Anti-vascular Endothelial Growth Factor Research Articles

Association of microaneurysms with retinal vascular alterations in patients with retinal vein occlusion

ObjectiveTo investigate the localization, distribution, and type of central microaneurysms (MAs) and their relationship with retinal vascular alterations in patients with retinal vein occlusion (RVO). MethodsIn this cross-sectional study, ultra-widefield color fundus photography (UWF-CF), standard and single-capture 65° widefield (WF) optical coherence tomography angiography (OCTA) were performed in consecutive patients with RVO treated at the Department of Ophthalmology and Optometry, Medical University of Vienna. UWF-CF, en face and B-Scans in 6 mm × 6 mm OCTA were examined for detection of MAs. Nonperfusion areas (NPA) and collateral vessels (CV) were evaluated on WF-OCTA, ghost vessels (GV), and tortuous vessels (TV) on UWF-CF. ResultsOne-hundred-and-twelve patients were included in the study, and data from 59 eyes of 59 patients with disease duration longer than 3 months, good image quality, and without relevant ocular comorbidities were eligible for statistical analysis. Fifty-six of 59 (94.9%) patients were previously treated with anti-vascular endothelial growth factor agents for macular edema, 31 of 59 (52.5%) patients presented with MAs in the central 6 mm and 60 MAs were found in total using multimodal imaging. There was no statistically significant difference in the greatest diameter of fluid-associated versus non-fluid-associated MAs (p = 0.53). Eyes with MAs were associated with CV, TV, and GV (χ2-test; p < 0.001, p = 0.0498, and p = 0.001). Median NPA was 27.3 mm2 (quartiles 1.3–62.8 mm2) in eyes with MAs and 0 mm2 (quartiles 0–36.2 mm2) in eyes without MAs (Mann-Whitney-U-test; p = 0.018). ConclusionMAs were associated with extensive NPA, the presence of CV, GV, and TV. There was no correlation between the diameter of the MA and the adjacent intraretinal fluid in our predominantly pretreated RVO study patients.

Real-World Efficacy of Intravitreal Faricimab for Diabetic Macular Edema: A Systematic Review.

Diabetic macular edema (DME) is a prevalent exudative maculopathy, and anti-vascular endothelial growth factor (anti-VEGF) therapy is the first-line choice for treatment. Faricimab, a novel anti-VEGF and anti-angiopoietin-2 bispecific agent, has recently been approved for the treatment of DME. In this study, we systematically reviewed the real-world evidence of the efficacy of faricimab for the treatment of DME. We searched 11 databases for eligible studies. Study selection and data extraction were made independently by two authors in duplicate. Eligible studies were reviewed qualitatively. We identified 10 eligible studies that summarized data from a total of 6054 eyes with a mean follow-up of between 55 days and 12 months. Five studies reported outcomes in a population of both treatment-naïve and previously treated eyes, and five studies reported outcomes exclusively in relation to eyes that were previously treated. Faricimab improved the best-corrected visual acuity and macular thickness. The extension of the treatment interval was possible in 61-81% of treatment-naïve eyes and 36-78% of previously treated eyes. Faricimab for DME yields clinical outcomes similar to those known from previous anti-VEGF treatments but with extended treatment intervals, thus lowering the burden of therapy for patients. Long-term real-world studies are warranted.

The Short-Term Efficacy and Safety of Faricimab in Refractory Neovascular Age-Related Macular Degeneration: The Real-World Experience in Taiwan

Introduction: Anti-vascular endothelial growth factor (VEGF) treatment stands as the primary approach for neovascular age-related macular degeneration (nAMD). Faricimab has recently emerged as a novel anti-VEGF option for nAMD. This study aimed to assess the efficacy of faricimab in patients with refractory nAMD. Method: This retrospective study focused on refractory nAMD patients treated with faricimab at Taipei Veterans General Hospital from March 2023 to December 2023. Primary outcomes assessed the change in mean best-corrected visual acuity (BCVA) and central retinal thickness (CRT) over the first 4 months. Secondary outcomes included the presence of subretinal and intraretinal fluid (SRF and IRF) and changes in pigment epithelial detachment (PED). Subgroup analysis for the successful and unsuccessful treatment groups was conducted to identify potential confounding factors influencing treatment response. Result: This study included 42 eyes with refractory nAMD treated with faricimab. During a 6-month follow-up, no significant improvement in BCVA was observed, while CRT significantly decreased at all time points, except during the 5-month follow-up. Height PED showed significant reduction up to 5 months. The prevalence of SRF decreased significantly, while IRF remained lower but not significant. According to the treatment criteria, 67.4% successfully met the treatment goals. Subgroup analysis between successful and unsuccessful groups showed no significant differences in baseline characteristics, except a higher predominantly serous PED percentage in the successful group. Conclusion: Faricimab showed favorable outcomes in refractory nAMD patients. Further investigations are needed to understand the factors contributing to its efficacy.

Association between time to treatment and outcome in branch retinal vein occlusion.

To investigate the association between the time from onset to initial treatment and changes in visual acuity or the number of treatments in patients with branch retinal vein occlusion (BVO). Retrospective. Thirty-nine eyes of 39 consecutive patients with untreated acute-phase BVO who visited the University of Tokyo Hospital and were followed up for at least one year were included. The patients were initially treated with anti-vascular endothelial growth factor (VEGF) therapy and additional pro re nata therapy within six months of onset. The patients were classified according to the time from disease onset to the first treatment (group A: 28days or less, group B: over 28days). The mean (SD) age was 73 ± 8years, and 19 patients were male. The mean (SD) time to the first treatment was 31.6 ± 17.9days. The mean (SD) logMAR visual acuity at first treatment was 0.37 ± 0.30. After 12months of treatment, the mean (SD) logMAR change was -0.15 ± 0.23, and the mean number (SD) of treatments was 3.1 ± 1.7. No significant association was observed between the timing of treatment initiation and changes in logMAR visual acuity. Patients in group A and central macular thickness at the initial visit were independently associated with the greater number of treatments at one year (p = 0.03 and p = 0.01, respectively). At one year, the time between onset and the start of anti-VEGF therapy for BVO was not associated with subsequent visual acuity changes. Meanwhile, it may have significant association with the number of treatments.

Prognostic analysis of peritoneal washing cytology during interval debulking surgery in advanced ovarian cancer

BackgroundInterval debulking surgery (IDS) following neoadjuvant chemotherapy is a treatment option for advanced ovarian cancer. Optimal surgery is required for better survival; however, while peritoneal washing cytology (PWC) has been identified as a prognostic factor, its comprehensive assessment during IDS remains unexplored. Therefore, we aimed to evaluate PWC efficacy during IDS, alongside other factors including residual disease and the modeled cancer antigen 125 (CA-125) ELIMination rate constant K (KELIM), by retrospectively reviewing the medical records of 25 patients with advanced ovarian cancer underwent neoadjuvant chemotherapy and IDS between January 2017 to June 2023.ResultsTwelve (48.0%) patients were PWC-positive, and the remainder were PWC-negative. PWC was performed at laparotomy during IDS, after which five (41.7%) PWC-positive and four (30.8%) PWC-negative patients received bevacizumab, an anti-vascular endothelial growth factor monoclonal antibody, for maintenance treatment. Four (33.3%) PWC-positive and 10 (76.9%) PWC-negative patients received poly adenosine diphosphate (ADP)-ribose polymerase inhibitors. In patients who received bevacizumab and poly ADP-ribose polymerase inhibitors, overall survival and progression-free survival did not significantly differ between those who were PWC-positive and PWC-negative (p = 0.27 and 0.20, respectively). Progression-free survival significantly differed between those with favorable and unfavorable CA-125 KELIM (p = 0.02). Multivariate analysis indicated that optimal surgery and favorable CA-125 KELIM were associated with better progression-free survival (p < 0.01 and 0.02, respectively), with only optimal surgery associated with better overall survival (p = 0.04).ConclusionsA positive PWC at IDS was not associated with survival in advanced ovarian cancer. Our findings indicate that although PWC status at IDS should be one of the factors determining survival in patients with advanced ovarian cancer, recent improvements in maintenance therapy may make the combination of CA-125 KELIM and PWC status a more useful prognostic factor in selecting treatment after IDS. Further studies are needed to validate these results, highlighting the potential importance of maintenance treatment after IDS and the need for further research to validate the clinical significance of a positive PWC.

Factors affecting quality of life in patients with neovascular age-related macular degeneration

PurposeThis study examines how factors such as age, sex, best corrected visual acuity (BCVA), driving ability, and perceived treatment effectiveness influence quality of life (QoL) among patients with neovascular age-related macular degeneration (nAMD) in treatment with anti-vascular endothelial growth factor (VEGF) injections. Such information might be invaluable for healthcare providers, enabling them to understand who benefits from treatment. DesignSurvey-based cross-sectional study MethodsWe used questionnaire responses from patients receiving intravitreal anti-VEGF injections for nAMD to evaluate self-reported QoL, measured by the Macular Degeneration Quality of Life questionnaire. Background questions in the survey gathered patient information, while BCVA was obtained from medical records. The associations between self-rated QoL and various factors were analyzed using binomial logistic regression and linear regression. We calculated crude odds ratio (OR) and β-coefficient as well as OR and β-coefficient adjusted for sex, age, and BCVA. ResultsThis study included 348 individuals, median age 79.2 years (IQR 75.0–84.0), with 58.3 % women. In the adjusted logistic model, factors associated with a QoL above average were male sex (OR 1.65, 95 % CI 1.04, 2.63), BCVA above 0.5 Snellen in best seeing eye (OR 11.16, 95 % CI 4.24, 29.35), preserved driving ability (OR 3.35, 95 % CI 1.80, 6.26), and perceiving treatment effectiveness (OR 2.15, 95 % CI 1.07, 4.34). The adjusted linear regression revealed the same associations, yet the positive relationship between QoL and biological sex was significant in the crude model but not in the adjusted model (β: 0.30, 95 % CI -0.04, 0.64). ConclusionGood visual acuity and driving ability strongly correlate with high QoL in patients with nAMD. Perceptions of the effectiveness of anti-VEGF treatment double the likelihood of high QoL, highlighting the need for further investigation into its potential clinical implications.

Intravitreal Dexamethasone Implant Switch after Anti-VEGF Treatment in Patients Affected by Retinal Vein Occlusion: A Review of the Literature.

Nowadays, retinal vein occlusion (RVO) is the second most prevalent cause of vision loss associated with retinal vascular disease. Intravitreal injections are currently known as a major advancement in ophthalmology, particularly in the treatment of RVO and other retinal disorders. Particularly, the first line of therapy is usually anti-vascular endothelial growth factor (VEGF) drugs. Notably, for RVO eyes that have not responded to anti-VEGF therapy, an intravitreal dexamethasone (DEX) implant 0.7 mg (Ozurdex®, AbbVie Inc., North Chicago, IL, USA) is considered a suitable therapeutical substitute. Actually, investigations carried out in the real world and clinical trials have shown the safety and the efficacy of intravitreal DEX implants for treating this retinal disease. For this reason, choosing patients carefully may thus be essential to reduce the number of injections that clinics and hospitals have to do to manage RVO and its complications. The primary aim of this review is to summarize the pathophysiology of this retinal vascular disease, as well as the clinical and ocular imaging features that may support a switch from prior anti-VEGF treatment to intravitreal DEX implant, to provide the RVO patients with the best possible treatment to ensure maximum visual recovery.

Incidence and risk factors of fellow-eyes wet conversion in unilateral neovascular age-related macular degeneration over 15-year follow-up.

Incidence and risk factors of fellow eye wet conversion in unilateral neovascular age-related macular degeneration (nAMD) over 15-years follow-up. This retrospective study reviewed 593 unilateral nAMD patients with a minimum of five years up to 15years of follow-up. The demographic data, visual acuity, fellow eye nAMD conversion rate, and the number of anti-vascular endothelial growth factor (anti-VEGF) injections in the primary eye were evaluated. Also, the nAMD-converted fellow eyes were divided into two groups based on the time of conversion (less and more than two years from the first injection in the primary eye). Based on the data types, the T-test, Chi-square, and Mann-Whitney U test were used to analyze. The total cases were 593 patients, and 248 eyes (41.82%) converted to nAMD in the mean interval of 34.92 ± 30.62months. The males exhibited a predisposition to wet conversion at 2.54years earlier than their female counterparts (P = 0.025). In all the converted fellow eyes, the mean age was 2.3years higher at presentation in the group who converted within two years of follow-up in compared to eyes that converted after two years (79.82 ± 8.64 vs 77.51 ± 8.5years, P = 0.035). Additionally, eyes converting within two years had a mean baseline LogMAR visual acuity of 0.44 ± 0.47, compared to 0.32 ± 0.41 for conversions after two years (P = 0.014). This study reported that males showed a predisposition to fellow eye nAMD conversion at an earlier age. Additionally, there was a trend of faster fellow eye nAMD conversion in individuals with higher age and lower baseline visual acuity. What is known • Certain risk factors may make the fellow eye of neovascular age-related macular degeneration (nAMD) more likely to progress to wet conversion. • Identifying these risk factors for fellow eye wet conversion can help prevent it, potentially preserving the patient's vision quality for a longer duration. • The studies on the incidence of wet conversion in the fellow eye have yielded controversial results. What is new • During the 15-year follow-up period, nearly half (47.58%) of the fellow eyes that underwent wet conversion did so within the initial two years following the wet conversion of the first eye. • Males showed a predisposition to fellow eye nAMD conversion at an earlier age. • There was a trend of faster fellow eye nAMD conversion in individuals with higher age and lower baseline visual acuity.

The efficacy of intravitreal anti-VEGF for radiation maculopathy: a systematic review and meta-analysis.

Anti-vascular endothelial growth factor (VEGF) therapy is the primary approach for managing radiation maculopathy. However, a noticeable gap exists in meta-analyses evaluating the efficacy of anti-VEGF therapy specifically in the context of radiation maculopathy. We conducted a review of comparative studies on anti-VEGF treatment up to October 2023. References were sourced from PubMed, EMBASE, and the Cochrane Library. The Cochrane Risk of Bias tool assessed the quality of randomized controlled trials (RCTs), while the Risk Of Bias In Non-randomized Studies of Interventions (ROBINS-I) tool evaluated non-RCTs. Thirteen articles originating from eleven trials involving 2,525 eyes of 2408 patients were included. Four trials with 2226 eyes examined the effect of preventive anti-VEGF. Four trials with 189 eyes assessed the effect of anti-VEGF for preexisting maculopathy, and three trials with 110 eyes compared different anti-VEGF treatment modalities. In the preventive anti-VEGF treatment meta-analysis over a 24-month follow-up, the anti-VEGF group exhibited significantly fewer cases of radiation maculopathy (OR: 0.40; 95% CI: 0.25, 0.66, P= .0003, I2 =45%). For the meta-analysis of anti-VEGF treatment for pre-existing radiation maculopathy over a 6-month follow-up, the anti-VEGF group showed improved visual acuity (SMD: -1.13, 95% CI: -1.69 to -0.56, P < .0000, I2 = 47%) and decreased central macular thickness (SMD: -0.59, 95% CI: -1.13 to -0.05, P = 0.03, I2 = 62%). Prophylactic anti-VEGF effectively prevents radiation maculopathy and is also beneficial in treating pre-existing radiation maculopathy. Intensive treatment initially provides early benefits, but the efficacy diminishes after transitioning to a treat-and-extend regimen.

Safety and tolerability of immune checkpoint inhibitors in people with HIV infection and cancer: insights from the national prospective real-world OncoVIHAC ANRS CO24 cohort study

BackgroundImmune checkpoint inhibitors (ICIs) have been a major advance in cancer management. However, we still lack prospective real-world data regarding their usage in people with HIV infection (PWH).MethodsThe ANRS CO24...

Outcomes of Pro Re Nata versus Treat-and-Extend Anti-VEGF Injections for Myopic Macular Neovascularization in Multiethnic Patients in the United States.

To compare visual outcomes and recurrence rates between pro re nata (PRN), treat-and-extend and stop (TES), and treat-and-extend with chronic maintenance dosing (TEM) regimens of anti-vascular endothelial growth factor (VEGF) injections for myopic macular neovascularization (MNV) in multiethnic patients. This retrospective study included patients treated with PRN, TES, or TEM for myopic MNV using intravitreal bevacizumab or ranibizumab. The primary outcome measure was visual improvement at 12 months. We included 127 eyes of 117 patients (75 females and 42 males). The mean follow-up duration was 37.9 months. We compared the outcomes of PRN (47 eyes [37%]), TES (52 eyes [41%]), and TEM (28 eyes [22%]). All groups showed significant visual improvement at 12 months and at the final follow-up (all P<0.05). Visual outcomes did not differ significantly between the three groups at 12 months and final follow-up (all P>0.05). However, the number of eyes with recurrences was significantly higher in the PRN group and significantly lower in the TEM group during follow-up (38%, 21%, and 11% in the PRN, TES, and TEM groups, respectively; P=0.020). The PRN group received the fewest injections during follow-up (5.3, 10.9, and 19.9 injections in the PRN, TES, and TEM groups respectively; P<0.001). Anti-VEGF injections with PRN, TES, or TEM regimens are effective for myopic MNV and have comparable visual outcomes. Since PRN provides favorable outcomes with fewer injections, it should be the first-line approach. However, a treat-and-extend approach with TES and TEM may be an option given individual patient factors.

Multimodal imaging diagnosis and analysis of prognostic factors in patients with adult-onset Coats disease.

To describe the multimodal imaging features, treatment, and outcomes of patients diagnosed with adult-onset Coats disease. This retrospective study included patients first diagnosed with Coats disease at ≥18 years of age between September 2017 and September 2021. Some patients received anti-vascular endothelial growth factor (VEGF) therapy (conbercept, 0.5 mg) as the initial treatment, which was combined with laser photocoagulation as needed. All the patients underwent best corrected visual acuity (BCVA) and intraocular pressure examinations, fundus color photography, spontaneous fluorescence tests, fundus fluorescein angiography, optical coherence tomography (OCT), OCT angiography, and other examinations. BCVA alterations and multimodal image findings in the affected eyes following treatment were compared and the prognostic factors were analyzed. The study included 15 patients who were aged 24-72 (57.33±12.61)y at presentation. Systemic hypertension was the most common associated systemic condition, occurring in 13 (86.7%) patients. Baseline BCVA ranged from 2.0 to 5.0 (4.0±1.1), which showed improvement following treatment (4.2±1.0). Multimodal imaging revealed retinal telangiectasis in 13 patients (86.7%), patchy hemorrhage in 5 patients (33.3%), and stage 2B disease (Shield's staging criteria) in 11 patients (73.3%). OCT revealed that the baseline central macular thickness (CMT) ranged from 129 to 964 µm (473.0±230.1 µm), with 13 patients (86.7%) exhibiting a baseline CMT exceeding 250 µm. Furthermore, 8 patients (53.3%) presented with an epiretinal membrane at baseline or during follow-up. Hyper-reflective scars were observed on OCT in five patients (33.3%) with poor visual prognosis. Vision deteriorated in one patient who did not receive treatment. Final vision was stable in three patients who received laser treatment, whereas improvement was observed in one of two patients who received anti-VEGF therapy alone. In addition, 8 of 9 patients (88.9%) who received laser treatment and conbercept exhibited stable or improved BCVA. Multimodal imaging can help diagnose adult-onset Coats disease. Anti-VEGF treatment combined with laser therapy can be an option for improving or maintaining BCVA and resolving macular edema. The final visual outcome depends on macular involvement and the disease stage.

Variceal bleeding following treatment with atezolizumab plus bevacizumab in two patients with unresectable hepatocellular carcinoma.

Bleeding-related adverse events may occur due to anti-vascular endothelial growth factors. Here, we report two cases of variceal rupture during atezolizumab plus bevacizumab (ATZ/BV) treatment for unresectable hepatocellular carcinoma (u-HCC).Case 1 involved a man in his 60s with alcoholic liver cirrhosis (LC) and u-HCC. Seventy-four days after ATZ/BV administration, the patient was admitted for hematemesis. Upper esophagogastroduodenoscopy (EGD) revealed worsening of the esophageal varices (EVs) to F2 grade with active bleeding. Endoscopic variceal ligation successfully achieved hemostasis.Case 2 involved a man in his 70s with alcoholic LC and u-HCC. The patient was admitted with hematemesis 114days after ATZ/BV administration. During EGD, the EVs deteriorated to F3 grade, although hemostasis had already been achieved. The evaluation was discontinued during the observation stage because of the worsening hepatic reserve.Neither patient had EVs warranting prophylactic treatment before ATZ/BV administration, showed a partial tumor response, or had portal vein tumor thrombus. Both patients demonstrated increased total diameters of the collateral veins and splenic volume compared to those before treatment. These findings suggest that ATZ/BV treatment may increase portal pressure. In conclusion, the administration of ATZ/BV to patients with LC and u-HCC necessitates careful management of EVs aggravation and rupture.

Efficacy of chemotherapy containing bevacizumab in patients with metastatic colorectal cancer according to programmed cell death ligand 1.

Bevacizumab, an anti-vascular endothelial growth factor (VEGF) monoclonal antibody, inhibits angiogenesis and reduces tumor growth. Serum VEGF-C, lactate dehydrogenase, and inflammatory markers have been reported as predictive markers related to bevacizumab treatment. Programmed cell death ligand 1 (PD-L1) could act upon VEGF receptor 2 to induce cancer cell angiogenesis and metastasis. To investigate the efficacy of bevacizumab-containing chemotherapy in patients with metastatic colorectal cancer (CRC) according to the expression of PD-L1. This analysis included CRC patients who received bevacizumab plus FOLFOX or FOLFIRI as first-line therapy between June 24, 2014 and February 28, 2022, at Samsung Medical Center (Seoul, South Korea). Analysis of patient data included evaluation of PD-L1 expression by the combined positive score (CPS). We analyzed the efficacy of bevacizumab according to PD-L1 expression status in patients with CRC. A total of 124 patients was included in this analysis. Almost all patients were treated with bevacizumab plus FOLFIRI or FOLFOX as the first-line chemotherapy. While 77% of patients received FOLFOX, 23% received FOLFIRI as backbone first-line chemotherapy. The numbers of patients with a PD-L1 CPS of 1 or more, 5 or more, or 10 or more were 105 (85%), 64 (52%), and 32 (26%), respectively. The results showed no significant difference in progression-free survival (PFS) and overall survival (OS) with bevacizumab treatment between patients with PD-L1 CPS less than 1 and those with PD-L1 CPS of 1 or more (PD-L1 < 1% vs PD-L1 ≥ 1%; PFS: P = 0.93, OS: P = 0.33), between patients with PD-L1 CPS less than 5 and of 5 or more (PD-L1 < 5% vs PD-L1 ≥ 5%; PFS: P = 0.409, OS: P = 0.746), and between patients with PD-L1 CPS less than 10 and of 10 or more (PD-L1 < 10% vs PD-L1 ≥ 10%; PFS: P = 0.529, OS: P = 0.568). Chemotherapy containing bevacizumab can be considered as first-line therapy in metastatic CRC irrespective of PD-L1 expression.

Short-term Outcomes of Faricimab for Neovascular Age-related Macular Degeneration with Limited Response to Ranibizumab or Aflibercept

Purpose: To evaluate the clinical outcomes of switching to faricimab for patients with neovascular age-related macular degeneration (AMD) demonstrating a limited response to prior anti-vascular endothelial growth factor (VEGF) treatments.Methods: We performed a retrospective analysis of patients with neovascular AMD who had residual subretinal fluid (SRF) or intraretinal fluid (IRF) despite treatment with ranibizumab or aflibercept, and who were subsequently treated with faricimab. The study assessed changes in best-corrected visual acuity (logarithm of the minimum angle of resolution) and central retinal thickness (CRT), as well as differences in the incidence of SRF, IRF, and serous retinal pigment epithelial detachment (S-PED) with versus without switching to faricimab.Results: The study included 22 eyes. Mean best-corrected visual acuity improved from 0.31 ± 0.21 before switching to faricimab to 0.28 ± 0.19 after the switch (&lt;i&gt;p&lt;/i&gt; = 0.172). CRT significantly decreased from 336.7 ± 83.3 to 279.9 ± 51.1 μm (&lt;i&gt;p&lt;/i&gt; = 0.002). Prior to switching, SRF was noted in 17 patients (94.4%), IRF in 5 (27.8%), and S-PED in 4 (22.2%). Following the switch to faricimab, these figures dropped to 13 (72.2%), 4 (22.2%), and 3 (16.7%), respectively. A complete resolution of retinal edema was achieved in four patients (22.2%) after the treatment switch.Conclusions: Switching to faricimab in patients with neovascular AMD who had a limited response to previous treatments led to significant anatomical improvements. Faricimab may be a valuable treatment option for these patients.

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.

Molecular Responses of Anti-VEGF Therapy in Neovascular Age-Related Macular Degeneration: Integrative Insights From Multi-Omics and Clinical Imaging.

The purpose of this study was to investigate the molecular mechanisms underlying anti-vascular endothelial growth factor (anti-VEGF) efficacy and response variability in neovascular age-related macular degeneration (nAMD) using longitudinal proteomic and metabolomic analysis alongside three-dimensional lesion measurements. In this prospective study, 54 treatment-naive patients with nAMD underwent "3+ pro re nata" (3+PRN) anti-VEGF regimens followed for at least 12 weeks. Aqueous humors were collected pre- and post-treatment for proteomic and metabolomic analysis. Three-dimensional optical coherence tomography (OCT) and OCT angiography assessed different types of nAMD lesion volumes and areas. There were 1350 proteins and 1268 metabolites that were identified in aqueous humors, with 301 proteins and 353 metabolites significantly altered during anti-VEGF treatment, enriched in pathways of angiogenesis, energy metabolism, signal transduction, and neurofunctional regulation. Sixty-seven changes of (Δ) molecules significantly correlated with at least one type of ΔnAMD lesion. Notably, proteins FGA, TALDO1, and ASPH significantly decreased during treatment, with their reductions correlating with greater lesion regression in at least two lesion types. Conversely, despite that YIPF3 also showed significant downregulation, its decrease was associated with poorer regression in total nAMD lesion and subretinal hyper-reflective material. This study identifies FGA, TALDO1, and ASPH as potential key molecules in the efficacy of anti-VEGF therapy, whereas YIPF3 may be a key factor in poor response. The integration of longitudinal three-dimensional lesion analysis with multi-omics provides valuable insights into the mechanisms and response variability of anti-VEGF treatment in nAMD.

Systemic effects of anti-VEGF intravitreal injection in patients with age-related macular degeneration: A multi-institutional real-world study.

In individuals aged >50 years, age-related macular degeneration (AMD) is the leading cause of irreversible blindness. Intravitreal injections of antivascular endothelial growth factor (VEGF) agents (bevacizumab, ranibizumab, and aflibercept) show good efficacy and similar incidences of systemic adverse events (SAEs). However, comparative studies between agents are limited. Our study aimed to compare the real-world SAE risks of bevacizumab, ranibizumab, and aflibercept users. This retrospective cohort study identified new bevacizumab, ranibizumab, and aflibercept users in a multi-institutional database in Taiwan between 2014 and 2019. Inverse probability of treatment weights (IPTW) with propensity scores was conducted to achieve homogeneity among groups. The Fine and Gray model was utilized to estimate the subdistribution hazard ratio and 95% confidence interval. This study included 701 bevacizumab, 463 ranibizumab, and 984 aflibercept users. After IPTW, all covariates were well-balanced. All three anti-VEGF agents had a low and comparable number per 100 person-years of major adverse cardiac events, heart failure, thromboembolic events, major bleeding, all-cause admission, and all-cause death (all P > 0.05). No significant differences in long-term change of systolic and diastolic blood pressure, low-density lipoprotein, estimated glomerular filtration rate, and alanine transaminase (all P for interaction > 0.05) were observed among groups. Bevacizumab, ranibizumab, and aflibercept had a good systemic safety profile in this study. All groups showed a low and similar SAE risk and no differences in their long-term change of laboratory data. Therefore, these anti-VEGF agents could be prescribed safely to patients with AMD.

Cellular and Biomaterial Approaches for Treating Age-Related Macular Degeneration

Tissue Engineering offers a novel, curative approach to treating Age-Re-lated Macular degeneration (AMD), a disease characterized by excessive drusen depo-sition beneath the retinal surface and consequent vision loss. Preclinical studies in rats have shown that transplanted Retinal Pigment Epithelium (RPE) derived from human Embryonic Stem Cells (hESC) have not only slowed AMD but have also restored vision. There are two main methods of delivering RPE cells: direct injection and monolayer surgical insertion, the latter demonstrating long-term integration. Biocompatible scaf-folds allow for better delivery of RPE cells, induced Pluripotent Stem Cells (iPSC), and Retinal Progenitor Cells (RPC). Unlike animal-derived extracellular matrix components, soft modulus biomaterials such as poly(lactic-co-glycolic acid) (PLGA) and poly(l-lactic acid) (PLLA) are ideal for AMD cell transplants because of fast degradation times, high cellular attachment proliferation, and strong adherence to Bruch’s membrane. These biomaterials can also be created at a 10-100μm thickness so that vision is not distorted. Use of biomaterials could be improved by cross-linking them with anti-vascular endothe-lial growth factors (VEGFs) like Brolucizumab and retinal growth factors such as fibro-blast growth factor (FGF). Similarly, hESC and iPSC cells can be genetically modified to secrete anti-VEGF factors.

Case report: heart failure related to intravitreal injection of anti-VEGF

BackgroundIntravitreal injection of anti-vascular endothelial growth factor is considered the first-line treatment for polypoidal choroidal vasculopathy. It has potential risks for circulatory system, which should be particularly carefully evaluated in older patients. In this case study, we aim to discuss the potential impact of this treatment regimen on cardiac health.Case presentationThis case report describes an elderly patient with no prior history of heart disease who exhibited unexpected heart enlargement and dysfunction. Throughout the patient’s hospital stay, various potential causes were investigated, leading to the hypothesis that a 10-year history of intravitreal injections of anti-vascular endothelial growth factor could be related to the observed clinical manifestations. The patient was advised to discontinue this treatment, and after a 2-month follow-up period, there was a gradual improvement in the patient’s cardiac structure and function.ConclusionThis manuscript highlights the importance of conducting cardiac examinations before and after anti-vascular endothelial growth factor treatment, especially for individuals at risk of heart diseases like the elderly. It emphasizes the need to carefully weigh the benefits and risks of treatment regimens to ensure optimal therapeutic outcomes.