Aflibercept Treatment Research Articles

Choroidal Morphology on Ultra-Widefield Indocyanine Green Angiography and Response to Aflibercept in Pachychoroid Neovasculopathy.

This study assessed the relationship between the choroidal morphology and short-term response to aflibercept treatment in pachychoroid neovasculopathy (PNV). This was a retrospective case-control study. Ultra-widefield indocyanine green angiography (UWICGA) and optical coherence tomography (OCT) images of 90 PNV eyes of 90 patients treated with aflibercept were enrolled. Responsiveness to aflibercept was defined as a complete resolution of sub- or intra-retinal fluid after three loading doses (50 dry and 40 non-dry eyes). Subfoveal choroidal thickness (SFCT) was measured on OCT images, and choroidal vessel density (CVD), CVD asymmetry, intervortex anastomosis, and choroidal vascular hyperpermeability (CVH) were assessed on UWICGA images. CVD on UWICGA differed between groups in terms of the total area (0.323 ± 0.034 in dry vs. 0.286 ± 0.038 in non-dry, p < 0.001) and area of each quadrant (superotemporal: 0.317 ± 0.040 vs. 0.283 ± 0.040, superonasal: 0.334 ± 0.040 vs. 0.293 ± 0.045, inferonasal: 0.306 ± 0.051 vs. 0.278 ± 0.052, inferotemporal: 0.334 ± 0.047 vs. 0.290 ± 0.046; all p ≤ 0.010). The CVH grade differed between groups (mean 1.480 ± 0.735 vs. 1.875 ± 0.822, p = 0.013). ST and IT intervortex anastomoses were common in the dry group, while SN, ST, and IT were most common in the non-dry group (p = 0.001). A poor short-term response to aflibercept treatment in PNV eyes was associated with a lower Haller vessel density, higher CVH grade, and intervortex anastomosis involving more quadrants on UWICGA.

Three year outcomes of intravitreal ranibizumab and aflibercept treatment of patients with diabetic macular edema: A comparative study.

Diabetic macular edema (DME) is the most common cause of visual deterioration in patients with diabetes mellitus. Various treatment options have been used for DME, including intravitreal injection of steroids and anti-vascular endothelial growth factors. To evaluate and compare the functional and anatomical outcomes of intravitreal ranibizumab (IVR) and intravitreal aflibercept (IVA) treatments in patients with DME. Retrospective study. Four hundred three eyes of 235 naïve patients who underwent IVR or IVA treatment for DME followed up to 36 months included in the study. Best corrected visual acuity (BCVA) and central macular thickness (CMT) were measured at baseline, year 1, 2 and 3. Primary endpoint of the study was the change in BCVA and CMT each year from baseline and requirement of additional treatment (laser/steroid injection). There were 198 eyes in IVR group and 205 eyes in IVA group. The changes in mean BCVA were 0.09 ± 0.32 versus 0.17 ± 0.41 Logarithm of the minimum angle of resolution (logMAR) (p = 0.042) at year 1, 0.09 ± 0.37 versus 0.12 ± 0.45 logMAR (p = 0.512) at year 2 and 0.13 ± 0.36 versus 0.15 ± 0.48 logMAR (p = 0.824) at year 3 in IVA and IVR groups, respectively. The baseline mean BCVA were lower (p = 0.004) in IVA group. The mean total number of injections was 7.93 ± 3.38 versus 7.42 ± 3.05 (p = 0.112). At year 1, change in mean BCVA was statistically significantly higher in IVA group; however this difference did not persist at years 2 and 3. Although the mean total number of injections was similar between groups, the requirement for adjuvant steroid treatment was significantly higher in ranibizumab group, which may affect the number of visits and treatment costs. Both ranibizumab and aflibercept treatments achieved a good long-term visual and anatomical response in DME patients.

The use of aflibercept (VEGF trap) in mitigating sulfur mustard-induced corneal neovascularization in a rabbit model.

Sulfur mustard (SM)-induced ocular injury is characterized by an acute inflammatory response that may become chronic or enter a latent phase with delayed pathology. This study aimed to evaluate the efficacy of ziv-aflibercept and aflibercept in preventing and ameliorating corneal neovascularization (NV), respectively, following chemical eye exposure to SM vapor in a rabbit model. Chemical SM ocular insult was induced in the right eye of rabbits. A single application of ziv-aflibercept was administered 2h or 9 days post-exposure. A single subconjunctival aflibercept treatment in an ocular formulation was administered 4 weeks after SM vapor exposure and subsequent to an initial 1-week treatment with 0.1 % dexamethasone. Clinical monitoring was performed 5-12 weeks post-exposure, and digital corneal pictures were taken to assess the extent of NV. The rabbits were euthanized and the corneas were processed for histological assessment. Treatment with ziv-aflibercept 2h and 9 days post-exposure moderately reduced insult severity and partially delayed or prevented corneal NV. Aflibercept application 4 weeks post-exposure significantly reduced the extent of NV for 8 weeks. The substantial decrease in existing corneal NV in this group was confirmed by histology. These results reveal the powerful anti-angiogenic efficacy of the VEGF-trap for ameliorating existing NV as opposed to preventing NV development, revealing the ability of this treatment to mitigate corneal NV.

Comparison of intravitreal ranibizumab, aflibercept and bevacizumab therapies in diabetic macular edema with serous retinal detachment.

To compare the effects of ranibizumab, aflibercept and bevacizumab treatments in treatment-naive diabetic macular edema(DME) patients with serous retinal detachment(SRD). This is a retrospective, comparative study. In a sample of 86 eyes of 86 untreated DME patients with accompanying SRD, 23 patients were treated with ranibizumab (IVR), 28 patients with aflibercept (IVA), and 35 patients with bevacizumab (IVB). All were injected intravitreally once a month for a 3-month loading dose. Subsequently, all participants were evaluated every months and if neccessary they received additional intravitreal treatments.Mean changes in best corrected visual acuity (BCVA), central retinal thickness (CRT), and SRD height over the 6-months study period were compared. At baseline, the groups did not differ in mean BCVA,CRT and SRD height. During the first 3 months, in IVA group the mean decrease in CRT and SRD height were significantly more than in the other two groups (p < 0.05 for all). However, these differences disappeared at 6 months.The number of injections was similar between the groups during the study period. In patients with DME accompanied by SRD, IVA is a more advantageous option in terms of reduction in CRT and SRD height from baseline to 3 months. In the 6-month period of treatment, IVR, IVA and IVB therapies areanatomically and functionally similar and significant effective modalities.

Retrospective analysis of the efficacy of early switching from bevacizumab to aflibercept or ranibizumab in diabetic macular edema.

The study aimed to compare the anatomical and functional gains of switching to ranibizumab or aflibercept in eyes with treatment-naive diabetic macular edema (DME) which has an inadequate response to three consecutive bevacizumab injections. This observational, retrospective, comparative study presented 12-month results of 80 patients with DME. One eye of each patient was enrolled, and bevacizumab was switched as aflibercept (40 eyes) or ranibizumab (40 eyes). DME was diagnosed based on a fundoscopic examination, fundus fluorescein angiography (FFA), central macular thickness (CMT), and best-corrected visual acuity (BCVA). Forty-one patients (51.2%) were male, and 39 (48.8%) were female, with a mean age of 62.3 ± 6.7 years. At the end of the study, the mean number of intravitreal injections was 8.1 ± 1.8 in the aflibercept group, whereas 8.9 ± 1.4 in the ranibizumab (p = 0.091). The mean CMT decreased from 449.2 ± 69.3 µm to 311.0 ± 48.9 µm in the aflibercept group, and from 444.9 ± 109.2 µm to 316.3 ± 54.5 µm in the ranibizumab group (for both, p < 0.0001). The mean BVCA increased from 49.2 ± 11.1 ETDRS letters to 62.5 ± 9.9 in the aflibercept group (p < 0.0001) and from 49.9 ± 12.0 ETDRS letters to 61.1 ± 9.1 in the ranibizumab group (p < 0.0001). Macular laser treatment was required in 17.5% of the aflibercept group and 22.5% of the ranibizumab group (p = 0.781). Significant improvement was observed with ranibizumab and aflibercept treatments in initial bevacizumab-resistant DME. Early switching therapy may contribute to better visual and anatomical outcomes.

Two-year outcomes of the APOLLON observational study of intravitreal aflibercept monotherapy in France in patients with diabetic macular edema

APOLLON (NCT02924311) was a prospective observational study to evaluate the effectiveness of intravitreal aflibercept (IVT-AFL) treatment of diabetic macular edema (DME) over 24 months in routine clinical practice in France. The primary endpoint was mean change from baseline in best-corrected visual acuity (BCVA; Early Treatment Diabetic Retinopathy Study letters) by 12 months, and safety was monitored throughout the study. Of 402 patients enrolled across 61 participating clinics and hospitals in France, 168 patients were followed for at least 24 months and included in the effectiveness analyses (79 treatment-naïve and 89 previously treated). After 24 months of IVT-AFL treatment, the mean (± standard deviation [SD]) change in BCVA from baseline was + 6.5 (± 10.7) letters in treatment-naïve patients (p < 0.001) and + 1.6 (± 17.0) letters in previously treated patients (p = 0.415) from a baseline of 63.8 (± 13.6) and 60.5 (± 16.5) letters. The mean number of IVT-AFL treatments over 24 months was 11.3 (± 4.9) and 11.9 (± 4.7) for treatment-naïve and previously treated patients. This final analysis of the APOLLON study indicated that following 24 months of IVT-AFL treatment in routine clinical practice in France, treatment-naïve patients with DME achieved significant gains in visual acuity and previously treated patients maintained prior visual acuity gains.Trial registration number: NCT02924311.

Clinical Phenotypes of Patients with Neovascular Age-Related Macular Degeneration and Poor Response to Aflibercept Treatment

The purpose: to identify and describe the clinical phenotypes of patients depending on their response to treatment with Aflibercept.Material and methods. The study had a prospective cohort design, including 92 eyes (n = 84) with a newly diagnosed diagnosis of nAMD and signs of disease activity. According to the OCT, the activity and type of macular neovascularization (MNV) were verified. Disease activity was monitored by central retinal thickness (CRT), the presence of subretinal and intraretinal fluid (SRF, IRF), and pigment epithelial detachment (PED). Eyes showing fresh hemorrhage ophthalmoscopically, OCT signs of SRF, IRC or sub-RPE, and dye leakage on the FAG were classified as having active nVMD. Treated with intravitreal injections (IVI) of Aflibercept 40 mg/ml in the “treat and extend” mode. The group with an unsatisfactory response to treatment was divided into 5 subgroups: true non-responders (without changes in activity throughout the course of treatment); partial nonrespondents (minimal regression of SRF and/or IRF) during treatment; dependent on anti-VEGF (complete regression on the background of injections, relapse after 4 weeks (increase in SRF/IRF, sub-RPE fluid, PED size); progression of anatomical changes, with exudation or hemorrhage, despite treatment; decreased response to treatment over time. Studied differences in baseline characteristics between the eyes among respondents and non-respondents and in five subgroups of incomplete respondents.Results. In the OCT characteristic, 45.5 % of eyes with tachyphylaxis showed normal CRT, lack of SRF (90.9 %) and IRF (90.9 %), high prevalence of fibrovascular PED (90.9 %); 90.0 % of the eyes showed type 1 MNV. In the subgroup of non-respondents with anatomical deterioration, type 2 and 3 of MNV were more often present (p = 0.00001) and fibrovascular-hemorrhagic PED was present in every sixth eye. Half (51.2 %) of the VEGF-dependent eyes (p = 0.0139) had the phenotype SRF+ and IRF- (91.3 % vs. 57.9 %, p = 0.0123), dominated by the OCT phenotype: SRF+/IRF-, as well as type 1 and 2 of MNV (91.3 % and 8.7 %, respectively). The eyes are partially non-respondent in 32 % had normal CRT, in 40 % of the eyes SRF+, in 24 % of IRF+, different types of PED, 1 and 3 types of MNV were present.Conclusion. The presented descriptions of clinical phenotypes of eyes with nVMD depending on their response to treatment with Aflibercept may be useful in predicting the response to treatment.

Comparison of intravitreal aflibercept and dexamethasone implant in the treatment of macular edema associated with diabetic retinopathy or retinal vein occlusion: a Meta-analysis and systematic review.

To compare the efficacy and safety of intravitreal aflibercept with dexamethasone implant in the treatment of macular edema (ME) associated with diabetic retinopathy (DR) or retinal vein occlusion (RVO). A comprehensive search of studies comparing dexamethasone and aflibercept in patients with ME was conducted at PubMed, Embase, and Cochrane Central Register of Controlled Trials from the beginning of library to April 16, 2021. Extracting the data including best-corrected visual acuity (BCVA), central retinal thickness (CRT), number of injections and serious adverse events (SAEs) from the final qualified articles. RevMan 5.3 software was used for Meta-analysis of the included studies. Totally 7 studies with 369 eyes were included. The causes of ME in the final screening study included RVO and DR. Compared with the aflibercept treatment group, the BCVA of the dexamethasone implant treatment group showed no significant difference in the follow-up for 3mo [mean difference (MD): -0.05, 95% confidence interval (CI): -0.11, 0.02; P=0.17] and 12mo (MD: -0.01, 95%CI: -0.38, 0.37; P=0.98), but it was slightly worse than the aflibercept group at 6mo (MD: 0.12, 95%CI: 0.03, 0.21; P=0.008). In terms of CRT reduction, there was no significant difference between the two groups at 3mo (MD: -28.14, 95%CI: -79.95, 23.67; P=0.29), 6mo (MD: 27.67, 95%CI: -84.89, 140.24; P=0.63), and 12mo (MD: -59.00, 95%CI: -127.37, 9.37; P=0.09). However, dexamethasone implant had fewer injections, but more adverse events such as elevated intraocular pressure (IOP) and cataract. Intravitreal injection of aflibercept and dexamethasone implant can both effectively increase BCVA and reduce CRT. Compared with aflibercept, dexamethasone implant is not inferior in improving vision and reducing CRT in the initial treatment period (3mo) and long-term treatment period (12mo). Besides, it has fewer injections and more likely to cause elevated IOP and cataract.

342P A signature of circulating microRNAs predicts the response to treatment with FOLFIRI plus aflibercept in metastatic colorectal cancer patients

The benefit of adding the antiangiogenic drug aflibercept to FOLFIRI regime in metastatic colorectal cancer (CRC) patients resistant to or progressive on an oxaliplatin-based therapy have been previously demonstrated. However, the absence of validated biomarkers to predict greater outcomes is a major challenge encountered when using antiangiogenic therapies. In this study we investigated profiles of circulating microRNAs (miRNAs) to build predictive models of response to treatment and survival. Plasma was obtained from 98 metastatic CRC patients enrolled in a clinical phase II trial before receiving FOLFIRI plus aflibercept treatment, and the circulating levels of 754 individual miRNAs were quantified using real-time PCR. A distinct signature of circulating miRNAs differentiated responder from non-responder patients. Remarkably, most of these miRNAs were found to target genes that are involved in angiogenic processes. Accordingly, some of these miRNAs had predictive value and entered in predictive models of response to therapy, progression of disease and survival of patients treated with FOLFIRI plus aflibercept. Among these miRNAs, circulating levels of hsa-miR-33b-5p efficiently discriminated between responder and non-responder patients and predicted the risk of disease progression. Moreover, the combination of circulating VEGF-A and miR-33b-5p levels improved clinical stratification of metastatic CRC patients who were to receive FOLFIRI plus aflibercept treatment. In conclusion, our study supports circulating miRNAs as valuable biomarkers for predicting better outcomes in metastatic CRC patients treated with FOLFIRI plus aflibercept.

Aflibercept Monotherapy or Bevacizumab First for Diabetic Macular Edema

BackgroundIn eyes with diabetic macular edema, the relative efficacy of administering aflibercept monotherapy as compared with bevacizumab first with a switch to aflibercept if the eye condition does not improve sufficiently (a form of step therapy) is unclear.MethodsAt 54 clinical sites, we randomly assigned eyes in adults who had diabetic macular edema involving the macular center and a visual-acuity letter score of 24 to 69 (on a scale from 0 to 100, with higher scores indicating better visual acuity; Snellen equivalent, 20/320 to 20/50) to receive either 2.0 mg of intravitreous aflibercept or 1.25 mg of intravitreous bevacizumab. The drug was administered at randomization and thereafter according to the prespecified retreatment protocol. Beginning at 12 weeks, eyes in the bevacizumab-first group were switched to aflibercept therapy if protocol-specified criteria were met. The primary outcome was the mean change in visual acuity over the 2-year trial period. Retinal central subfield thickness and visual acuity at 2 years and safety were also assessed.ResultsA total of 312 eyes (in 270 adults) underwent randomization; 158 eyes were assigned to receive aflibercept monotherapy and 154 to receive bevacizumab first. Over the 2-year period, 70% of the eyes in the bevacizumab-first group were switched to aflibercept therapy. The mean improvement in visual acuity was 15.0 letters in the aflibercept-monotherapy group and 14.0 letters in the bevacizumab-first group (adjusted difference, 0.8 letters; 95% confidence interval, −0.9 to 2.5; P=0.37). At 2 years, the mean changes in visual acuity and retinal central subfield thickness were similar in the two groups. Serious adverse events (in 52% of the patients in the aflibercept-monotherapy group and in 36% of those in the bevacizumab-first group) and hospitalizations for adverse events (in 48% and 32%, respectively) were more common in the aflibercept-monotherapy group.ConclusionsIn this trial of treatment of moderate vision loss due to diabetic macular edema involving the center of the macula, we found no evidence of a significant difference in visual outcomes over a 2-year period between aflibercept monotherapy and treatment with bevacizumab first with a switch to aflibercept in the case of suboptimal response. (Funded by the National Institutes of Health; Protocol AC ClinicalTrials.gov number, NCT03321513.)

Changes of Estimated Glomerular Filtration Rate and Glycated Hemoglobin A1c in Diabetic Macular Edema Patients Treated by Ranibizumab and Aflibercept in the Tertiary Referral Hospital.

Background and Objectives: Intravitreal injections (IVI) of vascular endothelial growth factor (VEGF) inhibitors are guideline-indicated treatments for diabetic macular edema (DME). However, some recent data have suggested that IVI VEGF inhibitors might, through systemic absorption, lead to a reduction in renal function. Our study aims to compare changes in glycated hemoglobin A1c (HbA1c) and estimated glomerular filtration rate (eGFR) between patients who received IVI ranibizumab and aflibercept treatment and patients who have not received IVI treatments. Materials and Methods: There were 17,165 DME patients with documented ophthalmology visits in the China Medical University Hospital-Clinical Research Data Repository. Those with a history of ESRD or bevacizumab treatment history, and those with missing information on HbA1c or eGFR, were excluded. After matching by age (±2 years), gender, and the year of clinical visit, 154 patients with medical treatment (including ranibizumab and aflibercept) and 154 patients without medical treatment were included in the study. The difference between HbA1c and eGFR at baseline and 3 and 12 months after the index date between the two groups was assessed. Results: Mean HbA1c and eGFR decreased between baseline and 12 months after the index date in both groups (p < 0.05). Compared with the non-treatment group, the treatment group had significantly lower HbA1c 3 and 12 months after the index date. There was no significant difference in eGFR between the two groups. In the generalized estimating equations (GEE) model, HbA1c in the treatment group was lower than the non-treatment group (−0.44%, 95% CI = −0.75, −0.14), but eGFR was similar after adjusting for age, gender, and index-year. HbA1c and eGFR decreased with the time in the adjusted GEE model (p < 0.0001) in both groups. Conclusions: This study showed that eGFR decreased with age and time and was not related to IVI anti-VEGF treatments in our tertiary referral hospital. IVI anti-VEGF therapy was also associated with better HbA1c control. It is suggested that DME patients can receive intravitreal VEGF inhibitors without inducing more renal impairment.

Effect of Intravitreal Aflibercept vs Laser Photocoagulation on Treatment Success of Retinopathy of Prematurity

Laser photocoagulation, which is the standard treatment for retinopathy of prematurity (ROP), can have adverse events. Studies of anti-vascular endothelial growth factor injections have suggested efficacy in the treatment of ROP, but few studies have directly compared them with laser treatments. To compare intravitreal aflibercept vs laser photocoagulation in infants with ROP requiring treatment. This noninferiority, phase 3, 24-week, randomized clinical trial was conducted in 27 countries (64 hospital sites) throughout Asia, Europe, and South America. Overall, 118 infants (gestational age ≤32 weeks at birth or birth weight ≤1500 g) with ROP severity (zone I stage 1+ [stage 1 plus increased disease activity], zone I stage 2+, zone I stage 3, zone I stage 3+, zone II stage 2+, or zone II stage 3+) requiring treatment or with aggressive posterior ROP in at least 1 eye were enrolled between September 25, 2019, and August 28, 2020 (the last visit occurred on February 12, 2021). Infants were randomized 2:1 to receive a 0.4-mg dose of intravitreal aflibercept (n = 75) or laser photocoagulation (n = 43) at baseline. Additional treatment was allowed as prespecified. The primary outcome was the proportion of infants without active ROP and unfavorable structural outcomes 24 weeks after starting treatment (assessed by investigators). The requirement for rescue treatment was considered treatment failure. Intravitreal aflibercept was deemed noninferior if the lower limit of the 1-sided 95% bayesian credible interval for the treatment difference was greater than -5%. Among 118 infants randomized, 113 were treated (mean gestational age, 26.3 [SD, 1.9] weeks; 53 [46.9%] were female; 16.8% had aggressive posterior ROP, 19.5% had zone I ROP, and 63.7% had zone II ROP) and 104 completed the study. Treatment (intravitreal aflibercept: n = 75; laser photocoagulation: n = 38) was mostly bilateral (92.9%), and 82.2% of eyes in the intravitreal aflibercept group received 1 injection per eye. Treatment success was 85.5% with intravitreal aflibercept vs 82.1% with laser photocoagulation (between-group difference, 3.4% [1-sided 95% credible interval, -8.0% to ∞]). Rescue treatment was required in 4.8% (95% CI, 1.9% to 9.6%) of eyes in the intravitreal aflibercept group vs 11.1% (95% CI, 4.9% to 20.7%) of eyes in the laser photocoagulation group. The serious adverse event rates were 13.3% (ocular) and 24.0% (systemic) in the intravitreal aflibercept group compared with 7.9% and 36.8%, respectively, in the laser photocoagulation group. Three deaths, which occurred 4 to 9 weeks after intravitreal aflibercept treatment, were considered unrelated to aflibercept by the investigators. Among infants with ROP, intravitreal aflibercept compared with laser photocoagulation did not meet criteria for noninferiority with respect to the primary outcome of the proportion of infants achieving treatment success at week 24. Further data would be required for more definitive conclusions regarding the comparative effects of intravitreal aflibercept and laser photocoagulation in this population. ClinicalTrials.gov Identifier: NCT04004208.

Retinal oxygen saturation, vessel diameter and flicker response in eyes with specific subtypes of neovascular age-related macular degeneration during aflibercept treatment.

PurposeTo evaluate the effect of intravitreal aflibercept monotherapy on arterial and venous oxygen saturation, retinal vessel diameter and flicker response in patients with newly diagnosed specific subtypes of exudative maculopathy.MethodsThis prospective study included forty-four eyes of 44 patients with treatment-naïve polypoidal choroidal vasculopathy (PCV, n = 12), hemorrhagic choroidal neovascularization (hCNV, n = 12), pigment epithelium detachment (PED, n = 9) and type 3 MNV (RAP, n = 11). All patients received three initial aflibercept 2mg/0.05ml injections (Eylea®) in monthly intervals (loading phase) and were subsequently treated until month 12. Measurements of arterial and venous oxygen saturation, vessel diameters and flicker response were performed using the Dynamic Vessel Analyzer (DVA; IMEDOS, Jena, Germany). Statistical analysis was performed on the total population at baseline, after loading dose and at the last follow-up visit.ResultsThe arterial oxygen saturation was 94.01±2.14% and showed no change after loading dose (93.94±2.88%, p = 0.4; estimated difference [confidence interval] -0.38 [-1.24; 0.48]) and at the last visit (95.48±1.90%; p = 0.1; -1.29 [-0.34; 2.91]). The venous oxygenation during treatment was 78.49±6.93% at baseline, 80.94±7.71% after 3-monthly injections (p = 0.7; -0.43 [-2.72; 1.86]) and 80.56±7.33% at month 12 (p = 0.5; 1.07 [-2.10; 4.24). The arterial and venous vessel diameters were 94±22μm and 131±19μm at baseline, and remained unchanged following aflibercept loading dose and at the last follow-up visit (p-value: p = 0.5; 2.30 [-5.00; 9.59] p = 0.8; 0.59 [-3.17; 4.34]). During stimulation with flicker light, arterial diameter changed by +1.24±4.93% at baseline and remained stable at month 3 (+2.70±5.95%; p = 0.5; 1.43 [-2.54; 5.41]) while the change in venous diameter during flicker stimulation was +4.52±4.45% at baseline and +4.13±3.65% after loading dose (p = 0.4, 5.18 [1.73; 8.63]).ConclusionDuring intravitreal aflibercept treatment oxygen saturation, vessel diameter and flicker response did not change in the total population of patients with specific subtypes of exudative maculopathy.

Patients with Neovascular Age-Related Macular Degeneration Requiring Intensive Intravitreal Aflibercept Treatment: An ARIES Post Hoc Analysis.

IntroductionThe aim of this post hoc analysis of the ARIES study is to explore the requirement for intravitreal aflibercept (IVT-AFL) treatment intervals of < 8 weeks (w) in patients with neovascular age-related macular degeneration (nAMD), and to assess vision and anatomic outcomes in such patients who require more intensive treatment.MethodsARIES was a multicenter, randomized, phase 3b/4 study that investigated the efficacy of two IVT-AFL proactive, individualized, treat-and-extend regimens over 2 years in treatment-naïve patients with nAMD. Patients were determined as injection-intensive if the study investigator identified that a treatment interval of < 8 w was needed and if they had ≥ 1 interval of < 8 w after three initial monthly doses. Treatment intervals could be extended subsequently if extension criteria were met. This is a post hoc analysis of patients enrolled in ARIES and statistical analysis is descriptive.ResultsOf 269 patients in the combined treatment arms, 23.0% (n = 62) were injection-intensive (Year 1: 13.8% [n = 37]; Year 2: 9.3% [n = 25]). Time from IVT-AFL initiation to injection-intensive determination varied (range, 16–100 w; median: 43.2 w). Mean treatment interval was 8.4 w before and 6.1 w after injection-intensive determination. Overall, 59.7% achieved treatment intervals of ≥ 8 w following injection-intensive determination. Vision improvements from baseline to Week 104 were smaller for injection-intensive patients than non–injection-intensive patients (mean [SD] best-corrected visual acuity change: + 2.3 [15.6] vs. + 5.9 [12.3] letters). Anatomic outcomes were similar between injection-intensive and non–injection-intensive patients (central retinal thickness change from baseline to Week 104: − 160 [154] vs. − 167 [136] µm).ConclusionsIn ARIES, 23% of treatment-naïve patients with nAMD experienced at least one treatment interval of < 8 w. Injection-intensive patients showed improved vision and anatomic outcomes. For most, treatment intervals could be extended to ≥ 8 w following injection-intensive determination. ClinicalTrials.gov Identifier: NCT02581891.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40123-022-00541-8.

Association between Polymorphisms in CFH, ARMS2, CFI, and C3 Genes and Response to Anti-VEGF Treatment in Neovascular Age-Related Macular Degeneration.

Neovascular age-related macular degeneration (nAMD) is the leading cause of vision loss in the elderly. The gold standard of nAMD treatment is intravitreal injections of vascular endothelial growth factor (VEGF) inhibitors. Genetic factors may influence the response to anti-VEGF therapy and result in a high degree of response variability. The aim of the study was to evaluate the association of the polymorphisms in genes related to the complement system (rs2285714-CFI, rs10490924-ARMS2, rs2230199-C3, rs800292-CFH, and rs6677604-CFH) with nAMD its clinical features and optical coherent tomography (OCT) biomarkers of treatment response to anti-VEGF therapy. Genotyping by allele-specific PCR was performed in 193 AMD patients and 147 age-matched controls. A prospective study of the dynamics of changes in OCT biomarkers during aflibercept treatment included 110 treatment-naive patients. Allele T rs10490924 was associated with the increased risk of nAMD. For both rs800292 and rs6677604, carriage of the A allele was protective and decreased the nAMD risk. Associations of rs2230199 with central retinal thickness (CRT) and intraretinal cysts were revealed. The height of pigment epithelium detachment and the height of neuroretinal detachment were significantly higher in carriers of the minor allele of rs2285714, both at baseline and during treatment. The reduction of CRT was associated with higher CRT at baseline and the presence of the T allele of rs2285714. By the end of one-year follow-up the patients homozygous for the minor allele rs2285714 had significantly higher odds of the presence of anastomoses and loops and active neovascular membrane. Furthermore, minor allele carriers had decreased levels of complement factor I level in aqueous humor but not in the plasma, which may be due to the influence of rs2285714 on tissue-specific splicing. Our results suggest that the severity of AMD macular lesions is associated with rs2285714 and rs2230199 polymorphisms, which could be explained by their high regulatory potential. Patients with the minor allele of rs2285714 respond worse to antiangiogenic therapy.

Three-Year Outcomes of Intravitreal Aflibercept Injections for Retinal Angiomatous Proliferation According to Disease Stage.

IntroductionTo evaluate the outcomes of intravitreal aflibercept injections for retinal angiomatous proliferation (RAP) according to disease stage.MethodsThis retrospective chart review included 68 eyes of 53 individuals diagnosed as having RAP and 109 neovascular age-related macular degeneration (nAMD) eyes of 109 patients as controls. All patients received intravitreal injections of aflibercept in a real-world setting. The main outcome measures were the changes in the mean of best-corrected visual acuity (BCVA) and central retinal thickness (CRT) as well as the total number of injections received during the 3-year follow-up period.ResultsThe average BCVA and CRT changes in eyes affected by RAP and the controls at 3 years were non-significant. Both populations received a similar number of injections. After 3 years of treatment, patients with RAP had visual decline despite stable anatomical outcomes. Approximately 50% of the eyes with stage II RAP exhibited significant BCVA decline at the end of the third year. Among those eyes that had deteriorated BCVA, persistently worsening BCVA and thinning CRT were observed from year 2 to year 3.ConclusionSimilar to treating nAMD, intensive injections or aggressive treatment strategies are required to treat RAP to achieve optimal visual outcomes in a real-world setting. The response to aflibercept treatment at the second year is associated with the final visual outcome of eyes with stage II RAP lesions.

OCTA changes following loading phase with intravitreal aflibercept for DME

ObjectifMesurer les variations observées à l'angiographie-tomographie par cohérence optique (OCTA) à la suite de l'administration intravitréenne d'anti-VEGF (facteur de croissance endothélial vasculaire) dans le traitement de l’œdème maculaire diabétique (OMD), et évaluer le lien entre les paramètres mesurés à l'OCTA avant le traitement et les résultats visuels. NatureÉtude de cohorte prospective. MéthodesUn groupe de 29 patients présentant un OMD ont reçu 5 injections intravitréennes mensuelles d'aflibercept. On a eu recours au test de Wilcoxon pour observations appariées afin de comparer les données mesurées à l'OCTA au départ et après 6 mois. Au nombre des paramètres mesurés à l'OCTA, citons l'aire de la zone fovéale avasculaire (ZFA), le périmètre de la ZFA, la circularité de la ZFA, la densité vasculaire du plexus vasculaire superficiel (segmenté conformément à la cartographie de l’étude ETDRS [Early Treatment of Diabetic Retinopathy Study], soit zone centrale, zone interne, zone externe et zone complète). Une sous-analyse a permis de séparer les patients en 2 groupes : sujets qui ont répondu au traitement (réduction de l’épaisseur du sous-champ central > 50 µm pendant le traitement) et sujets qui n'ont pas répondu au traitement. Une régression linéaire multiple et une régression logistique ont servi à déterminer les liens entre les paramètres mesurés à l'OCTA avant le traitement et les résultats en matière d'acuité visuelle. RésultatsUn total de 29 patients ont été inclus: 25 patients (86,2 %) présentaient une rétinopathie diabétique non proliférante et 4 (13,8 %), une rétinopathie diabétique proliférante. La densité vasculaire a diminué dans les zones centrale (p = 0,004) et interne (p = 0,013) selon la cartographie de l’étude ETDRS. Cet effet n’était significatif que chez les patients qui ont répondu au traitement (zone centrale; p = 0,002; zone interne; p = 0,017). Les paramètres OCT et OCTA mesurés avant le traitement n'ont pas influé sur les résultats ultimes en matière d'acuité visuelle. ConclusionOn a noté, après l'administration intravitréenne d'aflibercept dans le traitement de l'OMD, une diminution significative de la densité vasculaire du plexus vasculaire superficiel dans les zones centrale et interne selon la cartographie de l'ETDRS. Ce phénomène s'est produit exclusivement chez les patients qui ont répondu au traitement. Nos observations tiennent vraisemblablement aux limites de la technologie de l'OCTA elle-même, en ce sens que la densité vasculaire avant le traitement a potentiellement été surestimée par la présence d'artéfacts, soit quelques particules en suspension en mouvement. Les paramètres mesurés à l'OCTA avant le traitement n'ont pas pu servir de biomarqueurs permettant de prévoir les résultats visuels après l'administration d'un anti-VEGF.

Efficacy and Safety of Aflibercept Therapy for Diabetic Macular Edema

Purpose:To assess the real-world efficacy and safety of aflibercept for the treatment of diabetic macular edema (DME).Methods:A systematic search was conducted across multiple databases. Articles were included if participants had DME and received aflibercept treatment for a minimum of 52 ± 4 weeks. Primary outcomes included changes in best-corrected visual acuity (BCVA) and central macular thickness (CMT). A risk of bias assessment of studies was completed, pooled estimates were obtained, and a meta-regression was performed. Information on adverse events was collected.Results:The search yielded 2112 articles, of which 30 were included. Aflibercept was more effective than laser photocoagulation functionally (12-month BCVA-weighted mean difference [WMD] = 10.77 letters, P < 0.001; 24 months = 8.12 letters, P < 0.001) and anatomically (12-month CMT WMD = –114.12 μm, P < 0.001; 24 months = –90.4 μm, P = 0.004). Compared to bevacizumab, aflibercept was noninferior at improving BCVA at 12 months (WMD = 1.71 letters, P = 0.34) and 24 months (WMD = 1.58 letters, P = 0.083). One study found that aflibercept was more effective than bevacizumab anatomically at 1 and 2 years (P < 0.001 at 12 and 24 months). Compared to ranibizumab, aflibercept rendered a greater improvement in BCVA at 1 year (WMD = 1.76 letters, P = 0.001), but not 2 years (WMD = 1.66 letters, P = 0.072). CMT was not significantly different between both therapies at 12 months (WMD = −14.30 μm, P = 0.282) and 24 months (P = 0.08). One study reported greater functional improvement with aflibercept compared with dexamethasone (P = 0.004), but inferiority in reducing CMT (P < 0.001). Meta-regression analysis demonstrated that dosing schedule was found to impact outcomes at 12 and 24 months, while study design and sample size did not impact outcomes at 12 months. There were minimal safety concerns using aflibercept therapy.Conclusions:Aflibercept is a safe and effective therapy option for DME in the clinical setting, performing superiorly to laser photocoagulation. Evidence regarding comparisons with bevacizumab, ranibizumab, and dexamethasone is mixed and limited.

Functional and structural characteristics in patients with diabetic macular oedema after switching from ranibizumab to aflibercept treatment. Three year results in real world settings

BackgroundOur aim was to examine the long term anatomical and functional outcomes in patients with refractory diabetic macular oedema (DMO) undergoing treatment switch from ranibizumab to aflibercept.MethodsRetrospective review of patients with DMO undergoing treatment switch from ranibizumab to aflibercept at a single centre between 2015 and 2017. Primary outcomes were best corrected visual acuity (BCVA) and central macular thickness (CMT).Results57 eyes from 44 patients were included. Following switch to aflibercept, median (IQR) BCVA improved to 73 (64–77) letters at 3 months (p = 0.0006), to 73 (61–78) letters at 6 months (p = 0.0042), to 73 (65–77) at 9 months (p = 0.0006), and to 73 (63–75) letters at 18 months (p = 0.0444). At 36 months following switch, 12 eyes had gained > 10 letters, 5 eyes had gained 5–9 letters, 25 remained stable (± 5 letters), 7 eyes lost 5–9 letters and 8 eyes lost > 10 letters. A significant reduction in CMT at all trimesters following treatment switch was found except at month 24.ConclusionsWe provide real world data suggesting a sustained anatomical and functional benefit of switching from ranibizumab to aflibercept in the treatment of refractory DMO.

EFFECT OF BASELINE CENTRAL RETINAL THICKNESS ON THE RESULTS OF TREATMENT OF DIABETIC MACULAR EDEMA WITH AFLIBERCEPT: REAL-LIFE EVIDENCE IN THE CZECH REPUBLIC.

Presentation of the 1-year results of aflibercept treatment in patients suffering fromdiabetic macular edema (DME) and comparison of the response to treatment of patients with different baseline central retinal thickness (CRT). This was a multicentre, retrospective observational study of a series of cases. Patients with DME were treated in a fixed regimen (5 injections at 1-monthly intervals and then injections at 2-monthly intervals). The period of follow-up was 12 months. The development of best corrected visual acuity (BCVA) and CRT was evaluated. Measurements were performed prior to the commencement of treatment and then after 4, 6, 8, 10, and 12 months. The therapeutically naive group consisted of 82 eyes of 79 patients. The total cohort of patients was divided into 3 groups according to the baseline values of CRT. The first group was composed of 28 eyes with baseline CRT &lt; 450 &#956;m (34.1%), the second included 25 eyes with CRT in the range of 450-550 &#956;m (30.5%), and the third group consisted of 29 eyes with baseline CRT &gt; 550 &#956;m (35.4%). The average baseline BCVA and SD in the first group was 66 ±7.1 letters ETDRS optotypes, and then 70 ±7 letters, 69.6 ±7.3 letters, and 71.3 ±7 letters at the follow-ups after 4, 8, and 12 months. The average baseline value of CRT and SD in the first group was 379 ±48.6 &#956;m, and then 337.1 ±76.5 &#956;m, 320.2 ±74.1 &#956;m, and 315.1 ±62.2 &#956;m after 4, 8, and 12 months. The average baseline BCVA and SD in the second group was 64.1 ±9.7 ETDRS letters, and then 66.9 ±10 letters, 70 ±9.9 letters, and 70.5 ±11.5 letters after 4, 8, and 12 months. The average baseline value of CRT and SD in the second group was 497.4 ±76.4&#956;m,and then 376.5 ±106.1 &#956;m, 360.8 ±70 &#956;m, and 351.3 ±91.3 &#956;m after 4, 8, and 12 months.In the third group, the average baseline value of BCVA and SD was 59.7 ±10.4 ETDRS letters, and then 65 ±10.6 letters, 64.8 ±9.6 letters, and 67 ±10 letters after 4, 8, and 12 months. The average baseline value of CRT and SD in the third group was 639.4 ±79.6 &#956;m, and then 396.7 ±147.1 &#956;m, 416.9 ±139.8 &#956;m, and 368.5 ±109.9 &#956;m after 4, 8, and 12 months. All these changes were statistically significant (p &lt; 0.05). Aflibercept treatment in a fixed regimen in patients suffering from DME results in a statistically significant improvement in BCVA and a decrease in CRT in the first year of treatment. Patients with a higher baseline CRT showed the best anatomical and functional results of the 1-year treatment with aflibercept.