Aflibercept Treatment Research Articles

Impact of Prolonged Persisting Subretinal Fluid on the Outcome of Aflibercept Treatment in Neovascular Age-Related Macular Degeneration.

Purpose: To evaluate the effect of prolonged residual subretinal fluid (SRF) on the outcomes of aflibercept treatment in neovascular age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV). Methods: This retrospective study included patients diagnosed with neovascular AMD or PCV who presented with fovea-involving residual SRF that persisted for a minimum of 6 months while undergoing aflibercept treatment. Changes in best-corrected visual acuity (BCVA) during persistent SRF were evaluated. The factors associated with the risk of visual deterioration during this period were also investigated. Results: In total, 135 patients were included in this study. During this period, the duration of the presence of residual SRF was 17.1 ± 10.3 months and mean injection interval was 2.6 ± 0.7 months. The mean BCVA was changed from 0.30 ± 0.23(Snellen equivalents, 20/39) to 0.36 ± 0.28 (20/45). In 18 (13.3%) patients, ≥2 lines of visual deterioration was noted. The duration of persisting SRF (P = 0.008) and mean height of SRF (P = 0.005) were significantly associated with a high risk of visual deterioration. Among the 80 patients with mean SRF height <100 μm, ≥2 lines of visual deterioration were noted in 4 (5.0%) patients. Among 41 patients with the mean SRF height ≥100 μm and <200 μm and 14 patients with the mean SRF height ≥200 μm, the visual deterioration was noted in 8 (19.5%) and 6 (42.9%) patients, respectively. Conclusions: In cases of neovascular AMD or PCV in which SRF persists without complete resolution during treatment, minimizing the duration of persistent SRF and mean height of SRF is recommended to mitigate the risk of visual deterioration. ClinicalTrials.gov Identifiers: NCT05662943 (https://clinicaltrials.gov/study/NCT05662943?cond=type%201%20macular%20neovascularization&rank=2).

The impact of COVID-19 on aflibercept treatment of neovascular AMD in Sweden – data from the Swedish Macula Register

BackgroundThe purpose of the study was to compare the real-world aflibercept treatment and visual outcomes, and to examine the adherence to pandemic guidelines in two groups of patients with treatment-naïve neovascular age-related macular degeneration (nAMD) before and during the first year of the COVID-19 pandemic in Sweden up to the 1-year follow-up.MethodsThis is a retrospective observational study including 2915 treatment naïve eyes with nAMD. Using data from the Swedish Macula Register (SMR), 1597 eyes initiating treatment between 1 July 2018 and 31 January 2019 (pre-pandemic group) were compared with 1318 eyes starting treatment between 1 February and 31 August 2020 (pandemic group). The eyes were then followed for 1 year ± 2 months, hence the first group was unaffected by the pandemic while the second group was affected. The focus was on baseline characteristics, visual acuity (VA) change from baseline, number of injections, treatment regimen, number of appointments and the frequency and length of appointment delays. The Wilcoxon Signed-Rank Test was used to compare baseline VA to follow-up VA within the respective groups. The Mann-Whitney U-test and Fisher’s exact test were used to compare outcomes between the groups.ResultsBaseline characteristics were similar between the two groups. The percentage of eyes with an available follow-up VA after 1 year was 58% in the pre-pandemic group vs. 44% in the pandemic group. VA in the pre-pandemic group had increased significantly after 1 year, from 62.2 ± 14.1 letters to 64.8 ± 16.1 letters (n = 921); p < 0.0001. In the pandemic group, VA increased from 61.1 ± 15.8 to 64.9 ± 16.9 (n = 575); p < 0.0001. There was no significant difference in mean VA change between the groups; p = 0.1734. The pre-pandemic group had significantly more delays than the pandemic group, 45% vs. 36%; p < 0.0001.ConclusionsThe pre-pandemic and pandemic groups had similar VA gains at 1-year follow-up, but with a reduced number of available VA in the pandemic group. Clinics were able to implement and prioritize injection visits excluding VA measurements, helping to reduce delays and maintain VA gains during the COVID-19 pandemic.

Differences in aqueous humor protein profiles in patients with proliferative diabetic retinopathy before and after aflibercept treatment

PurposeTo investigate the changes in aqueous humor (AH) protein profiles before and after intravitreal aflibercept (IVA) treatment in patients with proliferative diabetic retinopathy (PDR).Methods5 PDR patients provided 10 samples of AH before and after IVA treatment (pre-group vs. post-group). Proteins were identified using liquid chromatography-tandem mass spectrometry. Then, bioinformatics was employed to investigate the functional significance of differentially expressed proteins (DEPs) and hub proteins.ResultsA total of 16 DEPs were identified, consisting of 8 downregulated proteins and 8 upregulated proteins. Bioinformatics analysis indicated that the most significantly enriched biological process was “blood coagulation, intrinsic pathway.” The most significantly enriched signaling pathway was “complement and coagulation cascades.” HBB, HPX, VEGFA, and CA1 were identified as hub proteins for IVA treatment.ConclusionsTogether with the downregulation of the intravitreal vascular endothelial growth factor level, IVA may also change the AH protein composition in PDR patients, with DEPs involved in the blood coagulation, intrinsic pathway, complement, and coagulation cascades. IVA treatment may protect against PDR by regulating HBB, HPX, VEGFA, and CA1 expression.

Efficacy of the combination of intravitreal aflibercept and triamcinolone injections in treatment of diabetic macular edema

Purpose: To investigate the clinical efficacy of intravitreal aflibercept combined with intravitreal triamcinolone injection in the treatment of diabetic macular edema (DME).&#x0D; Methods: 86 patients with diabetic macular edema (DME) were randomly assigned to either a combination therapy group (n = 43) or a control group (n = 43). Both groups received intravitreal aflibercept injection (2 mg, 5 injections per month) while combination therapy group received aflibercept treatment in addition. Central macular thickness (CMT), intraocular pressure (IOP), best-corrected visual acuity (BCVA), serum inflammatory factors (IL-6 and IL-8), VEGF and quality of life were determined before and after treatment at multiple time-points.&#x0D; Results: Combination therapy group achieved a significantly higher total effective rate compared to control group (p &lt; 0.05). When compared to the baseline, CMT and BCVA in both groups gradually decreased over 3 months after injection, with combination therapy group showing a greater reduction (p &lt; 0.05). The IOP and SQOL-DVI scores in both groups increased over time in both groups, with a greater increase observed in combination therapy group compared to the baseline (p &lt; 0.05). Serum inflammatory factors decreased in both groups, with combination therapy group having significantly lower levels (p &lt; 0.05).&#x0D; Conclusion: The combination of intravitreal aflibercept and triamcinolone injection has better efficacy than intravitreal aflibercept injection alone in the treatment of diabetic macular edema, improving visual function and enhancing the quality of life of the patients. More elaborate studies are required to elucidate the mechanism of this synagistic therapeutic combination.

XTEND: Two-Year Results from a Global Observational Study Investigating Proactive Dosing of Intravitreal Aflibercept in Neovascular Age-Related Macular Degeneration.

XTEND (NCT03939767) is a multicenter, observational, prospective study of patients with treatment-naïve neovascular age-related macular degeneration (nAMD) in routine clinical practice. The study aims to examine treatment outcomes of proactive intravitreal aflibercept (IVT-AFL) treatment regimens (fixed dosing or treat-and-extend) according to local marketing labels. Study eyes received IVT-AFL injections as per the local label. The mean changes in best-corrected visual acuity (BCVA) and central subfield thickness (CST) from baseline to month (M) 12 and M24 were measured and stratified by baseline factors. Treatment exposure and safety data were evaluated. Statistical analysis was descriptive. Overall, 1466 patients from 17 countries were treated. For the overall population, the mean ± standard deviation (SD) age was 78.7 ± 8.5 (range 50-100)years, and 891 patients (60.8%) were female. The mean ± SD baseline BCVA was 54.3 ± 20.3 letters and CST was 374 ± 126µm. At M12 and M24, mean (95% confidence interval [CI]) BCVA change was + 4.3 (3.4, 5.3) and + 2.3 (1.3, 3.3) letters, respectively. Mean (95% CI) CST was - 106 (- 114, - 99) μm and - 109 (- 117, - 102) μm at M12 and M24, respectively. At M24, 41.5% of patients had a BCVA ≥ 70 letters. Patients received a mean ± SD of 7.7 ± 2.7 injections by M12 and 10.8 ± 5.0 injections by M24 (3.1 injections between M12 and M24). Adverse events were consistent with the known safety profile of IVT-AFL. The 24-month results indicate that, in routine clinical practice, a proactive IVT-AFL regimen achieves functional improvements in patients with treatment-naïve nAMD. The proportion of patients achieving ≥ 70 letters at M24 increased, and patients with baseline BCVA ≥ 70 letters maintained vision regardless of the followed IVT-AFL label. ClinicalTrials.gov identifier: NCT03939767. A video abstract is available for this article. Supplementary file2 (MP4 364624 KB).

Aflibercept treatment for delayed retinotomy-associated choroidal neovascularization: A case report and literature review

Abstract: A 67-year-old male presented to our clinic with sudden onset of blurred vision and metamorphopsia of his left eye for 2 weeks. He had a history of combined rhegmatogenous retinal detachment and vitreous hemorrhage and underwent an uneventful pars plana vitrectomy, 360° scleral buckling, and drainage retinotomy for his left eye 3 years ago. The anatomic and visual outcomes after surgery were good, without complications. On examination during this visit, an orange–red subretinal mass connected to the previous drainage retinotomy scar was noted. Spectral-domain optical coherence tomography revealed severe subretinal fluid with type-2 choroidal neovascularization (CNV) mass at the superior nasal macular area in connection with the margin of the previous retinotomy scar. Fundus fluorescein angiography showed an active CNV. The patient underwent monthly intravitreal aflibercept in the left eye. After four doses of aflibercept, his CNV regressed with no recurrence on follow-up at 20 months. In conclusion, iatrogenic CNV is a rare complication following uneventful vitreoretinal surgery and can develop years after the operation. It is crucial to early diagnose and treat it with intravitreal antivascular endothelial growth factor treatment for a favorable outcome and long-term remission.

Aflibercept treatment with treatment-extend regimen in bevacizumab-resistant nAMD: Real-life experience

Aflibercept treatment with treatment-extend regimen in bevacizumab-resistant nAMD: Real-life experience

Expert Panel Consensus for Optimizing Outcomes in Neovascular Age-Related Macular Degeneration in the Context of Suboptimal Response to a Biosimilar: The Role of Aflibercept.

The inclusion of ranibizumab biosimilars into National Health Service England commissioning recommendations published in 2022 created a need for expert guidance to optimize treatment outcomes in patients with neovascular age-related macular degeneration (nAMD) who otherwise may not have received first-line ranibizumab. This article provides a consensus treatment pathway supporting timely identification and management of a suboptimal response to these therapies, thereby aiming to facilitate clinically meaningful outcomes and efficient management of service capacity under specific circumstances where ranibizumab biosimilars may be initiated as a first-line treatment. Two structured round-table meetings of UK medical retina specialists were held in person and virtually on September 22 and November 3, 2022, respectively. These meetings were organized and funded by Bayer. The panel provided guidance on the implementation of an early treatment optimization pathway in cases where ranibizumab biosimilars are used as a first-line treatment, including recommendations on patient suitability and capacity requirements, and criteria for identification and strategies for management of a suboptimal response. The panel discussed the role of aflibercept treatment and its potential benefits and outlined recommendations on switching ranibizumab biosimilar suboptimal responders to an aflibercept treat-and-extend regimen, where appropriate. Developed by a retinal expert panel, this early treatment optimization pathway provides guidance to facilitate optimal long-term patient outcomes while addressing capacity and resourcing constraints in circumstances of first-line ranibizumab biosimilar use for nAMD, including how aflibercept may be used in cases with a suboptimal response. Therefore, this fills an important gap in guidance on navigating the new treatment landscape.

Correlations between subfoveal choroidal thickness, macular thickness, and visual outcome in neovascular age-related macular degeneration using swept source OCT: insights from intravitreal aflibercept treatment

BackgroundAge-related macular degeneration (AMD) is a leading cause of visual impairment among individuals aged 50 and above, often resulting in irreversible vision loss (1). Currently, antiangiogenic therapy is the primary treatment approach for neovascular AMD (2). The choroid has gained significant attention in recent years due to its involvement in various ocular pathologies (7). The objective of this study was to evaluate visual acuity and correlate pre-treatment variables, such as foveal thickness and choroidal thickness, with post-treatment outcomes.Materials and MethodsThis study was designed as a prospective interventional study to investigate the changes in choroidal and macular thickness in patients with neovascular AMD who received intravitreal aflibercept injections. The study utilized medical records and employed Swept Source Optical Coherence Tomography (OCT-SS) for evaluation. The data was collected from patients treated in Presidente Prudente, Brazil, during a three-month load dose period.ResultsThe best-corrected mean visual acuity significantly improved from 1.0 logarithm of the minimum resolution angle (logMAR) units to 0.55 logMAR after treatment with aflibercept (p < 0.001). Patients undergoing treatment exhibited a significant decrease in average macular thickness from 323 μm to 232 μm (p = 0.001), as well as a reduction in choroidal thickness from 206 μm to 172 μm (p = 0.031), while maintaining intraocular pressure within the normal range (p = 0.719) without significant variation. Statistically significant associations were found between the difference in pre- and post-treatment choroidal thickness and the pretreatment values of macular thickness (p = 0.005) and choroidal thickness (p = 0.013). There was also a statistically significant correlation between the difference in pre- and post-treatment macular thickness and the pretreatment macular thickness value (p < 0.001).ConclusionIn this study, aflibercept exhibited remarkable effectiveness in reducing macular and choroidal thickness, as evaluated using OCT-SS, and significantly improved visual acuity in patients with neovascular AMD. The assessment of both choroidal and macular changes, as well as their correlations, can provide valuable insights for clinicians, enabling them to make well-informed therapeutic decisions and effectively monitor treatment outcomes. Notably, this study contributes to the existing body of literature as the first to establish a correlation between pretreatment foveal thickness, variation in choroidal thickness, and post-treatment choroidal thickness.

Real-World Management of Macular Edema Secondary to Retinal Vein Occlusion with Intravitreal Aflibercept: 24-month Results from the AURIGA Observational Study.

AURIGA is the largest real-world study to date to evaluate intravitreal aflibercept (IVT-AFL) treatment of diabetic macular edema or macular edema secondary to retinal vein occlusion (RVO) in routine clinical practice. Here, we report the 24-month outcomes in the RVO cohort from France, Germany, Italy, and Taiwan. AURIGA (NCT03161912) was a prospective observational study. Eligible patients with RVO were enrolled for whom the decision to treat with IVT-AFL had already been made by the attending physician. Patients were treated with IVT-AFL for up to 24 months at physician discretion according to local practice. The primary endpoint was mean change in visual acuity (VA; Early Treatment Diabetic Retinopathy Study [ETDRS] letters) from baseline to month (M) 12. All statistical analyses were descriptive. In 554 treatment-naïve and 65 previously treated patients with RVO, the respective mean (95% confidence interval) change in VA from baseline was + 12.5 (10.8, 14.3) and + 7.9 (3.3, 12.6) letters by M12 and + 11.4 (9.4, 13.3) and + 4.4 (- 0.6, 9.5) letters by M24 (baseline mean ± standard deviation: 51.0 ± 21.9 and 51.9 ± 20.4 letters); 44.0% of treatment-naïve and 27.9% of previously treated patients reported ≥ 15-letter gains by M24. By M24, the mean change in central retinal thickness from baseline was - 247 (- 267, - 227) µm in treatment-naïve patients and - 147 (- 192, - 102) µm in previously treated patients. From baseline to M6, M12, and M24, treatment-naïve patients received a total of 4.0 ± 1.3, 5.5 ± 2.5, and 6.9 ± 4.2 injections, respectively, and previously treated patients received 3.8 ± 1.5, 5.0 ± 2.2, and 6.3 ± 3.7 injections, respectively. The safety profile of IVT-AFL was consistent with that of previous studies. In AURIGA, patients with RVO experienced clinically relevant functional and anatomic improvements following IVT-AFL treatment in routine clinical practice. These improvements were largely maintained in treatment-naïve patients over the 24-month study despite the decreasing treatment frequency, suggesting long-term durability of IVT-AFL treatment outcomes.Infographic available for this article. ClinicalTrials.gov Identifier: NCT03161912 (May 19, 2017). INFOGRAPHIC.

Longitudinal Quantitative Ultrawidefield Angiographic Features in Diabetic Retinopathy Treated with Aflibercept from the Intravitreal Aflibercept as Indicated by Real-Time Objective Imaging to Achieve Diabetic Retinopathy Improvement Trial

To report longitudinal trends of quantitative ultrawidefield fluorescein angiography (qUWFA) biomarkers in the Intravitreal Aflibercept as Indicated by Real-Time Objective Imaging to Achieve Diabetic Retinopathy Improvement (PRIME) diabetic retinopathy (DR) clinical trial. Post hoc analysis of the PRIME prospective randomized DR clinical trial comparing intravitreal aflibercept treatment based on the DR severity score (DRSS) or quantitative leakage index for DR improvement (ClinicalTrials.gov identifier: NCT03531294). Patients were enrolled with a DRSS level of 47A to 71A and best-corrected visual acuity of 20/800 or better. Key exclusion criteria were previous intravitreal injection, panretinal photocoagulation, vitrectomy, central-involving macular edema, or vitreous hemorrhage. A previously validated, machine learning-based qUWFA analysis platform was used for panretinal leakage index assessment and differentiation of generalized and perivascular leakage phenotypes. Additionally, microaneurysm count and ischemic index were quantified in panretinal and macular regions. The trends in these biomarkers and therapeutic response were studied over 1 year. Longitudinal trends of qUWFA biomarkers. The impact of these qUWFA metrics on treatment response was assessed by studying their associations with time to 2-step DRSS improvement and number of treatment-free days. Forty eyes from 40 subjects with DR were enrolled. Lower baseline generalized leakage was noted in eyes that attained the 2-step DRSS improvement in < 16 weeks (1.9% vs. 2.8%; P= 0.026). Baseline macular perivascular-generalized leakage ratio had a significant correlation with the number of treatment-free days (r= 0.4; P= 0.012). At the end of 1 year, therapy significantly reduced the mean panretinal (3.9% vs. 5.8%; P= 0.002) and macular (6.2% vs. 12.2%; P= 0.008) generalized leakage indices compared with baseline, as well as the mean panretinal perivascular leakage index (1.5% vs. 2.3%; P= 0.002). The mean panretinal ischemic index demonstrated a small but likely clinically insignificant decrease from 12.5% at baseline to 11.6% at year 1 (P= 0.016). Down-trending leakage indices and microaneurysm counts were demonstrated over 1 year of anti-VEGF therapy. At baseline, DR eyes with lower generalized leakage responded to therapy more rapidly. Eyes with greater perivascular leakage relative to generalized leakage showed a longer-lasting anti-VEGF treatment response. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Factors Affecting Intensive Aflibercept Treatment Response in Diabetic Macular Edema: A Real-World Study.

To investigate the systemic and ocular factors that affect the response to intensive aflibercept treatment in diabetic macular edema (DME) in a real-world setting. This retrospective cohort study evaluated 30 eyes of 23 patients with DME who underwent intensive intravitreal aflibercept injections (five monthly loading doses). Treatment response was assessed by central retinal thickness (CRT) and best-corrected visual acuity (BCVA) at each monthly visit. The patients were categorized as good (<300 μm) and suboptimal (≥300 μm) responders based on CRT after the loading phase. Baseline systemic and ocular factors associated with treatment response were investigated. The mean CRT and BCVA significantly improved after five loading injections (486.87 ± 95.46 to 334.90 ± 69.47 μm and 0.51 ± 0.30 to 0.35 ± 0.25 LogMAR, respectively, all p < 0.05). During 12 months of follow-up, 16 eyes (53.33%) maintained CRT without additional treatment. Eyes with diabetes mellitus (DM) for ≥15 years, estimated glomerular filtration rate (eGFR) < 80 mL/min/1.73 m2, serum creatinine ≥ 0.95 mg/dL and potassium ≥ 4.7 mmol/L, and presence of epiretinal membrane (ERM) were more likely to have a suboptimal response to the treatment. Five monthly loading doses of intravitreal aflibercept injection provided significant anatomical and visual improvements in patients with DME. Patients with longer DM duration, lower eGFR, higher serum creatinine or potassium levels, or ERM were predisposed to a suboptimal treatment response. Individual response to intensive aflibercept treatment for DME can be predicted by these systemic and ocular risk factors.

Long-term surveillance provides real-world evidences of safety and effectiveness in intravitreal aflibercept treatment for age-related macular degeneration

This prospective, multicentre, postmarketing surveillance were conducted to report on the long-term safety and effectiveness of intravitreal aflibercept (IVT-AFL) treatment in clinical practice of Japanese patients with neovascular age-related macular degeneration (nAMD) who newly initiated IVT-AFL treatment. The primary outcomes were the incidence of adverse events (AEs) and of adverse drug reactions (ADRs) over 36 months. Number of injections, timing of ADR occurrence, and some effectiveness index were also summarised. A total of 3,872 patients received 7.2 ± 5.8 (mean ± standard deviation) injections, and AEs occurred in 5.73% of patients. ADRs were reported in 2.76% of patients, with ocular and nonocular ADRs in 2.07% and 0.72% of patients, respectively. Most vitreo-retinal events developed within 6 months of initial IVT-AFL treatment, and most instances of increased intraocular pressure and cerebral infarction developed after 6 months of follow-up. Mean best-corrected visual acuity and central retinal thickness were numerically better throughout the follow-up period compared with baseline. These results indicated acceptable tolerability and effectiveness of IVT-AFL treatment in patients with nAMD in clinical practice in Japan. Information regarding the risk and the timing of ADRs is valuable for safe and effective long-term treatment of patients with nAMD.Trial registration number: NCT01756248.

Faricimab Effectively Resolves Intraretinal Fluid and Preserves Vision in Refractory, Recalcitrant, and Nonresponsive Neovascular Age-Related Macular Degeneration.

To evaluate the functional and anatomic outcomes of faricimab treatment in patients with neovascular age-related macular degeneration (nAMD) who are unresponsive to other anti-vascular endothelial growth factor (VEGF) therapies. A retrospective interventional study was conducted on patients with refractory nAMD who were initially treated with intravitreal bevacizumab, ranibizumab, or aflibercept. These patients were switched to monthly faricimab injections. The central subfield thickness (CST), intraretinal fluid (IRF)or subretinal fluid (SRF) height, and visual acuities were compared before and after faricimab treatment. A total of 13 eyes (eight right eyes and five left eyes) from 11 patients were followed for 10.4 ± 6.9 months after bevacizumab treatment and 40.3 ± 28.7 months after aflibercept treatment before switching to faricimab. The follow-up time for patients receiving a mean number of 3.7 ± 1.3 faricimab injections was 3.4 ± 1.2 months. The overall median CST was reduced by 18µm (p=0.001) from 342µm to 318µm, along with a reduction of 89µm (p=0.03) in IRF/SRF height from 97µm to 40µm. Following three consecutive injections, the CST showed a significant reduction of 21.5µm (p=0.004) from 344µm to 322.5µm, and IRF/SRF height was reduced by 89µm (p=0.03) from 104µm to 18.5µm. The intraretinal fluid size decreased and leakage stopped, as seen on fluorescein angiography. Visual acuity remained stable after switching to faricimab treatment (0.59 ± 0.45 logMAR vs 0.58 ± 0.45 logMAR, p=1). Faricimab has proven to be an effective treatment for nAMD patients resistant to other anti-VEGF agents. It demonstrates significant anatomical improvement and vision preservation in this challenging patient population.

Aflibercept for long-term treatment of diabetic macular edema and proliferative diabetic retinopathy: a meta-analysis.

This meta-analysis compared the long-term (12 months or 24 months) efficacy and safety of intravitreal aflibercept injection (IAI) for diabetic macular edema (DME) and proliferative diabetic retinopathy (PDR). We selected 16 randomized controlled trials (RCTs) performed after 2015 that had a minimum of 12 months and up to 24 months of treatment and conducted a meta-analysis with Review Manager version 5.3. Visual acuity (VA), central subfield thickness (CST) and adverse events were the outcomes selected for evaluation from the eligible studies. Based on 16 RCTs, we evaluated a total of 7125 patients. For PDR and severe DME with poor baseline vision, after a minimum of 12 months and up to 24 months of treatment, the aflibercept treatment group obtained better VA improvement than the focal/grid laser photocoagulation treatment group (MD=13.30; 95%CI: 13.01~13.58; P<0.001) or other treatments (ranibizumab, focal/grid laser photocoagulation, PRP, etal.) group (MD=1.10; 95%CI: 1.05~1.16; P<0.001). In addition, the aflibercept treatment group got higher CST reduction than the focal/grid laser photocoagulation treatment (MD=-33.76; 95%CI: -45.53 ~ -21.99; P<0.001) or other treatments (ranibizumab, focal/grid laser photocoagulation, etal.) group (MD=-33.76; 95%CI: -45.53 ~ -21.99; P<0.001). There was no significant difference in the overall incidence of ocular and non-ocular adverse eventsin eachtreatmentgroup. This meta-analysis showed that the advantages of IAI are obvious in the management of DME and PDR with poor baseline vision for long-term observation (a minimum of 12 months and up to 24 months) with both VA improvement and CST reduction. Applied IAI separately trended to be more effective than panretinal photocoagulation separately in VA improvement for PDR. More parameters should be required to assess functional and anatomic outcomes.

Predictive factors for treatment outcomes with intravitreal anti-vascular endothelial growth factor injections in diabetic macular edema in clinical practice

BackgroundIntravitreal anti-vascular endothelial growth factor (anti-VEGF) injections are the standard of care for diabetic macular edema (DME), a common complication of diabetes. This study aimed to identify factors influencing DME intravitreal anti-VEGF treatment outcomes in real-world practice.MethodsThis was a multi-center retrospective observational study using medical chart review of participants receiving anti-VEGF injections for DME (N = 248). Demographic and clinical variables were assessed for association with best corrected visual acuity (BCVA) and central macular thickness (CMT) outcomes using regression models.ResultsThere was a significant improvement in BCVA (p < 0.001) and CMT (p < 0.001) after 12 months of treatment, although 21% of participants had decreased BCVA, and 41% had a < 10% CMT reduction at 12 months. Higher baseline BCVA (p = 0.022, OR=-0.024, 95% CI=-0.046,-0.004) and longer duration of diabetic retinopathy (p = 0.048, OR=-0.064, 95% CI=-0.129,-0.001) were negative predictors for BCVA response, whereas Aflibercept treatment (p = 0.017, OR = 1.107, 95% CI = 0.220,2.051) compared with other drugs and a positive “early functional response” (p < 0.001, OR=-1.393, 95% CI=-1.946,-0.857) were positive predictors. A higher baseline CMT (p < 0.001, OR = 0.019, 95% CI = 0.012,0.0261) and an “early anatomical response”, (p < 0.001, OR=-1.677, 95% CI=-2.456, -0.943) were predictors for greater reduction in CMT. Overall, the variables could predict only 23% of BCVA and 52% of CMT response.ConclusionsThe study shows a significant proportion of DME patients do not respond to anti-VEGF therapy and identifies several clinical predictors for treatment outcomes.Trial registrationThe study was approved through the Human Research Ethics Committee, University of Tasmania (approval number H0012902), and the Southern Adelaide Clinical Human Research Ethics Committee (approval number 86 − 067).

Evaluation of care with intravitreal aflibercept treatment for UK patients with diabetic macular oedema: DRAKO study 24-month real-world outcomes.

DRAKO (NCT02850263) was a 24-month, prospective, observational, multi-centre cohort study that enrolled patients diagnosed with diabetic macular oedema (DMO) including central involvement. The study aimed to evaluate standard of care intravitreal aflibercept (IVT-AFL) treatment in the UK. This analysis describes the 12-month outcomes for patients with prior anti-vascular endothelial growth factor (VEGF) treatment for DMO other than IVT-AFL (C2), and 2-year outcomes for both anti-VEGF treatment-naïve patients (C1) and C2 patients. Study eyes were treated with IVT-AFL as per local standard of care. Mean changes in best-corrected visual acuity (BCVA) in ETDRS letters and central subfield thickness (CST) were stratified by baseline factors. Changes in diabetic retinopathy assessments, glycated haemoglobin A1c levels and vision-related quality of life (QoL) were evaluated alongside numbers of injections administered and safety outcomes. For C1, mean (SD) changes from baseline in BCVA of +0.7 (12.7) letters and CST of -123.3 (104.3) µm were observed at Month 24. For C2, mean (SD) changes from baseline for BCVA of + 0.2 (10.2) letters and -0.3 (13.0) letters, and CST of -79.1 (137.6) µm and -91.6 (132.9) µm, were observed at 12 and 24 months, respectively. In Year 2, C1 and C2 patients received a mean of 3.7 and 4.3 injections, respectively. Year 2 results indicate that IVT-AFL is an effective treatment for DMO in real-world UK clinical practice, despite relatively low injection numbers. The high baseline visual acuity and QoL scores were maintained and there was further improvement in anatomical outcomes.

LONG-TERM MORPHOLOGIC CHANGES IN MACULAR NEOVASCULARIZATION UNDER AFLIBERCEPT TREATMENT WITH A TREAT-AND-EXTEND REGIMEN.

To examine the morphologic changes in macular neovascularization (MNV) secondary to age-related macular degeneration after 2 years of aflibercept treatment under a treat-and-extend (T&E) regimen. This retrospective study analyzed the medical records for 26 eyes of 25 patients diagnosed with treatment-naive neovascular age-related macular degeneration and treated with aflibercept under a treat-and-extend regimen for 2 years. The areas of the MNV and vascular structures were assessed using swept-source optical coherence tomography angiography at baseline and after 2 years of treatment. The mean MNV area increased significantly from 0.65 ± 0.42 mm 2 at baseline to 0.78 ± 0.45 mm 2 at 2 years. At 2 years, the mean change in the MNV area from baseline was 22% (interquartile range: 4%-60%). The baseline MNV area was negatively correlated with the change ratio of the MNV areas at 2 years and baseline ( R = -0.68, P < 0.001). Nine of the 26 eyes (34.6%) showed newly formed mature vessels, and 7 eyes (26.9%) showed prominently developing preexisting mature vessels. Macular neovascularization expanded and showed vascular maturation under aflibercept treatment with a treat-and-extend regimen. The smaller the MNV at baseline, the greater is its expansion in 2 years.

Four-Year Visual Outcomes in the Protocol W Randomized Trial of Intravitreous Aflibercept for Prevention of Vision-Threatening Complications of Diabetic Retinopathy

Anti-vascular endothelial growth factor (VEGF) injections in eyes with nonproliferative diabetic retinopathy (NPDR) without center-involved diabetic macular edema (CI-DME) reduce development of vision-threatening complications from diabetes over at least 2 years, but whether this treatment has a longer-term benefit on visual acuity is unknown. To compare the primary 4-year outcomes of visual acuity and rates of vision-threatening complications in eyes with moderate to severe NPDR treated with intravitreal aflibercept compared with sham. The primary 2-year analysis of this study has been reported. Randomized clinical trial conducted at 64 clinical sites in the US and Canada from January 2016 to March 2018, enrolling 328 adults (399 eyes) with moderate to severe NPDR (Early Treatment Diabetic Retinopathy Study [ETDRS] severity level 43-53; range, 0 [worst] to 100 [best]) without CI-DME. Eyes were randomly assigned to 2.0 mg aflibercept (n = 200) or sham (n = 199). Eight injections were administered at defined intervals through 2 years, continuing quarterly through 4 years unless the eye improved to mild NPDR or better. Aflibercept was given in both groups to treat development of high-risk proliferative diabetic retinopathy (PDR) or CI-DME with vision loss. Development of PDR or CI-DME with vision loss (≥10 letters at 1 visit or ≥5 letters at 2 consecutive visits) and change in visual acuity (best corrected ETDRS letter score) from baseline to 4 years. Among participants (mean age 56 years; 42.4% female; 5% Asian, 15% Black, 32% Hispanic, 45% White), the 4-year cumulative probability of developing PDR or CI-DME with vision loss was 33.9% with aflibercept vs 56.9% with sham (adjusted hazard ratio, 0.40 [97.5% CI, 0.28 to 0.57]; P < .001). The mean (SD) change in visual acuity from baseline to 4 years was -2.7 (6.5) letters with aflibercept and -2.4 (5.8) letters with sham (adjusted mean difference, -0.5 letters [97.5% CI, -2.3 to 1.3]; P = .52). Antiplatelet Trialists' Collaboration cardiovascular/cerebrovascular event rates were 9.9% (7 of 71) in bilateral participants, 10.9% (14 of 129) in unilateral aflibercept participants, and 7.8% (10 of 128) in unilateral sham participants. Among patients with NPDR but without CI-DME at 4 years treatment with aflibercept vs sham, initiating aflibercept treatment only if vision-threatening complications developed, resulted in statistically significant anatomic improvement but no improvement in visual acuity. Aflibercept as a preventive strategy, as used in this trial, may not be generally warranted for patients with NPDR without CI-DME. ClinicalTrials.gov Identifier: NCT02634333.

New individualized aflibercept treatment protocol for branch retinal vein occlusion with macular edema

We evaluated the long-term (24-month) efficacy of a novel individualized treatment protocol with 2 mg aflibercept for treatment-naive BRVO with macular edema. Each patient received an initial aflibercept injection and was then examined every 2 weeks until recurrence of edema. At recurrence, each patient received a second injection of aflibercept. The period of efficacy was defined as the time between the first and second injections. Subsequently, each patient was examined and re-injected with aflibercept at their personalized treatment interval, which was defined as 1 week shorter than the period of efficacy. Thirty-seven eyes of 48 patients showed recurrence after the initial injection. The mean period of efficacy was 92.5 ± 40.8 days, and the mean number of visits before recurrence, 7.6 ± 2.9. The mean 24-month best corrected visual acuity (BCVA) was significantly better than the mean baseline BCVA but significantly worse than the best BCVA during the period of efficacy. The mean gain of BCVA at 24 months was 0.07 ± 0.18 logMAR. The mean 24-month central macular thickness (CMT) was significantly lower than the mean baseline CMT but showed no difference from the mean best CMT (p = 0.060). The mean total number of visits during the 24 months was 15.8 ± 3.4. We conclude that the individualized treatment protocol that was based on the period of efficacy in treatment-naïve BRVO eyes with macular edema achieved satisfactory long-term visual outcome.