Intravitreal Aflibercept Treatment Research Articles

Twenty-four-month results of intravitreal aflibercept for macular edema due to branch retinal vein occlusion.

To investigate 24-month results of intravitreal aflibercept (IVA) for macular edema due to branch retinal vein occlusion (BRVO-ME). Retrospective study. Subjects were treatment-naïve BRVO-ME patients at the Ophthalmology Department of Juntendo University Urayasu Hospital from November 2015 to March 2017 who received IVA treatment for 24 months. After the first injection, reinjection was performed as needed when ME had recurred or was prolonged beyond 300 μm. Data included changes in best corrected visual acuity and central foveal thickness, total number of injections, and the case background factors that required reinjection after 12 months. ME remission was defined as patients without additional injections for 6 months. Forty eyes of 40 patients (64.5 ± 11.5 years), 21 men and 19 women, were included. Average best corrected visual acuity and central foveal thickness at baseline were logMAR 0.42 ± 0.21, 601.4 ± 181.3 μm, logMAR 0.08 ± 0.25, 214.6 ± 62.7 μm at 12 months, logMAR 0.02 ± 0.16, 216.6 ± 97.8 μm at 24 months, all significantly improved from baseline. The average number of injections was 2.2 ± 1.0 times in the first year and 0.4 ± 0.8 times in the second year. The rate of ME remission was 60.0% at 12 months and 87.5% at 24 months. Period between onset and injections was significantly associated with reinjection after 12 months (p =.030). IVA was effective over 24 months for ME due to BRVO in many cases. Early injection treatment may reduce the need for later injections.

Intravitreal Aflibercept Treatment Strategies in Routine Clinical Practice of Neovascular Age-Related Macular Degeneration in Belgium: A Retrospective Observational Study.

IntroductionSTELLAR was a Belgian, multicentre, retrospective, observational chart review that described the utilization (number of injections and treatment regimen) and effectiveness of intravitreal aflibercept (IVT-AFL) in patients with anti-vascular endothelial growth factor (VEGF) treatment-naïve neovascular age-related macular degeneration (nAMD) during the first 12 months of IVT-AFL treatment.MethodsPatients initiating IVT-AFL between July 2013 and July 2017 were included in STELLAR. Primary endpoints were number of visits and IVT-AFL injections, and number of patients who received ≥ 7 versus < 7 IVT-AFL injections during the first 12 months of treatment.ResultsA total of 337 patients completed ≥ 12 months of IVT-AFL treatment. The mean number of visits and mean number of injections during the first 12 months was 9.8 and 7.1 injections, respectively (64% received ≥ 7 injections). Overall, 96% of patients received ≥ 3 initial monthly injections. Of the 337 patients, 180 received VT-AFL as needed (pro re nata), 141 received it as treat-and-extend dosing and 16 received it as fixed dosing. The proportion of patients who received treat-and-extend dosing increased year-on-year. Mean best-corrected visual acuity (BCVA) (± standard deviation) was 61.6 (± 14.9) Early Treatment Diabetic Retinopathy Study (ETDRS) letters at baseline and improved by + 3.9 and + 5.7 ETDRS letters at 3 and 12 months, respectively. Mean BCVA improvement was numerically greater in patients who received ≥ 7 versus < 7 injections during the first 12 months 7 (+ 6.5 vs. + 4.4 ETDRS letters) and in patients who received ≥ 3 versus < 3 initial monthly injections (+ 5.2 vs. − 0.25 ETDRS letters [3 at months]; + 5.9 vs + 1.2 ETDRS letters [at 12 months]). No specific adverse events were reported.ConclusionMost patients in this Belgian study received ≥ 7 IVT-AFL injections during a mean of 9.8 visits over the 12 months assessed. IVT-AFL was an effective treatment for nAMD in clinical practice, with numerically higher BCVA gains in patients receiving ≥ 7 versus < 7 injections over the first 12 months and ≥ 3 versus < 3 injections in the first 3 months.Electronic supplementary materialThe online version of this article (10.1007/s40123-020-00300-7) contains supplementary material, which is available to authorized users.

Association of VEGF Gene Family Variants with Central Macular Thickness and Visual Acuity after Aflibercept Short-Term Treatment in Diabetic Patients: A Pilot Study

Introduction: Diabetic retinopathy (DR) is one of the major vision-threatening causes worldwide. Searching for an individualized therapeutic strategy to prevent its progress is challenging. Objective: This work aimed to investigate the association of angiogenesis-inducer vascular endothelial growth factor (VEGF) gene family and related receptor variants (rs833069, rs12366035, rs7664413, rs7993418, and rs2305948) with susceptibility of DR and the response to 1 dose of aflibercept treatment in type 2 diabetes mellitus (T2DM). Methods: Consecutive eligible patients with T2DM (n = 125) and 110 unrelated controls were enrolled in this preliminary prospective case-controlled study. Genotyping was identified using TaqMan real-time PCR. Adjusted odds ratio (OR) with 95% confidence interval (CI) was applied to assess the strength of the association with the clinical/ophthalmological characteristics and early response to intravitreal aflibercept treatment in terms of improved visual acuity (BCVA) and central macular thickness (CMT). Results: We found that both VEGFB rs12366035 and VEGFC rs7664413 conferred higher risk for DR progression under allelic (OR [95% CI]: 1.71 [1.07–2.74]), homozygote comparison (3.55 [1.32–9.57]), and recessive (3.77 [1.43–9.93]) models for the former and under allelic (2.09 [1.25–3.490, homozygote comparison (2.76 [1.02–7.45]), and recessive (2.62 [0.98–6.98] models for the latter. In contrast, VEGFR1 rs7993418 conferred protection against DR under heterozygote comparison and dominant models. The rs12366035*T/T genotype showed the worst pretreatment BCVA score (0.35 ± 0.24) compared to other corresponding genotypes (0.66 ± 0.26 in C/T and 0.54 ± 0.25 in C/C carriers) (p = 0.008). Meanwhile, patients with rs7993418*G/G of VEGFR1 exhibited a significant reduction in CMT after aflibercept injection (12.26 ± 35.43 µ in G/G vs. 3.57 ± 8.74 µ in A/A) (p = 0.037). Conclusions: Polymorphisms of the studied VEGF/receptors could be considered as genetic risk factors of DM/DR development and could play an important role in aflibercept early response for DR patients in the study population.

Four-year outcomes of aflibercept treatment for neovascular age-related macular degeneration: Results from real-life setting.

To assess long-term structural and functional outcomes of intravitreal aflibercept (Eylea®) treatment for neovascular macular degeneration (nAMD) in a real-word setting. This was a retrospective, single-centre, non-randomized interventional cohort analysis. Data from treatment-naive patients with nAMD funded for treatment with intravitreal aflibercept in the period between 1 September 2013 and 28 February 2014 and who finished 4-year follow-up entered the analysis. Epidemiological data, visual acuity (VA) measured on ETDRS charts and injection numbers were recorded. Spectral domain optical coherence tomography (SD-OCT) data including presence or absence of macular fluid and automated central subfield macular thickness (CSMT) at year 1, 2, 3 and 4 were also recorded. Ninety-four eyes of 89 patients finished 4-year follow-up. The mean number of aflibercept injections received over 4 years was 19.3. At baseline, the mean VA (SD) (Snellen) was 54.1 ± 15.5 (20/100) ETDRS letters whilst the mean CSM (SD) was 296 ± 81 µm. At 4 years, the mean VA (SD) (Snellen) was 60.4 ± 20.0 (20/63) ETDRS letters (p < 0.0001). Mean CSMT (SD) was 218 ± 79 μm (p < 0.0001). Thirty-three percent of eyes gained ⩾15 ETDRS letters at end of 4 years, and 66 (70%) eyes had no macular fluid at the end of the follow-up. The results suggest that good long-term morphological and functional treatment outcomes can be achieved using intravitreal aflibercept for nAMD in a real-life clinical setting.

Choroidal Thickness After Dexamethasone Implant or Aflibercept in Patients with Diabetic Macular Edema Persistent to Ranibizumab.

Purpose: This study aims to compare subfoveal choroidal thicknesses (SFCTs) after intravitreal dexamethasone (IVD) or intravitreal aflibercept (IVA) treatment in patients with persistent diabetic macular edema (DME) unresponsive to intravitreal ranibizumab (IVR). Methods: The study consisted of patients with DME unresponsive to IVR treatment in which 37 were administered 1 dose IVD (group A) and 34 patients who were administered 3 doses of IVA (group B), as well as 35 healthy individuals (group C). Detailed ophthalmological examination and optical coherence tomography parameters of group A and group B, including central retinal thickness and SFCT, were retrospectively evaluated before and after treatment. Results from preinjection, and 1, 2, and 3 months after injection were analyzed. Results of group A and group B were compared within themselves and also compared with group C. Results: SFCT measurements were compared within group A and group B (1 = preinjection; 2 = 1 month postinjection; 3 = 2 months postinjection; 4 = 3 months postinjection). There was significant thinning in SFCT between 1-2, 1-3, 1-4, 2-3, 2-4, and 3-4 time intervals within both group A and group B (both P < 0.001). Comparison of SFCT measurements showed preinjection, 1-, and 2-month values of group A were significantly thicker than those of group C (P < 0.001), whereas there was no significant difference between 3-month values (P = 0.09). Preinjection, 1-, and 2-month values of group B were significantly thicker than those of group C (P < 0.001), whereas there was no significant difference between 3-month values (P = 0.06). Conclusions: Three month follow-up showed thinning in SFCT measurements in patients with persistent DME unresponsive to IVR who were applied IVD or IVA treatment.

Impact of intravitreal aflibercept dosing regimens in treatment-na\xefve patients with neovascular age-related macular degeneration: 2-year results of RAINBOW

BackgroundTo review treatment outcomes from real-world data of patients with neovascular age-related macular degeneration (nAMD) treated with intravitreal aflibercept (IVT-AFL) injection.MethodsRAINBOW (ClinicalTrials.gov, NCT02279537) is an ongoing, observational, 4-year study to monitor the effectiveness and safety of IVT-AFL in patients with nAMD in clinical practice in France. Treatment-naïve patients diagnosed with nAMD who had been prescribed IVT-AFL by their treating physician were eligible. The regimens of interest were regular treatment interval cohort (patients who received three initial monthly IVT-AFL injections followed by regular injections every 2 months) and two irregular treatment interval cohorts (with and without three initial monthly injections). Here we describe results at 24 months in patients according to IVT-AFL treatment regimen.ResultsThe mean change in best-corrected visual acuity (BCVA) with IVT-AFL from baseline to 24 months was + 3.0 letters in the overall population (P < 0.05 vs baseline). The mean change was positive for the regular and irregular treatment interval cohorts with initial doses (+ 4.9 and + 4.0 letters, respectively; P < 0.05 vs baseline) and negative for the irregular treatment interval cohort without initial doses (− 2.5 letters; P = 0.365 vs baseline) at 24 months. The mean overall number of IVT-AFL injections over 12 and 24 months was 6.0 and 8.8, respectively. The most common ocular adverse events were lack of efficacy (6.3%), vitreous floaters (2.7%), and increased lacrimation (1.7%).ConclusionsIn the real-world RAINBOW study, visual outcomes observed at 24 months were consistent with results from the primary endpoint at 12 months. In this study, treatment-naïve patients who received three initial IVT-AFL doses and regular IVT-AFL treatment over the first 24 months experienced better visual outcomes than patients who received no initial doses and an irregular treatment regimen.Trial registrationwww.ClinicalTrials.gov (NCT02279537). Registered 29 October 2014.

Beneficial switch from aflibercept to ranibizumab for the treatment of refractory neovascular age-related macular degeneration

PurposeThe aim of this study was to evaluate the effects of switching to ranibizumab in patients with neovascular age-related macular degeneration (nAMD) refractory to aflibercept treatment and to identify predictive factors for switch response.MethodsA retrospective chart review was conducted including 32 eyes from 26 patients with refractory nAMD, who switched from monthly intravitreal aflibercept treatment (≥ 6 months) to ranibizumab. Outcome measures included changes in visual acuity (VA), intraretinal fluid (IRF), subretinal fluid (SRF), pigment epithelial detachment (PED), and central retinal thickness (CRT), evaluated at 6 months before switch (T1), at the time of switch (T2), and 3 months post-switch (T3).ResultsThere was an increase in CRT from T1 to T2, which decreased after switch from T2 to T3. Regression analysis of the changes per month observed between time points showed significant differences in PED height (p = 0.02), SRF (p = 0.01), and neuroretinal thickness as a measure for IRF (p = 0.03). No significant change was found for VA. Predictive factors for better switch response included an exacerbation between T1 and T2, thicker measurements at T2, male sex, shorter treatment duration before switch, and fewer preceding injections. No association with preceding switch was found.ConclusionPatients with nAMD refractory to aflibercept benefit from switching to ranibizumab, particularly those whose condition worsened prior to the switch. This may be explained by drug tolerance to aflibercept. Our findings may facilitate making appropriate treatment decisions, potentially improving patient outcomes.

REDUCED VASCULAR DENSITY IN THE CHOROID AFTER TREATMENT WITH PHOTODYNAMIC THERAPY COMBINED WITH AFLIBERCEPT IN PATIENTS WITH POLYPOIDAL CHOROIDAL VASCULOPATHY.

To investigate changes of vascular density in the choroid of patients with polypoidal choroidal vasculopathy treated with photodynamic therapy (PDT) combined with intravitreal aflibercept. This study examined 12 eyes of 12 patients, who were diagnosed as polypoidal choroidal vasculopathy. All patents underwent optical coherence tomography before and at 3 months after PDT combined with intravitreal aflibercept treatment. Using en face optical coherence tomography images, we analyzed vascular density of the area outside the polypoidal choroidal vasculopathy lesion and within the PDT exposure area at the level of the choriocapillaris and middle layer of the choroid. In the outer layer of the choroid, the thickest vessel was selected in the area exposed to PDT, with the diameter of the vessel analyzed. The vascular density in the choriocapillaris and middle layer of the choroid significantly decreased from 0.54 ± 0.09 before treatment to 0.44 ± 0.07 after PDT treatment in the choriocapillaris and from 0.53 ± 0.10 to 0.47 ± 0.08 in the middle layer of the choroid, respectively. There was also a significant reduction in the diameter of the largest vessel from 309 ± 85 µm at baseline to 220 ± 52 µm. Photodynamic therapy may cause occlusion of the choriocapillaris and middle vessels in the choroid, as well as stenosis of the large vessels.

Real-world outcomes following 12\xa0months of intravitreal aflibercept monotherapy in patients with diabetic macular edema in France: results from the APOLLON study

PurposeTo report the effectiveness of intravitreal aflibercept (IVT-AFL) treatment for diabetic macular edema (DME) in French clinical practice.MethodsAPOLLON (NCT02924311) was a prospective, observational cohort study of patients with DME. Effectiveness was evaluated by change from baseline in best-corrected visual acuity (BCVA) at 12 months in treatment-naïve patients (i.e., had not received any anti-vascular endothelial growth factor [anti-VEGF] agent, laser, or steroid at IVT-AFL treatment start) and previously treated patients (i.e., previously treated with anti-VEGF agents other than IVT-AFL, laser, or steroids at IVT-AFL treatment start). Secondary endpoints included change in central retinal thickness (CRT) over 12 months, frequency of injections, and proportion of patients with safety events.ResultsOf the 147 patients followed for at least 12 months and included in the effectiveness analysis, 52.4% (n = 77) were treatment-naïve and 47.6% (n = 70) were previously treated. Mean (standard deviation [SD]) BCVA score at baseline was 62.7 (14.3) Early Treatment Diabetic Retinopathy Study (ETDRS) letters in treatment-naïve patients and 60.0 (13.7) ETDRS letters in previously treated patients. At month 12, mean (SD) change in BCVA was + 7.8 (12.3) letters in treatment-naïve patients and + 5.0 (11.3) letters in previously treated patients. Mean CRT decreased in both patient cohorts. The mean (SD) number of IVT-AFL injections at month 12 was 7.6 (2.5) for treatment-naïve patients and 7.6 (2.3) for previously treated patients. Of 388 patients included in the safety analysis, ocular treatment-emergent adverse events occurred in 54.1% (n = 210) of patients.ConclusionIVT-AFL treatment was associated with improvements in functional and anatomic outcomes in both treatment-naïve and previously treated patients with DME in France.

Aflibercept for choroidal neovascularizations secondary to pseudoxanthoma elasticum: a prospective study

PurposeTo evaluate the use of 2 mg intravitreal aflibercept for treatment of choroidal neovascularization (CNV) secondary to angioid streaks in patients with pseudoxanthoma elasticum (PXE).MethodsIn this 12-month prospective, open-label, uncontrolled, non-randomized interventional clinical trial, 15 PXE patients with CNV (mean age: 53 years, range 22–65) received one initial intravitreal injection of 2 mg aflibercept. Further injections were based on CNV activity at monthly examinations. The primary endpoint was change of best corrected visual acuity (BCVA) after 12 months. Secondary outcomes were change of central retinal thickness (CRT), leakage from CNV, retinal sensitivity, and vision-related quality of life.ResultsBCVA improved from 75.0 ± 10.8 (± SD, Snellen equivalent 20/32) to 79.3 ± 7.3 ETDRS letters (20/32) at final visit (p = 0.083). CRT decreased from 317 ± 81 to 279 ± 51 μm (p = 0.004). Retinal sensitivity on microperimetry changed from 17.8 ± 4.5 to 18.5 ± 4.3 dB (p = 0.103) and vision-related quality of life from a VQF-25 score of 80.7 ± 10.4 to 83.5 ± 14.5 (p = 0.554). The mean number of injections was 6.7 ± 2.6, and 5 participants had persistent or reactivated CNV activity at final visit. The observed adverse events were comparable with studies on aflibercept for other indications.ConclusionThe results of this study indicate that intravitreal aflibercept is a treatment option for CNV secondary to PXE.

Comparison of Intravitreal Aflibercept and Ranibizumab for Treatment of Myopic Choroidal Neovascularization: One-Year Results-A Retrospective, Comparative Study.

Purpose To compare one-year treatment outcomes of intravitreal aflibercept (IVA) and intravitreal ranibizumab (IVR) for treatment of myopic choroidal neovascularization (mCNV). Methods The medical records of a total of 30 eyes diagnosed with mCNV and underwent IVA or IVR treatment for a minimum one-year follow-up were studied retrospectively. All the subjects had an axial length >26 mm and received a 1 + PRN (pro re nata) regimen IVA or IVR. Best-corrected visual acuity (BCVA) and central macular thicknesses (CMT) on optical coherence tomography were evaluated before and after treatment. Results There were 12 eyes in IVA group, with a mean age of 60.0 ± 10.2 years. The mean BCVA significantly improved from baseline 1.54 ± 0.76 to 0.85 ± 0.61 and the mean CMT significantly decreased from baseline 384.3 ± 119.1 μm to 305.9 ± 75.4 μm to 305.9 ± 75.4 p : 0.024 and p : 0.024 and μm to 305.9 ± 75.4 μm to 305.9 ± 75.4 p : 0.024 and p : 0.024 and p : 0.024 and p : 0.024 and Conclusions Both IVA and IVR treatment modalities resulted in similar anatomical outcomes but IVA had better visual outcomes in treatment of mCNV.

Diabetic macular edema treated with intravitreal aflibercept injection after treatment with other anti-VEGF agents (SWAP-TWO study): 6-month interim analysis

BackgroundDiabetic macular edema (DME) is an important cause of vision loss and despite the anatomical and functional improvement achieved with treatment, there are reports of persistent DME regardless of continuous anti-VEGF therapy. The purpose of this study is to examine the effect of patients with DME previously treated with other anti-VEGF agents who are transitioned to intravitreal aflibercept (IAI) on a fixed dosing regimen.MethodsThis prospective study included 20 patients presenting with DME with a history of previous anti-VEGF treatment with ranibizumab or bevacizumab. Patients received a 2 mg (0.05 mL) IAI every 4 weeks until no evidence of fluid by optical coherence tomography (OCT) followed by a fixed dosing schedule of 2 mg IAI once every 8 weeks through 24 months. There was a pre-planned interim analysis of the mean absolute change from baseline central foveal thickness at month 6 as measured by OCT. Secondary outcomes included mean change from baseline in ETDRS visual acuity and anatomic parameters. Optical Coherence tomography angiography (OCTA) capillary perfusion density (CPD) after transitioning to IAI therapy were also reported.ResultsAverage central subfield thickness on OCT at baseline was 419.7 ± 92.0 and improved to 303.8 ± 73.1 at 6-months (p < 0.001). At 6 months after IAI treatment, BCVA increased + 1.5 letters from baseline (p = 0.38). OCTA CPD analysis revealed significant increase from baseline in the foveal avascular zone in non-proliferative diabetic retinopathy group (p = 0.02).ConclusionsPatients with prior anti-VEGF therapy who were transitioned to IAI therapy revealed significant anatomic improvements through 6 months.Trial registration Treatment of Diabetic Macular Edema With Aflibercept in Subjects Previously Treated With Ranibizumab or Bevacizumab (SwapTwo), Trial registration number: NCT02559180. Date of registration: September 24, 2015.https://clinicaltrials.gov/ct2/show/NCT02559180

Multiple Effects of Intravitreal Aflibercept on Microvascular Regression in Eyes with Diabetic Macular Edema

To evaluate the effects of intravitreal aflibercept (IVA) on the number of microaneurysms and sizes of nonperfused areas (NPAs) in eyes with diabetic macular edema (DME). Interventional, prospective study. Twenty-five eyes of 25 DME patients (average age, 64.0±8.8 years) were treated with 3 consecutive monthly IVA injections. Fluorescein angiography (FA) and OCT were performed before the IVA injections (baseline) and at 1 week after the IVA treatment. The number of microaneurysms and the ischemic index (ISI), a measure of NPA, were determined. The correlations between central retinal thickness (CRT) and number of microaneurysms and the ISI were also determined. The mean number of microaneurysms and NPA evaluated as the ISI. At baseline, the mean CRT was 485.7±90.6 μm. After treatment, the mean CRT was reduced significantly to 376.9±81.6 μm (P= 0.1× 10-5, repeated analysis of variance). The mean number of microaneurysms was decreased significantly from 49.6±33.2 at baseline to 24.8±18.1 at 3 months after the initial treatment. This was a 50.4±21.2% reduction (P= 0.3× 10-5, paired t test). The mean ISI was also decreased significantly from 55.5±20.4% at baseline to 28.8±16.8% after treatment (P= 0.3× 10-5, paired t test). This was a reduction of 43.3±28.5%. A significant correlation was found between the CRT and number of microaneurysms at both baseline (r= 0.56; P= 0.004) and after treatment (r= 0.53; P= 0.006). A significant correlation was found between CRT and ISI at baseline (r= -0.39; P= 0.03) but not after treatment (r= -0.06; P= 0.79). The reduction in the number of microaneurysms was correlated with reduction in CRT.

Effect of intravitreal aflibercept treatment on retinal vessel parameters in diabetic macular oedema: Arteriolar vasoconstriction

Purpose: To evaluate the effects of intravitreal aflibercept (IVA) treatment on retinal vein parameters and choroidal thickness used in the treatment of diabetic macular oedema (DME).Methods: This retrospective study administered Afyonkarahisar Health Sciences University Department of Ophthalmology. Twenty-nine patients who were diagnosed with naive DME in a single eye were included in the study. A three consecutive, monthly intravitreal injection of 2 mg aflibercept were administered to patients. Each patient’s contralateral (untreated) eyes, which did not diagnose DME and did not receive any treatment, were the control group. The central retinal artery equivalent (CRAE), central retinal vein equivalent (CRVE), and artery–vein ratio (AVR) values were measured using a semi-automatically computer-based software before the first IVA injection and 30 d after the first, second, and third injections. The main outcome measurements were the central macular thickness (CMT), best-corrected visual acuity (BCVA), subfoveal choroidal thickness (sf-CT), CRAE, CRVE, and AVR.Results: The mean age of patients was 59.25 ± 9.48 years. Patients were 15 males and 14 females. A significant vasoconstriction of the retinal arterioles, a thinning of sf-CT and CMT, and an increase of BCVA have observed in IVA-treated eyes compared to baseline (respectively, p < 0.001, p < 0.001, p < 0.001, p < 0.001). But, no significant differences were found for CRVE and AVR in IVA-treated eyes compared to baseline. No significant difference was found for all parameters in untreated eyes compared to baseline.Conclusions: This study demonstrates that IVA treatment can change retinal blood flow by reducing retinal artery diameter and thinning in the choroid.

Effectiveness and safety of intravitreal aflibercept in patients with wet age-related macular degeneration treated in routine clinical practices across France: 12-month outcomes of the RAINBOW study

Background/aimsTo monitor treatment-naïve patients with wet age-related macular degeneration (wet AMD) receiving intravitreal aflibercept (IVT-AFL) in France.MethodsRAINBOW (Real life use of intravitreal Aflibercept In FraNce - oBservatiOnal study in Wet...

Intravitreal Aflibercept Injection and Treatment Regimens in Macular Edema due to Branch Retinal Vein Occlusion

Branch retinal vein occlusion (BRVO) is the most common form of retinal vein occlusions (RVO), which is the second most common retinal vascular disease after diabetic retinopathy. The most common cause of visual loss in BRVO is macular edema. Since the vascular endothelial growth factor (VEGF) was detected in the pathogenesis of macular edema due to BRVO, studies have been made with available anti-VEGF agents and different treatment regimens. Those treatment regimens can be listed as; monthly / bi-monthly fixed interval, as needed (Pro Re Nata; PRN), treat and extend (T&amp;E). Aflibercept acts as a decoy receptor that binds to VEGF-A, VEGF-B, and placental growth factor. There are publications indicating that this agent binds VEGF with a higher affinity than other anti-VEGF agents and thus provides a longer treatment efficacy. This review summarizes the studies about the use of aflibercept in different regimens for the treatment of macular edema due to BRVO.

Effect of Aflibercept on Cystoid Macular Edema Associated with Central Retinal Vein Occlusion. Results from a District Hospital in the United Kingdom.

The purpose of this study was to report the efficiency and safety of intravitreal aflibercept for the treatment of cystoid macular edema (CME) secondary to central retinal vein occlusion (CRVO). This is a retrospective cohort study. Ten naive eyes of ten patients with CME secondary to CRVO were included. All eyes received a loading dose of 3 monthly aflibercept injections followed by as-needed injections at monthly follow-up visits. Best corrected visual acuity (BCVA) and central retinal thickness (CRT) were evaluated at baseline and at the end of the follow-up period. The median follow-up period was 6 months (range: 6 - 9). The median number of injections was 4 (range: 3 - 5). Median BCVA improved from 1.05 LogMAR units (range: 0.7 - 1.6) at baseline to 0.65 (range: 0.4 - 1.6) at the end of the follow-up period (p = 0.02). Median CRT improved from 690 µm (range: 561 - 1235) at baseline to 243 µm (range: 207 - 531) at the end of the follow-up period (p = 0.002). The power of all statistical tests was greater than 0.8. No adverse effects or complications were documented. Intravitreal aflibercept treatment for CME secondary to CRVO significantly improved both macular anatomy and visual acuity without adverse effects.

Long-term Outcome of Intravitreal Aflibercept Treatment for Neovascular Age-Related Macular Degeneration Using a “Treat-and-Extend” Regimen

To report outcomes in patients with neovascular age-related macular degeneration (nAMD) after treatment with aflibercept for up to 4 years using a treat-and-extend (T&E) regimen. Observational study. Patients with newly diagnosed nAMD treated with aflibercept in a T&E protocol. Subjects received 3 injections of aflibercept at monthly intervals followed by a T&E protocol for at least 12 months. At each clinical visit after the loading phase, OCT and best-corrected visual acuity (BCVA) testing were performed to monitor disease activity. Change in BCVA over time, number of injections and visits per year, and percentage of patients reaching a treatment interval of ≥12 weeks. Of 231 consecutive eyes (231 patients) with a mean follow-up time of 2.9 (1-5.5) years, 173 were followed up for ≥2 years, 112 were followed up for ≥3 years, and 62 were followed up for ≥4 years. Mean BCVA increased from 59.8 letters (20/60) at diagnosis to 65.8 letters (20/50) after the loading phase (+6.0 letters; standard deviation [SD], 11.1) and to 65.5 letters at 12 months (+5.7 letters; [SD], 17). After 4 years of treatment, mean BCVA was maintained insignificantly better than baseline (63.4 letters,+3.6 letters gain, SD, 20.6; P>0.05). To achieve this, a mean of 7.7 (±1.2) injections and 4.4 (±1.6) clinic visits in the first year and 4.4 (±1.9) injections and 4.3 (±1.3) clinical visits per year thereafter were required. By 2 years of follow-up, 46.9% of patients reached a treatment interval of ≥12 weeks. By using a T&E regimen, patients with nAMD maintained stable visual function over 4 years in a real-world setting with a reasonable treatment burden.

Influence of myopic macular degeneration severity on treatment outcomes with intravitreal aflibercept in the MYRROR study

To determine the influence of baseline myopic macular degeneration (MMD) severity on outcomes with intravitreal aflibercept (IVT-AFL) in patients with myopic choroidal neovascularization (CNV). MYRROR was a randomized, double-masked study in patients with myopic CNV treated with IVT-AFL/sham over 48weeks. At baseline/week 48, images were retrospectively graded for MMD. At baseline, 115 eyes had a valid MMD grading result; at week 48, grading results were available for 99 eyes [IVT-AFL (n=78)/sham (n=21)]. Severity of baseline MMD was distributed as follows: category 1: 19/115 (17%); category 2: 67/115 (58%); category 3: 22/115 (19%); category 4: 7/115 (6%). Higher MMD category was associated with older age (nominal p=0.007) and longer axial length (nominal p=0.025). At week 48, patients in the mild and severe groups had visual acuity gains of +13.5 and +12.4 letters, respectively. Baseline MMD severity did not significantly affect visual/anatomical outcomes or number of treatments. Visual Functioning Questionnaire-25 scores improved more in mild (+5.6) versus severe (+0.4) MMD (nominal p=0.03). There were no new safety events. Visual acuity gains, morphological outcomes and dosing frequency were not affected by baseline MMD severity in patients treated with IVT-AFL. A benefit with IVT-AFL treatment was observed for all baseline MMD stages included in this study.

Efficacy and safety of intravitreal aflibercept therapy in diabetic macular edema

To conduct a retrospective evaluation of the efficacy and safety of intravitreal aflibercept treatment in diabetic macular edema. Patients treated with intravitreal aflibercept for diabetic macular edema participated in this study. Three injections were administered to the previously untreated 76 eyes of 50 patients for 3 consecutive months with one-month interval. The results were evaluated retrospectively by analyzing the patients’ medical records. The patients’ values of ‘‘best corrected visual acuity” inverted according to Snellen chart, and their central macular thickness and intraocular pressure were compared before and after treatment. The average age of the patients was 57.2 ± 10.1. Of the cases, 77.6% were phakic, and 22.4% were pseudophakic. The increases in “best corrected visual acuity” in the first month after each injection and at the end of the third month were statistically significant (p < 0.001). The mean central macular thickness was 405.63 ± 106.93 μm before treatment and 288.83 ± 62.49 μm after the third injection. This reduction in the mean central macular thickness was statistically significant (p < 0.05). During and after the three-month follow-up of the injection application process, the most common observed ocular side effect was subconjunctival hemorrhage (34.2%). During or after the applications, no systemic side effects, such as sudden death, thromboembolic events, or myocardial infarction, were seen. Functionally and anatomically, intravitreal aflibercept injection therapy in diabetic macular edema is an effective treatment option because it improves visual acuity and decreases central macular thickness.