retina, contain artifacts including blur‐edges, speckle noise, and so forth, which create difficulty in identifying retinal fluid. In this work, major image preprocessing techniques such as minimum filtering, block‐matching and 3D filtering, and Richardson–Lucy deconvolution method are applied to minimize noise and other degradation effects from OCT scans, ensured by maintaining image quality assessment scores, that is, blind‐less image spatial quality evaluator and sharpness estimation score. Furthermore, this work develops an automated method based on deep learning (DL) to detect the presence and progression of retinal fluid, that is, CME and its quantification. Specifically, U‐net model with efficient tuning of hyperparameters is proposed to obtain optimal results. The algorithm's performance is evaluated for accurate identification of fluid localization in the case of diabetic macular edema (DME), having CME regions, and compared against the manual segmentation of fluid by experts, which are highly correlated. This enhanced DL method achieves better performance than the algorithms previously reported. The proposed algorithm is evaluated on several performance metrics during training and reports the best score of 99.81, 0.50, 83.34, 86.56, 80.89, and 99.48% for model accuracy, binary cross‐entropy loss, Dice coefficient (DC), precision, recall, and area under the ROC‐curve, respectively. Additionally, fourfold cross‐validation technique is also applied and an average DC score of 84.00% is obtained. This approach can be helpful to prevent vision loss. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the effect of metformin combined with anti-VEGF agents in patients with diabetic macular edema (DME). Methods: This study was a prospective, nonrandomized case–control study. Patients were included in with a diagnosis of DME who received anti-VEGF agents injection. Basic information, medical history, best-corrected visual acuity (BCVA), central macular thickness (CMT), the number of intravitreal injections, panretinal photocoagulation (PRP), and macular grid photocoagulation treatment during the 6-month follow-up, were recorded for each patient. Results: A total of 50 DME patients were collected (24 patients with a history of oral metformin ≥ 6 months and 26 patients who had not taken metformin). The BCVA and the CMT were significantly improved after anti-VEGF treatment in two groups (F1 = 19.35, F2 = 26.78; F1 = 65.45, F2 = 76.23; P < 0.05). The BCVA in the metformin group was better than that in non-metformin group at every point after treatment (F = 34.45, P < 0.05). The CMT in metformin group decreased much more than that in non-metformin group during the follow-up period (F = 87.05, P < 0.05). The injection numbers decreased in the metformin group compared with the non-metformin group (t = 5.14, P < 0.05). However, there was no difference in PRP and macular grid photocoagulation therapy between the two groups during the 6-month follow-up. Conclusion: Metformin can enhance the therapeutic effect of anti-VEGF agents on DME patients to improve their visual acuity, improve the structure of the macular area, and reduce the number of intravitreal injections 90. [ABSTRACT FROM AUTHOR]

Objective: Diabetic macular edema (DME) and retinal vein occlusion (RVO) are the leading causes of visual impairments across the world. Vascular endothelial growth factor (VEGF) stimulates breakdown of blood-retinal barrier that causes accumulation of fluid within macula. Anti-VEGF therapy is the first-line treatment for both the diseases; however, the degree of response varies for individual patients. The main objective of this work was to identify the (i) texture-based radiomics features within individual fluid and retinal tissue compartments of baseline spectral-domain optical coherence tomography (SD-OCT) images and (ii) the specific spatial compartments that contribute most pertinent features for predicting therapeutic response. Methods: A total of 962 texture-based radiomics features were extracted from each of the fluid and retinal tissue compartments of OCT images, obtained from the PERMEATE study. Top-performing features selected from the consensus of different feature selection methods were evaluated in conjunction with four different machine learning classifiers: Linear Discriminant Analysis (LDA), Quadratic Discriminant Analysis (QDA), Random Forest (RF), and Support Vector Machine (SVM) in a cross-validated approach to distinguish eyes tolerating extended interval dosing (non-rebounders) and those requiring more frequent dosing (rebounders). Results: Combination of fluid and retinal tissue features yielded a cross-validated area under receiver operating characteristic curve (AUC) of 0.78±0.08 in distinguishing rebounders from non-rebounders. Conclusions: This study revealed that the texture-based radiomics features pertaining to IRF subcompartment were most discriminating between rebounders and non-rebounders to anti-VEGF therapy. Clinical Impact: With further validation, OCT-based imaging biomarkers could be used for treatment management of DME patients.

ObjectiveTo investigate body fluid status in diabetic macular edema (DME) patients and the extent to which it is affected by renal function.MethodsOne hundred and thirty-two eyes from 132 patients with diabetes mellitus (DM) were prospectively collected in this cross-sectional, observational study. Thirty-five were DM patients without diabetic retinopathy (DR), 31 were DR patients without DME, and 66 were DME patients. The fluid status of each participant was quantified with extracellular water-to-total body water ratio (ECW/TBW) using a body composition monitor. Central subfield thickness (CST) and macular volume (MV) were obtained using optical coherence tomography (OCT). Urine albumin-to-creatinine ratio (UACR), estimated glomerular filtration rate (eGFR), and albumin was obtained using serum and urine laboratory data.ResultsECW/TBW was significantly increased in DME patients (39.2 ± 0.9, %) compared to DM (38.1 ± 0.7, %, P = 0.003) and DR patients without DME (38.7 ± 0.9, %, P < 0.001). In multilinear regression, fluid overload was positively related to DME and UACR (DME vs. DM: β = 2.418, P < 0.001; DME vs. DR: β = 1.641, P = 0.001; UACR, per 102, β = 1.017, P = 0.01). In the binary logistic regression for DME risk, the area under the receiver operating characteristic curve (AUROC) increased significantly by adding ECW/TBW along with UACR and age (AUC: 0.826 vs. 0.768).ConclusionDME patients had elevated body fluid volume independent of kidney functions. The assessment of extracellular fluid status may help in the management of DME.

Purpose: This meta-analysis was conducted to evaluate the efficacy and safety of single-dose dexamethasone implantation for treating persistent DME (diabetic macular edema) refractory to anti-VEGF (anti-vascular endothelial growth factor) drugs over a period of 6 months. Methods: All related clinical trials were reviewed by searching electronic databases of PubMed, Medline, Web of Science, Cochrane Library, and EMBASE. The primary outcome parameters were best-corrected visual acuity (BCVA) and central macular thickness (CMT). We performed this meta-analysis by using Stata15.0. Results: Ten clinical trials involving 362 eyes from 328 patients were eligible in the final analysis. After single-dose dexamethasone implantation, there was a significant improvement in BCVA from baseline to 1, 3, and 6 months with an average increase of − 0.15 logMAR (p < 0.001), − 0.14 logMAR (p < 0.001), and − 0.07 logMAR (p = 0.004), respectively. Further, mean CMT decreased significantly with an average reduction of 249.18 μm (p < 0.001), 217.66 μm (p < 0.001), and 91.56 μm (p < 0.001) at months 1, 3, and 6, respectively. Conclusions: Our results indicate that switching to a dexamethasone implant could achieve significant anatomical and functional improvement among patients with refractory DME. Clinicians should be aware of this treatment option in refractory DME. [ABSTRACT FROM AUTHOR]

Acquired retinal diseases such as age-related macular degeneration and diabetic retinopathy rank among the leading causes of blindness and visual loss worldwide. Effective treatments for these conditions are available, but often have a high treatment burden, and poor compliance can lead to disappointing real-world outcomes. Development of new treatment strategies that provide more durable treatment effects could help to address some of these unmet needs. Gene-based therapeutics, pioneered for the treatment of monogenic inherited retinal disease, are being actively investigated as new treatments for acquired retinal disease. There are significant advantages to the application of gene-based therapeutics in acquired retinal disease, including the presence of established therapeutic targets and common pathophysiologic pathways between diseases, the lack of genotype-specificity required, and the larger potential treatment population per therapy. Different gene-based therapeutic strategies have been attempted, including gene augmentation therapy to induce in vivo expression of therapeutic molecules, and gene editing to knock down genes encoding specific mediators in disease pathways. We highlight the opportunities and unmet clinical needs in acquired retinal disease, review the progress made thus far with current therapeutic strategies and surgical delivery techniques, and discuss limitations and future directions in the field. [ABSTRACT FROM AUTHOR]

Abstract Background Here we report two patients who developed an atypical macular hole (MH) during the treatment course for diabetic macular edema (DME). Case presentations Patient 1 was a 73-year-old male. Optical coherence tomography (OCT) revealed perifoveal retinoschisis (RS) in addition to cystoid macular edema and serous retinal detachment (SRD) in his left eye, and that an MH had developed during the clinical course. A convex surface was formed at the MH margin toward the vitreous cavity, and granular shadows were observed in the fluid cuff. Intraoperative findings revealed a thin epiretinal macular membrane (ERM) around the MH. Patient 2 was a 79-year-old male. Although the patient underwent pars plana vitrectomy (PPV) for proliferative diabetic retinopathy (PDR) in both eyes, RS and a thin ERM in addition to SRD was observed in his left eye after surgery, and an MH developed during the clinical course. As in Patient 1, a convex surface was formed at the fluid cuff margin toward the vitreous cavity. Conclusions Both patients had persistent DME, SRD, RS, and a thin ERM before the development of the MH. OCT revealed the formation of a convex surface at the MH margin toward the vitreous cavity, suggesting that the fragility of the layered structure of the retina combined with tangential retinal traction may have been involved in the atypical MH form.

Spectral domain optical coherence tomography (SD-OCT) is a non-invasive imaging modality for assessing retinal diseases, such as diabetic retinopathy (DR), which is one of the most prevalent diseases responsible for visual impairment and blindness in the world. The main manifestations of DR are retinal deformation and fluid masses, termed diabetic macular edema (DME), which is the primary biomarker for assessing and diagnosing diseases. In the clinic, ophthalmologists can manually segment retinal layers and fluids to get quantitative and diagnostic information, which is the basement of the final diagnosis. However, this manual segmentation is time-consuming and labor-intensive. To facilitate and promote it, researchers have proposed many automated methods, where most of them usually ignore the priorities in ophthalmology and just regard this task as a standard semantic segmentation task. In this study, we consider the priority of the mutex relationship among different layers and introduce it into the dice loss function to build a novel one, named mutex dice loss (MDL). Besides, we propose a novel fully convolutional network based on our proposed depth max pooling (DMP) to segment retinal layers and fluids in SD-OCT images. Experimental results of the proposed method on two public datasets demonstrate promising performance, which also shows the potential to help ophthalmologists in the diagnostic process of DR or other related diseases.

Purpose: To evaluate factors associated with the presence of foveal bulge (FB) in resolved diabetic macular edema (DME) eyes.Methods: A total of 165 eyes with complete integrity of ellipsoid zone (EZ) at the fovea and resolved DME were divided into two groups according to the presence of FB at 6 months after intravitreal injection of ranibizumab treatment. Best-corrected visual acuity (BCVA), central foveal thickness (CFT), outer nuclear layer (ONL) thickness, height of serous retinal detachment (SRD) and non-SRD, and inner segment (IS) and outer segment (OS) lengths of the two groups were measured and compared at baseline and each follow-up. The correlations between the presence of FB and pre- and post-treatment factors were determined by logistic regression analysis.Results: At baseline, BCVA was significantly better, and CFT and incidence and height of SRD were significantly lower in the FB (+) group (all P < 0.05). At 6 months, FB was present in 65 (39.39%) eyes. Post-treatment BCVA was significantly better and OS length was significantly longer in the FB (+) group at 6 months (all P < 0.05). Multivariate analysis identified younger age, better BCVA, and lower CFT before treatment as significant predictors of the existence of FB at 6 months (all P < 0.05). At 6 months, better BCVA and longer OS length were significantly correlated with the existence of FB (all P < 0.05).Conclusions: Factors associated with the presence of FB after the resolution of DME include younger age, better baseline BCVA and lower baseline CFT, and better post-treatment BCVA and longer post-treatment OS length.

Background: Diabetic retinopathy (DR) afflicts more than 93 million people worldwide and is a leading cause of vision loss in working adults. While DR therapies are available, early DR development may go undetected without treatment due to the lack of sufficiently sensitive tools. Therefore, early detection is critically important to enable efficient treatment before progression to vision-threatening complications. A major clinical manifestation of early DR is retinal vascular leakage that may progress from diffuse to more localized focal leakage, leading to increased retinal thickness and diabetic macular edema (DME). In preclinical research, a hallmark of DR in mouse models is diffuse retinal leakage without increased thickness or DME, which limits the utility of optical coherence tomography and fluorescein angiography (FA) for early detection. The Evans blue assay detects diffuse leakage but requires euthanasia, which precludes longitudinal studies in the same animals. Methods: We developed a new modality of ratiometric fluorescence angiography with dual fluorescence (FA-DF) to reliably detect and longitudinally quantify diffuse retinal vascular leakage in mouse models of induced and spontaneous DR. Results: These studies demonstrated the feasibility and sensitivity of FA-DF in detecting and quantifying retinal vascular leakage in the same mice over time during DR progression in association with chronic hyperglycemia and age. Conclusions: These proof-of-concept studies demonstrated the promise of FA-DF as a minimally invasive method to quantify DR leakage in preclinical mouse models longitudinally.

Background: With the advent of aging society of China, fundus diseases related to pathological neovascularization, including age-related macular degeneration (AMD), diabetic macular edema (DME), and pathological myopia (PM), have become an increasingly serious medical and health problems. As effective drugs of the treatment, conbercept and ranibizumab have been commonly used and covered by the national basic medical insurance in China. However, the pharmacoeconomic evaluation of conbercept vs. ranibizumab for DME and PM remains lacking. This study would assess the cost-effectiveness of conbercept and ranibizumab for the treatment of AMD, DME, and PM from the perspective of Chinese payers.Methods: A Markov chain model was constructed based on the visual conditions of the patient indicated by the number of letters in best corrected visual acuity (BCVA). We conducted models based on real-world scenario to calculate the cost per the quality-adjusted life-year (QALY) gained. A 1-year cycle length and a 10-year simulation treatment were applied and the number of injections of conbercept and ranibizumab was assumed to the average number within 10 years. Transition probabilities, costs, utility data, and other parameters were obtained from literature searches. A 3.5% discounting rate was applied for both the costs and utilities.Results: The incremental cost-effectiveness ratios (ICERs) were more favorable for conbercept than ranibizumab in treatment of AMD, DME, and PM, with associated ICER of 66,669 renminbi (RMB), −258,813 RMB, and −373,185 RMB per QALY gained. Compared with ranibizumab, the incremental effectiveness of conbercept in treatment of AMD, DME, and PM was −0.665 QALYs, 0.215 QALYs, and 0.029 QALYs, respectively. The sensitivity analysis showed the same findings, although the ICER is sensitive to the costs of this program.Conclusion: Under the current Chinese healthcare setting, conbercept is suitable and cost-effective in treatment of AMD, DME, and PM compared with ranibizumab.