Anti-vascular Endothelial Growth Factor Agents Research Articles

Predictors of stoppage and recurrence of choroidal neovascularization with a Treat- Extend-Stop protocol: 4-year follow-up

To analyze the long-term results of treatment of active age-related macular degeneration (AMD) with anti-vascular endothelial growth factor (VEGF) agents using the treat-extend-stop (TES) approach, defining predictive factors for stoppage of the treatment and recurrences in a real-world setting. Data from 191 eyes treated with intravitreal injections for choroidal neovascularization due to AMD were retrospectively reviewed. Changes in best-corrected visual acuity (BCVA) and membrane activity (optical coherence tomography) were recorded and evaluated over a 48-month follow-up. Logistic regression analysis was used to determine predictors of treatment stoppage and recurrences after stoppage. BCVA improvement was found in 70.5% of eyes at 48 months, and remaining signs of activity in 27.9%. Disease inactivity was achieved in 69 eyes (31.9%), with a relapse of the membrane in 29 of these eyes (42.0%). Significant independent predictors of treatment stoppage were found: no foveal membrane, inactive membrane at 12, 24, 36 and 48 months, extension interval>8 weeks at 12 and 24 months,>15 injections at 24 months, and baseline BCVA>61 letters. Concerning recurrent membranes, only the presence of membrane activity at 36 months and baseline BCVA>61 letters were independent predictors. Anti-VEGF treatment of AMD using the TES protocol allows for successful visual restoration in most patients, with more likely disease inactivity in those eyes with better baseline BCVA, maintaining signs of membrane inactivity during the first two years of follow-up and requiring fewer injections.

Increases in Medicare Spending and Use after Private Equity Acquisition of Retina Practices

Private equity (PE) firms increasingly are acquiring physician practices in the United States, particularly within procedural-based specialties such as ophthalmology including retina. To date, the potential impact of ophthalmology practice acquisitions remains unknown. We evaluated the association between PE acquisition and Medicare spending and use for common retina services. Retrospective difference-in-differences analysis using the 20% Medicare fee-for-service claims dataset from January 1, 2015, through December 31,2019. Eighty-two practices acquired by PE during the study period and matched control practices. We used novel data on PE acquisitions of retina practices linked to the 20% sample Medicare claims data. Retina practices acquired by PE between 2016 and 2019 were matched to up to 3 non-PE (control) practices based on characteristics before acquisition. Private equity-acquired practices were compared with matched control practices through 6 quarters after acquisition using a difference-in-differences event study design. Data analyses were performed between August 2022 and April2023. Medicare spending and use of common retina services. Relative to control practices, PE-acquired retina practices increased the use of higher-priced anti-vascular endothelial growth factor (VEGF) agents including aflibercept, which differentially increased by 6.5 injections (95% confidence interval, 0.4-12.5; P= 0.03) per practice-quarter, or 22% from baseline. As a result, Medicare spending on aflibercept differentially increased by $13 028 per practice-quarter, or 21%. No statistically significant differences were found in use or spending for evaluation and management visits or diagnostic imaging. Private equity acquisition of retina practices are associated with modest increases in the use of higher-priced anti-VEGF drugs like aflibercept, leading to higher Medicare spending. This finding highlights the need to monitor the influence of PE firms' financial incentives over clinician decision-making and the appropriateness of care, which could be swayed by strong economic incentives. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Combination Systemic Therapies in Advanced Well-Differentiated Gastroenteropancreatic Neuroendocrine Tumors (GEP-NETs): A Comprehensive Review of Clinical Trials and Prospective Studies.

There is an evolving landscape of systemic combination regimens for patients with advanced well-differentiated gastroenteropancreatic neuroendocrine tumors (GEP-NETs). In this review, we provide a comprehensive outline of the existing clinical trials/prospective studies investigating these combinations. PubMed was searched using key relevant terms to identify articles referring to GEP-NETs and combination treatments. No systematic search of the literature or metanalysis of the data was performed, and we focused on the most recent literature results. Primarily, phase 1 and 2 clinical trials were available, with a smaller number of phase 3 trials, reporting results from combination treatments across a wide range of antiproliferative agents. We identified significant variability in the anti-tumor activity of the reported combinations, with occasional promising results, but only a very small number of practice-changing phase 3 clinical trials. Overall, the peptide receptor radionuclide therapy (PRRT)-based combinations (with chemotherapy, dual PPRT, and targeted agents) and anti-vascular endothelial growth factor (VEGF) agent combinations with standard chemotherapy were found to have favorable results and may be worth investigating in future, larger-scale trials. In contrast, the immune-checkpoint inhibitor-based combinations were found to have limited applicability in advanced, well-differentiated GEP-NETs.

Diabetes-induced retinopathy: An updated review on risk factors, diagnosis, and management strategies

Diabetes-induced retinopathy is a leading cause of visual impairment and blindness worldwide. This review provides an updated overview of the risk factors, diagnosis, and management strategies for diabetes-induced retinopathy. The pathogenesis of retinopathy in diabetes is multifactorial, involving both metabolic and vascular mechanisms. Several risk factors, including chronic hyperglycemia, hypertension, dyslipidemia, and duration of diabetes, contribute to the development and progression of retinopathy. Early detection and timely intervention are crucial for preventing vision loss and managing the disease effectively. Various diagnostic modalities, such as fundus photography, optical coherence tomography, and fluorescein angiography, play a pivotal role in the diagnosis and monitoring of retinopathy. Management strategies for diabetes-induced retinopathy encompass both medical and surgical interventions. Optimal glycemic control, blood pressure management, and lipid control are fundamental in preventing and slowing the progression of retinopathy. Additionally, novel therapeutic approaches, including anti-vascular endothelial growth factor (VEGF) agents, intravitreal steroids, and laser photocoagulation, are emerging as effective treatment options. This review aims to provide healthcare professionals with an updated understanding of the risk factors, diagnostic techniques, and management strategies for diabetes-induced retinopathy, ultimately promoting better patient care and visual outcomes.

Efficacy of as-needed intravitreal injection compared to 3-monthly loading of anti-vascular endothelial growth factor agents for branch retinal vein occlusion

We investigated the efficacy of intravitreal injection of anti-vascular endothelial growth factor (VEGF) agents in branch retinal vein occlusion (BRVO). Databases, including PubMed, EMBASE, and the Cochrane Library, were searched on November 11, 2022. Studies comparing the pro-re-nata (PRN) regimen after the first treatment (PRN group) to three consecutive monthly injection regimens followed by the PRN regimen (3 + PRN group) were investigated. The primary outcomes were the change in best-corrected visual acuity (BCVA) and the change in central retinal thickness (CRT), with the secondary outcome being the injection frequency. Among 195 reports on anti-VEGF treatment, six comparative studies were included in this meta-analysis. The two groups had no statistically significant differences in terms of BCVA or CRT. However, the total number of injections during follow-up was significantly lower in the PRN group than in the 3 + PRN group (95% CI − 2.09 to − 0.83). The as-needed injection regimen is as effective as 3-monthly loading in terms of anatomical and functional improvement for BRVO, along with a lower treatment burden for patients and physicians.

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

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

Sintilimab plus bevacizumab and CapeOx (BBCAPX) on first-line treatment in patients with RAS mutant, microsatellite stable, metastatic colorectal cancer: study protocol of a randomized, open-label, multicentric study

BackgroundRat sarcoma viral oncogene homolog (RAS) gene mutation is a common molecular event in colorectal cancer (CRC). The prognosis of mCRC (metastatic colorectal cancer) patients with RAS mutation is poor and capecitabine and oxaliplatin (CapeOx) plus bevacizumab has shown to be one of the standard therapeutic regimens as first line for these patients with objective response rate (ORR) of ~ 50% and median progression-free survival (mPFS) of 8–9 months. Immunotherapy, especially anti-programmed death 1 (PD-1) monoclonal antibody has demonstrated ground-breaking results in deficient mismatch repair (dMMR) / microsatellite instability-high (MSI-H) mCRC patients. However, the response rate of in microsatellite stable (MSS) patients is extremely low. In addition, preclinical studies have demonstrated that anti-Vascular endothelial growth factor (VEGF) agents, such as bevacizumab, can induce tumor vascular normalization and enhance antitumor immunity. Previous study indicated the combination of chemotherapy, anti-VEGF agents (bevacizumab) with immune checkpoint inhibitors may have promising clinical activity in RAS mutant, MSS refractory mCRC patients. Based on these evidences, we will explore the combination of CapeOx with bevacizumab and sintilimab (anti-PD-1 monoclonal antibody) in RAS mutant, MSS mCRC patients as first-line therapy.MethodsThis is a randomized, open-label, multicentric clinical trial. In the sintilimab arm, patients will receive sintilimab in combination with CapeOx and bevacizumab. In the control arm, patients will receive CapeOx and bevacizumab. This trial will recruit 494 patients from 20 centers and randomly (1:1) disseminated into two groups. The primary endpoint is the PFS. The secondary endpoints include overall survival, safety, ORR, and disease control rate.DiscussionThis study may provide new ideas for optimizing oncology treatment planning for RAS mutant, MSS mCRC patients in the first-line set.Trial registrationThis study is short for BBCAPX and has been registered at clinicaltrials.gov registry with identifier NCT05171660.

Long-term efficacy and complications of intravitreal anti-vascular endothelial growth factor agents combined with ablative therapies in juvenile Coats disease: a five year follow-up study.

To evaluate the long-term safety and efficacy of adjuvant intravitreal anti-VEGF therapy in juvenile Coats disease. This retrospective, observational study included a total of 62 eyes in 62 pediatric patients with juvenile Coats disease treated with intravitreal anti-VEGF agents followed for a mean of 67.08months (ranged from 60 to 93months). All affected eyes were managed initially with one session of ablative treatment plus adjuvant intravitreal anti-VEGF agent (0.5mg/0.05ml ranibizumab or conbercept). Ablative treatment was repeated if telangiectatic retinal vessels were not completely regressed or recurred. Anti-VEGF therapy was repeated if subretinal fluid or macular edema still existed. Treatments above were repeated every 2 to 3months. We reviewed clinical and photographic records of patients including the demographics, clinical characteristics and interventions. At final visit, all 62 affected eyes had partially or completely disease resolution; none progressed to advanced stage namely neovascular glaucoma or phthisis bulbi, respectively. No ocular or systemic side effects related to intravitreal injections were observed during follow-up. In terms of 42 affected eyes that could cooperate with visual examination, best corrected visual acuity improved in 14 (14/42, 33.3%) eyes, stabled in 25 (25/42, 59.5%) eyes, and worsened in 3 (3/42, 7.1%) eyes. In the field of complications, 22 (22/62, 35.5%) eyes developed cataracts; 33 (33/62, 53.2%) eyes developed vitreoretinal fibrosis, of whom 14 (14/33, 42.4%) eyes in the subgroup of stage 3B developed progressive TRD; 40 (40/62, 64.5%) eyes developed subretinal fibrosis. Multivariate regression analysis showed increased clinical stage may be associated with the development of vitreo- and subretinal fibrosis (adjusted odds ratio:16.77,17.59; 95% CI:4.50-62.53, 3.98-77.86, respectively, all P < 0.001). Adjuvant intravitreal ranibizumab or conbercept combined with ablative therapies may be a long-term safe and effective treatment for juvenile Coats disease.

Second eyes to develop neovascular age-related macular degeneration have fewer symptoms and better one-year visual outcomes

BackgroundThis study compares the visual and anatomical outcomes for the eyes of patients who developed sequential neovascular age-related macular degeneration (nAMD), both at the time of diagnosis and at one year after treatment.MethodsThe study comprised a retrospective case series of 52 patients whose eyes were diagnosed sequentially with nAMD. All eyes were treated with three monthly loading doses of anti-vascular endothelial growth factor agents, followed by further intravitreal injections, as required. Baseline characteristics and outcomes at one year after diagnosis and initial treatment were compared between first and second eyes and included visual acuity (VA), central macular thickness (CMT), and pigment epithelial detachment (PED) height on optical coherence tomography (OCT) imaging.ResultsVA at diagnosis was better for second eyes compared with first eyes to develop nAMD (logMAR 0.68 ± 0.51 versus logMAR 0.41 ± 0.34, P = 0.002) and remained so at one year (logMAR 0.61 ± 0.60 versus logMAR 0.42 ± 0.37, P = 0.041). Similarly, PED height at diagnosis was higher in first eyes (225 ± 176 μm versus 155 ± 144 μm, P = 0.003) and also at one year (188 ± 137 μm versus 140 ± 112 μm, P = 0.019). Whereas most patients reported symptoms at first eye diagnosis (71.2%), half as many second eyes were symptomatic (28.8%, P < 0.001). Significantly more symptomatic first eyes experienced visual distortions (32.4% versus 13.3%) or scotomas (29.4% versus 6.7%), compared with a less specific visual complaint of blurry vision (38.2% versus 80.0%, P = 0.006).ConclusionsCompared with first eyes to develop nAMD, second eyes tended to have better vision, smaller PED heights, and fewer symptoms likely because monitoring permitted earlier diagnosis.

The efficacy of different anti-vascular endothelial growth factor agents, and dexamethasone implant therapy in patients with serous retinal detachment caused by Irvine-Gass syndrome.

The aim of this study is to compare the efficacy of intravitreal aflibercept (IVA), bevacizumab (IVB), ranibizumab (IVR), and dexamethasone implant (IVDI) in the treatment of serous retinal detachment (SRD) caused by Irvine-Gass syndrome (IGS). Retrospective cohort, comparative study. The medical records of 128 eyes with no previous history of intravitreal agents in 128 IGS patients with SRD that received IVA, IVB, IVR, and IVDI monotherapy were retrospectively reviewed. The patients were divided into 4 groups, according to treatment. Patients with recurrence and/or were unresponsive following a course of topical steroids and non-steroidal anti-inflammatory drugs (NSAIDs) were included in the study. Best corrected visual acuity (BCVA), central macular thickness (CMT), subfoveal choroidal thickness (SFCT), and SRD were compared between the 4 treatment groups at baseline, at follow-up months 1, 3, 6, and 12, and at the final follow-up visit. Serous retinal detachment completely resolved in 74%, 45.7%, 66.4%, and 40.8% of the eyes at month 1 (P = 0.042), 87%, 50.9%, 75.8%, and 80.9% at month 3 (p = 0.031), 88.9%, 50.4%, 75.7%, 80.2% at month 6 (p = 0.028), 81.7%, 72.8%, 68.7%, 80.1% at month 12 (p = 0.580), and 100%, 66.4%, 87.9%, 93.2% (p = 0.478) at final follow-up visit in the IVA, IVB, IVR, and IVDI groups, respectively. BCVA was significantly better in the IVA group at all follow-up time points (month 1: p < 0.001; month 3: p < 0.001; month 6: p = 0.002; month 12: p = 0.009, final follow-up visit: p < 0.001). CMT was significantly lower in the IVA group at months 3 (p = 0.008), 6 (p = 0.011), and 12 (p = 0.010), and at the final follow-up visit (p < 0.001). Recurrence was observed after a longer period of time and fewer injections were needed in the IVDI and IVA groups (p < 0.05). Resolution of CME was most rapid in the IVA group (p = 0.032). All intravitreal agents were effective in terms of visual results in the SRD patients; however, eyes treated with IVA and IVDI required fewer injections, as compared to the eyes treated with IVB and IVR. Furthermore, SRD entirely resolved in all eyes in the IVA group at the final follow-up visit.

Lesion area progression in eyes with neovascular age-related macular degeneration treated using a proactive or a reactive regimen.

To compare the change in lesion area over 4 years of follow-up in eyes with neovascular age-related macular degeneration (nAMD) treated with anti-vascular endothelial growth factor (VEGF) agents using either a proactive or a reactive regimen in routine clinical practice. This was a multicentre, retrospective comparative study. Totally, 202 treatment-naïve nAMD eyes (183 patients) received anti-VEGF therapy according to a proactive (n = 105) or reactive (n = 97) regimen. Eyes were included if they had received anti-VEGF injections for a period of at least 4 years and had baseline fluorescein angiography and annual optical coherence tomography (OCT) imaging. Two masked graders independently delineated the lesion's margins from serial OCT images and growth rates were calculated. At baseline, the mean [SD] lesion area was 7.24 [5.6] mm2 in the proactive group and 6.33 [4.8] mm2 in the reactive group respectively (p = 0.22). After four years of treatment, the mean [SD] lesion area in the proactive group was 5.16 [4.5] mm2 showing a significant reduction compared to the baseline (p < 0.001). By contrast, the mean [SD] lesion area kept expanding in the reactive group during the follow-up and was 9.24 [6.0] mm2 at four years (p < 0.001). The lesion area at 4 years was significantly influenced by treatment regimen, baseline lesion area, and proportion of visits with active lesions. Eyes treated using a reactive strategy had an increased lesion area and worse visual outcomes at 4 years. By contrast, the proactive regimen was associated with fewer recurrences of active disease, shrinkage of the lesion area, and better vision at four years.

Characteristics and Treatment Patterns of Patients with Diabetic Macular Edema Non-Responsive to Anti-Vascular Endothelial Growth Factor Treatment in Ontario, Canada.

To understand the demographics, clinical characteristics, treatment patterns, visual and anatomic responses of patients with diabetic macular edema (DME) initially treated with anti-vascular endothelial growth factor (anti-VEGF) agents in the real-world clinical setting. This retrospective cohort study used electronic health records to identify consecutively presenting patients with DME who received their first documented anti-VEGF injection (index injection) on or after 1 October 2015 and before 30 September 2016 (index period) at 4 clinical sites in Ontario, Canada. Patients receiving anti-VEGF injections in the study eye were followed for ≥18 months. After the first 3 monthly injections, patients were classified as "responder" (≥20% reduction in central retinal thickness [CRT] from index date) or "nonresponder" (<20% reduction in CRT) to anti-VEGF treatment. At 12 months, change from baseline (CFB) in best visual acuity (BVA) of responders (n = 30) was mean (SD) 12.8 (13.00) letters; CFB in nonresponders (n = 56) was 3.2 (16.3) letters. Sensitivity analyses stratified by initial BVA were supportive. Mean (SD) change in CRT (μm) was -160.4 (111.4) in responders and -62.2 (98.6) in nonresponders. While changes in anti-VEGF therapy were lower in responders versus nonresponders (10.0% vs 23.2%), mean number of injections was similar (8.3 in each cohort). Despite receiving a substantial number of injections and requiring changes in therapy more frequently, nonresponders showed a lack of clinically meaningful change in BVA and CRT. Nonresponders could be identified after 3 anti-VEGF injections. There remains an unmet need for treatment options in patients with DME who show a nonresponse after 3 months of anti-VEGF treatment.

Intravitreal injections with anti-VEGF agent aflibercept versus subthreshold micropulse laser for chronic central serous chorioretinopathy: the alternative treatment regimens for verteporfin-shortage in China

Purpose To compare short-term anatomical outcomes observed in optical coherence tomography (OCT) between intravitreal injection (IVI) with anti-vascular endothelial growth factor (VEGF) agent aflibercept (IVA) and subthreshold micropulse laser (SML) therapy in chronic central serous chorioretinopathy (cCSC). Methods Thirty-nine eyes of 36 patients with symptomatic cCSC in this retrospective study received either IVA or SML between December 2020 and August 2022. Spectral-domain-OCT (SD-OCT) findings were compared between the two treatment groups in terms of central macular thickness (CMT), serous subretinal fluid (SRF) height, the presence of pigment epithelial detachment (PED) and subretinal hyperreflective foci (HF) at baseline and one-month follow-up visits. Results Both groups showed significant reductions in CMT and SRF at one-month follow-up visit. However, there were no statistically significant differences between the IVA and SML groups. Complete SRF resolution was observed in 10 out of 21 and 7 out of 18 eyes in the IVA and SML groups, respectively; however, retinal pigment epithelial (RPE) damage remained persistent in patients with PEDs at baseline. Conclusions Both IVA and SML were effective in treating cCSC. IVA and SML treatments had comparable effects in reducing CMT and SRF in eyes with cCSC. Further prospective studies with larger sample sizes and long-term follow-up visits are warranted to identify the long-term efficacy.

Evaluation of the efficacy of anti-vascular endothelial growth factors in diabetic macular edema with retinal inner and outer layers disorganization.

This study aims to compare the effectiveness of treatment between anti-vascular endothelial growth factor (anti-VEGF) agents in diabetic macular edema (DME) patients with disorganization of retinal inner layers (DRIL). Epiretinal membrane, serous macular detachment, ellipsoid zone (EZ) disorder, external limiting membrane (ELM) disorder, and hyperreflective foci were also examined. Patients treated for DME and also had DRIL were included in the study. The study design was retrospective and cross-sectional. The complete ophthalmologic records and imaging were scanned at the beginning, 3rd-month, 6th-month, and 12th-month follow-up, and the treatments administered were recorded. Anti-VEGF agents administered to the patients were examined in three groups: bevacizumab, ranibizumab, and aflibercept. A total of 141 eyes of 100 patients were included in our study. One hundred and fifteen eyes (81.6%) had a BCVA of 0, 5, or less at the beginning. There was no statistically significant difference between the three groups regarding initial BCVA and CMT and the change in BCVA and CMT at the beginning and the 12th month (p > 0.05). There was a negative correlation between EZ and ELM disorders in patients and the change in BCVA at 12months (r: 0.45 p < 0.001, r: 0.32 p < 0.001, respectively). The number of injections over five was positively correlated with the change in CMT but not with BCVA (r: - 2.35 p = 0.005 and r: 0.147 p = 0.082, respectively). No statistically significant difference was found between anti-VEGF agents when treating DME patients with DRIL. In addition, we have shown that anatomically better results were obtained in those who had five or more injections, although not in terms of BCVA.

A novel retinoic acid drug, EYE-502, inhibits choroidal neovascularization by targeting endothelial cells and pericytes

Choroidal neovascularization (CNV) occurs in neovascular age-related macular degeneration (AMD) and often leads to permanent visual impairment. Intravitreal injection of anti-vascular endothelial growth factor (VEGF) agents is the gold standard for the treatment of CNV. However, anti-VEGF treatment did not always cause vision improvement and sometimes had detrimental effects on normal retinal tissues. Herein, we identified a novel retinoic acid drug, EYE-502, which had great therapeutic effects on CNV. Administration of EYE-502 could inhibit VEGF-induced dysfunction of endothelial cells (ECs) and reduce platelet-derived growth factor (PDGF)-induced recruitment of pericytes to ECs in vitro. Administration of EYE-502 could reduce the area of choroidal sprouting and laser-induced CNV, exhibiting similar anti-angiogenic effects as aflibercept. Moreover, administration of EYE-502 could reduce pericyte coverage in the sprouting vessels and choroidal neovascularization. Mechanistically, EYE-502 primarily bound to retinoic acid receptors (RARs) and exerted the anti-angiogenic effects by targeting ECs and pericytes via affecting the activation of Wnt/β-catenin and PDGF/PDGFR/PI3K/Akt signaling. Taken together, this study reports a novel retinoic acid drug, EYE-502, which can exert the anti-angiogenic effects by simultaneous targeting of ECs and pericytes.

Pars plana vitrectomy versus intravitreal antibiotics for endophthalmitis management following intravitreal anti-VEGF agents: A meta-analysis.

In this meta-analysis, we aim to compare the efficacy and safety of pars plana vitrectomy (PPV) versus tap-and-inject (TAI) of intravitreal antibiotics for the management of endophthalmitis secondary to intravitreal injections of anti-vascular endothelial growth factor (VEGF) agents. A systematic literature search was conducted on Ovid MEDLINE, EMBASE, and Cochrane Central (January 2005-October 2022). The primary analysis compared initial PPV versus TAI and the secondary analysis examined the efficacy and safety of TAI alone compared to TAI followed by PPV. The quality of non-randomized observational studies was assessed using the Newcastle-Ottawa Scale. The quality of the evidence was assessed for each outcome. A random effects meta-analysis was performed. Weighted mean differences (WMDs) with 95% confidence intervals were reported. Of the 7474 screened studies, nine studies reporting on 153 eyes were included. The change in mean best corrected visual acuity (BCVA) between endophthalmitis presentation and last follow-up did not significantly differ between the initial TAI versus PPV groups (WMD = 0.05 units; 95% CI -0.12 to 0.22; p = 0.59; heterogeneity p = 0.41). The difference in pre- to post-treatment mean BCVA did not significantly differ between eyes that received TAI alone or TAI followed by PPV (WMD = 0.04 units; 95% CI -0.42 to 0.51; p = 0.85; heterogeneity p = 0.74). While the meta-analysis revealed no significant difference in the change in BCVA between PPV and TAI to treat endophthalmitis secondary to anti-VEGF agents, the quality of evidence was low with potential for confounding and selection bias. Further well-designed studies in this setting are needed.

The Efficacy, Safety, and Efficiency of the Off-Label Use of Bevacizumab in Patients Diagnosed With Age-Related Macular Degeneration: Protocol for a Systematic Review and Meta-Analysis

Background Age-related macular degeneration (AMD) is recognized as the leading cause of vision loss in older people. Considering the phenomenon of aging societies worldwide, the prevalence of AMD is expected to increase gradually in the future. AMD can be divided into early, intermediate, and late stages, with the early and intermediate stages being mainly asymptomatic, and the late stage being classified as geographic atrophy, neovascular AMD, or both. Current pharmacological treatments for neovascular AMD include anti–vascular endothelial growth factor agents, such as ranibizumab, pegaptanib, and aflibercept. Additionally, it has been reported that the off-label use of intravitreally administered bevacizumab is effective. It is also lower cost than other agents, which makes it an interesting pharmacological approach. Objective This review aims to evaluate the efficacy, safety, and efficiency of bevacizumab for the treatment of neovascular AMD. Methods This review will only consider randomized controlled clinical trials that compare the use of bevacizumab with another pharmacological agent or a placebo in patients aged 50 years and older who are diagnosed with vascular AMD. It will exclude studies that include participants diagnosed with polypoidal choroidal vasculopathy or retinal angiomatous proliferation. To identify and select relevant articles, we will develop a highly sensitive search strategy and apply it in MEDLINE via the PubMed platform. Upon selection of the studies and analysis of the titles, abstracts, and full texts, the results will be presented according to the Preferred Reporting Items of Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The analysis and extraction of the data will be performed by 2 independent reviewers. Risk of bias will be evaluated with the Critical Appraisal Skills Programme (CASP) checklist. Finally, the same reviewers will also perform a quality assessment of the included studies with the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) tool. Results The search strategy, after the application of the inclusion and exclusion criteria, identified 15 randomized clinical trials, which are currently being analyzed. This project has no funding and it has been developed by a multidisciplinary research team of pharmacologists and orthoptists. The study was initiated in May 2021 and it is expected to conclude by the end of 2023. Conclusions This review will provide a synthesis of current information and underlying evidence about the off-label use of bevacizumab in neovascular AMD. It will provide a clearer vision of a possible new pharmacological approach, as well as the most suitable treatment designs, for the treatment of neovascular AMD. Trial Registration PROSPERO CRD42021244931; https://tinyurl.com/p6m5ycpk International Registered Report Identifier (IRRID) DERR1-10.2196/38658

LONG-TERM PROGNOSIS OF CHOROIDAL NEOVASCULARIZATION COMPLICATING ANGIOID STREAKS.

To report the very long-term visual prognosis of choroidal neovascularization complicating angioid streaks in the antivascular endothelial growth factor era. Retrospective monocentric study aimed at analyzing patients' demographics, choroidal neovascularization features, angioid streak-associated conditions, and previous and current therapies for choroidal neovascularization. The main outcome measures were the quantitative measurement of central retinal pigment epithelial atrophy enlargement by comparing the ratio of pixels involved on automated infrared images acquired by spectral-domain optical coherence tomography and the changes in best-corrected visual acuity. The secondary outcome measures were the number of intravitreal injections and the changes in central choroidal thickness and central retinal thickness. Subgroup analyzes were performed to compare macular atrophy extent between eyes of patients with or without proven pseudoxanthoma elasticum ("PXE" or "no PXE") and between eyes previously treated or not with photodynamic therapy ("PDT" or "no PDT"). Thirty-three eyes of 23 patients were included. The mean best-corrected visual acuity decreased significantly from 66 ± 19 Early Treatment Diabetic Retinopathy Study letters at the time of the first antivascular endothelial growth factor injection to 52 ± 23 Early Treatment Diabetic Retinopathy Study letters at the end of the follow-up (mean follow-up duration: 109 ± 42 months, range: 47-175 months). The ratio of central retinal pigment epithelial atrophy enlargement was 201%, 110%, 240%, and 111% in the PXE, no PXE, PDT, and no PDT groups, respectively. Despite the use of antivascular endothelial growth factor agents, the very long-term prognosis appeared relatively poor, especially in patients with PXE. This study also suggests that PDT should be used with caution in the management of choroidal neovascularization in eyes with angioid streaks.

EE191 An Investigation of the Economic Burden of Treatment for Namd/Dme on Treatment Recipients and Caregivers in the US

Neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME) are conditions which can lead to irreversible vision loss. Intravitreal injection of anti-Vascular Endothelial Growth Factor (VEGF) agents is the standard of care for people with nAMD and DME in the US. We investigated the economic burden of treatment for nAMD and DME on patients and their caregivers.

Anti-vascular endothelial growth factors in combination with vitrectomy for complications of proliferative diabetic retinopathy.

Anti-vascular endothelial growth factors in combination with vitrectomy for complications of proliferative diabetic retinopathy.