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Introduction: We report on one case of age-related macular degeneration and one case of diabetic macular edema with concomitant retinal arterial macroaneurysm (RAM) that were treated with anti-vascular endothelial growth factor (VEGF) intravitreal injections. Case Presentation: Case 1 involved a 71-year-old woman with a 30-year history of diabetes who was undergoing dialysis. Pretreatment visual acuity in the right eye was 0.4. Fundus fluorescein angiography (FA) showed that numerous microaneurysms and RAM were located at a distance of two papillary diameters from the macular area. Diabetic macular edema was diagnosed. After 12 anti-VEGF injections, the macular edema resolved, microaneurysms decreased, and the RAM also disappeared. Visual acuity in the right eye improved to 0.7. Case 2 involved an 81-year-old woman receiving treatment for disorders including hypertension and dyslipidemia. Pretreatment visual acuity in the right eye was 0.03. And vitreous hemorrhage was present. After one ranibizumab intravitreal injection, the fundus became clearly visible. Macular subretinal hemorrhage and an RAM in the upper macula area were evident on FA and optical coherence tomography. After four intravitreal injections of ranibizumab, macular hemorrhage resolved, RAM disappeared, and visual acuity improved to 0.2. All cases were treated by intravitreal injection of anti-VEGF. After several injections, the macular hemorrhage or macular edema was resolved. RAM disappeared, and visual acuity improved. Conclusion: Intravitreal injection of anti-VEGF appears effective for age-related macular degeneration or diabetic macular edema with concomitant RAM. Although anti-VEGF intravitreal injections are not covered by health insurance for the treatment of RAM, their effectiveness means that the expansion of indications is desirable. [ABSTRACT FROM AUTHOR]

Introduction: Objectives of the study were to investigate the correlation between optical coherence tomography (OCT)-based grading of diabetic macular edema (DME) and systemic inflammatory indices, imaging biomarkers, and early anti-vascular endothelial growth factor (VEGF) treatment response. Methods: A total of 111 eyes from 111 patients with DME treated with intravitreous anti-VEGF therapy for 3 consecutive months every month were enrolled in this retrospective study. According to a protocol termed "TCED," DME was divided into early, advanced, severe, and atrophic stages. The best-corrected visual acuity (BCVA), subretinal fluid (SRF), and the number of hyperreflective foci (HRF) in the whole retinal layers were analyzed at baseline and 3 months after the first injection. Peripheral blood inflammatory indices were calculated, including neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet (PLT)-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), and C-reactive protein (CRP). Statistical analysis was performed to compare the visual and anatomical results and evaluate HRF and SRF in different stages of DME before and after treatment. Results: There were significant differences in systemic inflammatory indices among the four groups, including NLR, PLR, MLR, SII, and CRP (all p < 0.05). The CRP, NLR, PLR, MLR, and SII were significantly higher in the atrophic stage compared to the advanced stage (all p < 0.05). Conversely, the CRP, NLR, PLR, MLR, and SII were significantly lower in the advanced stage compared to the early stage (all p < 0.05). Except for the atrophic stage, BCVA and central retinal thickness (CRT) were significantly improved after treatment in early, advanced and severe stages (all p < 0.05), especially in the severe stage. The decline in the proportion of SRF and HRF ≥20 was the most significant in the advanced stage after anti-VEGF treatment (p < 0.001, p = 0.016), but not in the early and severe stages (all p > 0.05). Conclusion: Systemic inflammatory indices and the decline in the proportion of SRF and HRF ≥20 were closely associated with different stages of DME based on "TCED." Meanwhile, the "TCED" grading system can predict visual and anatomical prognosis of DME after anti-VEGF treatment, which may be a biomarker for identifying risk stratification and management of DME. [ABSTRACT FROM AUTHOR]

Background: The comparative safety and efficacy of different doses of intravitreal triamcinolone acetonide (IVTA) for diabetic macular edema (DME) and macular edema (ME) secondary to retinal vein occlusion (RVO) is unclear. Objectives: This meta-analysis aimed to compare the safety and efficacy of different doses of IVTA in this setting. Methods: A systematic literature search for randomized clinical trials (RCTs) was conducted on Cochrane Library, Ovid MEDLINE, and EMBASE from January 2005 to May 2022. Studies that reported on patients with DME or ME secondary to RVO that received treatment with different doses of IVTA were included. A random-effects meta-analysis was performed. Cochrane's Risk of Bias Tool 2 was used to assess the risk of bias, and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) guidelines were used to assess certainty of evidence. Results: Five RCTs reporting on 1,041 eyes at baseline were included in this meta-analysis. In eyes with ME secondary to RVO, high-dose (4 mg) IVTA achieved a significantly better change in best-corrected visual acuity (WMD = −4.75 ETDRS letters, 95% CI = [−7.73, −1.78], p = 0.002) and reduction in retinal thickness (WMD = −93.02 μm, 95% CI = [−153.23, −32.82], p = 0.002) at months 4–6 compared to low-dose (1–2 mg) IVTA. However, high-dose IVTA had a higher risk of intraocular pressure-related adverse events (RR = 2.99, 95% CI = [1.05, 8.50], p = 0.04) and cataract surgery (RR = 5.67, 95% CI = [3.09, 10.41], p < 0.00001) than low-dose IVTA in eyes with ME secondary to RVO. These efficacy and safety differences in high-dose and low-dose IVTA were not observed in DME eyes. Conclusions: The RCT evidence in this setting is limited. High-dose IVTA achieved greater improvements in visual acuity and reductions in retinal thickness than low-dose IVTA at months 4–6. However, high-dose IVTA had a less favorable safety profile than low-dose IVTA. The significance of these outcomes was based on patients with ME secondary to RVO, but not DME. [ABSTRACT FROM AUTHOR]

Introduction: The aim of this study was to evaluate the outcomes and complications associated with the use of same-day bilateral intravitreal dexamethasone (DEX) implants for the treatment of diabetic macular edema (DME). Methods: This retrospective analysis of an open-label, multicenter, consecutive case series included 130 eyes of 65 patients with bilateral DME who were treated with intravitreal DEX implants. The patients were divided into two groups: a control group (comprising 40 eyes treated with an alternating unilateral regimen) and a study group (comprising 90 eyes treated with concomitant bilateral DEX implants). All patients were followed up monthly after implantation. The changes in best-corrected visual acuity (BCVA) and central retinal thickness (CRT) from baseline to sixth month after implantation, and ocular adverse effects such as intraocular pressure, cataract, and tolerability of bilateral implantation were reviewed. The primary endpoint was to assess the safety of the same-day bilateral treatment protocol. The secondary endpoints focused on evaluating the functional and anatomical changes associated with bilateral simultaneous or alternating implantations. Results: At 6 months after implantation, mean BCVA increased and CRT decreased in both groups. Moreover, no serious ocular adverse effects were observed. In addition, no differences were observed between the two groups in the number of patients who required extra follow-up visits or the number of extra visits made in addition to the treatment schedule. Conclusions: Same-day bilateral intravitreal DEX implants are associated with a low complication rate and are well tolerated by patients. This safe practice may optimize efficiency and reduce the burden on both the health-care system and patients, when used to treat bilateral DME. [ABSTRACT FROM AUTHOR]

Introduction: Handheld retinal imaging cameras are relatively inexpensive and highly portable devices that have the potential to significantly expand diabetic retinopathy (DR) screening, allowing a much broader population to be evaluated. However, it is essential to evaluate if these devices can accurately identify vision-threatening macular diseases if DR screening programs will rely on these instruments. Thus, the purpose of this study was to evaluate the detection of diabetic macular pathology using monoscopic macula-centered images using mydriatic handheld retinal imaging compared with spectral domain optical coherence tomography (SDOCT). Methods: Mydriatic 40°–60° macula-centered images taken with 3 handheld retinal imaging devices (Aurora [AU], SmartScope [SS], RetinaVue 700 [RV]) were compared with the Cirrus 6000 SDOCT taken during the same visit. Images were evaluated for the presence of diabetic macular edema (DME) on monoscopic fundus photographs adapted from Early Treatment Diabetic Retinopathy Study (ETDRS) definitions (no DME, noncenter-involved DME [non-ciDME], and center-involved DME [ciDME]). Sensitivity, specificity, positive predictive value, and negative predictive value were calculated for each device with SDOCT as gold standard. Results: Severity by ETDRS photos: no DR 33.3%, mild NPDR 20.4%, moderate 14.2%, severe 11.6%, proliferative 20.4%, and ungradable for DR 0%; no DME 83.1%, non-ciDME 4.9%, ciDME 12.0%, and ungradable for DME 0%. Gradable images by SDOCT (N = 217, 96.4%) showed no DME in 75.6%, non-ciDME in 9.8%, and ciDME in 11.1%. The ungradable rate for images (poor visualization in >50% of the macula) was AU: 0.9%, SS: 4.4%, and RV: 6.2%. For DME, sensitivity and specificity were similar across devices (0.5–0.64, 0.93–0.97). For nondiabetic macular pathology (ERM, pigment epithelial detachment, traction retinal detachment) across all devices, sensitivity was low to moderate (0.2–0.5) but highly specific (0.93–1.00). Conclusions: Compared to SDOCT, handheld macular imaging attained high specificity but low sensitivity in identifying macular pathology. This suggests the importance of SDOCT evaluation for patients suspected to have DME on fundus photography, leading to more appropriate referral refinement. [ABSTRACT FROM AUTHOR]

Introduction: Central vision loss due to diabetic macular edema (DME) is related to the macular edema itself but also, in some cases, to alterations of the foveal avascular zone (FAZ). The aim of this trial was to study changes in macular vessels in eyes with DME treated with aflibercept using optical coherence tomography angiography (OCTA). Methods: This was a longitudinal, prospective, noncontrolled, single-arm study. The primary objective was the quantitative assessment of macular vessels over time in patients with DME treated with intravitreal aflibercept during a 48-week follow-up using OCTA. Results: Twenty-six DME eyes from 26 patients were included (mean age, 64.6 years; women, 53.8%; prior anti-VEGF treatment, 46.1%). Each eye received a mean (SD) of 7.2 (2.2) injections. The following parameters of the FAZ did not change during the 48-week follow-up: the mean (SD) FAZ area varied from 0.19 (0.19) mm2 at baseline (n = 22) to 0.23 (0.20) mm2 at week 48 (n = 15), boundary from 1.54 (1.21) to 2.04 (1.20) mm, and circularity from 0.45 (0.33)% to 0.57 (0.20)%. There was no change in perfusion density and vessel density of the macula in the 3-mm circle. As expected, mean central retinal thickness, macular volume, and visual acuity improved during follow-up. Conclusion: No change in macular perfusion was observed in eyes with DME during a 48-week follow-up after intravitreal injections of aflibercept. Randomized controlled trials using OCT angiography in large populations with extended observation periods are needed to assess changes in macular vessels after intravitreal anti-VEGF treatment. [ABSTRACT FROM AUTHOR]

Introduction: The objective of this study was to evaluate the impact of unplanned treatment gap, secondary to COVID-19 pandemic lockdowns, on visual acuity in previously treated diabetic macular edema (DME) patients. Methods: A multicenter, retrospective study of DME patients, previously treated with anti-VEGF injections, who were followed up during COVID-19 pandemic (2020) compared to pre-CO-VID-19 period (2019). Results: A total of 634 DME patients with a mean age of 68.4 years met the inclusion criteria, 385 were assessed in 2019 (pre-COVID-19) and 239 patients assessed in 2020 (COVID-19). Baseline best corrected visual acuity (BCVA) among patients in 2019 and 2020 was 0.52 ± 0.44, 0.45 ± 0.43 (logarithm of the minimal angle of resolution, respectively). There was no significant difference between the years 2020 and 2019 in baseline BCVA (p = 0.07). Mean number of anti-VEGF injections was significantly lower (5 vs. 6, p < 0.01), with a major lower ratio of injections per patient in the COVID-19 first lockdown period (March–June 2020) in the COVID-19 group. Baseline BCVA (p < 0.01) was the only significant predictor of final BCVA. Number of injections, age, gender, and the year were not found as predictors of final BCVA. Conclusions: In a large cohort of DME patients, an unplanned delay in treatment with anti-VEGF injections for 2–3 months, due to COVID-19 pandemic lockdown, had no significance impact on visual acuity. For most patients, returning to routine treatment regimen was sufficient for maintaining BCVA. [ABSTRACT FROM AUTHOR]

Background: Laser photocoagulation is an effective procedure for the treatment of diabetic macular edema (DME). However, the beneficial effects of conventional laser photocoagulation (CLP) are accompanied by the destruction of retinal photoreceptors. Therefore, subthreshold micropulse laser photocoagulation (SMLP) was proposed for DME. Objectives: This meta-analysis study was performed to evaluate the efficacy and safety of SMLP compared with CLP for the management of DME. Methods: The PubMed, Embase, Web of Science, Cochrane, SinoMed, ClinicalTrials.gov, Wanfang, and China National Knowledge Infrastructure (CNKI) databases, published until Dec 2021, were searched to identify studies evaluating the clinical outcomes of SMLP for DME. Results: Eight randomized controlled trials were selected for this meta-analysis involving a total of 546 eyes (275 eyes in SMLP group and 271 eyes in CLP group). SMLP of different wavelengths (577 nm and 810 nm) and duty cycles (5% and 15%) was applied. The pooled outcomes showed that SMLP group, especially 577 nm and 810 nm 15% duty cycle parameter settings, had a statistically significant higher efficacy than CLP group in terms of BCVA (MD = −0.02, 95% CI: −0.03 to −0.01, p < 0.01; MD = −0.09, 95% CI: −0.09 to −0.09, p < 0.01) and showed more significant advantages than CLP group in resolving macular edema assessed by reduction of CMT (MD = −32.87, 95% CI: −37.61 to −28.13, p < 0.01; MD = −8.01, 95% CI: −9.06 to −6.96, p < 0.01), whereas the efficacy of 577 nm and 810 nm 5% duty cycle SMLP subgroups remained numerically superior to CLP group, but nonsignificantly (p > 0.05). In the field of CS, SMLP group (no matter parameter settings) resulted in better preservation of CS compared to CLP group (MD = 1.96, 95% CI: 1.47–2.46, p < 0.01). Conclusions: Compared with CLP, SMLP may get superior efficacy and safety on improvement of BCVA, reduction of CMT, and preservation of CS. In clinical, SMLP can be considered as a safe and effective therapy in the management of DME. [ABSTRACT FROM AUTHOR]

Introduction: The aim of the study was to characterize the 2-year progression of risk phenotypes of nonproliferative diabetic retinopathy (NPDR) in type 2 diabetes (T2D) phenotype C, or ischemic phenotype, identified by decreased skeletonized retinal vessel density (VD), ≥2 SD over normal values, and phenotype B, or edema phenotype, identified by increased retinal thickness, i.e., subclinical macular edema, and no significant decrease in VD. Methods: A prospective longitudinal cohort study (CORDIS, NCT03696810) was conducted with 4 visits (baseline, 6 months, 1 year, and 2 years). Ophthalmological examinations included best-corrected visual acuity, color fundus photography (CFP), and optical coherence tomography (OCT) and OCT angiography. Early Treatment Diabetic Retinopathy Study grading was performed at the baseline and last visits based on 7-field CFP. Results: One hundred and twenty-two eyes from T2D individuals with NPDR fitted in the categories of phenotypes B and C and completed the 2-year follow-up. Sixty-five (53%) of the eyes were classified as phenotype B and 57 (47%) eyes as phenotype C. Neurodegeneration represented by thinning of the ganglion cell layer and inner plexiform layer was present in both phenotypes and showed significant progression over the 2-year period (p < 0.001). In phenotype C, significant progression in the 2-year period was identified in decreased skeletonized VD (p = 0.01), whereas in phenotype B microvascular changes involved preferentially decrease in perfusion density (PD, p = 0.012). Phenotype B with changes in VD and PD (flow) and preferential involvement of the deep capillary plexus (p < 0.001) is associated with development of center-involved macular edema. Discussion: In the 2-year period of follow-up, both phenotypes B and C showed progression in retinal neurodegeneration, with changes at the microvascular level characterized by decreases in PD in phenotype B and decreases in VD in phenotype C. [ABSTRACT FROM AUTHOR]

Introduction: Objectives of the study were to describe the hyperreflective foci (HRF) on optical coherence tomography angiography in diabetic macular edema (DME) with subretinal fluid (SRF) and explore the association of HRF in the outer retina with photoreceptor integrity and visual outcomes after anti-vascular endothelial growth factor (anti-VEGF) treatment. Methods: We retrospectively reviewed 46 eyes (36 patients) with DME treated with anti-VEGF drugs. The following parameters, including best-corrected visual acuity (BCVA), central macular thickness (CMT), the height of SRF, the number of HRF in the superficial capillary plexus, deep capillary plexus, and the outer retina, as well as the integrity of external limiting membrane (ELM) and ellipsoid zone (EZ), were evaluated and compared between the baseline and after 2 monthly injections of anti-VEGF drugs. The relationship between the HRF in the outer retina and the integrity of ELM and EZ, as well as BCVA, was analyzed. Results: BCVA was significantly improved in DME after anti-VEGF treatment; however, for the subgroup of DME patients with SRF, visual acuity remained unchanged after anti-VEGF treatment (p < 0.05 vs. p = 0.375). The number of HRF (p < 0.05), CMT (p < 0.001), and SRF height (p < 0.001) were significantly reduced, accompanied with partial restoration of ELM and EZ integrity after anti-VEGF injection. The HRF in the outer retina was correlated with the final ELM (p = 0.036) and EZ (p = 0.004) status. The final BCVA was significantly better in eyes with intact ELM (p = 0.002) and EZ at final visit (p < 0.001). Conclusion: The number of HRF in outer retina was negatively associated with the microstructural restoration of ELM and EZ, as well as the visual outcome in DME patients with SRF after anti-VEGF treatment. [ABSTRACT FROM AUTHOR]

Introduction: In this retrospective cohort study, we wanted to evaluate the performance and analyze the insights of an artificial intelligence (AI) algorithm in detecting retinal fluid in spectral-domain OCT volume scans from a large cohort of patients with neovascular age-related macular degeneration (AMD) and diabetic macular edema (DME). Methods: A total of 3,981 OCT volumes from 374 patients with AMD and 11,501 OCT volumes from 811 patients with DME were acquired with Heidelberg-Spectralis OCT device (Heidelberg Engineering Inc., Heidelberg, Germany) between 2013 and 2021. Each OCT volume was annotated for the presence or absence of intraretinal fluid (IRF) and subretinal fluid (SRF) by masked reading center graders (ground truth). The performance of an already published AI algorithm to detect IRF and SRF separately, and a combined fluid detector (IRF and/or SRF) of the same OCT volumes was evaluated. An analysis of the sources of disagreement between annotation and prediction and their relationship to central retinal thickness was performed. We computed the mean areas under the curves (AUC) and under the precision-recall curves (AP), accuracy, sensitivity, specificity, and precision. Results: The AUC for IRF was 0.92 and 0.98, for SRF 0.98 and 0.99, in the AMD and DME cohort, respectively. The AP for IRF was 0.89 and 1.00, for SRF 0.97 and 0.93, in the AMD and DME cohort, respectively. The accuracy, specificity, and sensitivity for IRF were 0.87, 0.88, 0.84, and 0.93, 0.95, 0.93, and for SRF 0.93, 0.93, 0.93, and 0.95, 0.95, 0.95 in the AMD and DME cohort, respectively. For detecting any fluid, the AUC was 0.95 and 0.98, and the accuracy, specificity, and sensitivity were 0.89, 0.93, and 0.90 and 0.95, 0.88, and 0.93, in the AMD and DME cohort, respectively. False positives were present when retinal shadow artifacts and strong retinal deformation were present. False negatives were due to small hyporeflective areas in combination with poor image quality. The combined detector correctly predicted more OCT volumes than the single detectors for IRF and SRF, 89.0% versus 81.6% in the AMD and 93.1% versus 88.6% in the DME cohort. Discussion/Conclusion: The AI-based fluid detector achieves high performance for retinal fluid detection in a very large dataset dedicated to AMD and DME. Combining single detectors provides better fluid detection accuracy than considering the single detectors separately. The observed independence of the single detectors ensures that the detectors learned features particular to IRF and SRF. [ABSTRACT FROM AUTHOR]

Introduction: The aim of this study was to compare posterior subtenon triamcinolone (PSTA) application and intravitreal dexamethasone phosphate (DEX) implant in the treatment of diabetic macular edema (DME) in vitrectomized eyes. Methods: This retrospective study included 64 (48.12%) patients who received PSTA and 69 (51.88%) patients who received DEX implants in DME treatment after vitrectomy. Best corrected visual acuity (BCVA), central macular thickness (CMT), and intraocular pressure (IOP) were analyzed before injection; at 1, 3, and 6 months after injection. The postinjection values were statistically compared with the preinjection value. Results: All postinjection CMT values in both groups were lower than the preinjection value (p < 0.05 for all). There were statistically significant increases in all postinjection BCVAs of the DEX group and postinjection 1-month BCVA of the PSTA group (p < 0.05 for all). However, there was no significant difference in BCVA values of the PSTA group at 3 and 6 months after injection (p > 0.05 for both). There was no statistically significant difference in all postinjection IOP values of the PSTA group (p > 0.05 for all). However, significant increases in IOP were observed in the DEX group at 1 and 3 months after injection (p < 0.05 and p = 0.02, respectively). The number of additional injections between the 3rd and 6th months after the initial injection was statistically higher in the PSTA group (p = 0.006). Conclusion: Both intravitreal DEX and PSTA administration are effective in the treatment of DME after vitrectomy. However, visual improvement persisted longer, and the need for additional injections was less in patients who received DEX. [ABSTRACT FROM AUTHOR]

Purpose: The aim of the study was to compare anatomical and functional outcomes of pars plana vitrectomy (PPV) with epiretinal membrane (ERM) peeling in diabetes retinopathy patients with and without diabetic macular edema (DME). Methods: A retrospective interventional case series of consecutive patients who underwent PPV with ERM peeling. Patients were divided into two groups: those with and without preoperative DME. Visual acuity (VA) and optical coherence tomography parameters were evaluated before surgery and during 12 months of follow-up. Results: A total of 354 patients underwent PPV with ERM peeling, of which 51 met the inclusion criteria. Twenty-three were diagnosed with DME and were younger (66.3 ± 9.6 vs. 73.1 ± 8.2 years, p = 0.001), had longer diabetes mellitus (DM) duration (18.9 ± 7.1 vs. 14.3 ± 10.9 years, p = 0.04) and higher HbA1C% (7.6 ± 1.4 vs. 7.1 ± 1.3, p = 0.04). VA improved from 20/105 to 20/60 Snellen (p = 0.004) and central macular thickness decreased from 469.3 ± 64.9 μm to 331.1 ± 92.2 μm (p < 0.001) in the DME group and from 20/87 to 20/44 Snellen (p < 0.001) and from 463.1 ± 53.5 μm to 341.3 ± 49.5 μm (p = 0.01) in the non-DME group. Yearly intravitreal injection rate decreased from 5.9 ± 2.5 to 2.9 ± 3.0 (p < 0.001) injections in the DME group. Conclusions: DME patients with ERM experience significant improvement in VA, macular thickness, and yearly intravitreal injections after PPV with ERM peeling. DME patients are younger, with longer duration of DM and higher HbA1C% levels at presentation in comparison to diabetic ERM patients without DME. [ABSTRACT FROM AUTHOR]

Recently, good postoperative visual acuity has been reported using surgical removal of hard exudates (HEs) through an intentional macular hole (iMH). We report 3 cases of subfoveal HE secondary to diabetic maculopathy (DM) treated with HE removal via an iMH. Pars plana vitrectomy (PPV) was performed in three eyes of 3 patients with subfoveal HE secondary to DM. In all eyes, after PPV, internal limiting membrane (ILM) peeling of the lower half was performed within the range of papilla diameter 2 centered on the fovea, leaving the upper half for subsequent inverted ILM flap technique. Then, by grabbing the inner layer of the fovea using ILM forceps, an iMH was created. The HE was then flushed from the iMH with a balanced salt solution as much as possible. Finally, the inverted ILM flap technique was performed using the upper half of the ILM that was left during the previous maneuver. At the end of the surgery, the eyes were flushed with 50 mL of 20% sulfur hexafluoride (SF6) after the fluid-air exchange of the vitreous cavity. After surgery, HE was adequately removed, iMH was completely closed, and visual acuity improved in all eyes. This surgical procedure did not cause a central scotoma but rather improved the central sensitivity of the visual field in all eyes. No serious surgery-related complications occurred. In conclusion, HE removal via an iMH hole can be one of the treatment options for patients with subfoveal HE secondary to DM. [ABSTRACT FROM AUTHOR]

Introduction: The objective of this study is to compare changes in ganglion cell layer (GCL) between vitrectomized and nonvitrectomized eyes with diabetic macular edema (DME) over a 2-year period following treatment with 0.2 µg/day fluocinolone acetonide (FAc) implant. Methods: Eighteen vitrectomized (group 1) and 8 nonvitrectomized (group 2) eyes were included in this cohort study. Changes in central macula GCL thickness were measured using the Spectralis spectral domain-optical coherence tomography at baseline and 6, 12, and 24 months of follow-up. Other parameters analyzed included best-corrected visual acuity (BCVA), central foveal thickness (CFT), and intraocular pressure (IOP). Results: Treatment with the FAc implant led to small reductions in mean global GCL thickness versus baseline and contrasts with the control group that was stable or slightly increased versus baseline. FAc therapy also led to improvements in mean BCVA and CFT that were observed at Month 6 and maintained to Month 24. For vitrectomized and nonvitrectomized eyes, no differences were observed between mean global GCL, BCVA, and CFT values during follow-up. Linear correlations revealed that in all groups mean BCVA at Month 24 positively correlated with mean GCL thickness at baseline and at Month 24. IOP remained stable throughout the 24 months. Conclusion: There was no evident retinal neurodegeneration in the 2-year period following treatment with FAc in both groups. GCL thickness may be a useful biomarker for assessing safety and effectiveness in patients with DME. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to compare the prevalence of diabetic retinopathy (DR) and diabetic macular edema (DME), as well as their risk factors in patients with early-onset diabetes (EOD, ≤40 years) and late-onset diabetes (LOD, >40 years). Methods: Patients were recruited from a community-based study, Fushun Diabetic Retinopathy Cohort Study (FS-DIRECT), conducted between July 2012 and May 2013 in China. The presence and severity of DR and DME were determined by a modified Early Treatment Diabetic Retinopathy Study (ETDRS) retinopathy scale of six-field fundus photographs. Results: A total of 1,932 patients (796 male, 41.2%) with gradable fundus photography were included. The prevalence of any DR and DME was 67.0% (95% confidence interval [CI]: 60.3–73.7%) and 39.3% (95% CI: 32.1–46.5%) in the EOD patients, respectively, which were both significantly higher than that in the LOD patients (DR: 41.9%, 39.6–44.2%, p < 0.001; DME: 14.4%, 12.7–16.1%, p < 0.001). Insulin use was associated with both the presence of DR and DME in both EOD and LOD patients. Besides insulin use, a high level of income (odds ratio [OR], 95% CI: 0.05, 0.01–0.51) was negatively associated with DR, and higher high-density lipoprotein (OR, 95% CI: 4.14, 1.44–11.91) was associated with DME among EOD patients. Conclusion: In this sample of patients with type 2 diabetes, both prevalence of DR and DME were apparently higher in patients who developed diabetes ≤40 years of age than those who developed it later. [ABSTRACT FROM AUTHOR]

Diabetic macular edema (DME) is the most common cause of vision loss in diabetic eyes, and due to the rapid rise in the number of diabetic patients, the treatment burden has increased exponentially. The introduction of antivascular endothelial growth factor (anti-VEGF) therapy has been a major breakthrough in the management of center-involving DME, replacing laser photocoagulation as the first-line treatment. Despite the improvement in DME treatment with anti-VEGF therapy, persistent DME remains a challenge due to the extremely complex pathogenesis and the involvement of several different biochemical pathways. This review focuses on therapeutic options for persistent DME, which include corticosteroids, laser, and surgery. Novel agents for DME control such as new anti-VEGF, interleukin inhibitor, Rho-kinase inhibitor, and neuroprotective agents that are being investigated are reviewed as well. Future treatment perspectives include an individualized DME management. [ABSTRACT FROM AUTHOR]

Diabetic macular edema (DME) is the main cause of visual loss in patients with diabetic retinopathy. DME has been treated using intravitreal anti-vascular endothelial growth factor (VEGF) drugs, steroids, laser photocoagulation, vitreoretinal surgery, and their combinations. These modalities are generally effective in preserving vision, but they sometimes produce only limited responses in patients with persistent or refractory DME. The levels of various inflammatory factors, including cytokines, chemokines, and extracellular matrices, as well as VEGF in the vitreous fluid, are increased in patients with DME. Excessive fibrinogen/fibrin levels in the vitreous fluid or fibrin deposition in the retina also contribute to DME pathogenesis. Tissue plasminogen activator (t-PA) promotes the degradation of fibrinogen or fibrin. Intravitreal t-PA injection is a commonly used treatment for subretinal hemorrhage secondary to age-related macular degeneration. Intravitreal t-PA injections have previously been used to restore vision by inducing posterior vitreous detachment in patients with DME. Herein, we describe the visual outcomes of intravitreal t-PA injection in a 78-year-old woman with treatment-resistant DME in her vitrectomized eye after several previous treatments. Before the injection, her best-corrected visual acuity (BCVA) was 0.7 logMAR and central foveal retinal thickness (CRT) was 735 μm. At 1 month after the injection, her BCVA was 0.8 logMAR and CRT was 558 μm, and 3 months later, her BCVA was 0.8 logMAR and CRT was 207 μm. Her BCVA was sustained, and CRT showed gradual improvements. These findings suggested the effectiveness of intravitreal t-PA injections for DME in the vitrectomized eye. [ABSTRACT FROM AUTHOR]

Background: The 0.19-mg fluocinolone acetonide (FAc) implant (ILUVIEN®; Alimera Sciences Ltd., Hampshire, UK) was approved for the treatment of vision impairment associated with chronic and refractory diabetic macular edema (DME). Objectives: To quantitatively assess functional and structural features in nonvitrectomized and vitrectomized DME patients after being treated with an FAc implant. Methods: Retrospective review of patients with DME receiving a single intravitreal injection of the FAc implant. The study was designed to analyze the presence of quantitative structural OCT biomarkers at baseline and 12 months after FAc therapy according to vitreous status. Results: A total of 41 eyes from 30 patients were included in this study. At 12 months after injection, vitrectomized patients had a lower central foveal thickness (p = 0.017) and fewer hyperreflective dots (p = 0.028) compared with nonvitrectomized. Thirty (73%) patients presented a significant functional improvement with 17 (42%) increasing at least 15 ETDRS letters. Overall, 22 (54%) eyes had a complete resolution of DME at the 12-month visit. Patients who needed additional therapy had a higher prevalence of subretinal fluid (42 vs. 3%, p = 0.005) at baseline. Conclusions: This study supports the effectiveness of the FAc implant and reports significant changes at 12 months after FAc injection. [ABSTRACT FROM AUTHOR]

Purpose: To assess the efficacy, safety, and follow-up of 36-month treatment with ranibizumab in patients with diabetic macular edema (DME) in real-life setting. Methods: This is a prospective phase 4 observational study. Between December 2013 and April 2015, 84 ophthalmologists enrolled a total of 290 adult patients initiating ranibizumab for visual impairment due to DME and treated them according to their routine practice. The primary outcome (mean change in best-corrected visual acuity [BCVA] after 12 months) was previously reported. Here, we present outcomes after 36 months of follow-up for BCVA and change in central subfield thickness (CSFT) and report how participating ophthalmologists treated DME over a 3-year period (number of visits and injections and evolution of treatment strategy). Results: Of the 290 patients enrolled, 187 (64.5%) completed the 36 months of the study (entire cohort). In the entire cohort, 97 patients were treated exclusively with ranibizumab throughout the study, and 90 patients switched to other intravitreal treatments. Mean BCVA was 64.2 (20.1) letters, representing a gain of +4.1 (19.9) letters from baseline to month 36 (M36). CSFT improved over the study, and by M36 had decreased by 127 (138) µm compared to baseline. Over the 36 months of follow-up, patients in the entire cohort paid their ophthalmologists a mean of 30.9 (12.2) visits and had a mean of 7.6 (5.2) any injections. Results for quality of life questionnaires NEI-VFQ25 and HUI-3 remained stable throughout the study. Multivariate analysis on the 145 patients with evaluable BCVA data at M36 found that male gender and milder baseline DME characteristics (BCVA ≥59 and CSFT <500 µm) were predictive factors for achieving a BCVA of ≥70 letters at M36. This study did not find any new safety signals, compared to the known profile of ranibizumab. Conclusions: Gains in BCVA in this real-life study were lower than those observed in randomized clinical trials with ranibizumab, mainly due to undertreatment. Safety analysis of ranibizumab did not yield any new safety concerns. [ABSTRACT FROM AUTHOR]

Aim: To evaluate long-term macular changes following pars plana vitrectomy (PPV) with internal limiting membrane (ILM) peeling for diabetic macular edema (DME). Methods: Forty eligible eyes of 37 patients were included in this retrospective study. Best corrected visual acuity (BCVA), central macular thickness (CMT), and 5-mm macular volume (5-MV) were examined preoperatively, postoperatively after 1, 2, 3, 6, 12, and 24 months, and at a final visit. Response to surgical treatment was considered as recurrence, reincrease, or recovery of DME based on macular changes. Results: Mean follow-up time was 51.1 ± 19.0 months after surgery. Recurrence (n = 5) and reincrease (n = 17) of DME was observed in 22 eyes (55%) and additional treatments were applied. Recovery of DME was observed in 18 eyes (45%). Preoperative and final-visit mean BCVA (logMAR) was 1.08 ± 0.37 and 0.93 ± 0.45, respectively (p = 0.02). Preoperative and final-visit mean CMT was 514.74 ± 155.65 and 281.87 ± 112.58 µm, respectively (p < 0.001). The 5-MV significantly decreased following surgery (from 8.18 ± 1.57 to 6.52 ± 1.39 mm3; p < 0.001). DME was present in 12 eyes (30%) at the final visit. Conclusion: Although PPV with ILM peeling had efficacy in DME management, this effect tended to decrease over time, such that a considerable number of patients required additional treatment. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of the study was to investigate longer term functional and morphological outcomes and their predictors in diabetic macular edema (DME) following a treat-and-extend regimen (TER) without loading dose under ranibizumab. Methods: Patient data were reviewed and analyzed retrospectively over a period of 24 months after initiation of TER. Best-corrected visual acuity (BCVA), treatment frequency, and quantitative and qualitative spectral-domain optical coherence tomography parameters were assessed. Results: 118 eyes of 87 patients were included. A mean of 9.74 ± 2.13 injections in the first and 7.63 ± 2.29 in the second year were applied. There were significant gains of BCVA and reductions in central retinal thickness from baseline to 12 and 24 months (all p < 0.001). Percentage of eyes with an intact inner segment/outer segment (IS/OS) junction increased from 15.3% at baseline to 42.1% at 24 months (p < 0.001). An intact IS/OS junction at baseline increased the probability of having a dry retina after 12 months by 79.3% (p = 0.017) and after 24 months by 88.1% (p = 0.040). Less IS/OS disruption at baseline predicted longer maximum recurrence-free treatment intervals at 2 years (r = −0.345, p < 0.001) and better BCVA at 1 year (r = −0.347, p < 0.001). Baseline bigger intraretinal cysts were associated with more IS/OS disruption at 24 months (r = 0.305, p = 0.007). Younger age and lower BCVA at baseline were predictive for a higher BCVA gain at 24 months (p = 0.046, p < 0.001). Conclusion: Ranibizumab applied in a TER without loading dose in DME significantly improves visual acuity and retinal anatomical structure throughout 2 years. The evaluated predictors might help guide routine clinical treatment in DME. [ABSTRACT FROM AUTHOR]

Introduction: We have recently shown that defects in interdigitation and ellipsoid zones (IZ and EZ) can predict response to anti-VEGF therapy in a small group of treatment-naive diabetic macular edema (DME) patients. The aim of the current study is to further evaluate this association in a larger study group of patients over a longer follow-up time. Methods: Thirty eyes of 30 treatment-naive DME patients were analyzed in this retrospective study. The integrity of foveal IZ and EZ was evaluated using optical coherence tomography at the diagnosis of DME and following anti-VEGF injections. The defect size was correlated with best-corrected visual acuity (BCVA) and central macular thickness (CMT). Results: The mean patients' age at baseline was 63.0 ± 10.0 years. Patients underwent 3.9 ± 2.9 anti-VEGF injections for a mean of 9.1 ± 4.8 months. Following treatment, the mean Snellen visual acuity (VA) improved from 20/52 to 20/44 (p = 0.05), CMT decreased from 432.5 ± 141.4 μm to 375.2 ± 121.4 µm (p = 0.05) and IZ/EZ defect size decreased from 259.83 ± 375.94 µm to 65.34 ± 143.97 µm (p = 0.001). In patients with no IZ/EZ defects at baseline, the mean Snellen VA was better when compared to those with IZ/EZ defects (20/36 vs. 20/70, p = 0.031). The number of eyes with IZ/EZ defects decreased from 17 (57%) at baseline to 6 (20%) at end of follow-up (p < 0.01). BCVA gain correlated with IZ/EZ defect size reduction (r = 0.41, p = 0.02) but not with improvement in CMT (r = 0.28, p = 0.121). Conclusions: IZ/EZ defect size correlated not only with baseline BCVA but also predicted the change in BCVA after anti-VEGF treatment. Possible future automatic measurement of IZ/EZ defect size might prove helpful for the evaluation of treatment response. [ABSTRACT FROM AUTHOR]

Introduction: The objective of this study was to explore visual and anatomical outcomes in patients who underwent intravitreal anti-vascular endothelial growth factor (anti-VEGF) injection for visual impairment from center-involved diabetic macular edema (CI-DME) in clinical practice. Methods: Medical records of consecutive CI-DME patients who initiated treatment with intravitreal bevacizumab injection between January 2012 and December 2016 and were followed for at least 12 months were retrospectively reviewed. Visual and anatomical changes after treatment over a 36-month period were evaluated. Results: There were 286 patients (423 eyes) with a mean (standard deviation, SD) age of 56.8 (8.5) years included in this study. One hundred and forty-six (51%) patients were female, and 137 (47.9%) patients received bilateral eye treatment. Mean (SD) presenting visual acuity (VA) of overall eyes was 50.2 (19.6) letter scores. Stratified by baseline vision, eyes with initial VA worse than 20/40 achieved a statistically significant VA improvement, compared to baseline, by +8.4, +6.9, and +5.4 letters at 12, 24, and 36 months, respectively, with all p values <0.001. However, when initial VA was 20/40 and better, a non-statistically significant change in mean VA by +2.0, −3.5, and −3.6 letters were noted at the same time point (p value between 0.078 and 0.273). Unlike visual changes, a statistically significant decline in central subfield thickness compared to baseline was noted at the end of months 12, 24, and 36 in both initial VA subgroups (all p values <0.001). Nevertheless, even though the median number of given injections considerably decreased from 6 in the first 12 months to 2 in the second 12-month period and 1 in the final 12-month interval, required ophthalmic clinic visits decreased in frequency with median numbers of 10, 7, and 6 appointments in each consecutive 12-month duration. Conclusion: This study supports the benefits of practical intravitreal anti-VEGF utilization to manage CI-DME in real-world settings. The improvement of vision in eyes presenting with poor baseline VA and maintenance of vision in eyes with better baseline VA were demonstrated through the 3-year review of each case. However, the burden of frequent monitoring warrants further evaluation of long-term compliance and efficacy. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to investigate retinal layers' changes in patients with diabetic macular edema (DME) treated with anti-vascular endothelial growth factor (anti-VEGF) agents and to evaluate if these changes may affect treatment response. Methods: Participants in this prospective study were 110 treatment-naïve patients with center involved DME, who were treated with anti-VEGF agents and followed up for at least 12 months. A qualitative and quantitative analysis of retinal layers that can affect visual acuity was performed. Patients with persistent DME were defined, and factors which could affect this outcome were determined. Results: Visual acuity was significantly improved, while there was also a statistically significant reduction in central retinal thickness and in all separate retinal layers' thickness at month 12 compared to baseline (p < 0.001). Visual acuity was associated with central retinal thickness and outer retinal layers' thickness;51.8% of the patients presented with persistent DME at month 12, which was found to be significantly associated with baseline visual acuity and HbA1C levels. Conclusions: Anti-VEGF treatment is effective in reducing retinal thickness as a whole and in all separate retinal layers at 12-month follow-up in patients with DME. Changes in central retinal thickness and in outer retinal layers were found to affect visual acuity. HbA1c was the most significant factor to determine persistence of DME at month 12. [ABSTRACT FROM AUTHOR]

Purpose: Correlations among the aqueous flare value (an indicator of inflammation), several functional-morphologic parameters, and aqueous humor levels of multiple cytokines or inflammatory factors were investigated in patients with diabetic macular edema (DME) receiving intravitreal rani-bizumab injection (IRI). Methods: Aqueous humor levels of 12 cytokines, growth factors, or inflammatory factors were measured in 46 DME patients who received IRI. Vascular endothelial growth factor (VEGF), soluble VEGF receptor (sVEGFR), and the other cytokines/inflammatory factors were measured by the suspension array method. In addition, aqueous flare values were measured with a laser flare meter, and central macular thickness (CMT) was examined by optical coherence tomography. Results: At 1 month after IRI therapy, the aqueous flare value showed a significant decrease compared with before treatment (baseline). Significant correlations were noted between the aqueous flare value and the aqueous humor levels of 6 factors/cytokines, including sVEGFR-1, placental growth factor, monocyte chemoattractant protein 1, soluble intercellular adhesion molecule-1, interleukin (IL)-6, and interferon-inducible 10-kDa protein (IP-10). There was also a significant correlation between the change in aqueous flare value and improvement in CMT 1 month after IRI. Conclusions: These findings suggest that IRI reduces subclinical inflammation and that the aqueous flare value is influenced by inflammatory factors/cytokines. In addition, the change in the aqueous flare value may be an indicator of the response of CMT to IRI in patients with DME. [ABSTRACT FROM AUTHOR]

Objective: To gain information about multiple dexamethasone intravitreal implant (DEX-I) injections in diabetic macular edema (DME) eyes in real-life clinical settings. Methods: Patients with DME treated with multiple (≥5) DEX-I injections between January 1, 2014, and December 31, 2018, were retrospectively enrolled regardless of previous treatment with anti-VEGF agents. All patients were evaluated with best-corrected visual acuity (BCVA) in logMAR, ocular fundus, and spectral domain optical coherence tomography (SD-OCT) at baseline and at 3 months after the last DEX-I injection. Multiple DEX-I injections were administered when necessary in case of DME recurrence. Main efficacy measures were changes in BCVA and central retinal thickness (CRT) from baseline to 3 months after the last DEX-I injection; main secondary measures were an increase in intraocular pressure (IOP), the need for cataract surgery, endophthalmitis, and vitreous hemorrhage. Results: Seventeen patients (18 eyes) with DME and mean age (± SD) of 54.3 ± 8.16 years were treated with DEX-I injections between 2014 and 2018. The majority of eyes (77.8%) had been treated with a mean of 6.3 ± 3.2 anti-VEGF agents before switching to DEX-I. During a mean follow-up period of 37.6 months and after a mean number of 5.9 DEX-I injections, visual acuity improved or stabilized in 77.8% of all eyes, accompanied by a significant reduction in CRT. An increase in IOP was recorded in 38.8% of all patients, while a surgical procedure was needed for cataract in 73.3% of all phakic patients. Conclusions: In this real-life experience in Italy, multiple DEX-I treatments showed good efficacy with no new safety concerns. The follow-up duration of >3 years and a greater number of DEX-I intravitreal injections compared to other observations confirm the positive balance between risks and benefits of DEX-I in the long term. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the epidemiological status of diabetes mellitus (DM)-related complications in Japan. Methods: The subjects were 3.11 million Japanese individuals who were registered in the Japanese claim database between 2005 and 2014. Subjects with a diagnosis associated with codes related to DM and/or DM-related complications as classified by the International Classification of Diseases version 10 and those who were prescribed any therapeutic agents for DM were considered to have DM. The status of ocular, renal, and neural complications was investigated. Results: A total of 66,923 patients with DM were included. The prevalence of subjects with DM was 3.8% in 2005 and 4.2% in 2014. The most frequent complication was diabetic retinopathy (23.6%, 95% CI: 21.7–25.5%), followed by diabetic nephropathy (14.8%, 95% CI: 14.0–15.6%) and diabetic neuropathy (4.9%, 95% CI: 4.5–5.3%). Among the subjects with ocular complications, 1.8% had proliferative diabetic retinopathy, 1.1% had diabetic macular edema (DME), 0.3% had neovascular glaucoma, and 1.5% had vitreous hemorrhage. Only DME significantly increased during the study period. The frequencies of the ocular and neural complications significantly decreased, while that of renal complications significantly increased during the study period. Conclusions: Ocular complications were the most common DM-related major complications in Japan. Notably, DME significantly increased in recent years. [ABSTRACT FROM AUTHOR]

Purpose: To define and develop a model of excellence for the clinical management of diabetic macular edema (DME) patients in a real-world setting. Methods: A multidisciplinary joint commission (5 ophthalmologists, 1 nurse, and 1 pharmaceutic) established a series of preliminary recommendations based on clinical guidelines and DME activity results from 8 Pilot Hospitals (PH). These were validated by members of each PH and a group of DME patients in discussion workshops. Thus, the validated guideline (VG) took into consideration different aspects, namely, main core points (ranging 0-100), criteria, and indicators. Finally, each PH own setting was compared to the VG in order to settle down a starting point to clinical excellence. Results: Mean PH score was 51.5 (range 30-65). As compared to their maximum, main points that showed best scores were Clinical Guidelines and Protocols (78%) and Portfolio of Services (73%). Topics reaching close to 50% scoring included Resources (55%), Innovation (54%), Care Process (53%), Organization (52%), and Leadership (50%). Lowest scores were observed in the Strategic Alliances (46%) and Staff (37%) points. Conclusions: Analysis of each PH by the VG delivered a global vision of the starting situation, especially focused in the identification of the different improvement areas. In order to further extend this model into the Public Health System, the effect of implementing it in different hospitals should be assessed to analyze its impact on daily clinical practice and health economics. [ABSTRACT FROM AUTHOR]

Purpose: Evaluation of the impact of the injection frequency of ranibizumab on best-corrected visual acuity (BCVA) outcomes in patients with diabetic macular edema (DME). Methods: A meta-analysis of randomized controlled trials (RCTs) and real-world studies was performed to quantify the effect of ranibizumab treatment on BCVA and central foveal thickness (CFT) in DME as well as the relationship between the number of injections and the change in BCVA/CFT. Results: All combined sources (29 RCTs and 11 real-life studies) showed a significant increase in BCVA from baseline following anti-vascular endothelial growth factor (VEGF) treatment (8.2, 9.4, and 10.3 ETDRS letters gained after 12, 24, and 36 months of ranibizumab treatment, respectively). The largest changes in BCVA were observed in RCTs and the smallest in real-life studies at 12 months. A significant relationship was found between the number of injections and change in BCVA at 12 months. Conclusions: Inferior vision outcomes were observed in clinical practice compared with RCTs and might be partly attributable to administration of fewer anti-VEGF injections. Physicians should be aware that early and appropriate anti-VEGF treatment regimens are necessary to obtain the results reported in RCTs and help prevent irreversible vision loss in DME patients. [ABSTRACT FROM AUTHOR]

Introduction: The purpose of this study was to report the one-year results of treatment of diabetic macular edema (DME) with aflibercept using a treat-and-extend regimen (TER). Methods: This was a prospective, multicenter, single-arm study planned for 2 years. The eyes received 5 consecutive intravitreal injections of 2 mg of aflibercept every 4 weeks, and the interval between injections was then adjusted by 2 weeks based on changes in the central subfield macular thickness (CSMT). If the CSMT was worse, stable, or better, the interval was shortened, extended, or maintained, respectively. The primary outcome measure was the change in best-corrected visual acuity (BCVA) from baseline to 104 weeks, and the secondary outcome was the change in BCVA from baseline to 52 weeks. Results: Of the 48 patients enrolled, 46 completed a 1-year visit. BCVA improved significantly by 9.1 letters (95% confidence interval: 5.3–13.0 letters) from 56.2 letters at baseline (p < 0.001), and CSMT decreased by –171.7 μm from 489.4 to 317.7 μm (p < 0.001). The proportion of eyes having 20/40 or better vision increased from 17.4 to 41.3%, and the proportion of eyes that gained ≥15 letters was 28.3%. The mean number of injections was 8.5 times for 52 weeks. Worsening of macular edema did not occur in 76.1% of eyes during the extension period, and the interval between injections was extended to 12 weeks in 73.9% of eyes at 52 weeks. Conclusions: The TER showed 1-year efficacy comparable to that of the fixed dosing regimen of pivotal trials, and its flexible dosing would prevent overtreatment. [ABSTRACT FROM AUTHOR]

In the last decades, significant changes have been taking place regarding the pathogenesis of diabetic retinopathy (DR) and the complex mechanisms that eventually lead to the various manifestations of the disease, including diabetic macular edema (DME). DR was first considered a pure microvascular disease, due to the evident capillary structural changes (microaneurysms), fluid extravasation, and lipid exudation. With the advent of fundus fluorescein angiography, the concept of ischemia and the correlation between peripheral nonperfusion and neovascularization has been introduced, which was eventually followed by the advent of new therapeutic strategies, such as peripheral photocoagulation. Nowadays, thanks to more advanced imaging techniques, namely optical coherence tomography (OCT), OCT angiography, and wide-field imaging (imaging up to 200° of the retina in a single shot), it became clear that other elements participate in the occurrence of DR and DME, including inflammation and neurodegeneration. In the future, integration of standard investigations with new diagnostic devices would allow the prompt recognition of DR even before clinical signs of the disease are ophthalmoscopically evident, and the development of personalized treatment for both retinopathy and DME will be available. [ABSTRACT FROM AUTHOR]

Background: First-line treatment for diabetic macular edema (DME) is usually with antivascular endothelial growth factor agents, followed by intravitreal corticosteroids as a second-line treatment option. Long-term corticosteroids may offer quality of life and effectiveness benefits over short-term implants. Objectives: To evaluate outcomes of patients with persistent or recurrent DME who switched from a short-term (dexamethasone) to a long-term (fluocinolone acetonide, FAc) corticosteroid intravitreal implant in a real-world setting. Methods: This is a retrospective study in 9 Portuguese centers. An FAc intravitreal implant was administered according to product labeling. Effectiveness outcomes were mean change in visual acuity (VA; ETDRS letters), central retinal thickness (CRT; µm), and macular volume (MV; mm3). The safety outcome was mean change in intraocular pressure (IOP; mm Hg). All were analyzed at months 1 and 3, and then quarterly until month 24 after implantation. Results: Forty-four eyes from 36 patients were analyzed. Mean duration of DME was 3.3 ± 1.9 years, and mean follow-up was 8 months. From baseline following FAc implantation, VA increased significantly at months 1 and 6 (mean +6.82 and +13.02 letters, respectively; p = 0.005), and last observation carried forward (LOCF; mean +8.3 letters; p = 0.002). CRT improved significantly at months 1 and 6 (mean –71.81 and –170.77 µm, respectively; p = 0.001), and LOCF (mean –121.46 µm; p = 0.001). MV was consistently, but not significantly, decreased from baseline to LOCF (mean –0.69 mm3; p = 0.062). The mean change in IOP was –0.25 and +0.88 mm Hg at months 1 and 6, respectively (p = 0.268), and +1.86 mm Hg at LOCF (p = 0.036). Increases were controlled with topical medication in most cases. Conclusions: The FAc intravitreal implant is effective in patients previously treated with short-term corticosteroid implants. Thus, after a suboptimal response to antiangiogenics or a short-term corticosteroid, a single FAc implant may be considered an effective and tolerable treatment that can improve long-term outcomes for patients with sight-threatening DME. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the thickness of individual retinal layers in eyes with resolved diabetic macular edema (DME) after treatment with ranibizumab (RBZ). Methods: Spectral-domain optical coherence tomography (OCT) scans of 25 eyes (25 patients) with DME that had been treated with RBZ (and shown resolution of edema as evident by the absence of fluid in a high-resolution grid placed on the fovea) were acquired using Spectralis HRA + OCTTM. Thickness measurements of individual layers were calculated using papillomacular bundle (PMB), central subfield, and inner- and outer-ring Early Treatment Diabetic Retinopathy Study (ETDRS) grids. Measurements were compared to 45 normal eyes with no known retinal disease. A post-hoc analysis was done correlating visual acuity (VA) with individual retinal layer thickness. Results: Full retinal thickness (FRT) was thinner than normal individuals across all 4 grids. There were similarities and differences among the 4 grids; however, PMB and inner-ring ETDRS grids displayed the most resemblance. The VA significantly correlated with the FRT measured in PMB (p = 0.004), central subfield (p = 0.02), and inner-ring (p = 0.006) ETDRS. Conclusions: Segmentation of OCT scans revealed significant differences in the overall thickness of the retina and of individual retinal layers in patients with resolved DME. PMB grid showed a stronger correlation between affected retinal layers and VA compared to ETDRS. PMB also showed significance with VA in layers that were shown to be not significant in ETDRS grid. [ABSTRACT FROM AUTHOR]

Over the past two decades, the Diabetic Retinopathy Clinical Research Network (now known as the DRCR Retina Network) has contributed to multiple and substantial advances in the clinical care of diabetic eye disease. Network studies helped establish anti-vascular endothelial growth factor (VEGF) agents as an effective alternative to panretinal photocoagulation for eyes with proliferative diabetic retinopathy (PDR) and as first-line therapy for eyes with visual impairment for diabetic macular edema (DME), defined treatment algorithms for the use of intravitreal medications in these conditions, and provided critical data to understand how to better evaluate the diabetic eye using optical coherence tomography and other imaging modalities. Ongoing DRCR.net studies will address whether anti-VEGF therapy is effective at preventing vision-threatening complications in eyes with severe non-proliferative diabetic retinopathy, if photobiomodulation has a beneficial effect in eyes with DME, and whether initiation of DME treatment with bevacizumab and rescue with aflibercept can provide visual outcomes as good as those achieved with aflibercept alone. Future plans for the Network also include the expansion into non-diabetic eye disease in areas such as age-related macular degeneration. [ABSTRACT FROM AUTHOR]

Inflammation is substantially contributing to the development and worsening of diabetic retinopathy in general and diabetic macular edema (DME) in particular, which provides the rationale to treat DME with corticosteroids. While anti-vascular endothelial growth factor (VEGF) agents are mostly chosen as a first-line treatment, there is an important role for steroids in the treatment algorithm for DME. A slow-release bioerodible dexamethasone implant and an extended-release nonbioerodible fluocinolone acetonide insert are both approved for the treatment of DME and provide the advantage of sustained drug delivery and reduced treatment burden. Steroids bare the complications of cataract progression and increase of intraocular pressure (IOP). However, with dexamethasone implant, IOP rise is well manageable with topical treatment in almost all cases. Dexamethasone implant has been shown to be effective in the treatment of naive DME as well as in eyes nonresponding to anti-VEGF agents. In these cases, early switching to steroids may be considered and has been shown to be beneficial. Fluocinolone acetonide is reserved for severe cases of chronic DME insufficiently responsive to other available therapies. Future randomized controlled trials are needed to realize the role of steroids in the current treatment algorithm of DME. [ABSTRACT FROM AUTHOR]

Purpose: To report the real-world effectiveness and safety of ranibizumab 0.5 mg in patients with visual impairment due to diabetic macular edema (DME). Methods: This is a French, 36-month, multicenter, observational cohort study. Between December 2013 and April 2015, ophthalmologists enrolled diabetic patients aged ≥18 years with DME-related visual impairment and for whom ranibizumab 0.5 mg was initiated. Here, we present the 12-month results from this cohort. The primary endpoint was the mean change in best-corrected visual acuity (BCVA); sample size calculations were based on RESTORE trial data (BCVA mean change = 6.8 letters, preci sion = 0.7 letters). Secondary endpoints included the change in central subfield thickness (CSFT), number of visits, number of injections received, and frequency of ocular and nonocular adverse events and serious adverse events. Results: Between December 2013 and April 2015, a total of 290 patients with DME were enrolled by 84 ophthalmologists; 12-month data are available for 242 patients (due to low recruitment rates, precision was recalculated for 242 evaluable patients: the precision was then of 1.0 letters). Mean age (± standard deviation) was 66.1 ± 11.0 years and 56.6% were male. The mean baseline BCVA and CSFT were 59.2 letters (95% confidence interval [CI] 57.3, 61.0) and 457 μm (95% CI: 438, 476), respectively. At month 12, the mean gain in BCVA from baseline was 7.4 letters (95% CI: 5.4, 9.4), with 36.8% of patients with BCVA > 70 letters versus 13.2% at baseline. Mean change in CSFT was −125 μm (95% CI: −146, −103). The mean number of ranibizumab injections was 5.1 ± 2.3 over an average of 10.4 ± 3.0 visits. No new safety findings were identified. Conclusions: The BOREAL study confirms the effectiveness and safety of ranibizumab for the treatment of DME-related visual impairment in routine clinical practice with fewer injections than reported in clinical trials. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate real-life outcomes in treatment-naive patients with diabetic macular edema (DME) treated with anti-vascular endothelial growth factor (VEGF) agents using a treat-and-extend regimen without a fixed loading phase. Methods: Best-corrected visual acuity (BCVA) and central retinal thickness (CRT) measured using optical coherence tomography at baseline and after 1 year of treatment, intervals and number of injections were analyzed. Subgroup analysis was performed to compare anatomical and functional outcomes between patients receiving ranibizumab or aflibercept. Results: Seventy-five eyes of 61 patients met the inclusion criteria and had follow-up for 1 year. Baseline BCVA and CRT were 68.1 ± 13.2 letters and 424 ± 135 µm, retrospectively. After 1 year, there was a significant mean gain in BCVA of +5.8 ± 7.4 letters (paired t test: p < 0.0001) and a significant decrease in mean CRT of –117 ± 134 µm (paired t test: p < 0.0001). The mean number of anti-VEGF injections was 10.0 ± 1.6 (range 6–12). The mean maximum interval between injections was 8.5 ± 2.9 weeks (range 4–14) and the mean interval 6.0 ± 1.2 weeks (range 4.1–8.9). 96% of eyes could be extended after a mean of 5.3 injections and 17% of patients could be extended before reaching a formal loading dose of 3 injections. Subgroup analysis did not reveal any differences in outcomes between patients treated with ranibizumab or aflibercept. Subretinal fluid at baseline was associated with better BCVA gain after 1 year (stepwise forward regression analysis, p = 0.003). Conclusion: Our results suggest that not all patients with DME require a fixed loading phase when initiating anti-VEGF treatment. Finding anatomical predictors to identify this subgroup of patients would help to reduce treatment burden and optimize clinical outcomes. [ABSTRACT FROM AUTHOR]

Purpose: To assess the efficacy and safety of sub-Tenon injection of triamcinolone acetonide (WP-0508ST) for the patients with diabetic macular edema (DME). Methods: This multicenter, randomized, double-masked, comparative, controlled study was performed in 95 patients with DME. The patients were randomly divided into 20 mg WP-0508ST, 40 mg WP-0508ST, and control groups. Results: A significant improvement in central macular thickness (CMT) was observed (p < 0.001) at 12 weeks after a single sub-Tenon injection of 20 mg WP-0508ST. The 40 mg group also demonstrated improvement in CMT, but the difference was not significant. In addition, the best-corrected visual acuity was improved in both the 20 mg and 40 mg groups at 12 weeks. The major side effects were increased intraocular pressure (9.4% in the 20 mg group and 13.3% in the 40 mg group) and lenticular opacity (6.3% in the 20 mg group and 10.0% in the 40 mg group). However, none of the patients with increased intraocular pressure required surgery. Conclusion: The efficacy and tolerability of WP-0508ST in the treatment of DME were confirmed, and 20 mg was determined to be the optimal dose. [ABSTRACT FROM AUTHOR]

Purpose: To determine whether serum chitinase-3-like protein 1 (CHI3L1) and interleukin-6 (IL-6) levels correlate with serous retinal detachment (SRD) in diabetic macular edema (DME) using spectral-domain optical coherence tomography (SD-OCT). Methods: In this cross-sectional case-control study, 394 patients (treatment-naive DME patients, n = 218; diabetic patients without DME, n = 96; nondiabetic controls, n = 80) were included in the study. Eyes were classified according to SD-OCT features of DME: SRD, cystoid macular edema (CMO), and diffuse retinal thickness (DRT). Serum concentrations of CHI3L1 and IL-6 were analyzed using enzyme-linked immunosorbent assay. Results: Serum CHI3L1 and IL-6 levels were significantly higher in DME with SRD compared to patients with CMO and DRT (p < 0.001 for all groups). Multivariate regression analysis showed that CHI3L1 and IL-6 had a stronger influence on the presence of SRD in DME (r = 1.162, p = 0.026, and r = 1.242, p = 0.016, respectively). Serum concentration of CHI3L1 was significantly correlated with that of IL-6 (r = 0.386, p = 0.0015). Conclusions: Our data suggest that serum concentrations of CHI3L1 and IL-6 are involved in the process of SRD in DME. CHI3L1 can be investigated further as a new diagnostic biomarker for DME with SRD. [ABSTRACT FROM AUTHOR]

Objective: The aim of this paper is to compare intravitreous aflibercept versus dexamethasone implant followed by aflibercept (sequential treatment group) in patients with diabetic macular edema (DME). Methods: We conducted an observational retrospective study in naïve DME patients, 15 treated only with aflibercept (a monthly injection for the first 5 consecutive doses, followed by an injection every 2 months), and 15 treated with a single dexamethasone implant followed by bimonthly aflibercept. Best-corrected visual acuity (BCVA), central macular thickness (CMT), and qualitative features as well as adverse events were assessed at baseline and at 2, 6, and 12 months. Results: BCVA increased from 70.8 ± 4.1 to 83.5 ± 2.7 letters with aflibercept and from 75.6 ± 2.7 to 86.5 ± 2.5 with sequential treatment (p = 0.551). CMT decreased from 411 ± 26.1 to 288.1 ± 10.5 with aflibercept and from 411.4 ± 24.3 to 260.8 ± 17.9 in the sequential treatment group. The differences between the 2 groups, in terms of visual gain and decreased MT, were not statistically significant (p > 0.05). Nine and 6 injections and 9 and 7 monitoring visits were performed. Conclusion: Sequential treatment in DME, starting with dexamethasone and followed by aflibercept, is a promising alternative that can reduce the treatment burden in the first year without statistically significant differences in terms of visual gain and decreased MT compared to aflibercept only. [ABSTRACT FROM AUTHOR]

Purpose: Evaluate the effect of foveal leaking microaneurysms (MAs) on the required number of intravitreal ranibiz-umab (IVR) injections in the treatment of center-involving diabetic macular edema (DME) when treated with focal/grid laser. Design: A pilot study of prospective, nonrandomized, multicenter clinical trial. Methods: This study enrolled 21 eyes with DME for which pro re nata IVR injections were combined with short-pulse focal/grid laser. At 12 months, best-corrected visual acuity (BCVA), central subfield macular thickness (CMT), and the required number of IVRs to maintain CMT < 300 µm were compared between eyes with or without foveal leaking MAs, termed the MA(+) and MA(–) groups, respectively. Results: Significant CMT improvements (p < 0.0001) and increased BCVA of 4.0 ± 8.5 letters were observed at 12 months. The MA(–) group required significantly fewer IVRs than did the MA(+) group (mean: 4.9 ± 3.0 vs. 8.6 ± 3.0; p = 0.0306). In the latter 6 months of the 1-year follow-up, 50% (4/8) of MA(–) eyes did not require any IVR administration to sustain CMT < 300 µm. Conclusions: A combination therapy of short-pulse focal/grid laser and reduced IVR injections appeared noninferior to previous reports of IVR monotherapy. Further large-scale investigations are warranted. [ABSTRACT FROM AUTHOR]

Purpose: To assess the progression of diabetic hard exudates over an 8-week period, using a high-resolution adaptive optics camera. Design: Prospective observational study. Methods: Five eyes of three patients presenting diabetic maculopathy with hard exudates were studied. An area of clinically visible exudates was imaged sequentially using SD-OCT and high-resolution flood illumination adaptive optics for 2 months, on a weekly basis. A time-lapse video was obtained for each eye studied. Changes in terms of surface, number of free elements (foci), and central macular thickness were recorded. Results: Short-term modifications in terms of disposition, size, and number of exudates were observed. Two patterns of progression were identified: two eyes showed exudate dislocation concomitant with the regression of the underlying macular edema, with hard exudates being progressively replaced by a multitude of smaller foci. These exudates were labeled resorption exudates. In three other eyes with persistent diabetic macular edema, foci aggregated into larger exudates. Conclusion: Diabetic hard exudate changes occurred over a short period of time but were not assessable clinically. Adaptive optics was able to document these subtle changes precisely. Further studies using this imaging modality may improve our understanding of the natural history of exudates and eventually help assess the efficacy of the various treatments available such as lipid-lowering drugs and anti-VEGFs injections. [ABSTRACT FROM AUTHOR]

Introduction: There are few real-life studies on the intravitreal 0.7-mg dexamethasone implant for the treatment of diabetic macular edema (DME) conducted in Latin America. We aimed to assess the effectiveness and safety of this implant in clinical practice. Methods: Twenty-seven centers from Brazil and one from Argentina provided information on patients with DME treated with Ozurdex. The efficacy outcome variables were best-corrected visual acuity (BCVA) in Snellen and central retinal thickness (CRT). Safety was assessed by the elevation in intraocular pressure (IOP), occurrence of cataracts, and adverse events. Results: A total of 329 eyes (both treated cases and naïve eyes) from 282 patients underwent treatment. The time since diagnosis of DME ranged from 1 to 156 months. The median BCVA was 0.7 logMAR/50 letters at baseline and 0.3 logMAR/70 letters after treatment (both p < 0.001). Median CRT values decreased from 425 µm at baseline to 270 µm after treatment (p < 0.001). Increases in IOP of at least 10 mm Hg were observed in 7.4% of eyes, and 4% of eyes had cataract evolution. No cases of endophthalmitis were reported. Conclusion: These real-life results suggest that the intravitreal dexamethasone implant is effective and safe for eyes with DME. [ABSTRACT FROM AUTHOR]

Purpose: We compared the efficacy of sub-Tenon triamcinolone acetonide (STTA) to intravitreal triamcinolone aceto-nide (IVTA) injections during cataract surgery (CS) for patients with diabetic macular edema (DME). Methods: The medical records of 33 eyes (26 patients) with DME which had undergone CS with STTA were compared to those of 34 eyes (27 patients) with DME which had undergone CS with IVTA. Central foveal thickness and best-corrected visual acuity (BCVA) were measured at the baseline and 1, 3, and 6 months after the surgery. Results: The BCVAs after STTA and IVTA were significantly improved at 3 and 6 months. Thirteen eyes in the IVTA group and 21 eyes in the STTA group required other therapies (p < 0.05). One case developed intraocular pressure elevation after IVTA and underwent selective la ser trabeculoplasty. Conclusions: Ophthalmologists should consider the merits and demerits of IVTA and STTA for DME treatment after CS. [ABSTRACT FROM AUTHOR]

Diabetes mellitus (DM) is a metabolic disease frequently associated with comorbidities that include diabetic macular edema (DME). The current medical approach to treating DME involves intravitreal injections with either anti-vascular endothelial growth factors or steroids. However, the burden associated with intravitreal injections and DM-derived complications is high, underlining the need to find optimal treatment regimens. In this article we describe the considerations we apply when treating DME patients with dexamethasone intravitreal implants (Ozurdex®), particularly those that influence the clinical decision-making process during the follow-up period. These considerations are based both on the available medical literature and on our clinical experience following the use of these implants in this type of patient, the goal being to optimize the number of injections and the clinical outcome of this therapy. We also provide a general overview of the pathophysiology of DME, highlighting the inflammatory component as a rationale to use steroids in these patients. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the effectiveness of an intravitreal triamcinolone acetonide injection (IVTA) combined with cataract surgery for diabetic macular edema (DME) resistant to anti-vascular endothelial growth factor (anti-VEGF) therapy. Procedure: IVTA combined with cataract surgery was performed on 29 eyes of patients with DME (aged 70.5 ± 6.2 years) who were refractive to anti-VEGF treatments. The visual acuity, central retinal thickness (CRT), and the central retinal sensitivity were assessed at 1, 4, 12, and 24 weeks after the treatment. Results: The visual acuity improved significantly from 0.49 ± 0.30 logMAR units to 0.35 ± 0.33 logMAR units at 24 weeks after the treatment (p < 0.05; repeated ANOVA). The CRT decreased significantly from 435.1 ± 112.3 μm to 350.8 ± 123.3 μm at 12 weeks after the treatment (p < 0.05). The retinal sensitivity threshold also improved significantly from 18.2 ± 4.3 dB to 20.4 ± 3.8 dB at 4 weeks after the treatment (p < 0.05). Conclusions: IVTA combined with cataract surgery is effective for successful treatment of eyes with DME refractive to anti-VEGF therapy. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to define a new pathogenetic classification of diabetic macular edema (DME) and to present the results of its application in common clinical practice. Methods: One hundred and seventy-seven consecutive patients with center-involving DME, central retinal thickness (CRT) ≥250 µm, were prospectively enrolled. A complete ophthalmological examination included best-corrected visual acuity (BCVA) assessment, fundus photography, and spectral-domain optical coherence tomography (OCT). The DME classification was broken down into 4 categories, combining the presence of retinal thickening with the presence/absence of visible vascular dilations and OCT-detectable macular traction. The OCT parameters included were as follows: CRT, subretinal fluid, intraretinal cysts, and hyper- reflective foci (HF). Results: Four subtypes of DME were identified: vasogenic (131 eyes, DME with vascular dilation), nonvasogenic (46 eyes, DME without vascular dilation), tractional (11 eyes), and mixed DME (13 eyes). Vasogenic DME was the pattern mainly represented in each subclass of CRT (< 300, 300–400, and > 400 µm), with tractional DME observed especially with CRT > 400 µm. Internal and external cysts and a greater presence of hard exudates were predominantly found in vasogenic DME, whereas HF was equally distributed in the 4 DME subgroups. Conclusion: The study offers a new pathogenetic classification able to detect significant differences among DME subtypes. A tailored therapeutic approach could take into consideration specific changes associated with the different DME subtypes. [ABSTRACT FROM AUTHOR]

Objective: To compare the visual and anatomical outcomes of intravitreal ranibizumab (group 1), bevacizumab (group 2), and triamcinolone (group 3) for center-involving diabetic macular edema. Methods: We retrospectively enrolled 275 eyes of 208 consecutive patients. Visual acuity (VA) in Early Treatment Diabetic Retinopathy Study (ETDRS) letters and central macular thickness (CMT) values on optical coherence tomography were extracted. Reported side effects were noted. Results: At 6 months, the mean changes in VA in group 1, group 2, and group 3 were +4.9, +4.3, and +4.6 letters, respectively (p = 0.911). Improvement of CMT at 6 and 24 months was significantly better in group 3 compared to groups 1 and 2 (p = 0.012 and p = 0.001, respectively). At 24 months, the only independent variable affecting the change in VA was initial VA (p = 0.020). Cataract and glaucoma prevalences were higher in group 3 (p = 0.000 and p = 0.001, respectively). Conclusions: Three treatment methods had similar effects with regard to improvement in VA; however, intravitreal triamcinolone provided additional anatomical improvement. [ABSTRACT FROM AUTHOR]

Objective: To examine the relationship between early response to anti-vascular endothelial growth factor (VEGF) treatment and visual prognosis. Methods: We retrospectively separated 20 patients with persistent diabetic macular edema (DME) into two responder status groups based on the reduction of central macular thickness (CMT) from baseline to month 3: a delayed responder group (DRG) (≤25% CMT reduction, n = 11) and an immediate responder group (IRG) (>25% CMT reduction, n = 14). We also separated the patients into two responder status groups based on the logarithm of the minimum angle of resolution (logMAR) best-corrected visual acuity (BCVA): a visual nonimprovement group (VNIG) (≥0 logMAR BCVA improvement, n = 11) and a vi sual improvement group (VIG) (<0 logMAR BCVA improvement, n = 14). Finally, we assessed the correlations between logMAR BCVA changes from baseline to month 3 (ΔBCVAM3) and those from baseline to month 12 (ΔBCVAM12). Results: At month 12, BCVA was significantly more improved in the VIG than the VNIG (p < 0.005), but was not significantly different between the DRG and the IRG (p = 0.75). The Pearson correlation coefficient showed a significant relationship between ΔBCVAM3 and ΔBCVAM12 (r = 0.60, p < 0.005). Conclusions: BCVA showed significantly greater improvement in the VIG than in the VNIG. ΔBCVAM3 may predict the visual outcome at month 12 in DME patients treated with anti-VEGF drugs. [ABSTRACT FROM AUTHOR]