Treatment Of Diabetic Macular Edema Research Articles

Comparison of Suprachoroidal Triamcinolone Injection with Intravitreal Bevacizumab Vs Intravitreal Bevacizumab only in Treatment of Refractory Diabetic Macular Edema

Background: Macular edema due to diabetic retinopathy is among the most common causes of blindness in diabetics from working age group around the world . Diabetic macular edema which involves the center of the macula is among the major cause of visual decline in patients with diabetes mellitus. Intra-Vitreal Triamcinolone Acetonide with intravitreal Bevacizumab and intravitreal Bevacizumab only have been in practice as treatment options for cases not responsive to anti-vascular endothelial growth factor agents. Objective: To compare safety and efficacy profile of suprachoroidal injection of triamcinolone acetonide with intravitreal Bevacizumav Vs intravitreal injection of Bevacizumab alone in management of resistant diabetic macular edema. Patients & Methods: In this study, Fourty eyes of fourty patients who had resistant diabetic macular edema were randomly divided into two groups of 20 patients each (n=20) , our group A was injected with suprachoroidal triamcinolone acetonide 2 mg along with intravitreal Bevacizumab 1.25mg and the group B wasinjected with intravitreal Bevacizumab 1.25 mg only. Change in central macular thickness was observed after one month on Optical coherence tomography. Data was collected and analyzed by using SPSS software. Results: The mean age of subjects in this study was 58.46±3.62 years ( 30-65 years) . Out of 40 patients 26 were male patients and 14 were female .The mean decline (change) in central macular thickness in comparison to baseline thickness on OCT in group A was 113±10microns and mean change in the central thickness of macula on OCT in group B was 83+-10 microns with a p value of 0.01. Conclusion: Suprachoroidal triamcinolone acetonide with intravitreal bevacizumab is superior to intravitreal Bevacizumab alone in reducing central macular thickness among patients with resistant diabetic macular edema. Keywords: Macular edema, Suprachoroidal triamcinolone , intravitreal Bevacizumab, Optical coherence tomography

Intravitreal Diclofenac compared to Intravitreal Ranibizumab in Treatment of Diabetic Macular Edema

Intravitreal Diclofenac compared to Intravitreal Ranibizumab in Treatment of Diabetic Macular Edema

Evaluation of macular vascular density and foveal avascular zone changes by optical coherence tomography angiography (OCT-A) after intravitreal dexamethasone implant in diabetic macular edema resistant to Anti-VEGF treatment.

Analysis of foveal avascular zone (FAZ) width and vascular density (VD) changes before and after intravitreal dexamethasone implant (IDI) treatment in diabetic macular edema (DME) patients resistant to anti-VEGF treatment. In this retrospective study, patients who were regularly treated with at least 5 doses of intravitreal Anti-VEGF (bevacizumab, ranibizumab or aflibercept) for DME and whose DME continued were considered resistant to Anti-VEGF and were treated with IDI for the first time. Thirty-four eyes of 34 patients were included in the study. FAZ and VD values of optical coherence tomography angiography (OCT-A) scans at 0, 1 and 3months were examined. In OCT-A measurements, the pre-IDI superficial plexus FAZ (SFAZ) area (0.350 ± 0.120 mm2) was decreased at 1 (0.292 ± 0.132 mm2, p < 0.001) and at 3months (0.311 ± 0.153 mm2, p = 0.017). Pre-IDI deep plexus FAZ (DFAZ) area (0.651 ± 0.313 mm2) was decreased at 1-month post-IDI (0.481 ± 0.247 mm2, p < 0.001) while no significant change was observed at 3months (0.575 ± 0.259 mm2, p = 0.197). There was no significant change in the mean post-IDI total VD rate in both superficial (pre 39.2% ± 2.4; 1st month 39.2% ± 2.6%; 3rd month 39.5% ± 3.4%) and deep retinal plexus (pre 43.3% ± 2.6%; 1st month 43.5 ± 2.8%; 3rd month 43.6% ± 4.6%) (p = 0.408 and p = 0.607, respectively). The study showed that IDI caused a significant decrease in the FAZ area without any change in VD in patients with DME resistant to the anti-VEGF agents. IDI might be related to a decrease in the macular ischemia secondary to diabetic retinopathy.

Risk of dialysis in patients receiving intravitreal anti-vascular endothelial growth factor treatment: a population-based cohort study.

We utilized the Longitudinal Health Insurance Database which was stemmed from the Taiwan's National Health Insurance Research Database to conduct a retrospective cohort study investigating the risk of becoming dialysis dependent after receiving intravitreal anti-vascular endothelial growth factor (VEGF) agents for retinal diseases. Patients newly receiving intravitreal ranibizumab or aflibercept from 2000 to 2017 for age-related macular degeneration, polypoidal choroidal vasculopathy, diabetic macular edema, retinal vein occlusions, or myopic choroid neovascularization were included as the study group, and patients with same retinal diseases but did not receive intravitreal anti-VEGFs served as controls extracted by age- and sex-matched (1:4) and further propensity score matching (PSM). Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the risk of dialysis. A cohort of 2447 anti-VEGF users and 2447 controls by PSM were evaluated. Higher dialysis risks were observed among patients newly receiving anti-VEGF agents compared to controls (adjusted HR: 1.849; 95% CI: 1.378–2.482) in the PSM cohort. For subgroup analysis, patients newly receiving anti-VEGF treatment for diabetic macular edema had significant risk (adjusted HR: 1.834; 95% CI: 1.448–2.324) of becoming dialysis-dependent, while patients in other subgroups demonstrated similar risks as the controls. In conclusion, intravitreal anti-VEGF agents might increase the risk of becoming dialysis-dependent, especially in patients who are treated for diabetic macular edema.

Current and Novel Therapeutic Approaches for Treatment of Diabetic Macular Edema.

Diabetic macular edema (DME) is a major ocular complication of diabetes mellitus (DM), leading to significant visual impairment. DME’s pathogenesis is multifactorial. Focal edema tends to occur when primary metabolic abnormalities lead to a persistent hyperglycemic state, causing the development of microaneurysms, often with extravascular lipoprotein in a circinate pattern around the focal leakage. On the other hand, diffusion edema is due to a generalized breakdown of the inner blood–retinal barrier, leading to profuse early leakage from the entire capillary bed of the posterior pole with the subsequent extravasation of fluid into the extracellular space. The pathogenesis of DME occurs through the interaction of multiple molecular mediators, including the overexpression of several growth factors, including vascular endothelial growth factor (VEGF), insulin-like growth factor-1, angiopoietin-1, and -2, stromal-derived factor-1, fibroblast growth factor-2, and tumor necrosis factor. Synergistically, these growth factors mediate angiogenesis, protease production, endothelial cell proliferation, and migration. Treatment for DME generally involves primary management of DM, laser photocoagulation, and pharmacotherapeutics targeting mediators, namely, the anti-VEGF pathway. The emergence of anti-VEGF therapies has resulted in significant clinical improvements compared to laser therapy alone. However, multiple factors influencing the visual outcome after anti-VEGF treatment and the presence of anti-VEGF non-responders have necessitated the development of new pharmacotherapies. In this review, we explore the pathophysiology of DME and current management strategies. In addition, we provide a comprehensive analysis of emerging therapeutic approaches to the treatment of DME.

One-Month Outcomes of Intravitreal Anti-VEGF vs. Dexamethasone Implant in the Treatment of Diabetic Macular Edema in Vitrectomized Eyes.

ObjectivesTo compare short-term effect of intravitreal ranibizumab with dexamethasone implant for diabetic macular edema (DME) in vitrectomized eyes.MethodsSingle-center, prospective, randomized study of vitrectomized eyes with DME. Study eyes were divided into two groups, receiving ranibizumab (IVV group, n = 35 eyes) or dexamethasone implant (IVD group, n = 35 eyes) respectively. Patients were evaluated at baseline, Week 1 and Month 1. The main outcome measures included best-corrected visual acuity (BCVA), central retinal thickness (CRT) and intraocular pressure (IOP).ResultsBCVA and CRT were similar in the two groups at baseline. At Week 1, the CRT improvement was significant in two groups (P = 0.041 in IVV group, P = 0.030 in IVD group), but at Month 1, only IVD group had significant improvement in CRT (P < 0.001). And BCVA gains were significant at Week 1 (P = 0.029) and Month 1 (P = 0.001) in IVD group, whereas IVV group did not show significant BCVA gains (P = 0.056 at Week1, P = 0.166 at Month 1). The changes of BCVA and CRT were significantly higher in IVD group than IVV group at Month1, but the changes were not significant at Week1.ConclusionsComparing to anti-VEGF therapy, DEX implant is more effect in improving BCVA and reducing CRT in vitrectomized eyes at 1 month, which indicated DEX implant is a better strategy.

Visual outcomes of observation, macular laser and anti-VEGF in diabetic macular edema in type 1 diabetes: a real-world study

BackgroundThe treatment for diabetic macular edema (DME) has revolutionized during the last 15 years after the introduction of intravitreal anti-VEGF agents. The aim of the current study is to evaluate the real-world visual outcomes of diabetic macular edema (DME) treatment in patients with type 1 diabetes (T1D) in long-term follow-up.MethodsA real-world, descriptive, population-based cohort and follow-up of all patients with T1D and DME in 2006-2020 in 34 communities of the Northern Ostrobothnia Hospital District. The main outcome measures included age, gender, duration of T1D at the onset of DME, stage of retinopathy, treatment of DME (observation, laser, intravitreal treatments, combination), and visual outcomes.ResultsA total of 304 eyes of 206 T1D patients with DME were included. 75% (n=155) had non-proliferative diabetic retinopathy during the onset of DME. 15% of the cases were observed, 33% had macular laser, 41% intravitreal anti-VEGF and 12% combination of laser and intravitreal injections. Patients in anti-VEGF and in combination groups gained 4.9 and 5.5 ETDRS letters after the initial DME episode (p<0.001 and p<0.001), and the long-term visual improvements were 4.1 and 5.1 ETDRS letters (p<0.001 and p<0.001), respectively. In observation and laser groups the initial gain of 0.1 (p>0.90) and loss of 0.4 ETDRS letter (p=0.61), respectively, was noted. After the follow-up, a 3.7 ETDRS letter decrease was documented in the observation group (p>0.90) and a 1.1 (p=0.14) ETDRS letter decline in the laser group of patients. At the beginning of treatment, eyes subjected to anti-VEGF alone or in combination with laser had lower visual acuity compared to eyes subjected to observation or macular laser. The average of a 6.1±4.8 anti-VEGF injections were needed to dry DME. Visual impairment due to DME decreased from 2.4% to 1.0% during the 15-year period.ConclusionsAnti-VEGF alone or in combination with macular laser seems to be beneficial in terms of visual outcomes and treatment stability in T1D patients with central DME.Moreover, satisfying long-term visual outcomes were achieved with anti-VEGF treatment in a real-world setting.

Effect of intravitreal ranibizumab on serous retinal detachment in diabetic macular edema

PurposeTo evaluate the functional and anatomical results of intravitreal ranibizumab (IVR) treatment in diabetic macular edema (DME) with and without serous retinal detachment (SRD). Material and methodsFifty-one eyes treated with three consecutive intravitreal injections of ranibizumab for DME with and without SRD were retrospectively analyzed. Patients were divided into two groups according to optical coherence tomography (OCT) findings. Group 1 consisted of 25 DME patients with SRD, Group 2 consisted of 26 DME patients without SRD. After three consecutive IVR injections, changes in best-corrected visual acuity (BCVA) and central macular thickness (CMT) were analyzed and compared between groups. ResultsThe mean age was 64.16 ± 6.43 and 68.77 ± 7.19 years, respectively (p = 0.036). Initial BCVA was 0.55 ± 0.36, 0.62 ± 0.39 LogMAR, respectively (p: 0.613). Initial CMT was 548.7 ± 111.6 μm, 446.4 ± 104.1 μm in groups, respectively and it was significantly higher in Group 1 (p = 0.001). After three consecutive IVR, mean BCVA improved to 0.47 ± 0.30 LogMAR (p = 0.281) and CMT decreased to 331.6 ± 165.1 μm (p = 0.000) in Group 1. Mean BCVA improved to 0.40 ± 0.34 LogMAR (p = 0.005) and CMT decreased to 287.2 ± 148.8 μm (p = 0.000) in Group 2. While the decrease in CMT values was similar between the groups, the increase in BCVA was more pronounced in Group 2 after IVR treatment. ConclusionsSimilar morphological results were obtained in both of the groups, but the visual gain was lower in patients with SRD.

Proliferative Diabetic Retinopathy Events in Patients With Diabetic Macular Edema: Post Hoc Analysis of VISTA and VIVID Trials.

This work aimed to assess the incidence of proliferative diabetic retinopathy (PDR) events and improvement to mild non-PDR (NPDR) or better after intravitreal aflibercept injection (IAI) or laser treatment (control) in diabetic macular edema (DME). PDR events in the VISTA (NCT01363440) and VIVID (NCT01331681) phase 3 clinical trials were evaluated in a combined IAI-treated group (IAI 2 mg every 4 weeks or 2 mg every 8 weeks after 5 initial monthly doses; n = 475) and a macular laser control group (n = 235) through week 100 in eyes without PDR at baseline (Diabetic Retinopathy Severity Scale [DRSS] score ≤ 53). Improvement in the DRSS score to 35 or better was evaluated in those with a baseline DRSS score of 43 or greater. A lower proportion of eyes in the IAI group than in the laser group developed a PDR event through week 100 (4.4% vs 11.1%; adjusted difference, -6.7%; 97.5% CI, -11.7 to -1.6; nominal P = .0008). All PDR events occurred in eyes with a baseline DRSS score of 43, 47, or 53 and not in those with a score of 35 or less. A greater proportion of eyes in the IAI group than in the control group achieved a DRSS score of 35 or less (20.0% vs 3.8%; nominal P < .0001). Fewer eyes with NPDR and DME treated with IAI than eyes treated with a laser had a PDR event. More eyes treated with IAI improved to mild NPDR or better (DRSS score ≤ 35) through 100 weeks.

469-P: Sodium–Glucose Cotransporter 2 Inhibitors Decrease the Frequency of Antivascular Endothelial Growth Factor Agent Injection in Patients with Type 2 Diabetes Complicated by Diabetic Macular Edema

Aims: Diabetic macular edema (DME) leads to impaired vision. The first line of treatment is intravitreal injection of anti-vascular endothelial growth factor (VEGF) agent. However, there are patients who are refractory to this. We reported patients whose DME were refractory to anti-VEGF agents and showed improvement by using sodium glucose cotransporter 2 inhibitors (SGLT2is) . The effectiveness of SGLT2is for DME was assessed using a health insurance claim database. Methods: The JMDC inc. database covering million Japanese patients between 2005-20was used for analysis. Patients with type 2 diabetes (T2D) with DME were included, and those who were undergo dialysis, had other ocular diseases that may be treated by anti-VEGF agents, or were not on treatment with any antidiabetic drug introduced after 2014 were excluded. Propensity score matching was performed between SGLT2i users and non-users. The frequency and the duration of intravitreal injection of anti-VEGF agent after the period from the start of SGLT2is or other antidiabetic drugs were analyzed. Results: In this study, 340 matched patients with T2D were analyzed. Initiation of SGLT2is revealed a decrease in the frequency of anti-VEGF agent injection (2.7 ± 4.1 vs. 3.8 ± 4.6 times, p &amp;lt; 0.001; the Wilcoxon signed rank test, p &amp;lt; 0.001, 95%CI -0.25 to -0.085; the Poisson regression, p &amp;lt; 0.001, HR 0.80, 95% CI 0.73 to 0.87; the recurrent event analysis) and an extension in the duration for the requirement of the first injection of anti-VEGF agent (the number of patients who received no anti-VEGF agents, 96 vs. 32, p &amp;lt; 0.001; the log-rank test) . Conclusion: Using SGLT2is for patients with T2D complicated by DME extended the duration for the requirement of the first anti-VEGF agent injection and decreased the frequency of anti-VEGF agent injection. SGLT2is may be an option for DME treatment. Disclosure R.Ishibashi: Research Support; Astellas Pharma Inc., Boehringer Ingelheim International GmbH, Daiichi Sankyo, Mitsubishi Tanabe Pharma Corporation, Taiho Pharmaceutical Co. Ltd., YL Biologics, ZERIA Pharmaceutical Co.,Ltd. E.Kawakami: None. M.Koshizaka: None. Y.Maezawa: None. K.Yokote: None. Y.Takatsuna: None. T.Tatsumi: None. S.Yamamoto: None. Y.Inaba: None. Y.Shiko: None.

Differential gene expression analysis using RNA sequencing: retinal pigment epithelial cells after exposure to continuous-wave and subthreshold micropulse laser.

Subthreshold micropulse laser (SMPL) is more clinically efficient for the treatment of diabetic macular edema (DME) than the conventional continuous-wave (CW) laser. We aimed to characterize transcriptome changes after the application of these lasers and to compare the transcripts. Human pluripotent stem cell-derived retinal pigment epithelial cells were exposed to laser irradiation. Differentially expressed genes (DEGs), distribution of heat shock protein (Hsp) family, gene expression profile, and gene ontology (GO) enrichment analysis based on RNA sequencing data were investigated at 3 h and 24 h after irradiation. CW laser induced more DEGs than SMPL (1771 vs. 520 genes). The expression of the Hsp family was confirmed in both groups: however, the induction patterns was different for different genes. GO enrichment analysis revealed that CW laser upregulated the expression of DEGs involved in vasculature development (GO: 0001944), related to apoptosis and repair after cell injury whereas SMPL upregulated the expression of DEGs involved in photoreceptor cell maintenance (GO: 0045494), photoreceptor cell development (GO: 0042461), and sensory perception of light stimuli (GO: 0050953). The results provide insights into the genetic responses and may contribute to the understanding of the molecular mechanisms of laser-induced thermal effects.

Automatic Segmentation of Retinal Fluid and Photoreceptor Layer from Optical Coherence Tomography Images of Diabetic Macular Edema Patients Using Deep Learning and Associations with Visual Acuity.

Diabetic macular edema (DME) is a highly common cause of vision loss in patients with diabetes. Optical coherence tomography (OCT) is crucial in classifying DME and tracking the results of DME treatment. The presence of intraretinal cystoid fluid (IRC) and subretinal fluid (SRF) and the disruption of the ellipsoid zone (EZ), which is part of the photoreceptor layer, are three crucial factors affecting the best corrected visual acuity (BCVA). However, the manual segmentation of retinal fluid and the EZ from retinal OCT images is laborious and time-consuming. Current methods focus only on the segmentation of retinal features, lacking a correlation with visual acuity. Therefore, we proposed a modified U-net, a deep learning algorithm, to segment these features from OCT images of patients with DME. We also correlated these features with visual acuity. The IRC, SRF, and EZ of the OCT retinal images were manually labeled and checked by doctors. We trained the modified U-net model on these labeled images. Our model achieved Sørensen–Dice coefficients of 0.80 and 0.89 for IRC and SRF, respectively. The area under the receiver operating characteristic curve (ROC) for EZ disruption was 0.88. Linear regression indicated that EZ disruption was the factor most strongly correlated with BCVA. This finding agrees with that of previous studies on OCT images. Thus, we demonstrate that our segmentation network can be feasibly applied to OCT image segmentation and assist physicians in assessing the severity of the disease.

Clinical Comparative Study of Intravitreal Injection of Triamcinolone Acetonide and Aflibercept in the Treatment of Diabetic Retinopathy Cystoid Macular Edema.

Objective To compare the curative effect of intravitreal injection of triamcinolone acetonide and aflibercept on diabetic retinopathy (DR) cystoid macular edema. Methods A total of 102 patients with DR cystoid macular edema admitted to the hospital were enrolled between July 2018 and July 2021. According to random number table method, they were divided into the control group (intravitreal injection of triamcinolone acetonide) and the observation group (intravitreal injection of aflibercept), 51 cases in each group. All were followed up for half a year. The clinical curative effect, visual acuity, central subfield macular thickness (CSMT), macular volume, scores of quality of life, and levels of cytokines in aqueous humor (vascular endothelial growth factor (VEGF), monocyte chemoattractant protein-1 (MCP-1), human angiopoietin-like protein 4 (ANGPTL4)] at different time points (before and at 6 months after surgery) were compared between the two groups. The times of drugs injection and occurrence of adverse reactions in both groups were statistically analyzed. Results The total effective rate in observation group was higher than that in the control group (96.08% vs 82.35%) (P < 0.05). After 6 months of treatment, visual acuity was improved, and CSMT and macular volume were decreased in both groups. Also, the above changes were more significant in the observation group than those in the control group (P < 0.05). After 6 months of treatment, levels of cytokines in aqueous humor were decreased in both groups. The levels of VEGF, MCP-1, and ANGPTL4 in observation group were lower than those in the control group (P < 0.05). After 6 months of treatment, quality of life scores in observation group were higher than those in the control group (P < 0.05). In the follow-up period, average times of drugs injection in the observation group were more than those in the control group, and the incidence of adverse reactions was lower than that in control group (5.88% vs 21.57%) (P < 0.05). Conclusion The curative effect of intravitreal injection of both triamcinolone acetonide and aflibercept is good on DR cystoid macular edema. The curative effect of aflibercept is better, which can improve visual acuity and quality of life, and regulate cytokines in aqueous humor, with high safety. However, aflibercept has a high price, and further research is needed to determine whether its price can be matched with clinical benefits. In clinic, medication plan should be selected according to the actual situation.

Treatment of diabetic macular edema in real-world clinical practice: The effect of aging.

ABSTRACTAims/IntroductionIn older patients, the management of diabetic macular edema (DME) can be complicated by comorbidities, geriatric syndrome, and socioeconomic status. This study aims to evaluate the effects of aging on the management of DME.Materials and MethodsThis is a real‐world clinical study including 1,552 patients with treatment‐naïve center‐involved DME. The patients were categorized into 4 categories by age at baseline (C1, <55; C2, 55–64; C3, 65–74; and C4, ≥75 years). The outcomes were the change in logarithm of the minimum angle of resolution best‐corrected visual acuity (logMAR BCVA) and central retinal thickness (CRT), and the number of treatments from baseline to 2 years.ResultsFrom baseline to 2 years, the mean changes in logMAR BCVA from baseline to 2 years were −0.01 in C1, −0.06 in C2, −0.07 in C3, and 0.01 in C4 (P = 0.016), and the mean changes in CRT were −136.2 μm in C1, −108.8 μm in C2, −100.6 μm in C3, and −89.5 μm in C4 (P = 0.008). Treatments applied in the 2 year period exhibited decreasing trends with increasing age category on the number of intravitreal injections of anti‐VEGF agents (P = 0.06), selecting local corticosteroid injection (P = 0.031), vitrectomy (P < 0.001), and laser photocoagulation outside the great vascular arcade (P < 0.001).ConclusionsCompared with younger patients with DME, patients with DME aged ≥75 years showed less frequent treatment, a lower BCVA gain, and a smaller CRT decrease. The management and visual outcome in older patients with DME would be unsatisfactory in real‐world clinical practice.

OCTA changes following loading phase with intravitreal aflibercept for DME

ObjectifMesurer les variations observées à l'angiographie-tomographie par cohérence optique (OCTA) à la suite de l'administration intravitréenne d'anti-VEGF (facteur de croissance endothélial vasculaire) dans le traitement de l’œdème maculaire diabétique (OMD), et évaluer le lien entre les paramètres mesurés à l'OCTA avant le traitement et les résultats visuels. NatureÉtude de cohorte prospective. MéthodesUn groupe de 29 patients présentant un OMD ont reçu 5 injections intravitréennes mensuelles d'aflibercept. On a eu recours au test de Wilcoxon pour observations appariées afin de comparer les données mesurées à l'OCTA au départ et après 6 mois. Au nombre des paramètres mesurés à l'OCTA, citons l'aire de la zone fovéale avasculaire (ZFA), le périmètre de la ZFA, la circularité de la ZFA, la densité vasculaire du plexus vasculaire superficiel (segmenté conformément à la cartographie de l’étude ETDRS [Early Treatment of Diabetic Retinopathy Study], soit zone centrale, zone interne, zone externe et zone complète). Une sous-analyse a permis de séparer les patients en 2 groupes : sujets qui ont répondu au traitement (réduction de l’épaisseur du sous-champ central > 50 µm pendant le traitement) et sujets qui n'ont pas répondu au traitement. Une régression linéaire multiple et une régression logistique ont servi à déterminer les liens entre les paramètres mesurés à l'OCTA avant le traitement et les résultats en matière d'acuité visuelle. RésultatsUn total de 29 patients ont été inclus: 25 patients (86,2 %) présentaient une rétinopathie diabétique non proliférante et 4 (13,8 %), une rétinopathie diabétique proliférante. La densité vasculaire a diminué dans les zones centrale (p = 0,004) et interne (p = 0,013) selon la cartographie de l’étude ETDRS. Cet effet n’était significatif que chez les patients qui ont répondu au traitement (zone centrale; p = 0,002; zone interne; p = 0,017). Les paramètres OCT et OCTA mesurés avant le traitement n'ont pas influé sur les résultats ultimes en matière d'acuité visuelle. ConclusionOn a noté, après l'administration intravitréenne d'aflibercept dans le traitement de l'OMD, une diminution significative de la densité vasculaire du plexus vasculaire superficiel dans les zones centrale et interne selon la cartographie de l'ETDRS. Ce phénomène s'est produit exclusivement chez les patients qui ont répondu au traitement. Nos observations tiennent vraisemblablement aux limites de la technologie de l'OCTA elle-même, en ce sens que la densité vasculaire avant le traitement a potentiellement été surestimée par la présence d'artéfacts, soit quelques particules en suspension en mouvement. Les paramètres mesurés à l'OCTA avant le traitement n'ont pas pu servir de biomarqueurs permettant de prévoir les résultats visuels après l'administration d'un anti-VEGF.

Optical Coherence Tomography Classification Systems for Diabetic Macular Edema and Their Associations With Visual Outcome and Treatment Responses - An Updated Review.

Optical coherence tomography (OCT) is an invaluable imaging tool in detecting and assessing diabetic macular edema (DME). Over the past decade, there have been different proposed OCT-based classification systems for DME. In this review, we present an update of spectral-domain OCT (SDOCT)-based DME classifications over the past 5 years. In addition, we attempt to summarize the proposed OCT qualitative and quantitative parameters from different classification systems in relation to disease severity, risk of progression, and treatment outcome. Although some OCT-based measurements were found to have prognostic value on visual outcome, there has been a lack of consensus or guidelines on which parameters can be reliably used to predict treatment outcomes. We also summarize recent literatures on the prognostic value of these parameters including quantitative measures such as macular thickness or volume, central subfield thickness or foveal thickness, and qualitative features such as the morphology of the vitreoretinal interface, disorganization of retinal inner layers, ellipsoid zone disruption integrity, and hyperreflec-tive foci. In addition, we discuss that a framework to assess the validity of biomarkers for treatment outcome is essentially important in assessing the prognosis before deciding on treatment in DME. Finally, we echo with other experts on the demand for updating the current diabetic retinal disease classification.

Treatment of chronic diabetic macular oedema with intravitreal fluocinolone acetonide implant; real-life analysis of outcomes during overall treatment period.

To assess the clinical efficacy of the fluocinolone acetonide (FA) intravitreal implant (Iluvien, Alimera Sciences) over a 12-month period in a population resistant to treatment with first-line anti-VEGF agents. This study is a retrospective cohort study assessing functional and anatomical outcomes in 13 eyes of 12 patients treated for diabetic macular oedema (DMO) with a single fluocinolone implant (FA) (Iluvien) under real-world conditions. The follow-up period includes the time of first intravitreal treatment (incl anti-VEGF or short-lasting steroids) given until 12 months post FA implant insertion. Primary outcomes were best corrected visual acuity (BCVA), measured using the modified Early Treatment Diabetic Retinopathy Study (ETDRS) grading scale, and central foveal thickness (CFT), measured using Topcon 3DOCT-2000 (Topcon Inc) SD-OCT imaging. Mean BCVA and CFT were measured before anti-VEGF treatment, after anti-VEGF treatment, at the time of Iluvien implant insertion, and 6 and 12 months after Iluvien implant insertion. The t-paired sample test was used to ascertain statistical significance of changes in comparison of two samples while the ANOVA analysis was used in comparison of three or more samples. The baseline BCVA (SD) of the cohort prior to initiation of anti-VEGF treatment was 47.45 (12.27) ETDRS letters whilst the mean CFT (SD) was 579 (203) microns. Following completion of anti-VEGF therapy, the mean improvement in vision was 8.9 ETDRS letters (p = 0.1) whilst the mean reduction in CFT was 197 microns (p = 0.028). Mean BCVA (SD) at the time of insertion of the FA implant was 55.15 (11.16) ETDRS letters and mean (SD) CFT at time of insertion of the FA was 454.62 μm (109.51). Following the 12-month treatment period with the FA implant, BCVA (SD) was 62.15 (10.25) ETDRS letters (p = 0.0331) and the mean (SD) CFT was 404.36 μm (142.92), a change of -50.26 μm from baseline (p = 0.0369). This study has shown that statistically significant improvements in BCVA and CFT can be achieved over a 12-month period with the Iluvien implant. The implant has been shown to be a safe option in the treatment of DMO and may have a role to play in achieving good functional and anatomical outcomes in DMO while also reducing the frequency of follow-up appointments required to maintain stable vision in the working-age population.

Osteopontin-induced vascular hyperpermeability through tight junction disruption in diabetic retina

Diabetic retinopathy is a major cause of blindness in developed countries, and is characterized by deterioration of barrier function causing vascular hyperpermeability and retinal edema. Vascular endothelial growth factor (VEGF) is a major mediator of diabetic macular edema. Although anti-VEGF drugs are the first-line treatment for diabetic macular edema, some cases are refractory to anti-VEGF therapy. Osteopontin (OPN) is a phosphoglycoprotein with diverse functions and expressed in various cells and tissues. Elevated OPN level has been implicated in diabetic retinopathy, but whether OPN is involved in hyperpermeability remains unclear. Using streptozotocin-induced diabetic mice (STZ mice) and human retinal endothelial cells (HRECs), we tested the hypothesis that up-regulated OPN causes tight junction disruption, leading to vascular hyperpermeability. The serum and retinal OPN concentrations were elevated in STZ mice compared to controls. Intravitreal injection of anti-OPN neutralizing antibody (anti-OPN Ab) suppressed vascular hyperpermeability and prevented decreases in claudin-5 and ZO-1 gene expression levels in the retina of STZ mice. Immunohistochemical staining of retinal vessels in STZ mice revealed claudin-5 immunoreactivity with punctate distribution and attenuated ZO-1 immunoreactivity, and these changes were prevented by anti-OPN Ab. Intravitreal injection of anti-OPN Ab did not change VEGF gene expression or protein concentration in retina of STZ mice. In an in vitro study, HRECs were exposed to normal glucose or high glucose with or without OPN for 48 h, and barrier function was evaluated by transendothelial electrical resistance and Evans blue permeation. Barrier function deteriorated under high glucose condition, and was further exacerbated by the addition of OPN. Immunofluorescence localization of claudin-5 and ZO-1 demonstrated punctate appearance with discontinuous junction in HRECs exposed to high glucose and OPN. There were no changes in VEGF and VEGF receptor-2 expression levels in HRECs by exposure to OPN. Our results suggest that OPN induces tight junction disruption and vascular hyperpermeability under diabetic conditions. Targeting OPN may be an effective approach to manage diabetic retinopathy.

A preliminary observation on rod cell photobiomodulation in treating diabetic macular edema

PurposeTo evaluate the safety and effectiveness of photobiomodulation (PBM) in the treatment of diabetic macular edema (DME). MethodsIt was a single-center, self-controlled prospective study. The clinical records of 12 diabetic retinopathy patients (5 males and 7 females, 20 eyes in total) who were treated with PBM for DME at the Second Affiliated Hospital, Zhejiang University School of Medicine, were analyzed. The mean age was 56 (26–68) years. All the participants received PBM treatment during darkness at night in no less than 5 days per week and no less than 8 ​h per day. In the baseline check and follow-up checks (1, 2, 6, 10, and 12 months after the start of treatment), the best-corrected visual acuity, the thickness of the retina in the macula, and the changes of the fundus lesions were observed. Wilcoxon signed rank test was used to compare the results before and after treatment. P ​< ​0.05 was considered statistically significant. ResultsNo fundus complication was observed during follow-up checks. In baseline and 12-month follow-up checks, the best-corrected visual acuity was 71.75 ​± ​12.47 and 79.50 ​± ​10.85, maximal retinal thickness in macular area was 390.95 ​± ​77.12 ​μm and 354.13 ​± ​55.03 ​μm, average retinal thickness in macular area was 334.25 ​± ​36.45 ​μm and 314.31 ​± ​33.28 ​μm, foveal thickness was 287.00 ​± ​46.79 ​μm and 265.63 ​± ​67.14 ​μm. The best-corrected visual acuity, average retinal thickness in macular area in consecutive follow-up results except that in the 1st month showed significant difference compared with baseline results. There were significant difference between every follow-up result and baseline result of maximal retinal thickness in macular area (P ​< ​0.05). All follow-up results of foveal thickness were not significantly different (P ​> ​0.05) from the baseline result, except that in the 6th month (P ​= ​0.049). Obvious improvement could be observed in retinal fundus fluorescein angiography images. ConclusionsPBM is a safe and effective treatment of DME, which deserves further investigation.

Faricimab: First Approval.

Faricimab (faricimab-svoa; Vabysmo™) is a bispecific antibody that binds to and inhibits both vascular endothelial growth factor (VEGF)-A and angiopoietin-2 (Ang-2). Administered by intravitreal injection, faricimab is being developed by Roche/Genentech for use in the treatment of retinal vascular diseases. In January 2022 faricimab received its first approvals, in the USA, for use in the treatment of patients with neovascular (wet) age-related macular degeneration (nAMD) or diabetic macular edema (DME). Faricimab has also recently been approved in Japan, and is currently under regulatory review in the EU, for use in nAMD and DME. PhaseIII clinical development of faricimab for use in the treatment of nAMD, DME, and macular edema due to retinal vein occlusion is continuing in multiple other countries worldwide. This article summarizes the milestones in the development of faricimab leading to these first approvals for nAMD and DME in the USA.