Health, hope and worry: A qualitative study of people with diabetes' experiences with anti‐ VEGF treatment

Diabetic macular edema (DME) is a common complication of diabetic retinopathy (DR) and is a leading cause of vision loss in developed countries during the working age. Understanding the role of vascular endothelial growth factor (VEGF) in the pathogenesis of DME has emphasized the importance of using anti-VEGF agents in treatment. Anti-VEGF drugs such as pegaptanib, ranibizumab, bevacizumab, and aflibercept have been studied in the treatment of DME. Aflibercept is a recombinant fusion protein with an inhibitory effect on VEGF-A, VEGF-B, placental growth factor (PIGF) 1 and 2. It is believed that this agent has a longer duration of action than other anti-VEGF molecules due to its high-affinity binding to the VEGF molecule. This review summarizes the pharmacological properties of aflibercept in terms of clinical efficacy, use, and tolerability in the treatment of DME.

Introduction: Diabetic retinopathy is the leading cause of vision loss in working-age adults; it is a highly prevalent cause of vision loss overall and has a potent impact on the quality of life in those with diabetes mellitus and public health in general. Diabetic macular edema (DME) is the most common cause of vision loss from diabetic retinopathy. In patients with diabetes mellitus, chronic hyperglycemia leads to activation of the inflammatory cascade and retinal capillary damage that result in microaneurysm formation in the retina. In addition to the possibility of associated ischemia, microaneurysms are hyperpermeable; the resultant loss of the blood–retinal barrier leads to vision loss if consequent edema involves the center of the fovea. The standard of DME therapy for >25 years was focal laser photocoagulation applied to or near the microaneurysms. However, results from clinical trials of intravitreal vascular endothelial growth factor (VEGF) blockers and corticosteroids for the treatment of DME have led to a dramatic paradigm shift away from laser therapy to primary treatment with these pharmacologic agents. Methods: Medline literature search of approaches for treating DME. Results: Intravitreal pharmacologic treatments with anti-VEGF agents and corticosteroids have recently been shown to be superior to laser treatment of DME. Conclusion: The existence of pharmacologic treatment of DME, shown to be superior to laser monotherapy, has created a seismic change in the approach of treatment of these patients. This review provides a summary of the therapies and the rationale regarding the current pharmacologic therapy of DME.

Diabetic Macular Edema

Introduction: 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). Methods: 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. Results: 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 >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). Conclusion: More durable treatments with reduced frequency of injections/visits may reduce treatment burden and improve patient satisfaction, which may enhance adherence and visual outcomes.

Background: Diabetic macular edema being a foremost cause of visual loss in the diabetic population, is typically managed with intra-vitreal anti-VEGF therapy. The unilateral intra-vitreal bevacizumab (IVB) injections are standard, but the possible bilateral effect on the un-injected eye remains unclear, specifically in the African population. Aims: This study intended to evaluate the anatomical and visual outcomes in the un-injected eye after a single dose intra-vitreal bevacizumab injection and to identify systemic and ocular factors associated with these outcomes in patients with Diabetic Macular edema (DME). Study Design: A hospital-based prospective cohort study. Place and Duration of Study: Department of Ophthalmology, Kilimanjaro Christian Medical Centre (KCMC), between Jun 2024 and July 2025. Methodology: We included 105 patients (53 male, 52 female, mean age 64.1(±9.06) years) with diabetic macular edema (DME). Each patient received a single intra-vitreal bevacizumab injection in the eye with worse baseline Central Subfield Macular Thickness (CSMT). The un-injected eye was assessed for changes in CSMT and Best Corrected Visual Acuity (BCVA) after 4 weeks post injection. Paired t-tests and Wilcoxon signed-rank tests were applied for within-eye assessments. Pearson and Spearman correlations evaluated inter-eye associations. Generalized linear models (GLM) with a gamma distribution and log link were used to identify factors associated with anatomical and visual outcomes. Results: The mean CSMT of un-injected eye changed from (300.9 ± 31.5 μm) to 304.7 ± 36.9 μm), p = 0.1472, and median BCVA remained unchanged (LogMAR 0.3 at baseline and follow-up), p = 0.1154). Nevertheless, significant associations were observed between increased CSMT and systemic hypertension (ARR = 1.07; p = 0.021), elevated serum creatinine (ARR = 1.002; p = 0.038), and history of prior bevacizumab use (ARR = 1.09; p = 0.001). The history of PRP was associated with decrease in mean CSMT (ARR = 0.94; p = 0.021). Conclusion: A single unilateral IVB injection did not produce significant anatomical or visual improvements in the contralateral eye after 4 weeks. Though, systemic comorbidities such as hypertension and good renal function significantly influenced anatomical outcome, highlighting the need for integrated systemic and ocular management in DME treatment.

Diabetic macular edema (DME) is a leading cause of vision loss in diabetic people. DME can be treated with various medications, including intravitreal injections, laser therapy, and surgery. Early detection and treatment of DME is essential to prevent vision loss. The study aimed to describe patients' demographic and clinical characteristics with DME, optical coherence tomography (OCT) findings, and visual acuity outcomes. A retrospective study reviewed case records of patients with DME between 2017 and 2020. Demographic data, clinical characteristics, and examination results were extracted and analyzed using Microsoft Excel (2013). All patients clinically diagnosed with DME underwent assessment by OCT examination. DME was classified based on OCT findings. Statistical significance was observed at P < 0.05. This retrospective study included 213 eyes of 134 patients, of which 77.6% were male and 22.4% were female. Nonproliferative diabetic retinopathy (NPDR) was present in 51.64% of eyes, and PDR was present in 48.36%. Focal, diffuse, and cystoid macular edema was observed in 68, 31, and 65 eyes, respectively. Tractional macular edema was seen in 16 eyes with posterior hyaloid traction, 13 with epiretinal membrane (ERM), and one with both conditions. DME associated with subretinal fluid (SRF) detachment was seen in 8.92% of eyes. The mean (standard deviation) central retinal thickness was 284.5 (28.9), 434.0 (97.5), 426.5 (27.5), 510.5 (14.1), and 465.5 (280.7) μm in focal, diffuse, cystoid, ERM, and SRF, respectively. Increased central retinal thickness was associated with decreased visual acuity (P < 0.05). The findings of this study suggest that DME is a common and visually significant complication of diabetes. The OCT findings can be used to classify DME into different subtypes, which may help to guide treatment decisions. Focal edema was the most common type of DME with the least central retinal thickness. In NPDR, focal macular edema was the most common; in PDR, cystoid edema was the most common. Cystoid edema was the most common type in the subgroup of patients with recurrent DME following anti-vascular endothelial growth factor injection.

Diabetic macular edema (DME) represents the most common cause of vision loss in patients affected by diabetes mellitus. Diabetic retinopathy has a significant impact on public health and the quality of life of many patients, and thus requires noteworthy consideration. The first line of treatment remains the management of systemic risk factors, but is often insufficient in controlling DME. For 25 years, the focal/grid laser photocoagulation was considered the standard of care for DME. Laser treatment reduces the risk of moderate visual loss by approximately 50%, but it is not associated with remarkable effects on visual improvement. Lately, new approaches in the treatment of DME have been considered; in particular the employment of anti-vascular endothelial growth factor (anti-VEGF) drugs. VEGF is a pluripotent growth factor that functions as a vasopermeability factor and an endothelial cell mitogen, and thereby represents an appealing candidate as a therapeutic target for the treatment of DME. Recent trials have been investigating many anti-VEGF agents in the treatment of DME. The goal of this review is to present the evidence behind the use of anti-VEGF drugs in the treatment of DME.

Diabetic macular edema (DME) and choroidal neovascularization (CNV) associated with age-related macular degeneration (AMD) are the leading causes of vision loss in the industrialized world. The mainstay of treatment for both conditions has been thermal laser photocoagulation, while there have been recent advances in the treatment of CNV using photodynamic therapy with verteporfin. While both of these treatments have prevented further vision loss in a subset of patients, vision improvement is rare. Anti-vascular endothelial growth factor (VEGF)-A therapy has revolutionized the treatment of both conditions. Pegaptanib, an anti-VEGF aptamer, prevents vision loss in CNV, although the performance is similar to that of photodynamic therapy. Ranibizumab, an antibody fragment, and bevacizumab, a full-length humanized monoclonal antibody against VEGF, have both shown promising results, with improvements in visual acuity in the treatment of both diseases. VEGF trap, a modified soluble VEGF receptor analog, binds VEGF more tightly than all other anti-VEGF therapies, and has also shown promising results in early trials. Other treatment strategies to decrease the effect of VEGF have used small interfering RNA to inhibit VEGF production and VEGF receptor production. Corticosteroids have shown efficacy in controlled trials, including anacortave acetate in the treatment and prevention of CNV, and intravitreal triamcinolone acetonide and the fluocinolone acetonide implant in the treatment of DME. Receptor tyrosine kinase inhibitors, such as vatalanib, inhibit downstream effects of VEGF, and have been effective in the treatment of CNV in early studies. Squalamine lactate inhibits plasma membrane ion channels with downstream effects on VEGF, and has shown promising results with systemic administration. Initial results are also encouraging for other growth factors, including pigment epithelium-derived factor administered via an adenoviral vector. Ruboxistaurin, which decreases protein kinase C activity, has shown positive results in the prevention of diabetic retinopathy progression, and the resolution of DME. Combination therapy has been investigated, and may prove to be quite effective in the management of both DME and AMD-associated CNV, although ongoing and future studies will be crucial to treatment optimization for each condition.

Introduction: Diabetic macular edema (DME) is a leading cause of vision loss in patients with diabetic retinopathy. Laser therapy, used for many years in the treatment of DME, allows for the reduction of edema and protection of vision. Aim of the Study: The aim of this paper is to review the role of laser therapy in the treatment of DME, covering traditional methods such as panretinal and focal photocoagulation, as well as newer approaches like micropulse laser therapy. The paper also analyzes a comparison of laser therapy with other treatment methods, such as VEGF inhibitor injections and steroid therapies, highlighting the advantages and limitations of each. Challenges related to treatment precision and therapy resistance, as well as new technologies and future directions in the development of laser therapy for DME, will also be discussed. The goal is to provide a comprehensive overview of the role of laser therapy in DME treatment and its place in modern ophthalmologic practice. Materials and Methods: A literature review was conducted in databases such as PubMed, Scopus, Web of Science, and Google Scholar, using relevant keywords. The selection of studies was limited to those with full access to the content or available in open-access repositories. Conclusions: Diabetic macular edema (DME) remains a leading cause of vision loss in patients with diabetes, and effective treatment, including laser therapy and pharmacological therapies, is crucial for reducing edema and improving vision. The future of DME treatment lies in the integration of modern technologies, including artificial intelligence, VEGF therapy, and gene therapies, which could significantly improve treatment outcomes and reduce the number of required interventions.

Diabetic retinopathy is a common microvascular complication of diabetes mellitus. It affects a substantial proportion of US adults over age 40. The condition is a leading cause of visual loss. Much attention has been given to expanding the role of current treatments along with investigating various novel therapies and drug delivery methods. In the treatment of diabetic macular edema (DME), intravitreal pharmacotherapies, especially anti-vascular endothelial growth factor (anti-VEGF) agents, have gained popularity. Currently, anti-VEGF agents are often used as first-line agents in center-involved DME, with recent data suggesting that among these agents, aflibercept leads to better visual outcomes in patients with worse baseline visual acuities. While photocoagulation remains the standard treatment for proliferative diabetic retinopathy (PDR), recent FDA approvals of ranibizumab and aflibercept in the management of diabetic retinopathy associated with DME may suggest a potential for pharmacologic treatments of PDR as well. Novel therapies, including small interfering RNAs, chemokines, kallikrein-kinin inhibitors, and various anti-angiogenic agents, are currently being evaluated for the management of diabetic retinopathy and DME. In addition to these strategies, novel drug delivery methods such as sustained-release implants and refillable reservoir implants are either under active evaluation or have recently gained FDA approval. This review provides an update on the novel developments in the treatment of diabetic retinopathy.

Plasma kallikrein, a member of the kallikrein-kinin system, catalyzes the release of the bioactive peptide bradykinin, which induces inflammation, vasodilation, vessel permeability, and pain. Preclinical evidence implicates the activity of plasma kallikrein in diabetic retinopathy, which is a leading cause of visual loss in patients suffering from diabetes mellitus. Employing a technology based on phage-display combined with chemical cyclization, we have identified highly selective bicyclic peptide inhibitors with nano- and picomolar potencies toward plasma kallikrein. Stability in biological matrices was either intrinsic to the peptide or engineered via the introduction of non-natural amino acids and nonpeptidic bonds. The peptides prevented bradykinin release in vitro, and in vivo efficacy was demonstrated in both a rat paw edema model and in rodent models of diabetes-induced retinal permeability. With a highly extended half-life of ∼40 h in rabbit eyes following intravitreal administration, the bicyclic peptides are promising novel agents for the treatment of diabetic retinopathy and diabetic macular edema.

Foreword: Evaluation of New Treatment Paradigms for Diabetic Retinopathy and Macular Edema

Since their introduction in the late 2000s, anti-vascular endothelial growth factor (VEGF) agents have become the first-line choice for center-involved diabetic macular edema (DME). Even with its proven effectiveness, there are still cases that do not respond satisfactorily. In those cases, a treatment option is to change to another anti-VEGF drug. In this paper, the authors review studies on switching between different anti-VEGF drugs in the treatment of persistent DME. An extensive bibliographic review was done using PubMed, Embase, and Scopus. Fourteen studies published from March 2010 to April 2017 reporting switching from anti-VEGF drugs in DME treatment were included. All reported good anatomical results after conversion; however, visual acuity outcomes showed great variability between publications. Therefore, switching to other anti-VEGFs in patients with DME not responding to previous anti-VEGF therapy may be an option, but the results are still not well-known due to a lack of randomized clinical trials. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:748-754.].

This study characterizes the impact of race, ethnicity, insurance status, and geographic location on anti-vascular endothelial growth factor (VEGF) use for the treatment of diabetic macular edema (DME). This study is a retrospective cohort study. The American Academy of Ophthalmology Intelligent Research in Sight Registry was queried for patients diagnosed with DME who received at least one anti-VEGF injection between 2012 and 2020 (n = 203,707). Multivariate regression analyses investigated associations between race, ethnicity, insurance status, and geographic location and anti-VEGF use and visual outcomes. White race, non-Hispanic/Latino ethnicity, and private insurance were associated with higher use of anti-VEGF injections during a 60-month period (incidence rate ratio, 1.2, 1.25, and 1.17, respectively; P < .01). Furthermore, being of non-Hispanic/Latino ethnicity and having private health insurance were associated with higher longitudinal visual acuity (odds ratio, 1.44 [P = .02] and odds ratio, 1.43 [P < .01], respectively). Ethnicity and insurance status are associated with anti-VEGF use and visual acuity outcomes in DME. [Ophthalmic Surg Lasers Imaging Retina 2022; 53:380-391.].

ABSTRACTDiabetes mellitus is a chronic disease that affects 415 million people worldwide. Despite treatment advances, diabetic eye disease remains a leading cause of vision loss worldwide. Diabetic macular edema (DME) is a common cause of vision loss in diabetic patients. The pathophysiology is complex and involves multiple pathways that ultimately lead to central retinal thickening and, if untreated, visual loss. First-line treatment of DME has evolved from focal/grid laser established by the Early Treatment of Diabetic Retinopathy Study (ETDRS) to intravitreous pharmacologic therapy. Landmark prospective clinical trials examining the effect of intravitreous injections of vascular endothelial growth factor (VEGF) inhibitors in the treatment of DME have demonstrated improved visual outcomes over focal grid laser. This review focuses on the scientific evidence treatment of DME, disease pathophysiology, clinical disease course, current treatment standards, and emerging novel therapeutic approaches.