Refractory Diabetic Macular Edema Research Articles

Real-Life Results after the Administration of a Single 0.19 mg Fluocinolone Acetonide (ILUVIEN®) Implant in Patients with Refractory Diabetic Macular Edema

Introduction: The aim of this study was to evaluate real-life data on the functional and anatomical outcome of intravitreal fluocinolone acetonide (FAc) in patients with refractory diabetic macular edema (DME). Methods: Retrospective study on 44 eyes with chronic DME that received intravitreal FAc implant and were previously treated with intravitreal dexamethasone, triamcinolone, or anti-vascular endothelial growth factor. We assessed best-corrected visual acuity (BCVA), central maximum thickness (CMT), and foveal thickness (FT) as measured by spectral-domain optical coherence tomography (Spectralis OCT; Heidelberg Engineering). Secondary outcomes were intraocular pressure (IOP), adverse events, time to additional treatments. Results: The FAc implant significantly reduced the CMT (baseline 541.23 ± 155.29 µm, p < 0.001) and FT (baseline 460.34 ± 139.28 µm, p < 0.001) for up to 36 months. Despite postoperative visual improvement over time, BCVA did not significantly shift from baseline (0.55 ± 0.38 logMAR, p = 0.568). The FAc implant effect diminished after 21.34 ± 12.74 months. IOP increased in 9% of eyes (n = 4) but was well controlled under topical (n = 1) or surgical therapy (n = 3). Conclusion: Even though patients’ visual recovery does not benefit significantly, the FAc implant addresses the important pillars of chronic DME therapy regarding reduced injection frequency and reduced DME.

Fluid aspiration from intraretinal cysts for refractory diabetic macular edema

PURPOSE: To report the surgical outcome of fluid aspiration in intraretinal cysts as a novel treatment approach for the refractory cystoid macular edema (CME) associated with diabetic retinopathy. METHODS: This retrospective consecutive case series examined eight patients with refractory CME who underwent intraretinal cyst fluid aspiration using a 38-gauge subretinal infusion needle during pars plana vitrectomy. We reviewed changes in central retinal thickness (CRT), best-corrected visual acuity (BCVA), and central sensitivity among patients followed up for 12 months post-surgery. RESULTS: CRT on optical coherence tomography (μm) significantly improved at 12 months post-surgery (308 ± 99) compared to before surgery (480 ± 141) (P &lt; 0.005). During the follow-up period, CME relapsed in one eye. The BCVA (logarithm of the minimal angle of resolution) at 12 months post-surgery (0.23 ± 0.32, Snellen equivalent: 20/50) was significantly better than the preoperative BCVA (0.39 ± 0.29, Snellen equivalent: 20/63) (P &lt; 0.01). The mean deviation value of central sensitivity did not significantly change between preoperative (-2.5 ± 2.1) and postoperative (-2.2 ± 2.2) assessments (P = 0.07). CONCLUSIONS: Fluid aspiration in intraretinal cysts may be a treatment option for refractory CME in eyes with diabetes.

Современные алгоритмы терапии диабетического макулярного отека (Обзор литературы. Часть II)

This review presents up-to-date information on officially approved intravitreal angiogenesis inhibitors, provides the comparative analysis of the data obtained during large-scale randomized trials on their efficacy and safety as well as possible schemes of their administration. Special attention is paid to the problem of refractory diabetic macular edema and alternative therapies, including the use of glucocorticoids, inhibition of Rho/ROCK signaling pathway. The dynamics of the central foveal thickness according to optical coherence tomography and best-corrected visual acuity are the main criteria for evaluating the diabetic macular edema therapy effectiveness. According to current data, intravitreal injection of angiogenesis inhibitors is a first-line treatment. In diabetic macular edema, the following drugs have been registered in Russia: ranibizumab, aflibercept, brolucizumab, faricimab. Laser retinal photocoagulation is used mainly for the non-central edema treatment. Intravitreal glucocorticoids are considered as an alternative therapy, but their use is limited by the presence of side effects in the form of secondary drug-induced ophthalmic hypertension and/or glaucoma and the development of cataracts. However, the suboptimal response to standard treatment and the development of refractory forms stimulate the development of novel drugs and delivery systems, as well as the use of several types of therapy that affect different points of the pathogenesis. The review emphasizes the need to further study the trigger points of the diabetic retinopathy pathogenesis and the development of diabetic macular edema in order to find novel drugs and individualize the treatment of each patient. Key words:diabetic retinopathy, diabetic macular edema, vascular endothelial growth factor, VEGF-therapy

Комбинированный метод лечения рефрактерного диабетического макулярного отека

Purpose. To determine the effectiveness of the anatomical and functional results of treatment of refractory diabetic macular edema after removal of the inner limiting membrane using the latest generation anti-VEGF drug. Material and methods. We examined 6 patients with 1st type and 2nd type diabetes mellitus. The average age of the subjects was 47.45 ± 27.15 years. Of these, there were 4 women and 2 men. 1st type diabetes mellitus was detected in 2 people, in other patients — 2nd type. 3 patients had previously undergone pan-retinal photocoagulation (from 1st to 2nd stages). All patients received intravitreal injections (anti-VEGF) of Eylea (4–5 injections) during the last year. According to the optical coherence tomogram (OCT), macular edema was recorded, recurring on average after 1.36 ± 0.85 months. All patients underwent surgical treatment. In the presence of lens opacity, surgical treatment was started with phacoemulsification of cataracts. A microinvasive subtotal vitrectomy was performed with the removal of the posterior layers of the vitreous body and proliferative membranes fixed to the retina. The removal of the inner boundary membrane was performed after its staining in the size of two to three diameters of the optic disc without any tamponade. After 2 months, two patients had an increase in retinal thickness in the fovea. These patients received one injection of Vabismo. Results. The compared groups did not differ in morphofunctional characteristics. In the postoperative period, there was a tendency to increase visual acuity and decrease retinal thickness, regression of hard exudates in 4 patients. In 2 patients, an increase in retinal thickness in the fovea was noted after 2 months. After intravitreal injection of the latest generation anti-VEGF drug (Vabismo), these patients also showed an increase in visual acuity, regression of solid exudates and a decrease in retinal thickness. Conclusion. Microinvasive subtotal vitrectomy with removal of the inner limiting membrane in combination with intravitreal injection of the latest generation anti-VEGF drug (Vabismo) is an effective method of treating refractory diabetic macular edema. Keywords: anti-VEGF, Vabismo, diabetic macular edema, intravitreal injections, optical coherence tomogram, subtotal vitrectomy, inner boundary membrane

Анализ эффективность применения антиангиогенной терапии в комплексном лечении пациентов с диабетическим макулярным отеком

Currently, priority in the treatment of diabetic macular edema (DME) with use from inhibitors of vascular endothelial growth factor (VEGF), the effectiveness of this method has been proven by multicenter researches. The aim of our research is investigation the effectiveness of usage for antiangiogenic therapy in the complex treatment of patients with diabetic macular edema. Material and methods. We analysed with refractory laser photocoagulation resistant DME in 61 eyes of 49 patients for effectiveness of this drug. Ophthalmological examinations in patients (visometry, biomicroscopy, non-contact tonometry, optical coherence tomography (OCT), refractometry and color photographing of fundus) were performed the day after the injection, then on the 2nd, 4th, 8th, 12th , 16th, 20th and 24th week and next every 3 months until the end of the observation period. Results and conclusion. The competent use of drugs from this group in compliance with the developed schemes and techniques for intravitreal injection, well-defined indications for repeated injections, as well as compact dynamic monitoring of patients can become the key to success in maintaining and improving visual functions in patients with diabetic macular edema (DME). Keywords: diabetic macular edema (DME), vascular endothelial growth factor (VEGF), visual acuity, ophthalmoscopy, optical coherence tomography (OCT)

Is Intravitreal Injection of Recombinant Tissue Plasminogen Activator Effective for the Treatment of Refractory Diabetic Macular Edema in Patients With Posterior Vitreous Detachment?

To determine whether intravitreal injection of recombinant tissue plasminogen activator (rTPA) is effective for the treatment of refractory diabetic macular edema (DME) in patients who already had posterior vitreous detachment (PVD). It is a retrospective chart review of the patients with refractory DME and PVD. The efficacy of intravitreal injection of rTPA was assessed based on the changes in central macular thickness (CMT) and best-corrected visual acuity (BCVA) in these patients. Nine eyes of nine patients as the study group and 14 eyes of the 14 patients as the control group were examined. Before the injections, the mean CMT was 470.0± 107.6 in the study group, compared to 536.2± 150.5 in the control group, with no statistical significance (p=0.403). The statistical analysis revealed no significant differences in the mean changes in CMT from baseline to one and three months after injections between the study and control groups (p=0.439, p=0.781, respectively). Likewise, no statistically significant disparities were observed in the mean pre-injection BCVA between the study group (0.877± 0.349) and the control group (0.950± 0.300) (p=0.415). Additionally, after three months of injection, there were no significant changes in the mean BCVA of the study group (0.844± 0.304) and the control group (0.864± 0.253) (p=0.512). This study showed that rTPA has no effect on changes in CMT and BCVA in patients who had refractory DME and PVD at the same time. This may suggest that the improvement in CMT in previous studies may be due to the induction of PVD.

Should intravitreal dexamethasone implant in refractory diabetic macular edema be used as an adjuvant therapy or switch therapy?

To compare the outcomes of intravitreal dexamethasone implant used as either an adjuvant or a switching therapy for diabetic macular edema in patients with poor anatomic response after three consecutive monthly injections of ranibizumab. This retrospective study included patients with diabetic macular edema who received three consecutive doses of ranibizumab as initial therapy and demonstrated poor response. A single dose of intravitreal de xamethasone implant was administered to these patients. The patients were divided into two groups according to the treatment modalities: the adjuvant therapy group, consisting of patients who continued treatment with ranibizumab injection after receiving intravitreal dexamethasone implant, and the switch therapy group, consisting of patients who were switched from ranibizumab treatment to intravitreal dexamethasone implant as needed. The main outcome measurements were best corrected visual acuity and central retinal thickness at baseline and at 3, 6, 9, and 12 months of follow-up. In this study that included 64 eyes of 64 patients, the best corrected visual acuity and central retinal thickness values did not significantly differ between the groups at baseline and at 6 months of follow-up (p>0.05). However, at 12 months, the best corrected visual acuity values in the adjuvant and switch therapy groups were 0.46 and 0.35 LogMAR, respectively (p=0.012), and the central retinal thickness values were 344.8 and 270.9, respectively (p=0.007). In a real-world setting, it seems more reasonable to use intravitreal dexamethasone implant as a switch therapy rather than an adjuvant therapy for diabetic macula edema refractory to ranibizumab despite three consecutive monthly injections of ranibizumab. Patients switched to intravitreal dexamethasone implant were found to have better anatomic and visual outcomes at 12 months than those who continued ranibizumab therapy despite their less-than-optimal responses.

Comparative Analysis of Intravitreal Dexamethasone Implant (Ozurdex) and Brolucizumab Injection in the Treatment of Diabetic Macular Edema with Hyperreflective Intraretinal Dots: A Retrospective Study.

This retrospective study aimed to compare the efficacy and safety of intravitreal Dexamethasone Implant (DEX) and Brolucizumab Injection in treating Diabetic Macular Edema (DME) with Hyperreflective Intraretinal Dots (HRID). A single-center retrospective study in India included 40 eyes (20 per group) with controlled diabetes and HRID on optical coherence tomography. Patients received either DEX or Brolucizumab, with outcomes assessed at various intervals up to 24weeks. Primary measures included Best-Corrected Visual Acuity (BCVA), Central Macular Thickness (CMT), and safety parameters. Both treatment groups demonstrated comparable baseline characteristics. Both treatments significantly improved the BCVA at weeks 4, 12, and 24, with the DEX implant showing significantly better results at week 12 than brolucizumab (P=0.04). In treatment-naïve eyes, BCVA improvements were similar across all time points. In recalcitrant DME eyes, DEX showed significant BCVA improvements at all time points, while brolucizumab showed significant improvements only at weeks 4 (P=0.005) and 24 (P=0.04). The CMT also improved with both treatments, with DEX showing superior reduction at weeks 4 (P=0.003), 12 (P=0.003), and 24 (P=0.002) respectively. In treatment-naïve eyes, DEX showed consistently better CMT reductions. In refractory DME eyes, both treatments significantly reduced CMT, with DEX performing better at week 12 (P=0.042). DEX required fewer injections (DEX: 1.5±0.61; brolucizumab: 2.4±0.82; P=0.0002) and less supplementary laser treatment (DEX:8/20, 40% eyes; brolucizumab: 16/20, 80%; P=0.01) compared to brolucizumab. No adverse events were observed in either group. The study suggests the potential superiority of intravitreal DEX implant over brolucizumab in managing DME with HRID. DEX exhibited sustained positive responses in BCVA and CMT, requiring fewer injections and supplementary interventions. Future research should explore extended follow-up durations, personalized treatment strategies, and refined biomarkers to optimize DME management.

Use of Ranibizumab for evaluating focal laser combination therapy for refractory diabetic macular edema patients: an exploratory study on the RELAND trials

Anti-vascular endothelial growth factor (VEGF) therapy is the first-line treatment for diabetic macular edema (DME), but is less effective in some patients. We conducted a prospective study to determine whether laser combination therapy with anti-VEGF was more effective than Ranibizumab monotherapy in anti-VEGF-resistant DME patients. There was no significant difference in the improvement of the best-corrected visual acuity (BCVA) between the laser combination therapy and Ranibizumab monotherapy groups (3.2 letters and -7.5 letters, p = 0.165). BCVA did not significantly change between visits 1 and 7 (the laser combination group, 64.3 letters 70.3 letters, respectively, p = 0.537; the Ranibizumab monotherapy group, 72.3 letters and 64.8 letters, respectively, p = 0.554), with no significant improvements in central foveal retinal thickness (the laser combination therapy group, 9.3%: the Ranibizumab monotherapy groups, − 7.3%; p = 0.926). There was no significant difference in the number of Ranibizumab intravitreal therapy (IVT) sessions between the groups (laser combination therapy, 5.2; ranibizumab monotherapy, 6.0; p = 0.237). This study did not show that laser combination therapy was significantly more effective for anti-VEGF-resistant DME than anti-VEGF monotherapy alone. Therefore, for anti-VEGF-resistant DME, alternative therapeutic approaches beyond combined laser therapy may be considered.

Pars Plana Vitrectomy for the Treatment of Diabetic Macular Edema with or without Internal Limiting Membrane Peeling: A Systematic Review and Meta-Analysis

Background Diabetic macular edema (DME) is defined as a retinal thickening in one-disc diameter (DD) of the centre of the macula. It is a number of microvascular retinal changes that lead to blood–retinal barrier (BRB) disruption, causing leakage of fluid and plasma components into the inner and outer plexiform layers. Aim of the Work The aim of the study was to conduct a systematic review and a meta-analysis estimating the efficacy of pars plana vitrectomy with and without internal limiting membrane peeling in treating non tractional refractory diabetic macular edema. Materials and Methods A comprehensive literature search was conducted using the databases Google scholar, PubMed, MEDS, web of science, EMBASE and Cochrane Library for published studies from 1 January 2000 to 1 August 2020. This meta-analysis included 14 studies. They were randomized controlled clinical trials (RCTs), and about 647 patients with DME (753 eyes) participated in these studies. Results This study demonstrated no statistically significant change in the mean of best corrected visual acuity (BCVA) improvement and central macular thickness (CMT) in both groups when comparing the baseline to one- and three-month follow-ups after the procedure, though with no statistically significant difference in the ILM compared to the non ILM group. Conclusion Pars plana vitrectomy with or without ILM peeling improves the long-term visual acuity of nontractional diabetic macular edema. Internal limiting membrane peeling, does not affect the postoperative best-corrected visual acuity significantly.

Intravitreal fasudil monotherapy for treatment of refractory diabetic macular edema: A prospective interventional case series

Suboptimal response to conventional treatments in refractory diabetic macular edema (rDME) encourages efforts to identify new therapeutic options. To evaluate the effect of three monthly intravitreal injections of a Rho-associated protein kinase (ROCK) inhibitor (Fasudil, Asahi Kasei Pharma Corporation, Tokyo, Japan) in eyes with rDME. Ten eyes of 10 patients with DME unresponsive to at least six previous intravitreal bevacizumab (IVB) injections were recruited and underwent 3 consecutive monthly intravitreal injection of 0.025mg/0.05mL Fasudil. Best-corrected visual acuity (BCVA) and central macular thickness (CMT) were evaluated as functional and anatomical response indicators, respectively. The mean age was 60.1±5.1 years (range, 53-68). Five cases responded to treatment, two with both anatomical and functional responses (reduction of CMT from 521 to 395 and from 390 to 301 microns and improvement of BCVA from 0.3 to 0.1 LogMAR and 0.6 to 0.4 LogMAR, respectively) and three with only functional improvement (0.7 to 0.4; 0.7 to 0.4; and 0.3 to 0.1 LogMAR). Of note, cases with no significant change in CMT showed morphologic improvement of the retinal microstructure to some extent. No adverse event was observed during the study period. Monotherapy with intravitreal injection of ROCK inhibitors appears to have moderate visual benefits in eyes with DME refractory to IVB. Such effects may be functionally significant without obvious anatomical improvement.

The role and efficacy of vitrectomy for the management of refractory diabetic macular edema: Systematic review and meta-analysis

This study aimed to evaluate the role and efficacy of vitrectomy in the management of chronic diabetic macular edema (DME) refractory to intravitreal anti-vascular endothelial growth factor (anti-VEGF) and corticosteroid treatments. A systematic review and meta-analysis were performed by searching the Embase, Medline, and gray literature. Eight hundred and thirty-nine studies were retrieved and eight were selected (three for quantitative synthesis and five for qualitative synthesis). Visual acuity (VA) and central macular thickness (CMT) were compared between the vitrectomy-treated and control groups (treated with anti-VEGF and intravitreal corticosteroid injection) using the standardized mean difference (SMD) with 95% confidence intervals (CIs) and P-values. There was no significant difference in post-operative VA between the vitrectomy-treated and control groups (SMD = −0.31, 95% CI: −0.76, 0.14, P = 0.18). However, CMT was significantly lower in the vitrectomy group than in the control group (SMD = −0.31, 95% CI: −0.76, 0.14, P = 0.18). In addition, the incidence of postoperative complications was higher in the control groups than that in the vitrectomy group.This systematic review and meta-analysis suggest that vitrectomy may be viable for the management of chronic DME refractory to anti-VEGF and corticosteroid agents. Although there was no significant difference in VA, the CMT was significantly reduced in the vitrectomy group. Moreover, the incidence of post-operative complications was lower in the vitrectomy group than that in the control group. Further studies are needed to confirm these findings and identify patient subgroups that may benefit from vitrectomy.

The additive effect of intravitreal dexamethasone combined with bevacizumab in refractory diabetic macular edema

PurposeTo evaluate the short-term structural and visual outcomes and side effects associated with intravitreal dexamethasone (IVD) combined with bevacizumab (IVB) in treating patients with diabetic macular edema (DME) and an inadequate response to anti-vascular endothelial growth factor (anti-VEGF) agents. MethodsIn this prospective interventional case series, a total of 81 eyes of 81 patients with type 2 diabetes mellitus (T2DM) and refractory DME were included and assigned to one of two groups: I) those receiving three monthly intravitreal injections of combined bevacizumab and dexamethasone (IVB+IVD) and II) those receiving three monthly intravitreal injections of bevacizumab alone (IVB). The primary outcome was the inter-group difference in central macular thickness (CMT); secondary outcomes included best-corrected visual acuity (BCVA), baseline optical coherence tomography (OCT) biomarkers, and intraocular pressure (IOP) one month after the last injection. ResultsReduction in CMT and improvement in BCVA were significantly greater in the IVB+IVD group than the IVB group (109.88±156.25 vs. 43±113.67, respectively, P=0.03; and −0.13±0.23 vs. −0.01±0.17, respectively, P=0.008). Presence of neurosensory retinal detachment (NSD) (P<0.001) and complete inner segment/outer segment junction (IS-OS) disruption (P=0.049) on baseline OCT scans were associated with further CMT reductions in response to IVD. Conversely, identifiable epiretinal membrane (ERM) (P=0.002) and multiple hyperreflective foci (>20) (P=0.049) were associated with smaller reductions in CMT. Vitreomacular traction correlated with worse visual outcomes in the IVB+IVD group (P=0.003). The intergroup IOP difference was not clinically significant. ConclusionIn patients with refractory DME, addition of IVD to the standard IVB regimen can improve visual and structural outcomes without increasing the risk of endophthalmitis, IOP rise, or intraocular inflammation. Patients with NSD are more likely to respond well to IVD. The presence of ERM may predict poor treatment response.

Retinal changes after fluocinolone acetonide implant (ILUVIEN®) for DME: SD-OCT imaging assessment using ESASO classification.

A detailed understanding of the anatomical and structural changes occurring in the retina following intravitreal fluocinolone acetonide implantation may help improve the management and prognosis of persistent or recurrent diabetic macular edema (DME). Overall, 45 eyes (from 35 patients) with refractory center-involved DME received an intravitreal fluocinolone acetonide implant. They were monitored at baseline and at 6, 12, 24, and 36 months for best-corrected visual acuity (BCVA), central foveal thickness (CFT), and the seven retinal parameters used in the classification of diabetic maculopathy recently developed at the European School for Advanced Studies in Ophthalmology (ESASO). Within 6 months of implantation, significant improvements were evident in BCVA, CFT, maculopathy stage, and the percentage of eyes with: intraretinal cysts; CFT > 30% above the upper normal value; and disrupted or absent ellipsoid zone (EZ) and/or external limiting membrane (ELM). Significant improvements were still maintained at 36 months post-implantation. At month 36, early treatment with the implant (i.e., after < 6 previous intravitreal injections for DME) trended toward being more effective than later treatment in improving BCVA, CFT, maculopathy stage, and the percentage of eyes with CFT > 30% above the upper normal value. However, statistical significance was not achieved. In persistent or recurrent DME, fluocinolone acetonide implantation can be effective in improving maculopathy stage and reducing the percentage of eyes with: intraretinal cysts; CFT > 30% above the upper normal value; and disrupted or absent EZ and/or ELM. It can also increase BCVA and reduce CFT.

Combined Treatment of Persistent Diabetic Macular Edema with Aflibercept and Triamcinolone Acetonide in Pseudophakic Eyes.

Background and Objectives: The main cause of the vision loss in diabetics is the development of diabetic macular edema, regardless of the stage of diabetic retinopathy. The paper aimed to examine whether the additional intravitreal application of triamcinolone acetonide to continuous anti-vascular endothelial growth factor therapy could improve therapeutic outcomes for pseudophakic eyes with persistent diabetic macular edema. Materials and Methods: twenty-four pseudophakic eyes with refractory diabetic macular edema, that had appeared despite three previously administered intravitreal injections of aflibercept, were divided into two groups (twelve eyes in each group). The first group continued to have aflibercept administered according to a fixed dosing regimen (once in two months). Triamcinolone acetonide 10 mg/0.1 mL (administered once per four months) was included for the second group, i.e., their treatment continued with a combination of aflibercept + triamcinolone acetonide. Results: The reduction in central macular thickness was higher in the eyes treated with combined therapy (aflibercept + triamcinolone acetonide) compared with the use of aflibercept alone during the entire 12-month follow-up period (3rd month p = 0.019; 6th month p = 0.023; 9th month p = 0.027; 12th month p = 0.031). As was evident from the p-values, the differences were statistically significant. No statistically significant difference was recorded for visual acuity: 3rd month p = 0.423; 6th month p = 0.392; 9th month p = 0.413; 12th month p = 0.418. Conclusions: Combined anti-vascular endothelial growth factor and steroid therapy leads to a better anatomical outcome of persistent diabetic macular edema in pseudophakic eyes, but does not lead to a more significant improvement in visual acuity than continuous anti-VEGF therapy alone.

Comparison of Optical Coherence Tomography Biomarkers between Bevacizumab Good Responders and Nonresponders Who were Switched to Dexamethasone Implant in Diabetic Macular Edema.

To compare volumetric optical coherence tomography (OCT) biomarkers in bevacizumab responsive and bevacizumab refractory diabetic macular edema (DME) patients switched to the dexamethasone implant to ultimately identify possible prognostic indicators. Retrospective analysis of DME patients treated with bevacizumab were done. Patients were divided into those who showed response to bevacizumab (bevacizumab only group) and others who were switched to the dexamethasone implant due to lack of response to bevacizumab (switching group). Volumetric OCT biomarkers such as central macular thickness (CMT), inner and outer cystoid macular edema (CME) volume, serous retinal detachment (SRD) volume, retinal volume (CME + SRD volume) within the 6-mm Early Treatment of Diabetic Retinopathy Study circle were calculated. OCT biomarkers were followed up throughout treatment. Among total of 144 eyes, 113 patients were included in the bevacizumab only group and 31 patients were included in the switching group. Compared to the bevacizumab only group, the switching group showed higher baseline CMT (558.00 ± 209.60 µm vs. 454.96 ± 125.88 µm, p = 0.003), larger inner CME (6.02 ± 1.43 mm3 vs. 5.12 ± 0.87 mm3, p = 0.004) and SRD volume (0.32 ± 0.40 mm3 vs. 0.11 ± 0.09 mm3, p = 0.015) and higher proportion of patients with SRD (58.06% vs. 31.86%, p = 0.008). In the switching group, CMT, inner CME and SRD volume all showed significant reduction after switching to the dexamethasone implant. DME with large SRD and inner nuclear layer edema volume may be more effectively treated with the dexamethasone implant than bevacizumab.

Role of Vitrectomy in Nontractional Refractory Diabetic Macular Edema.

Currently, the gold standard of diabetic macular edema (DME) treatment is anti-vascular endothelial growth factor (VEGF) injections, although a percentage of patients do not respond optimally. Vitrectomy with or without internal limiting membrane (ILM) peeling is a well-established treatment for DME cases with a tractional component while its role for nontractional cases is unclear. The aim of this study is to evaluate the role of vitrectomy with or without ILM peeling in nontractional refractory DME. We performed a retrospective review of twenty-eight eyes with nontractional refractory DME treated with vitrectomy at San Giuseppe Hospital, Milan, between 2016 and 2018. All surgeries were performed by a single experienced vitreoretinal surgeon. In 43.4% of cases, the ILM was peeled. Best corrected visual acuity and optical coherence tomography (OCT) scans were assessed preoperatively and at 6, 12, and 24 months post-vitrectomy. The mean central macular thickness improved from 413.1 ± 84.4 to 291.3 ± 57.6 μm at two years (p < 0.0001). The mean logarithm of the minimum angle of resolution logMAR best-corrected visual acuity (BCVA) improved after two years, from 0.6 ± 0.2 to 0.2 ± 0.1 (p < 0.0001). We found no difference between ILM peeling vs. no ILM peeling group in terms of anatomical (p = 0.8) and visual outcome (p = 0.3). Eyes with DME and subfoveal serous retinal detachment (SRD) at baseline had better visual outcomes at the final visit (p = 0.001). We demonstrated anatomical and visual improvement of patients who underwent vitrectomy for nontractional refractory DME with and without ILM peeling. Improvement was greater in patients presenting subretinal fluid preoperatively.

Clinical Application of Intravitreal Aflibercept Injection for Diabetic Macular Edema Comparing Two Loading Regimens.

Background and Objectives: We investigated and compared the efficacy of three and five monthly loading regimens of an intravitreal aflibercept injection (IVA) in patients with diabetic macular edema (DME). Materials and Methods: This was a retrospective study that included patients diagnosed with DME and treated with an either three or five monthly aflibercept loading regimen from July 2018 to March 2022. Information on clinical characteristics and changes in the central retinal thickness (CRT) were obtained from medical records. Results: In total, 44 eyes of 44 patients with DME treated with IVA were included in this study, with 30 eyes treated with 3-monthly loadings (three-loading group) and 14 eyes with 5-monthly loadings (five-loading group). The mean CRT significantly decreased from the baseline one month after loading in both the three-loading and five-loading groups (p < 0.001). Four cases were refractory to treatment in the three-loading group, while there were no cases of refractory DME in the five-loading group. The stability rate was significantly higher in the five-loading group at three months after loading (p = 0.033). Conclusions: Five-monthly loading regimens of IVA might be favorable for DME considering the rate of refractory cases, stable duration, and the importance of early responsiveness to IVA in DME.

Combined intravitreal dexamethasone and bevacizumab injection for the treatment of persistent diabetic macular edema (DexaBe study): a phase I clinical study

PurposeThe aim of this study is to investigate the safety of combined intravitreal injection of dexamethasone aqueous-solution (IVD) and bevacizumab (IVB) in patients with refractory diabetic macular edema (DME) and its effect on intraocular pressure (IOP), best-corrected visual acuity (BCVA) and central subfield thickness (CSFT).MethodsThis prospective study included 10 patients (10 eyes) with DME refractory to laser photocoagulation and/or anti-vascular endothelial growth factor (anti-VEGF) therapy. A complete ophthalmological examination was performed at baseline, during the first week of treatment, and monthly through week 24. Therapy consisted of monthly injections of combined IVD and IVB “pro re nata” (PRN) if CST > 300 µm. We investigated the impact of the injections on intraocular pressure (IOP), cataract development, Early Treatment Diabetic Retinopathy Study (ETDRS) best corrected visual acuity (BCVA), and central sub-foveal thickness (CSFT) measured by spectral-domain optical coherence tomography (OCT).ResultsEight patients (80%) completed 24 weeks of follow-up. Compared to baseline, mean IOP increased significantly (p < 0.05) and anti-glaucomatous eye drops were necessary for 50% of the patients, CSFT was significantly reduced at all follow-up visits (p < 0.05), although mean BCVA showed no significant improvement. One patient developed dense cataract progression and another showed vitreoretinal traction at week 24. No inflammation or endophthalmitis was observed.ConclusionTreatment of DME refractory to laser and/or anti-VEGF therapy with combined PRN IV dexamethasone aqueous solution and bevacizumab was associated with adverse effects related to the use of corticosteroids. However, there was a significant improvement in CSFT meantime best-correct visual acuity remained stable or improved in 50% of patients.

Role of Microaneurysms in the Pathogenesis and Therapy of Diabetic Macular Edema: A Descriptive Review

Background and Objectives: This study aims to elucidate the role of microaneurysms (MAs) in the pathogenesis and treatment of diabetic retinopathy (DR) and diabetic macular edema (DME), the major causes of acquired visual impairment. Materials and Methods: We synthesized the relevance of findings on the clinical characteristics, pathogenesis, and etiology of MAs in DR and DME and their role in anti-vascular endothelial growth factor (VEGF) therapy. Results: MAs, a characteristic feature in DR and DME, can be detected by fluorescein angiography, optical coherence tomography (OCT) and OCT angiography. These instrumental analyses demonstrated a geographic and functional association between MA and ischemic areas. MA turnover, the production and loss of MA, reflects the activity of DME and DR. Several cytokines are involved in the pathogenesis of MAs, which is characterized by pericyte loss and endothelial cell proliferation in a VEGF-dependent or -independent manner. Ischemia and MAs localized in the deep retinal layers are characteristic of refractory DME cases. Even in the current anti-VEGF era, laser photocoagulation targeting MAs in the focal residual edema is still an effective therapeutic tool, but it is necessary to be creative in accurately identifying the location of MAs and performing highly precise and minimally invasive coagulation. Conclusions: MAs play a distinctive and important role in the pathogenesis of the onset, progression of DR and DME, and response to anti-VEGF treatment. Further research on MA is significant not only for understanding the pathogenesis of DME but also for improving the effectiveness of treatment.