Treatment Of Diabetic Macular Edema Research Articles

Pro Re Nata brolucizumab for early onset and treatment-naïve diabetic macular edema: A prospective study.

To determine the efficacy and safety of brolucizumab therapy administered on a pro re nata (PRN) basis without loading dose in treatment naïve patients with diabetic macular edema (DME) for 1 year follow-up. Patients with recent DME (<6 months) received a mandatory brolucizumab injection at inclusion and other injections could be given on a PRN basis with an 8-week interval (between injections) at minimum. Rescue therapy with other anti-VEGF was possible in case of incomplete DME resolution after the second brolucizumab with a minimum of 1-month treatment free interval between 2 injections. The primary outcome measure was the change in (BCVA) at 12 months. Secondary outcome measures included the change in central subfield thickness (CST), the change in hard exudate surface area and microaneurysms at 1 year. A total of 53 patients were included. At 12 months, the mean (SD) number of injections was 2.6 (0.8) in addition to the first mandatory injection. The mean (SD) interval between 2 consecutive injections was 3.2 (1.4) months. The mean (SD) BCVA improved from 0.62 (0.1) logMAR to 0.40 (0.16) logMAR (p = 0.012). The mean CST reduced from 397.0 (47.2) µm to 224.5 (28.1) µm (p = 0.013). The hard exudate surface area decreased significantly (p = 0.012) as did microaneurysms (p = 0.02). Seven patients required at least 1 rescue therapy. No patients experienced intra-ocular inflammatory adverse events. Brolucizumab therapy for DME is a safe and effective modality for the treatment of recent DME and has the potential to reduce the number of injections.

Optimizing Diabetic Macular Edema Treatment: A Meta-Analysis of Subthreshold Micropulse Laser and Anti-Vascular Endothelial Growth Factor Combination Therapy.

Background: Diabetic macular edema (DME) is the primary cause of visual impairment in individuals with diabetes. Anti-vascular endothelial growth factor (VEGF) is the current first-line treatment for DME owing to its effectiveness. However, frequent anti-VEGF injections may be inconvenient for patients. Therefore, this study aimed to investigate whether the addition of subthreshold micropulse laser (SML) to anti-VEGF therapy could reduce the requirement for anti-VEGF injections while maintaining the treatment efficacy for DME. Methods: Clinical trials retrieved from the databases of PubMed, EMBASE, and the Cochrane Library were evaluated to determine the effectiveness of combination treatment with SML and anti-VEGF medication compared with that of anti-VEGF treatment alone. The primary outcome measures were the changes in CMT, best-corrected visual acuity (BCVA), and the total number of intravitreal injections (IVIs). Results: The IVI + SML group revealed a substantial increase in the logarithm of the minimum angle of the resolution BCVA and a reduction in CMT at the 12-month follow-up (BCVA: random-effects; mean difference [MD], -0.05; 95% confidence interval [CI]: -0.10 to -0.01; p-value = 0.28, and CMT: random-effects; MD, -18.27; 95% confidence interval, -27.36 to -9.18; p-value = 0.20). The number of required IVIs in the IVI + SML group was lower than that in the IVI only group (random-effects; MD, -2.22; 95% CI: -3.13 to -1.31; p-value < 0.01). Conclusions: Combining SML therapy with anti-VEGF injections may reduce the total number of injections required, improve VA, and reduce CMT at the 12-month follow-up. Although the included studies used different SML regimens and anti-VEGF agents, this review indicates that the application of additional SML therapy results in positive clinical outcomes.

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.

Assessment of Retinal Microvascular Changes by Oct Angiography after use of Argon Micropulse Laser Versus Traditional Argon Laser for Treatment of Diabetic Macular Edema

Assessment of Retinal Microvascular Changes by Oct Angiography after use of Argon Micropulse Laser Versus Traditional Argon Laser for Treatment of Diabetic Macular Edema

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.

Potential in the treatment of neovascular Age-related Macular Degeneration and Diabetic Macular Edema in Poland. The population needs and access to therapy

Potential in the treatment of neovascular Age-related Macular Degeneration and Diabetic Macular Edema in Poland. The population needs and access to therapy

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.

Early Recurrence Following Intravitreal Ranibizumab Versus Aflibercept for Treatment of Egyptian Diabetic Macular Edema

Early Recurrence Following Intravitreal Ranibizumab Versus Aflibercept for Treatment of Egyptian Diabetic Macular Edema

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.

Морфофункциональные параметры диабетического макулярного отека после витреоретинальной хирургии

Background. Diabetic macular edema (DME) is a socially significant disease of our time. At the moment, intravitreal administration of antivasoproliferative drugs is the “gold standard” for the treatment of DME. Currently, indication for vitrectomy and membrane peeling for macular edema is the presence of an epiretinal membrane or vitreoretinal traction syndrome. Some authors consider use of vitrectomy with internal limiting membrane peeling to be justified in patients with DME. Purpose. To evaluate changes in the morphofunctional parameters of the retina in patients after vitreoretinal intervention for resistant diabetic macular edema. Methods. 44 patients diagnosed with DME with no response to previous conservative treatment (laser coagulation, angiogenesis inhibitors) underwent surgery at the ophthalmology center of the National Medical Research Center named after N. I. Pirogov. Results When analyzing BCVA after vitreoretinal surgery, a significant increase in functional parameters was revealed in patients of group 2 (vitrectomy) compared with similar parameters in patients of group 1 (continuing treatment) within 6 months from the date of surgery (p = 0.027). There is also a statistically significant decrease in retinal thickness in patients of group 2 compared with patients of group 1 within 1 month (p = 0.035). When assessing photosensitivity, there was a significant increase in parameters in patients of group 2 compared with preoperative parameters and with similar parameters in patients of group 1 within 1 week from the moment of surgery (p = 0.023). Conclusion. It was found that vitreoretinal surgery with membrane peeling provides a higher functional result compared to the group where only angiogenesis inhibitors and retinal laser coagulation were used from 6 to 12 months of observation. By the 1st week of observation, in patients of group 2, in comparison with the results of patients in group 1, there was a more pronounced positive dynamics of photosensitivity which persisted for 12 months. More pronounced edema resorption was also observed in the group in which vitrectomy with internal limiting membrane peeling was used. Thus, these data confirm that use of vitreoretinal surgery is possible in the treatment of diabetic macular edema. Further study of this issue is required. This study was conducted on a small sample of patients. To confirm the statistical reliability of the results, it is necessary to study the data when examining a larger sample in groups. Key words: DME; diabetic macular edema; vitrectomy; membrane peeling.

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.

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.