Treatment Of Diabetic Macular Edema Research Articles

Measuring the individualization potential of treatment individualization rules: Application to rules built with a new parametric interaction model for parallel-group clinical trials.

For personalized medicine, we propose a general method of evaluating the potential performance of an individualized treatment rule in future clinical applications with new patients. We focus on rules that choose the most beneficial treatment for the patient out of two active (nonplacebo) treatments, which the clinician will prescribe regularly to the patient after the decision. We develop a measure of the individualization potential (IP) of a rule. The IP compares the expected effectiveness of the rule in a future clinical individualization setting versus the effectiveness of not trying individualization. We illustrate our evaluation method by explaining how to measure the IP of a useful type of individualized rules calculated through a new parametric interaction model of data from parallel-group clinical trials with continuous responses. Our interaction model implies a structural equation model we use to estimate the rule and its IP. We examine the IP both theoretically and with simulations when the estimated individualized rule is put into practice in new patients. Our individualization approach was superior to outcome-weighted machine learning according to simulations. We also show connections with crossover and N-of-1 trials. As a real data application, we estimate a rule for the individualization of treatments for diabetic macular edema and evaluate its IP.

Lipid-based nanocarriers mediated Axitinib retinal delivery after topical instillation: Formulations setting up and in vivo evidence

Axitinib (AXB) is a multi-receptor tyrosine kinase inhibitor molecule. It acts by blocking the receptors for vascular endothelial growth factor (VEGFR) and platelet-derived growth factor (PDGFR), which are responsible for the development of neovascularization. To date, intravitreal injections of anti-VEGF have become the first-line medical treatment for diabetic macular oedema, a degeneration of diabetic retinopathy. Despite the efficacy of intravitreal injections, the complications of this type of administration are manifold. Our study aimed to design a nanotechnological formulation capable of delivering AXB to the retinal area after topical administration. Two different lipid-based formulations, namely solid lipid nanoparticles (SLN) and nanostructured lipid nanocarriers (NLC) were developed through a design of experiment (DoE) approach. The formulations possessed a mean particle size below 200 nm, low PDI values and a high drug encapsulation efficiency, thus designating them as suitable for ocular administration. Stability studies were performed at different storage conditions according to ICH guidelines. Strategies to improve AXB concentration in the retinal target were finally developed, such as using cationic lipids and increasing AXB loading in the nanocarriers. The in vivo PK studies indicated that cationic NLC loaded with AXB at 4 mM were the most efficient in delivering the drug to the retina, proposing them as a potential topical treatment for DR.

Adverse drug events in cost-effectiveness models of pharmacological interventions for diabetes, diabetic retinopathy, and diabetic macular edema: a scoping review.

The objective of this review was to examine the role of adverse drug events (ADEs) caused by pharmacological interventions in cost-effectiveness models for diabetes mellitus, diabetic retinopathy, and diabetic macular edema. Guidelines for economic evaluation recognize the importance of including ADEs in the analysis, but in practice, consideration of ADEs in cost-effectiveness models seem to be vague. Inadequate inclusion of these harmful outcomes affects the reliability of the results, and the information provided by economic evaluation could be misleading. Reviewing whether and how ADEs are incorporated in cost-effectiveness models is necessary to understand the current practices of economic evaluation. Studies included were published between 2011-2022 in English, representing cost-effectiveness analyses using modeling framework for pharmacological interventions in the treatment of diabetes mellitus, diabetic retinopathy, or diabetic macular edema. Other types of analyses and other types of conditions were excluded. The databases searched included MEDLINE (PubMed), CINAHL (EBSCOhost), Scopus, Web of Science Core Collection, and NHS Economic Evaluation Database. Gray literature was searched via the National Institute for Health and Care Excellence, European Network for Health Technology Assessment, the National Institute for Health and Care Research, and the International Network of Agencies for Health Technology Assessment. The search was conducted on January 1, 2023. Titles and abstracts were screened for inclusion by 2 independent reviewers. Full-text review was conducted by 3 independent reviewers. A data extraction form was used to extract and analyze the data. Results were presented in tabular format with a narrative summary, and discussed in the context of existing literature and guidelines. A total of 242 reports were extracted and analyzed in this scoping review. For the included analyses, type 2 diabetes was the most common disease (86%) followed by type 1 diabetes (10%), diabetic macular edema (9%), and diabetic retinopathy (0.4%). The majority of the included analyses used a health care payer perspective (88%) and had a time horizon of 30 years or more (75%). The most common model type was a simulation model (57%), followed by a Markov simulation model (18%). Of the included cost-effectiveness analyses, 26% included ADEs in the modeling, and 13% of the analyses excluded them. Most of the analyses (61%) partly considered ADEs; that is, only 1 or 2 ADEs were included. No difference in overall inclusion of ADEs between the different conditions existed, but the models for diabetic retinopathy and diabetic macular edema more often omitted the ADE-related impact on quality of life compared with the models for diabetes mellitus. Most analyses included ADEs in the models as probabilities (55%) or as a submodel (40%), and the most common source for ADE incidences were clinical trials (65%). The inclusion of ADEs in cost-effectiveness models is suboptimal. The ADE-related costs were better captured than the ADE-related impact on quality of life, which was most pronounced in the models for diabetic retinopathy and diabetic macular edema. Future research should investigate the potential impact of ADEs on the results, and identify the criteria and policies for practical inclusion of ADEs in economic evaluation.

Real-World Use of Off-Label MVASI in the Treatment of Patients With Neovascular AMD and DME.

The purpose of this study was to evaluate the efficacy and safety of bevacizumab-awwb in the off-label treatment of neovascular age-related macular degeneration (n-AMD) and diabetic macular edema (DME). All patients with n-AMD and DME treated in the maintenance phase according to the "treat and extend" strategy, who underwent forced drug substitution from bevacizumab to bevacizumab-awwb from October 2022 to April 2023 at the Tor Vergata Polyclinic in Rome, were evaluated in a retrospective study. The primary outcome was changes in central retinal thickness (CRT) over time following drug substitution. The secondary outcomes were variations in drug durability, best corrected visual acuity (BCVA) and retinal fluid, and the incidence of drug-related local and systemic serious adverse events. Of 80 eyes of 76 patients with n-AMD and 55 eyes of 44 patients with DME included, before and after drug substitution, the average CRT did not statistically differ; the proportion of patients within time intervals of q8, q12, and q16 was not different; and the mean BCVA remained constant. Of a cumulative 3496 bevacizumab-awwb treatments (2154 for patients with n-AMD and 1342 for patients with DME), no local severe complications were detected. Out of a total of 544 patients (342 affected by n-AMD and 202 affected by DME), no serious adverse events were reported. In our cohort of patients with n-AMD and DME in the maintenance phase, bevacizumab-awwb seems to represent a viable and cost-effective intravitreal therapy with comparable efficacy and safety to the originator. This study provides a preliminary assessment of the efficacy and safety of intravitreal bevacizumab-awwb, which is widely used off-label in retinal vascular diseases.

The effect of intravitreal antiangiogenic diabetic macular edema treatment on the corneal endothelium cell count

BACKGROUND: Antiangiogenic treatment of diabetic macular edema is a first-line therapy in modern ophthalmology. Novel antiangiogenic drugs are increasingly being developed to improve treatment results and solve certain issues. However, owing to the advent of new drugs, more questions arise about their effect on the patient’s retina and other structures of the eye, such as the cornea. AIM: The study aimed to investigate the effect of intravitreal administration of the anti-VEGF drug brolucizumab on the corneal endothelium in patients with diabetic macular edema. METHODS: 106 patients (106 eyes) were included in the prospective study: 31 men and 75 women. The main group consisted of 56 patients (56 eyes) were included in the prospective study: 14 men and 42 women with different stages of diabetic retinopathy with diabetic macular edema, the average age of patients was 62.2±8.4 years. The average number of endothelial cells per 1 mm2 in these patients before the loading dose of brolucizumab was 2378.9±393.3 cl/mm2. The control group included 50 patients (50 eyes) without diabetes who did not receive intravitreal injections or any other surgical interventions on the examined eye for 1 year. All patients underwent endothelial microscopy using the Tomey EM-4000 endothelial microscope (REN 2017/6294), estimated: CD (the number of endothelial cells per 1 mm2); CCT (the central thickness of the cornea, microns); CV (the coefficient of variation, %); 6A (the proportion of hexagonal cells, %). All study participants received intravitreal injections of brolucizumab in a volume of 0.05 ml (5 injections with an interval of 6 weeks). RESULTS: In the main group before intravitreal injections, the indices of the central corneal thickness and the number of endothelial cells per 1 mm2 were 549.7±30.1 microns and 2378.9±393.3 cells/mm2, respectively. After a course of antiangiogenic diabetic macular edema therapy, the central thickness of the cornea was 548.2±30.6 microns, and the number of endothelial cells per 1 mm2 was 2382.3±424.9 cells/mm2. The indicators CV (coefficient of variability, %) and 6A (proportion of hexagonal cells, %) before the start of intravitreal injections were 36.9±5% and 46.8±6.3%, respectively, after the introduction of the loading dose drugs, the average values were 37.9±4.3% and 45.8±6.3%. Changes in all indicators were not static significant. CONCLUSION: The use of brolucizumab as therapy in patients with diabetic macular edema did not cause a negative effect on the cornea, there were no statistically significant changes in the central thickness of the cornea, the number of endothelial cells per 1 mm2, the coefficient of variation and the proportion of hexagonal cells.

Clinical observation of the subthreshold micropulse laser combined with ranibizumab for treatment of diabetic macular edema

Objective: To evaluate the efficacy and safety of the subthreshold micropulse laser (SMPL) combined with ranibizumab in treating diabetic macular edema (DME). Methods: This was a prospective randomized controlled study. Patients diagnosed with DME in the Ophthalmology Department of Beijing Hospital were enrolled from January 2020 to December 2022. Patients were randomized in a ratio of 1∶1 using a table of random numbers into the ranibizumab monotherapy group and the SMPL combined with ranibizumab therapy group. We compared the changes of best-corrected visual acuity, central macular thickness measured by optical coherence tomography and optical coherence tomography angiography parameters, including the vessel density of the superficial and deep capillary plexus (DCP), foveal avascular zone size and peripapillary vessel density, at baseline, 6 and 12 months after the treatment. After 12 months of follow-up, fundus fluorescein angiography results, adverse events, and the number of injections or laser therapies were recorded. The Fisher's exact test and group t-test were used for statistical analysis. Results: Seventy-two patients (72 eyes) were enrolled, with a mean age of (61.1±8.2) years. Patients in the combination therapy group included 19 males and 17 females, while patients in the ranibizumab monotherapy group were 17 males and 19 females. There was no statistically significant difference in baseline characteristics between the two groups (P>0.05). A significant improvement in best-corrected visual acuity was shown in both groups at 6 and 12 months [(58.5±12.9) and (58.2±12.2) ETDRS letters in the combination therapy group, and (63.3±13.1) and (63.8±12.5) ETDRS letters in the ranibizumab monotherapy group]. A significant reduction in central macular thickness was shown in both groups at 6 and 12 months [(451.0±185.5) and (380.4±159.3)μm in the combination therapy group, and (387.5±135.5) and (372.8±146.1)μm in the ranibizumab monotherapy group]. However, there was no significant difference between groups at each timepoint (all P>0.05). At 12 months, the vessel density of the superficial capillary plexus showed no statistical difference compared to the baseline value in each group or between groups (42.6%±5.9% in the ranibizumab monotherapy group and 42.2%±5.5% in the combination therapy group, P>0.05). The vessel density of the DCP in the combination therapy group significantly increased to 47.5%±5.6% at 12 months, significantly different from that in the ranibizumab group (43.4%±5.1%; P<0.05). The foveal avascular zone size in the ranibizumab monotherapy group reduced to (0.32±0.13) mm2, significantly different from that in the combination therapy group [(0.34±0.16) mm2] at 12 months (P<0.05). Patients in the ranibizumab monotherapy group received (7.3±2.5) intravitreal injections, while patients in the combination therapy group received 3 injections. No unfavorable outcomes on fundus fluorescein angiography or systemic or topical severe adverse events were observed during the follow-up. Conclusions: The SMPL combined with intravitreal ranibizumab injections was effective and safe in treating DME patients. The combination treatment significantly reduced the number of injections and improved the vessel density of the DCP and macular ischemia, compared to the ranibizumab monotherapy.

Prediction of Long-Term Treatment Outcomes for Diabetic Macular Edema Using a Generative Adversarial Network.

The purpose of this study was to analyze optical coherence tomography (OCT) images of generative adversarial networks (GANs) for the prediction of diabetic macular edema after long-term treatment. Diabetic macular edema (DME) eyes (n = 327) underwent anti-vascular endothelial growth factor (VEGF) treatments every 4 weeks for 52 weeks from a randomized controlled trial (CRTH258B2305, KINGFISHER) were included. OCT B-scan images through the foveal center at weeks 0, 4, 12, and 52, fundus photography, and retinal thickness (RT) maps were collected. GAN models were trained to generate probable OCT images after treatment. Input for each model were comprised of either the baseline B-scan alone or combined with additional OCT, thickness map, or fundus images. Generated OCT B-scan images were compared with real week 52 images. For 30 test images, 28, 29, 15, and 30 gradable OCT images were generated by CycleGAN, UNIT, Pix2PixHD, and RegGAN, respectively. In comparison with the real week 52, these GAN models showed positive predictive value (PPV), sensitivity, specificity, and kappa for residual fluid ranging from 0.500 to 0.889, 0.455 to 1.000, 0.357 to 0.857, and 0.537 to 0.929, respectively. For hard exudate (HE), they were ranging from 0.500 to 1.000, 0.545 to 0.900, 0.600 to 1.000, and 0.642 to 0.894, respectively. Models trained with week 4 and 12 B-scans as additional inputs to the baseline B-scan showed improved performance. GAN models could predict residual fluid and HE after long-term anti-VEGF treatment of DME. The implementation of this tool may help identify potential nonresponders after long-term treatment, thereby facilitating management planning for these eyes.

Long-term visual outcomes and fluid compartment changes in limited-early versus early response to anti-VEGF treatment for diabetic macular edema

ObjectiveThis study assessed best visual acuity (BVA) and central subfield thickness (CST) outcomes for LER (limited early responder) and ER (early responder) patients at 24 and 36 months. DesignRetrospective chart review ParticipantsOne-hundred and twelve patients characterized at 3 months after their first anti-VEGF injections as either LER if they met the anatomic criteria (aLER = CST reductions ≤ 10%), visual criteria (vLER = ETDRS letter gains < 5 letter), or both (cLER). All other patients were classified as ER (aER/vER/cER). MethodsVariables collected include CST and ETDRS letters at baseline, 3, 24, and 36 months following injections, comorbidities, smoking status, demographics, baseline systemic factors, and the type and quantity of anti-VEGF injections. Analyses were performed using Welch's t-test, multivariable linear and multivariable logistic regression. ResultsBVA changes from 3 months were significant between cLER versus cER and vLER versus vER groups (p < 0.05). There was a greater decrease in mean BVA from 3 months to 36 months in the cER group compared to the cLER group. Alternatively, mean BVA decreased in the vER cohort, while the vLER cohort slightly increased. CST changes from 3 months were statistically significant (p < 0.01) between all LER and ER groups with LER groups showing greater reductions compared to ER counterparts. BVA and CST changes from baseline to 24 and 36 months were not significant after controlling for baseline differences between LER and ER groups. ConclusionResults highlight the value of long-term anti-VEGF treatment and the need to further explore options that may lead to continued BVA improvements beyond 3 months.

Summary of Research: Cost‑Effectiveness of Faricimab in the Treatment of Diabetic Macular Oedema (DMO): A UK Analysis.

This is a summary of the original article ‟Cost‑Effectiveness of Faricimab in the Treatment of Diabetic Macular Oedema (DMO): A UK Analysis". DMO, a serious eye condition that can lead to vision loss in people with diabetes, is a significant health concern and a lack of knowledge exists about the cost-effectiveness (the balance of a treatment's cost and its effectiveness) of new treatments. This research assessed the cost-effectiveness of a new medication named faricimab, using a mathematical model that simulated the progression of DMO and its treatment over 25 years. The model compared faricimab against relevant therapeutic alternatives for DMO in the UK, including ranibizumab, aflibercept, and bevacizumab. The research discovered that faricimab could offer improved vision results and be cost saving or cost-effective. It also suggested that faricimab could lessen the strain on healthcare services due to its less frequent dosing schedule. Overall, such findings suggest that faricimab is a promising new treatment option for DMO that could benefit patients and the healthcare system. This could have implications for future treatment guidelines and the management of DMO in clinical practice.

Aflibercept 8 mg/0.07 mL (Eylea HD)

CADTH recommends that aflibercept 8mg/ 0.07 mL (Eylea HD) be reimbursed by public drug plans for treating diabetic macular edema (DME) if certain conditions are met. Eylea HD should only be covered to treat adult patients with DME due to type 1 or 2 diabetes mellitus, with a central retinal thickness (CRT) of 300 µm or more (or 320 µm or more on the Spectralis scan) and a score of 78 to 24 letters in the eye with decreased vision primarily due to DME according to the early treatment diabetic retinopathy study (ETDRS) scoring system. Eylea HD should only be reimbursed if it is prescribed by an ophthalmologist with experience managing DME, it is used in combination with other antivascular endothelial growth factor (VEGF) drugs, and the cost of Eylea HD is not more than the least costly anti-VEGF drug covered by the public drug plans for the treatment of DME. Eylea HD should only be authorized for reimbursement for 12 months the first time it is used. Eylea HD should no longer be reimbursed if injections need to be given more frequently than every 12 weeks or if the patient experiences &gt; 10 letter loss in best-corrected visual acuity (BCVA) from week 12 in association with persistent or worsening DME and &gt; 50 μm increase in CRT from week 12.

Sodium-glucose cotransporter 2 inhibitor therapy reduces the administration frequency of steroid injection in patients with diabetic macular edema: A cohort study using the Japanese health insurance claims database.

Severe diabetic macular edema (DME) is often resistant to anti-vascular endothelial growth factor therapy. Steroids are particularly effective at reducing edema by suppressing inflammation; they are also used as an alternative to expensive anti-vascular endothelial growth factor therapy in some patients. Therefore, the use of steroids in DME reflects an unmet need for anti-vascular endothelial growth factor therapy. Notably, triamcinolone acetonide (TA) injections are widely used in Japan. Here, we evaluated the frequency of TA as an indicator of the efficacy of sodium-glucose cotransporter 2 inhibitors (SGLT2is) in DME treatment using a health insurance claims database. In this cohort study, we retrospectively analyzed the health insurance claims data of 11 million Japanese individuals from 2005 to 2019. The frequency and duration of TA injection after the initiation of SGLT2is or other antidiabetic drugs were analyzed. Among the 2,412 matched patients with DME, the incidence rate of TA injection was 63.8 times per 1,000 person-years in SGLT2i users and 94.9 times per 1,000 person-years in non-users. SGLT2is reduced the risk for the first (P = 0.0024, hazard ratio 0.66, 95% confidence interval 0.50-0.87), second (P = 0.0019, hazard ratio 0.53, 95% confidence interval 0.35-0.80) and third TA (P = 0.0053, hazard ratio 0.44, 95% confidence interval 0.25-0.80) injections. A subanalysis of each baseline characteristic of the patients showed that SGLT2is were effective regardless of the background factors. The use of SGLT2is reduced the frequency of TA injection in patients with DME. Therefore, SGLT2i therapy might be a novel, noninvasive and low-cost adjunctive therapy for DME.

Résultats anatomiques et fonctionnels du protocole thérapeutique « 3 + PRN » dans le traitement de l’œdème maculaire diabétique

Purpose: To evaluate the anatomical and functional results of the “3 + PRN” protocol in the treatment of diabetic macular edema (DME), determine the predictive factors for good final visual acuity, and compare it to other protocols.Materials and methods: We conducted a retrospective, descriptive, comparative, cross-sectional study of patients with DME, which we dubbed HTSM. All patients were treated with three monthly initial intravitreal injections (IVT) of 1.25 mg bevacizumab and followed according to the pro re nata (PRN) protocol for a period of 3 years. The protocol was based on a monthly monitoring schedule for the first 3 months, then increasingly spaced out over time. “On-demand” treatment was indicated with resumption of bevacizumab IVT in the event of worsening of DME.Results: A total of 52 patients were included. The mean age was 65 years. Type 2 was the most frequently observed type of diabetes. The mean duration of the PRN protocol was 6 months, and the mean number of injections was 6. The mean visual acuity (VA), initially 1/10, improved to 3/10 by the conclusion of the 3+PRN protocol, with an improvement of more than 5 letters in 77.6% of cases. The mean initial central macular thickness (CMT) was 451.5 µm. The final mean EMC decreased to 298.5 µm, which corresponds to a reduction of 153 µm compared to the initial value. The mean subfoveal choroidal thickness, initially 304.2 µm, decreased to a mean of 284.5 µm at completion. Comparative analysis of the results before and after the PRN protocol confirmed the existence of a statistically significant correlation between VA and CMT (p<0.05). No correlation was observed between age and visual acuity or between initial and final VA. The analysis of the various tomographic parameters and VA revealed a significantly better visual improvement in the group in whom the external limiting membrane (MLE) and ellipsoid zone (ZE) were intact (p = 0.04), as well as in the group in whom serous retinal detachment (SRD) was absent (p<0.001). Posterior vitreous detachment (PVD) was the most frequently observed vitreomacular anomaly. The final VA was similar in the groups with and without PVD (p = 0.04).Conclusion: The 3+PRN protocol is effective both functionally and tomographically in the treatment of DME. Various tomographic parameters might influence therapeutic efficacy. However, further in-depth studies are needed to better investigate these parameters.

Intravitreal Lucentis (Ranibizumab) as A Treatment for Diffuse Diabetic Macular Edema

Introduction: Humanized anti-VEGF (Vascular endothelial growth factor) antibody fragment Lucentis (Ranibizumab) is prescribed to treat neovascular (wet) age-related macular degeneration, diabetic macular edema, diabetic retinopathy, and myopic choroidal neovascularization. It is also used to treat macular edema following retinal vein occlusion. Objective: This study was carried out to evaluate the anatomic effect and visual acuity response following intravitreal Lucentis (Ranibizumab). Methodology: In this investigation, diffuse diabetic macular edema was present in 30 eyes belonging to 30 patients with stable diabetes mellitus. Every eye had undergone argon laser photocoagulation, either Focal, Grid, or pan-retinal photocoagulation (PRP), for a minimum of three months. The patients with a mean age was 58.13±5.17 years were treated with two intravitreal injections of 0.5 mg of ranibizumab in 0.05 ml spaced four weeks apart. A skilled ophthalmologist assessed each patient's best-corrected visual acuity (BCVA), also assessed their central macular thickness (CMT) using optical coherence tomography, and assessed their diabetic retinopathy at both the baseline and follow-up sessions. The results: The results showed that the means of BCVA were significantly (P&lt;0.01) decreased from baseline (1.189±0.077 logMAR) to 1 month (0.162±0.058 logMAR) and 3 months (1.109±0.049 logMAR) after injection. Also the results revealed that the mean of CMT were significantly (P&lt;0.01) declined from the baseline (477.47±151.32 µm) to 1 month (438.27±115.68 µm) and 3 month (396.80±115.26 µm) after treatment. Conclusions: The study concluded that after three months of the second injection of Lucentis (ranibizumab) significantly reduced central macular thickness and improved visual acuity, then diffuse diabetic macular edema is significantly improved and treated using Lucentis (ranibizumab).

Advancements in the Treatment of Diabetic Macular Edema: Current Strategies and Future Directions

This narrative review examines current and emerging treatment strategies for diabetic macular edema (DME), a complication of diabetic retinopathy characterised by fluid accumulation in the macula, which can lead to vision impairment. The incidence of DME is particularly high in patients with long-standing diabetes and advanced retinopathy. The current treatment options for DME include anti-vascular endothelial growth factor (anti-VEGF) agents, corticosteroids, and laser therapies. Anti-VEGF agents, including bevacizumab, ranibizumab, aflibercept, and the more recently developed brolucizumab and faricimab, have been demonstrated to reduce macular thickness and improve visual acuity. Brolucizumab offers the advantage of fewer injections due to its longer duration of action, although it carries a higher risk of ocular inflammation compared to other anti-VEGF agents. The dual inhibition of the VEGF and angiopoietin-2 (Ang-2) pathways by faricimab may enhance vascular stability and reduce inflammation, potentially improving patient outcomes. Steroid therapies, including dexamethasone, fluocinolone acetonide, and triamcinolone acetonide, represent an alternative for patients who do not respond adequately to anti-VEGF treatment. Laser therapies, including focal, navigated, and subthreshold laser treatments, remain a crucial component in the management of DME, with the ability to seal leaking vessels and reduce fluid accumulation. In order to achieve the best outcomes for patients, it is essential to continue to advance these treatment modalities and adopt a personalised, multifaceted approach.

Timing of Switching to Steroid Implants in Cases of Recalcitrant Diabetic Macular Edema Not Responding to Anti-vascular Endothelial Growth Factor (VEGF) Therapy: A Real-World Study.

Purpose The purpose of this study is to examine the impact of the timing of the steroid switch on both visual and anatomical outcomes in diabetic macular edema (DME) eyes that have shown an inadequate response to multiple intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections. In the treatment of DME, anti-VEGF injections are typically the initial course of action. However, in cases where DME persists despite anti-VEGF treatment, intravitreal dexamethasone implants (Ozurdex®, Allergan Inc., Irvine, CA) are often utilized. Despite this, there remains a lack of consensus regarding the optimal timing for transitioning to steroid treatment. This study aims to shed light on the potential benefits of adjusting the timing of the steroid switch in cases of recalcitrant DME. Methods The eyes (n = 105) of 77 patients with recalcitrant DME were included in this retrospective, interventional, comparative study comprising three groups: participants switched to steroid implants after three anti-VEGF injections (Group I), four to six anti-VEGF injections (Group II), and more than six anti-VEGF injections (Group III). Anti-VEGF treatment failure was defined as a central retinal thickness (CRT) of ≥300 microns and/or a lack of visual improvement (≤1 line of visual gain according to Snellen acuity). The last follow-up took place after 10-12 weeks of Ozurdex® injections. Results Improvement was observed in 19 eyes (46%), 17 eyes (50%), and 10 eyes (33%) in Groups I, II, and III, respectively, after switching to dexamethasone implants. The best overall results (an improvement in vision and stabilization) were seen in Group II (32 eyes, 94%). The decrease in CRT was statistically significant in all three groups. Conclusion Intravitreal dexamethasone implants improved functional and morphological outcomes in anti-VEGF-resistant DME eyes. After four to six anti-VEGF injections, switching to a steroid implant resulted in the best functional results.

Effect of ranibizumab combined with laser photocoagulation in the treatment of diabetic macular edema.

To explore the clinical effect of ranibizumab combined with laser photocoagulation (LP) in treating diabetic macular edema (DME). We retrospectively reviewed the clinical data of 118 patients with DME admitted to The Affiliated Eye Hospital of Nanchang University from May 2021 to March 2023. Among them, 38 patients received LP alone (Laser-group), 39 patients received ranibizumab alone (Ranibizumab-group), and 41 patients received LP combined with ranibizumab (Combined-group). The improvement of macular edema (ME), visual acuity, and complications between the groups were compared. The time of ME regression, exudation absorption and fundus hemorrhage absorption in the Combined-group was shorter than in the Laser-group and the Ranibizumab-group (P<0.05). After treatment, the CMT and RNV of the three groups decreased compared to pretreatment levels and were lower in the Combined-group compared to the Laser-group and the Ranibizumab-group (P<0.05). BCVA increased after the treatment in all groups, and was markedly higher in the Combined-group than in the Laser and the Ranibizumab-groups (P<0.05). NO were higher in the Combined-group compared to the Laser-group and the Ranibizumab-group. The post-treatment VEGF levels decreased in all groups, and were significantly lower in the Combined-group compared to the Laser-group and the Ranibizumab-group (P<0.05). The incidence of complications in the Combined-group was lower than in the Laser-group and the Ranibizumab-group (P<0.05). Compared to ranibizumab or LP alone, ranibizumab combined with LP is more effective in reducing ME in patients with DEM, and is associated with fewer complications.

IMPACT OF TREATMENT OF DIABETIC MACULAR EDEMA ON VISUAL IMPAIRMENT IN PEOPLE WITH TYPE 2 DIABETES MELLITUS: A COMPREHENSIVE SYSTEMATIC REVIEW AND METAAANALYSIST STUDY

Background: Diabetic retinopathy (DR) and diabetic macular edema (DME) are among the most significant and disabling chronic complications of diabetes mellitus. DME is an important cause of severe vision loss in type 2 diabetes. Hyperpermeability of retinal blood vessels and subsequent formation of edema and hard exudates are the key clinical features. Method: This systematic review and meta-analysis, conducted following PRISMA guidelines and employing the PICO format, aim to explore about impact of treatment of diabetic macular edema on visual impairment in people with type 2 diabetes mellitus, focusing on treatment, complications, and prognosis. Inclusion criteria encompass diverse study designs (RCTs, observational, quasi-experimental, and case-control studies) investigating impact of treatment of diabetic macular edema on visual impairment in people with type 2 diabetes mellitus among treatment, complications, and prognosis, while exclusion criteria filter out studies lacking relevance to impact of treatment of diabetic macular edema on visual impairment in people with type 2 diabetes mellitus. Result: After conducting three levels of screening, the results of our search in Pubmed get 6 articles, whereas the results of our search on SageJournal get 42 articles, on Lancet 21, and on Scient direct get 60 articles. Records remove before screening are 91, so we get 78 articles for screening. After we screened based on record exclude, we compiled a total of 10 papers. We included four research that met the criteria. Conclusion: There is a particularly robust response to anti-VEGF therapy in both groups when glycemic control is optimized, highlighting the critical importance of communication between the physicians managing the DME and those managing systemic diabetes control. Improving our understanding of the factors that contribute to anti-VEGF response for DME therapy may help to enhance DME treatment outcomes, particularly through the concerted coordinated efforts of the treating retina specialist and the endocrinologist or primary care physician.

Beyond VEGF: Angiopoietin-Tie Signaling Pathway in Diabetic Retinopathy.

Complications from diabetic retinopathy such as diabetic macular edema (DME) and proliferative diabetic retinopathy (PDR) constitute leading causes of preventable vision loss in working-age patients. Since vascular endothelial growth factor (VEGF) plays a major role in the pathogenesis of these complications, VEGF inhibitors have been the cornerstone of their treatment. Anti-VEGF monotherapy is an effective but burdensome treatment for DME. However, due to the intensive and burdensome treatment, most patients in routine clinical practice are undertreated, and therefore, their outcomes are compromised. Even in adequately treated patients, persistent DME is reported anywhere from 30% to 60% depending on the drug used. PDR is currently treated by anti-VEGF, panretinal photocoagulation (PRP) or a combination of both. Similarly, a number of eyes, despite these treatments, continue to progress to tractional retinal detachment and vitreous hemorrhage. Clearly there are other molecular pathways other than VEGF involved in the pathogenesis of DME and PDR. One of these pathways is the angiopoietin-Tie signaling pathway. Angiopoietin 1 (Ang1) plays a major role in maintaining vascular quiescence and stability. It acts as a molecular brake against vascular destabilization and inflammation that is usually promoted by angiopoietin 2 (Ang2). Several pathological conditions including chronic hyperglycemia lead to Ang2 upregulation. Recent regulatory approval of the bi-specific antibody, faricimab, may improve long term outcomes in DME. It targets both the Ang/Tie and VEGF pathways. The YOSEMITE and RHINE were multicenter, double-masked, randomized non-inferiority phase 3 clinical trials that compared faricimab to aflibercept in eyes with center-involved DME. At 12 months of follow-up, faricimab demonstrated non-inferior vision gains, improved anatomic outcomes and a potential for extended dosing when compared to aflibercept. The 2-year results of the YOSEMITE and RHINE trials demonstrated that the anatomic and functional results obtained at the 1 year follow-up were maintained. Short term outcomes of previously treated and treatment-naive eyes with DME that were treated with faricimab during routine clinical practice suggest a beneficial effect of faricimab over other agents. Targeting of Ang2 has been reported by several other means including VE-PTP inhibitors, integrin binding peptide and surrobodies.

Comparative Effectiveness of Glucagon-Like Peptide-1 Receptor Agonists, Sodium-Glucose Cotransporter 2 Inhibitors, Dipeptidyl Peptidase-4 Inhibitors, and Sulfonylureas for Sight-Threatening Diabetic Retinopathy

To investigate whether the choice of glucose-lowering agent for type 2 diabetes (T2D) impacts a patient's risk of developing sight-threatening diabetic retinopathy complications. Retrospective observational database study emulating an idealized target trial. Adult (≥21 years) enrollees in United States commercial, Medicare Advantage, and Medicare fee-for-service plans from January 1, 2014, to December 31, 2021, with T2D and moderate cardiovascular disease (CVD) risk who had no baseline history of advanced diabetic retinal complications, initiating treatment with glucagon-like peptide-1 receptor agonists (GLP-1 RA), sodium-glucose cotransporter 2 inhibitors (SGLT2i), dipeptidyl peptidase-4 inhibitors (DPP-4i), and sulfonylureas. We used inverse propensity scoring weights in time-to-event Cox proportional hazards models. Treatment for either diabetic macular edema or proliferative diabetic retinopathy. The final study population included 371 698 patients, of whom 42 265 initiated GLP-1 RA, 53 476 initiated SGLT2i, 78 444 initiated DPP-4i, and 197 513 initiated sulfonylurea agents. The probability of treatment for sight-threatening retinopathy within 2 and 5 years was 0.3% and 0.7% for patients initiating SGLT2i (median follow-up 830 [interquartile range (IQR), 343-1401] days), 0.4% and 1.0% for GLP-1 RA (669 [IQR, 256-1167] days), 0.4% and 0.9% for DPP-4i (1263 [IQR, 688-1938] days), and 0.5% and 1.2% for sulfonylurea (1223 [IQR, 662-1879] days). Sodium-glucose cotransporter 2 inhibitors use was associated with a lower risk of treatment for sight-threatening retinopathy compared with all other medication classes, including GLP-1 RA (hazard ratio [HR], 0.73; 95% confidence interval [CI], 0.55-0.97), DPP-4i (HR, 0.79; 95% CI, 0.64-0.97), and sulfonylurea (HR, 0.61; 95% CI, 0.50-0.74). Glucagon-like peptide-1 receptor agonists use was associated with a similar risk of sight-threatening retinopathy as DPP-4i (HR, 1.07; 95% CI, 0.85-1.35) and sulfonylurea (HR, 0.83; 95% CI, 0.67-1.03). Sodium-glucose cotransporter 2 inhibitors use was associated with a lower risk of sight-threatening diabetic retinopathy among adults with T2D and moderate CVD risk compared with other glucose-lowering therapies. Glucagon-like peptide-1 receptor agonists does not confer increased retinal risk, relative to DPP-4i and sulfonylurea medications. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Patient Experience Survey of Anti-Vascular Endothelial Growth Factor Treatment for Neovascular Age-Related Macular Degeneration and Diabetic Macular Edema.

Understanding patient perspectives of treatment may improve adherence and outcomes. This study explored real-world patient experiences with anti-vascular endothelial growth factor (anti-VEGF) treatment for diabetic macular edema (DME) and neovascular age-related macular degeneration (nAMD). This multinational, non-interventional, quantitative, cross-sectional, observational survey assessed treatment barriers/burden, patient-reported visual functioning, and treatment satisfaction in DME and nAMD patients in the USA, the UK, Canada, France, Italy, and Spain. Treatment patterns and visual outcomes were extracted from medical charts. Regression models evaluated relationships between adherence, total missed visits, number of anti-VEGF injections, and clinical and patient-reported outcomes for visual functioning. Association between treatment satisfaction and aspects of burden were assessed. The survey was completed by 183 DME and 391 nAMD patients. Patients had moderately high vision-related functioning (25-item National Eye Institute Visual Functioning Questionnaire score: mean = 74.8) and were satisfied with their current treatment (mean total score: Macular Disease Treatment Satisfaction Questionnaire = 59.2; Retinopathy Treatment Satisfaction Questionnaire = 61.3). Treatment satisfaction scores were worse with higher time-related impacts of treatment (nAMD/DME), higher impacts on finances and daily life (nAMD), negative impacts on employment and lower expectations for treatment effectiveness (DME). Most patients reported ≥1 barrier (66.1% DME, 49.2% nAMD patients) related to treatment (35.0%), clinic (32.6%), and COVID-19 (21.1%). Moreover, 44.9% of patients reported some impairment in activities of daily living. Work absenteeism was observed among &gt;60% of working patients. Nearly one-quarter (24.2%) of patients needed ≥1 day to recover from intravitreal injections; most reported ≥30 min of travel time (73.7%) and clinic wait time (54.2%). In unadjusted univariable analyses, treatment adherence (vs. nonadherence) was related to higher most recent visual acuity (β = 8.98 letters; CI, 1.34-16.62) and lower odds of visual acuity below driving vision (≤69 letters) (OR = 0.50; CI, 0.25-1.00). More durable treatments with reduced frequency of injections/visits may reduce treatment burden and improve patient satisfaction, which may enhance adherence and visual outcomes.