Diabetic Macular Edema Patients Research Articles

Clinical Outcome and Drug Expenses of Intravitreal Therapy for Diabetic Macular Edema: A Retrospective Study in Sardinia, Italy.

Background: Diabetic macular edema (DME) is a leading cause of visual loss in working-age adults. The purpose of this retrospective study was to perform an epidemiological analysis on DME patients treated with intravitreal drugs in a tertiary hospital. The clinical outcome, adverse drug reactions (ADRs), and intravitreal drug expenses were assessed. Methods: All DME patients treated with Ranibizumab, Aflibercept, Dexamethasone implant, and Fluocinolone Acetonide implant at the Sassari University Hospital, Italy, between January 2017 and June 2020 were included. Central macular thickness (CMT) and best corrected visual acuity (BCVA) were measured. ADRs and drug expenses were analyzed. Results: Two-hundred thirty-one DME patients (mean age: 65 years) received intravitreal agents. Mean CMT and BCVA were 380 μm and 0.5 LogMAR at baseline, 298 μm and 0.44 logMAR after one year (p = 0.04), and 295 μm and 0.4 logMAR at the end of the follow-up period. A total of 1501 intravitreal injections were given; no major ADRs were reported. Treatment cost was €915,000 (€261,429/year). Twenty non-responders to Ranibizumab or Aflibercept were switched to a Dexamethasone implant. In these patients, mean CMT and BCVA were 468 µm and 0.5 LogMar at the time of switching and 362 µm and 0.3 LogMar at the end of the follow-up (p = 0.00014 and p = 0.08, respectively). Conclusion: Results confirm that Ranibizumab, Aflibercept, and Dexamethasone implant are effective and safe in DME treatment. A switch to Dexamethasone implant for patients receiving Aflibercept or Ranibizumab with minimal/no clinical benefit should be considered.

The diagnostic value of systemic immune-inflammation index in diabetic macular oedema

ABSTRACT Clinical relevance Diabetic macular oedema (DME) is a significant cause of visual impairment and inflammation plays an important role in its pathophysiology. Background This study evaluates the diagnostic value of systemic immune-inflammation index (SII) in the occurrence of DME in patients with non-proliferative diabetic retinopathy. Methods In this prospective study, the SII was applied to 150 consecutive patients with non-proliferative diabetic retinopathy. The relationship between the SII and the occurrence of DME was examined. Patients with DME were also divided into two subgroups according to the presence of accompanying sub-retinal fluid. The SII value was calculated as follows: platelet count × (neutrophil/lymphocyte). The risk factors for DME were evaluated using multivariate logistic regression analysis. A receiver operating characteristic (ROC) curve analysis of SII for predicting DME was performed. Results Patients with DME had significantly higher levels of SII than those without DME (599.7 ± 279.2 and 464. 9 ± 172.2, respectively, p < 0.001). However, The SII values were similar between sub-retinal fluid subgroups. Multivariate regression analysis indicated that SII, together with duration of diabetes, was an independent factor for DME occurrence [Odds ratio (OR) = 1.005, 95% confidence interval = 1.001–1.009, p = 0.04, and OR = 1.146, 95% CI = 1.049–1.252, p = 0.003, respectively]. ROC curve analysis revealed that the best cut-off value of SII was 399 (area under the curve: 0.633; sensitivity: 70%; specificity: 60%). Conclusion An elevated SII value is strongly associated with the development of DME. The SII may be a diagnostic biomarker for identifying DME to improve the risk stratification and management of non-proliferative patients with diabetic retinopathy.

Macular and peripapillary microvasculature after dexamethasone injection in diabetic macular edema.

To evaluate the microvascular changes in the macular and peripapillary area after intravitreal dexamethasone implant in diabetic macular edema (DME). We included 31 eyes of 31 patients treated with a single dose dexamethasone implant for DME. All subjects underwent swept-source optical coherence tomography (OCT) and OCT angiography imaging before (T0), and one month (T1), two months (T2), and four months (T4) after dexamethasone injection. The foveal avascular zone (FAZ) area of superficial and deep capillary plexus (SCP and DCP) was calculated by delineating the FAZ border using the measurement tool of the device. The vessel density (VD) of SCP and DCP and choriocapillaris (CC) in the macular and peripapillary area were automatically calculated. There was an insignificant reduction in FAZ area measurements of SCP after dexamethasone injection in DME patients (p = 0.846). The FAZ area of DCP were significantly smaller compared to T0 measurements at T1, T2, and T4 (p = 0.013, p = 0.031, and p = 0.029, respectively). The mean average parafoveal VD measurements were significantly decreased after dexamethasone injection in SCP and DCP (p = 0.004, p = 0.005). The peripapillary VD in retinal capillary plexuses and choriocapillaris showed no significant difference after dexamethasone injection. Intravitreal dexamethasone leads to a significant FAZ area decrease in DCP with a reduction in parafoveal VD measurements. In addition, no significant VD changes were observed in the peripapillary area after dexamethasone. These findings indicate that dexamethasone may improve macular ischemia with no significant effects on peripapillary microvasculature in DME patients.

Aqueous humor analyses of diabetic macular edema patients with subretinal fluid

We identified treatment-naïve diabetic macular edema (DME) patients with or without subretinal fluid (SRF). We compared their baseline characteristics: aqueous concentrations of interleukin (IL)-1β, IL-2, IL-6, IL-8, IL-10, and IL-17, as well as tumor necrosis factor-α, vascular endothelial growth factor (VEGF), and placental growth factor (PlGF). We also compared fundus and optical coherence tomography (OCT) findings, and responsiveness to anti-VEGF treatments. Of 67 DME patients, 18 (26.87%) had SRF. Compared to the no SRF group, the SRF group had significantly higher levels of IL-6, IL-8, VEGF, and PlGF in aqueous humor. After grouping according to diabetic retinopathy stage, non-proliferative diabetic retinopathy (NPDR) patients with SRF had higher aqueous levels of IL-6 and IL-8, compared to NPDR patients without SRF. Moreover, proliferative diabetic retinopathy (PDR) patients with SRF had higher aqueous levels of VEGF and PlGF, compared to PDR patients without SRF. Fundus and OCT analyses revealed that the SRF group had a greater proportion of patients with succinate or patch-shaped hard exudates involving the macula, and greater central subfield thickness (CST) at baseline. After 6 months of anti-VEGF treatments, the SRF group showed better responsiveness in terms of CST; however, visual acuity was not correlated with responsiveness. Considering higher aqueous levels of VEGFs and pro-inflammatory cytokines, SRF could be a biomarker related to diabetic retinopathy activity. DME patients with SRF showed better anatomical responsiveness to anti-VEGF treatments, but did not show better functional improvement on short-term evaluation compared to those of DME patients without SRF.

Tumor necrosis factor ligand-related molecule 1A maintains blood-retinal barrier via modulating SHP-1-Src-VE-cadherin signaling in diabetic retinopathy.

An impaired blood-retinal barrier (BRB) leads to diabetic macular edema (DME), which is a major complication of Diabetic retinopathy (DR). Mediators such as inflammation cause BRB breakdown. However, the explicit mechanism of its disruption is largely unknown. In this study, we identified tumor necrosis factor ligand-related molecule 1A (TL1A) as a crucial factor which protect retinal endothelial cells integrity in DR. By providing both human and mouse data, we show that TL1A is significantly decreased in the retinas of DME patients and diabetic rodents. We further demonstrate that the loss of TL1A accelerated diabetes-induced retinal barrier breakdown. TL1A supplementation protects the diabetic retina against BRB breakdown. Mechanistically, TL1A stabilize intracellular junctions and protect vascular integrity by blocking SHP1-Src-regulated VE-cadherin phosphorylation. Collectively, our findings reveal that loss of TL1A in the retina leads to increased vascular permeability in DR, and that TL1A treatment is of potential therapeutic interest for the treatment of DME.

Intravitreal corticosteroids for diabetic macular edema: a network meta-analysis of randomized controlled trials

BackgroundTo evaluate the efficacy and safety of different intravitreal corticosteroids for treating diabetic macular edema (DME).MethodsFour databases were systematically searched for randomized controlled trials comparing different intravitreal corticosteroids for treating DME. The primary outcome was the change in best-corrected visual acuity (BCVA) within 6 months after the first injection (short-term BCVA). Secondary outcomes were the change in BCVA over 1 year (long-term BCVA) and changes in central macular thickness (CMT) and intraocular pressure (IOP) within 6 months after the first injection. Network meta-analysis was performed to aggregate the results from the individual studies.ResultsNineteen trials involving 2839 eyes were included. Intravitreal triamcinolone acetonide (TA) injections (≥ 8 mg and 4–8 mg), fluocinolone acetonide (FA) implants (0.5 µg/day) and dexamethasone (DEX) implants (700 µg) improved short-term BCVA (mean changes in logMAR [95% confidence interval] − 0.27 [− 0.40, − 0.15]; − 0.12 [− 0.18, − 0.06]; − 0.10 [− 0.21, − 0.01]; and − 0.06 [− 0.11, − 0.01]). Intravitreal TA injections (4 mg, multiple times), FA implants (0.5 µg/day and 0.2 µg/day), and DEX implants (350 µg) improved long-term BCVA (mean changes in logMAR [95% confidence interval] − 0.11 [− 0.21, − 0.02]; − 0.09 [− 0.15, − 0.03]; − 0.09 [− 0.14, − 0.02]; and − 0.04 [− 0.07, − 0.01]). All intravitreal corticosteroids reduced CMT, and different dosages of TA did not show significant differences in increasing IOP.ConclusionsIntravitreal corticosteroids effectively improved BCVA in DME patients, with higher dosages showing greater efficacies. TA was not inferior to FA or DEX and may be considered a low-cost alternative choice for DME patients. The long-term efficacy and safety of different corticosteroids deserve further investigation.Trial registration Prospectively registered: PROSPERO, CRD42020219870

Ellipsoid Zone Integrity and Visual Acuity Changes during Diabetic Macular Edema Therapy: A Longitudinal Study.

Purpose Ellipsoid zone (EZ) integrity is identified as a potential biomarker for therapy surveillance and outcome prediction of visual acuity (VA). However, only a few studies report long-term results of over 1 year of clinical and anatomical changes in patients with diabetic macular edema (DME). This study is aimed at describing the long-term VA and anatomical outcomes in spectral domain optical coherence tomography (OCT) (relative ellipsoid zone reflectivity ratio, central macular thickness, and volume) in patients with DME treated with antivascular endothelial growth factor (anti-VEGF) therapy. Furthermore, we studied the correlation between EZ integrity and changes in visual acuity. Methods 71 eyes of 71 patients were included in this retrospective study. Clinical characteristics were reviewed yearly. OCT data were assessed at baseline and after 1, 3, and 5 years. EZ parameters were quantified automatically. OCT parameters and visual outcome were correlated and analyzed in multivariable regression models. Results EZ reflectivity ratio correlated with functional outcome in DME patients from baseline to fifth year at all time points (for all p < 0.05). EZ reflectivity improved the most in the first year of treatment (0.68 to 0.75; p < 0.05) and declined gradually until year 5 of therapy (0.71; compared to baseline p > 0.05). Similarly, best VA was achieved after 1 year (0.40 logarithm of the minimum angle of resolution (logMAR) to 0.28 logMAR; p < 0.001) and declined gradually until year 5. Final VA in year 5 was comparable to baseline (0.45 logMAR, compared to baseline p > 0.05). Together with baseline VA, baseline EZ parameters did predict VA outcome after 1 year (p < 0.05). Concordantly, VA and EZ parameters from year 1 were associated with VA outcome in year 2. Conclusion This study described the long-term course of EZ changes during anti-VEGF treatment in DME patients. In addition, our results underlined the potential of EZ parameters as novel OCT biomarkers for prediction of VA outcomes during therapy.

Expression of Long Non-Coding RNA (lncRNA) SNHG5 in Patients with Refractory Diabetic Macular Edema and Its Regulatory Mechanism.

BackgroundThe aim of this study was to assess use of lncRNAs as biomarkers in serum and aqueous humor of patients with diabetic macular edema (DME).Material/MethodsOptical coherence tomography and fundus photography were used to analyze the retinal features of the patients. RT-qPCR was used to analyze the differential expression of lncRNA snhg5 in patients who have idiopathic macular hole (MH), DME, or refractory DME. The relationship between SNHG5 and the clinical characteristics of the patients was analyzed. The effect of SNHG5 on the hyperplasia and apoptosis of human retino-microvascular endothelial cells (HRMECs) and its mechanism were analyzed in vitro.ResultsPatients with idiopathic MH developed retinal nerve epithelium rupture and retinal fundus thickening, and patients with DME or refractory DME showed significant macular edema with hemorrhaging. The refractory DME patients improved after treatment but still showed significant macular edema and multiple laser scarring. SNHG5 expression was not only low in the atrial fluid and plasma in DME patients, but also lower in the refractory DME group compared to the idiopathic MH patients. SNHG5 expression in the aqueous humor and plasma was negatively correlated with disease duration, body mass index, and levels of fasting blood glucose, glycated hemoglobin, proteinuria, and glycosuria. In the in vitro experiments, SNHG5 expression was significantly downregulated in high glucose-induced HMECs. After SNHG5 overexpression, cell proliferation, angiogenesis, and VEGF-A protein levels were distinctly downregulated.ConclusionsSNHG5 correlates with the development of DME and is a potential target for therapy.

Baseline Subfoveal Choroidal Thickness as a Predictor for Response to Short-Term Intravitreal Bevacizumab Injections in Diabetic Macular Edema.

PurposeThis article aims to evaluate how the subfoveal choroidal thickness (SFCT) and best-corrected visual acuity (BCVA) respond to the intravitreal injection of bevacizumab and to assess the correlation between these changes. It will also assess the use of the baseline SFCT as a predictor for BCVA changes in eyes of treatment-naive, diabetic macular edema (DME) patients.MethodsThis retrospective, consecutive case series comprised 59 eyes of 39 treatment-naive DME patients. Complete slit-lamp assessment, swept-source optical coherence tomography (SS-OCT) scans to measure SFCT and BCVA values were performed at two stages: baseline and one month after the third monthly injection of intravitreal bevacizumab.ResultsPatients’ ages ranged from 46.3 to 76.4 years (mean: 62.6 ± 2.3). The mean SFCT was 318 ± 82 μm at baseline, which decreased after 3 months to 300 ± 66 μm (P-value = 0.021). There was an improvement in the mean of the logMAR best-corrected visual acuity (BCVA) from 0.7 (decimal equivalent: 0.2) to 0.5 (decimal equivalent: 0.3) (P-value = 0.019). There was no association between SFCT changes and BCVA changes (P-value = 0.180). Wilcoxon signed-rank test disclosed that a better BCVA improvement was related to a greater subfoveal choroidal thickness at baseline P-value <0.00.ConclusionEyes with a higher baseline subfoveal choroidal thickness (SFCT) attained greater BCVA improvement than eyes with a lower baseline SFCT. In addition to this, changes to SFCT do not appear to correlate with BCVA changes. These findings do not support using OCT SFCT changes as a prognostic factor for changes to BCVA after intravitreal bevacizumab treatment in evaluating treatment-naive DME eyes.

Порушення агрегації тромбоцитів як чинник розвитку діабетичної макулопатії та діабетичного макулярного набряку у хворих на непроліферативну діабетичну ретинопатію при цукровому діабеті 2-го типу

Актуальність. Аналіз сучасних даних дає можливість висунути припущення, що патогенетичні чинники цукрового діабету (ЦД) можуть провокувати проагрегантний статус тромбоцитів (Тц) та викликати порушення мікроциркуляції в оболонках ока і розвиток діабетичної макулопатії (ДМП) та діабетичного макулярного набряку (ДМН). Мета дослідження — проаналізувати порушення агрегації Тц при ДМН та ДМП за умов непроліферативної діабетичної ретинопатії (НПДР) при ЦД 2-го типу. Матеріали та методи. Дослідження включало 32 хворих (32 ока) із ЦД 2-го типу, у яких за класифікацією ETDRS виявлена легка (14 хворих, 14 очей) і помірна (18 хворих, 18 очей) стадії НПДР. Для дослідження Тц in vitro використовували аденозиндифосфат (АДФ), адреналін, ангіотензин-2 (Анг-2), фактор активації тромбоцитів (ФАТ) і колаген. Оцінку агрегації Тц проводили турбидиметричним методом на аналізаторі Chronolog (США). Результати. У пацієнтів з ДМП при помірній стадії НПДР виявлена більша реактивність Тц до Анг-2, ФАТ і адреналіну, ніж при легкій стадії (p &lt; 0,01). Даний феномен відбивав підвищення агрегації Тц внаслідок порушень симпатоадреналової та ренін-ангіотензинової систем та зростання тяжкості запалення. Гіперреактивність Тц до Анг-2 була причиною розвитку ДМН у хворих з ДМП при помірній стадії НПДР. Висновки. Патогенетичні чинники ЦД можуть провокувати проагрегантний статус Тц і тим самим викликати порушення мікроциркуляції в оболонках ока, що супроводжується розвитком ДМП і ДМН.

Multifocal Electroretinogram, Central Macula Thickness and Visual Acuity in Diabetic Macular Edema Following Intravitreal Injection of anti-VEGF

Introduction : Diabetic Retinopathy (DR) is one of the major cause of visual acuity deterioration in diabetic patients. The loss of central visual acuity in diabetic patients are mainly due to macula edema, which is found in 29% diabetic patients with the over 20 years duration of disease. The aim of this study is to evaluate and investigate the possible correlation among changes of visual acuity (VA), central macular thickness (CMT) using Spectral Domain Optical Coherence Tomography (SD-OCT). Electrophysiological responses using multifocal electroretinography (MfERG) in diabetic macular edema (DME) following intravitreal injection of bevacizumab.&#x0D; Methods: Single arm clinical trial. Thirty-three eyes of 33 DME patients (16 non-proliferative diabetic retinopathy and 17 non-high-risk proliferative diabetic retinopathy), receives intravitreal bevacizumab 1,25mg. All patients underwent complete ophthalmic examination including ETDRS VA testing, Sixty-one scaled hexagon MfERG and SD-OCT scan at baseline, 1-week and 1-month post-injection. Components of the first order kernel (N1, N2 and P1) in central 2o were measured.&#x0D; Result : MfERG showed reduced P1 amplitude (P&lt;0.05) at 1-week after injection followed by increased P1 amplitude (P&gt;0.05) at 1-month after treatment as compared to the baseline in all subjects. There was 19% improvement CMT and 0.2Logmar VA improvement in 1-month post-injection compared to the baseline (P&lt;005). This study showed no serious ocular adverse effects. There was no significant correlation between changes in visual acuity with changes in CMT or other MfERG parameters.&#x0D; Conclusion: Intravitreal injection bevacizumab resulting in improved VA, reduction in CMT and mild improvement in the MfERG responses. Although VA changes did not correlate with reduced CMT nor with improved responses of MfERG, the combined use of SD-OCT and MfERG may be used to evaluate macular function in DME patient with worsened visual acuity post anti-VEGF injection.

Visual/anatomical outcome of diabetic macular edema patients lost to follow-up for more than 1\xa0year

To investigate the visual/anatomical outcome of diabetic macular edema (DME) patients lost to follow-up (LTFU) for more than 1 year during intravitreal anti-VEGF treatment. A retrospective review of 182 treatment-naïve DME patients was performed. Among them, we identified patients LTFU for more than 1 year during anti-VEGF treatment. Visual acuity and anatomic outcomes at the first visit, last visit before being LTFU, return visit, and after re-treatment were analyzed and compared with those of DME patients with regular follow-up. Patients who had continuous follow-up visits were assigned to the control group. Sixty patients (33%) with DME were LTFU for more than 1 year during anti-VEGF treatment. Multivariate analysis revealed that the ratio of male (p = 0.004), diabetes mellitus (DM) duration less than 5 years (p = 0.015), and poor early anatomic response (p = 0.012) were higher compared to the control group. Eighteen patients returned to the clinic and received re-treatment. After re-treatment with anti-VEGF, central subfield thickness (CST) was significantly improved to the CST of before LTFU. However, visual acuity did not recover to the level before LTFU (0.63 ± 0.26 vs. 0.45 ± 0.28, p = 0.003). About thirty percent of DME patients were LTFU for more than 1 year. Permanent visual loss was observed in these LTFU patients. Patients with a high risk of LTFU such as male, early DM, and poor response after initial injections should be treated more aggressively to improve the visual outcomes.

EFFECT OF STATIN USE ON STATUS OF DIABETIC ETINOPATHY/ DIABETIC MACULAR EDEMA IN PATIENTS OF TYPE 2 DIABETES MELLITUS

AIM: Effect of statin use on status of diabetic retinopathy /diabetic macular edema in patients of type 2 diabetes mellitus Check the lipid profile and detail fundus examination of all patients included in study. Effect of lipid lowering agents (statin) on Diabetic retinopathy. Asses the changes in fundus of DME patients after giving statin. MATERIALS AND METHODS:- A prospective study was conducted in the OPD of upgraded department of ophthalmology at LLRM Medical College, Meerut over the duration of from July 2019 to June 2020. The proposed study was in association of status use and hyper triglyceridemia with diabetes macular edema in patients with type-2 diabetes and diabetic retinopathy. Clearance from institution ethics committee was obtained before the study was started. An informed consent was obtained from all the patients before including them in to the study. A total of 86 patients were divided in to two equal groups randomly RESULTS:- A prospective study was conducted in the OPD of upgraded department of ophthalmology at LLRM Medical College, Meerut over the duration of from July 2019 to June 2020 and sample size of patients taken was 86 About 70.9% of the patients in this study were males and 29.1% were females. About 26.7% of the study subjects in this study had diabetes mellitus since 16 – 20 years,25.6% since more than 20 years and 20.9% since 11 – 15 years. During the baseline the CSME in left eye was present in 24.4% of the cases and during follow up,the CSME was present in 10.5% of the cases . At the time of baseline,about 64% of the patients had no CSME in right eye and 36% had CSME.At the time of follow up 87.2% of the cases had no CSME and 12.8% had CSME. In mild NPDR during follow up,44.2% had mild NPDR,24.4% had moderate NPDR and 8.1% had severe NPDR at baseline. About17.4%ofthepatientswhohadmoderateNPDRatbaselinealsohadmoderateNPDRduringfollowupvisits inlefteye. Among all the patients with mild NPDR during follow up, 54.7% had mild NPDR, 22.1% had moderate NPDR and 10.5% had severe NPDR during baseline. About 12.8% who had moderate NPDR during baseline also had moderate NPDR during follow up in right eye Mean cholesterol level during baseline was 154.13 mg/dl and during follow up was 138.12 mg/dl which was statistically significant (p=0.000). The mean triglyceride level during the baseline was 178.37 mg/dl and during follow up was 156 mg/dl which was statistically significant between the two groups (p=0.000). Mean LDL cholesterol level during the baseline was 94.99 mg/dl and during follow up was 61.24 mg/dl which was statistically significant between baseline and follow up (p=0.000). This study had shown improvement of visual acuity,decrease in macular edema and progression of diabetic retinopathy. The study also revealed that ,the statins are effective in decreasing the total cholesterol, LDL cholesterol, and triglycerides. CONCLUSION:- This study had shown improvement of visual acuity,decrease in macular edema and progression of diabetic retinopathy in patients whom statins was given The study also revealed that,the statins are effective in decreasing the total cholesterol(mean value during baseline was 154.13 mg/dl which reduces to 138.12 mg/dl during follow up),LDL cholesterol (mean value reduces from 94.99 mg/dl during baseline to 61.24 mg/dl during follow up)and triglycerides (mean value during baseline 178.37 mg/dl to 156 mg/dl during follow up).as given.

Immune Cell Landscape of Patients With Diabetic Macular Edema by Single-Cell RNA Analysis.

Purpose: We performed single-cell RNA sequencing (scRNA-seq), an unbiased and high-throughput single cell technology, to determine phenotype and function of peripheral immune cells in patients with diabetic macular edema (DME).Methods: Peripheral blood mononuclear cells (PBMCs) were isolated from DME patients and healthy controls (HC). The single-cell samples were loaded on the Chromium platform (10x Genomics) for sequencing. R package Seurat v3 was used for data normalizing, clustering, dimensionality reduction, differential expression analysis, and visualization.Results: We constructed a single-cell RNA atlas comprising 57,650 PBMCs (24,919 HC, 32,731 DME). We divided all immune cells into five major immune cell lineages, including monocytes (MC), T cells (TC), NK cells (NK), B cells (BC), and dendritic cells (DC). Our differential expression gene (DEG) analysis showed that MC was enriched of genes participating in the cytokine pathway and inflammation activation. We further subdivided MC into five subsets: resting CD14++ MC, proinflammatory CD14++ MC, intermediate MC, resting CD16++ MC and pro-inflammatory CD16++ MC. Remarkably, we revealed that the proinflammatory CD14++ monocytes predominated in promoting inflammation, mainly by increasingly production of inflammatory cytokines (TNF, IL1B, and NFKBIA) and chemokines (CCL3, CCL3L1, CCL4L2, CXCL2, and CXCL8). Gene Ontology (GO) and pathway analysis of the DEGs demonstrated that the proinflammatory CD14++ monocytes, especially in DME patients, upregulated inflammatory pathways including tumor necrosis factor-mediated signaling pathway, I-kappaB kinase/NF-kappaB signaling, and toll-like receptor signaling pathway.Conclusion: In this study, we construct the first immune landscape of DME patients with T2D and confirmed innate immune dysregulation in peripheral blood based on an unbiased scRNA-seq approach. And these results demonstrate potential target cell population for anti-inflammation treatments.

The Effect of Ranibizumab Loading Treatment on Vision-Related Quality of Life in Diabetic Macular Edema.

Aims: To investigate the changes in vision-related quality of life after a loading dose of three consecutive intravitreal ranibizumab (IVR) injections in patients with unilateral diabetic macular edema (DME). Materials and Methods: Fifty-two eyes of 52 patients who received IVR injections in only one eye with DME were included in our study. The following characteristics of the patients were recorded: gender, education status, marital status, work status, presence of chronic disease. The changes in best-corrected visual acuity (BCVA) and central macular thickness (CMT) were evaluated at baseline (before treatment) and 1 month after the third intravitreal injection (after treatment). Patients were administered the Turkish form of the National Eye Institute 25-Item Visual Functions Questionnaire (NEI VFQ-25 TR). The quality of life scores assessed by the NEI VFQ-25 TR, the BCVA, intraocular pressure (IOP), and CMT measurements were compared at baseline (before treatment) and 1 month after the third intravitreal injection (after treatment). Results: We enrolled 52 patients (25 females, 27 males) in our study; mean age was 64.35 ± 9.26 years. After treatment, BCVA improved significantly (p = 0.001), and macular thickness decreased significantly (p < 0.001). All NEI VFQ-25 TR subscale scores were significantly higher after treatment (p < 0.05). However, no significant correlation was found between the change in BCVA and CMT and the change in NEI VFQ-25 TR subscale and composite scores. The increase in near activities scores was significantly higher in males (p = 0.020) and in the retired group (p = 0.022). There were no significant differences in the changes in NEI VFQ-25 TR subscale and composite scores in relation to educational status. Discussion: Significant improvements in BCVA, macular edema, and vision-related quality of life were found in DME patients who received IVR injections with a loading dose, as shown by the NEI VFQ-25 TR. Interestingly, a significant improvement in quality of life was observed even though the patients could see well with the fellow eye. In conclusion, the NEI VFQ-25 TR is a useful scale to evaluate the changes in visual function and psychosocial characteristics of DME patients after treatment.

Comparison of Inflammatory and Angiogenic Factors in the Aqueous Humor of Vitrectomized and Non-Vitrectomized Eyes in Diabetic Macular Edema Patients.

Objectives: To compare the aqueous concentrations of inflammatory and angiogenetic factors in vitrectomized vs. non-vitrectomized eyes with diabetic macular edema (DME).Methods: Aqueous samples were obtained from 107 eyes with DME before intravitreal injection of anti-VEGF, 36 eyes with previous pars plana vitrectomy (PPV) combined with pan-retinal endolaser photocoagulation (PRP), and 71 treatment-naïve. Interleukin (IL)-6, IL-8, interferon-induced protein (IP)-10, monocyte chemoattractant protein (MCP)-1, and vascular endothelial growth factor (VEGF) were measured by cytometric bead array (CBA). Optical coherence tomography (OCT) was used for measuring central retinal thickness (CRT).Results: IL-6, IL-8, IP-10, and MCP-1 in aqueous humor of DME vitrectomized eyes were significantly higher than in non-vitrectomized DME eyes, while VEGF was lower than in non-vitrectomized DME eyes. VEGF in aqueous humor significantly correlated with CRT for DME in non-vitrectomized DME eyes. IL-6, IL-8, IP-10, and MCP-1 in aqueous humor were not significantly associated with VEGF for DME in vitrectomized eyes.Conclusions: Inflammation might play an important role in the pathogenesis of DME in vitrectomized eyes. Moreover, inflammation might play a central role in the development of DME via the VEGF-independent pathway. Thus, anti-inflammatory therapy might be a strategy for DME in vitrectomized eyes.

Impact de la pandémie du SARS-CoV-2 sur l’œdème maculaire diabétique et facteurs pronostiques

ButDécrire le retentissement sur l’acuité visuelle et l’épaisseur centromaculaire après arrêt des injections intravitréennes d’anti-VEGF chez les patients diabétiques marocains au cours de la pandémie du Coronavirus. Et étudier les facteurs pouvant être associés à l’aggravation.Matériel et méthodesCette étude transversale monocentrique a inclus les patients programmés pour injections intravitréennes de Bevacizumab au cours de la période du confinement (20 mars 2020–20 mai 2020) et qui n’en ont pas bénéficié. Ont été recueillis : l’âge, le sexe, l’ancienneté du diabète, le nombre d’injections reçues avant le confinement, l’acuité visuelle en pré-confinement et post-confinement ainsi que l’épaisseur centromaculaire pré-confinement et post-confinement.RésultatsCent cinquante quatre yeux de 104 patients ont été analysés. 57,8 % étaient des hommes avec une moyenne d’âge de 59,4 ± 9,04 ans. La durée moyenne d’arrêt des injections intravitréennes est de 57,3 ± 6,7 jours. Le nombre moyen d’injections intravitréennes de Bevacizumab reçues avant le confinement a été estimé à 2,29 ± 2,1. L’aggravation de l’acuité visuelle a été notée chez 44,8 % de nos patients. Les facteurs associés à l’aggravation fonctionnelle sont le faible nombre d’injections intravitréennes de Bevacizumab reçues avant le confinement (p = 0,001) ainsi que le déséquilibre diabétique (p = 0,04). L’aggravation structurelle a été constatée chez 26,6 % des patients et elle était associée au faible nombre d’injections réalisées avant le confinement (p = 0,038).ConclusionLe report des injections intravitréennes au cours du confinement a eu des effets négatifs sur l’acuité visuelle et l’épaisseur centromaculaire des yeux avec OMD. Un report prolongé des injections intravitréennes d’anti-VEGF chez les patients diabétiques doit être évité.

Assessment of Reinjection Numbers and Intervals for Diabetic Macular Edema Patients Who Received Dexamethasone Intravitreal Implants in Germany and Switzerland.

PurposeThe purpose was to assess the number and intervals of dexamethasone intravitreal implant (DEX) reinjections in a real-world setting for the treatment of diabetic macular edema (DME) and to determine the relationship with effectiveness and safety.Patients and MethodsData were abstracted from medical records of DME patients in Germany and Switzerland for this retrospective, multicenter, drug utilization study. Best-corrected visual acuity (BCVA) and central retinal thickness (CRT) changes 7−12 weeks post-injection(s) measured effectiveness. Adverse events (AEs) of special interest were reported.ResultsA total of 141 patients, 108 from Germany and 33 from Switzerland, were assessed. Mean (SD) reinjection interval was 5.7 (4.2) months. Mean baseline BCVA was 61.6 letters, and mean baseline CRT was 413.3 µm. The mean BCVA and CRT changes at 7−12 weeks after baseline, reinjection 1, 2, and 3 were +3.4, +3.7, +3.2, and −1.4 letters and −88.3, −81.6, −102.4, and −124.1 μm, respectively. The Spearman correlation between change in BCVA and CRT and DEX reinjection interval was r=0.03 (P=0.66) and r=0.07 (P=0.38), respectively. Only 18% of patients experienced at least 1 AE.ConclusionThere was no statistically significant correlation between drug effectiveness and reinjection intervals in either country. Although these results are preliminary, they indicate that DEX improves BCVA and CRT in real-world clinical practice.

Algorithm for Detection and Quantification of Hyperreflective Dots on Optical Coherence Tomography in Diabetic Macular Edema.

Purpose: To develop an algorithm to detect and quantify hyperreflective dots (HRDs) on optical coherence tomography (OCT) in patients with diabetic macular edema (DME).Materials and Methods: Twenty OCTs (each OCT contains 128 b scans) from 20 patients diagnosed with DME were included in this study. Two types of HRDs, hard exudates and small HRDs (hypothesized to be activated microglia), were identified and labeled independently by two raters. An algorithm using deep learning technology was developed based on input (in total 2,560 OCT b scans) of manual labeling and differentiation of HRDs from rater 1. 4-fold cross-validation was used to train and validate the algorithm. Dice coefficient, intraclass coefficient (ICC), correlation coefficient, and Bland–Altman plot were used to evaluate agreement of the output parameters between two methods (either between two raters or between one rater and proposed algorithm).Results: The Dice coefficients of total HRDs, hard exudates, and small HRDs area of the algorithm were 0.70 ± 0.10, 0.72 ± 0.11, and 0.46 ± 0.06, respectively. The correlations between rater 1 and proposed algorithm (range: 0.95–0.99, all p < 0.001) were stronger than the correlations between the two raters (range: 0.84–0.96, all p < 0.001) for all parameters. The ICCs were higher for all the parameters between rater 1 and proposed algorithm (range: 0.972–0.997) than those between the two raters (range: 0.860–0.953).Conclusions: Our proposed algorithm is a good tool to detect and quantify HRDs and can provide objective and repeatable information of OCT for DME patients in clinical practice and studies.

Prediction of anti‐VEGF efficacy in diabetic macular oedema using intraocular cytokines and macular optical coherence tomography

In eyes with diabetic macular oedema (DME), aqueous humour (AH) cytokine levels before and after anti-vascular endothelial growth factor (VEGF) treatment were compared and correlated with optical coherence tomography structural parameters. This prospective study included 56 control patients with cataracts and 83 patients with DME manifesting as diffuse retinal thickening (DRT), cystoid macular oedema and serous retinal detachment (SRD). AH samples were obtained before intravitreal injection of anti-VEGF or cataract surgery. VEGF, interleukin (IL)-6, IL-8, IL-10, interferon-inducible protein 10 (IP-10) and monocyte chemotactic protein 1 (MCP-1) levels were measured by multiplex bead assay. AH cytokine levels, central macular thickness (CMT), number of hyper-reflective foci (HF), continuity of external limiting membrane and ellipsoid zone (EZ) and best-corrected visual acuity were evaluated. In SRD, IL-6 and MCP-1 levels and HF were increased (all p < 0.05) compared to DRT. At baseline, the number of HF was correlated with VEGF, IL-6, IL-8, IP-10 and MCP-1 (all p < 0.05). Eyes sensitive to anti-VEGF treatment had high baseline levels of VEGF, MCP-1, HF and many EZ disruptions (all p < 0.05). DME patients with normal VEGF levels but with high levels of IL-8, IP-10 and MCP-1 (all p < 0.05) had little change in CMT after anti-VEGF treatment (p = 0.678). AH concentrations of some inflammatory cytokines in DME were differentially expressed among the three DME morphologies. HF was associated with VEGF and other inflammatory cytokine levels. Multiple HF at baseline predicted a significant decrease in CMT, and eyes with normal VEGF but increased inflammatory cytokines may be insensitive to anti-VEGF treatment.