Single Intravitreal Aflibercept Injection Research Articles

Choroidal neovascularization as first sign of Best's vitelliform dystrophy in a child

Aims/Purpose: To report a case of choroidal neovascularization secondary to Best's vitelliform dystrophy in a child managed by intravitreal aflibercept.Methods: Interventional, case report.Results: A 9‐year‐old boy reported decreased visual acuity (VA) with metamorphopsia in his right eye (RE) for the previous month. VA was RE 20/100 and left eye (LE) 20/20. Funduscopy revealed right‐eye macular oedema with deep macular haemorrhage associated to a bilateral orange‐yellowish deposit. Optical coherence tomography (OCT) showed sub‐ and intraretinal fluid in the foveal area along with a hyperreflective subretinal deposit and a localized retinal pigment epithelium (RPE) elevation. Blue autofluorescence (BAF) imaging disclosed a central hyper autofluorescence area as well as a larger defect corresponding to the haemorrhage and the subretinal deposit. The LE was positive for a central deposit located under the RPE with hyper autofluorescence at BAF. Familiar history was unknown for ocular conditions and the clinical history was irrelevant for fever, inflammation, adenopathy, articular, neurological or respiratory conditions. The condition was diagnosed as choroidal neovascularization (CNV) secondary to Best's vitelliform dystrophy and a single intravitreal injection of aflibercept was performed under general anaesthesia. Genetic study revealed a likely pathogenic mutation c.874G>C (p.Glu292Gln) in the BEST1 gene (missense change, not previously published) affecting a functional dominion. The subretinal bleeding and fluid resolved after one single injection of aflibercept and VA improved to 20/20. No recurrences have been observed during the subsequent five years in either eye.Conclusions: We report a case of CNV as first manifestation of a previously not reported mutation of Best's vitelliform dystrophy in a 9‐year‐old boy that was successfully treated with one single intravitreal injection of aflibercept.

Morphological and functional changes in the macular area in diabetic macular edema after a single intravitreal injection of aflibercept.

To evaluate the changes in macular morphology and function after a single intravitreal injection of aflibercept in diabetic macular edema (DME) using optical coherence tomography angiography (OCTA) and MP-3 microperimetry. Twenty-eight patients (42 eyes) diagnosed with DME were treated with intravitreal injection of aflibercept. The changes in best corrected visual acuity (BCVA), central retinal thickness (CRT), foveal avascular zone (FAZ) area, vessel density of superficial retinal capillary plexus (SVD), vessel density of deep retinal capillary plexus (DVD), mean light sensitivity (MLS), 2° fixation rate (P1), 4° fixation rate (P2), and other indicators 1mo after treatment were compared; of these, BCVA was converted into logarithm of the minimum angle of resolution (logMAR), and the correlation among the factors was analyzed. After treatment, logMAR BCVA was 0.47±0.24, which was significantly better than that before treatment (0.63±0.28, P<0.001). The CRT was 359.21±107.87 µm after treatment, which was significantly lower than before treatment (474.10±138.20 µm, P<0.001). The FAZ area, SVD, and DVD were not significantly changed after treatment compared with the baseline. MLS was 22.16±4.20 dB after treatment, which was significantly higher than before treatment (19.63±4.23 dB, P<0.001). P2 significantly increased after treatment than before treatment (P=0.007). P1 had no significant change after treatment than before treatment (P=0.086). A single intravitreal injection of aflibercept effectively reduces macular edema and improves retinal sensitivity, fixation stability, and visual acuity, possibly without causing significant changes in the retinal vascular condition in a short time.

Effect of Intravitreal Injection of Aflibercept on Cardiovascular Risk Parameters in Patients with Neovascular Age-Related Macular Degeneration.

Systemic administration of anti-Vascular Endothelial Growth Factors (anti- VEGFs) has been associated with severe cardiovascular adverse events in oncologic patients. The purpose of this pilot study is to evaluate the short-term effect of a single intravitreal injection of aflibercept on biomarkers related to increased risk of cardiovascular disease. Forty-seven treatment naïve patients with neovascular age-related macular degeneration in one eye were enrolled in the study. The patients underwent treatment with one intravitreal injection of aflibercept in the affected eye. Laboratory biomarkers of cardiovascular disease were evaluated before the first intravitreal injection of aflibercept and at 7 and 30 days after aflibercept administration. More precisely, we evaluated the levels of homocysteine, total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol and Creactive protein. There was not any statistically significant change in the levels of the evaluated parameters up to one month after the first intravitreal injection of aflibercept. According to our study, the administration of a single dose of aflibercept in eyes with neovascular age-related macular degeneration does not seem to affect the evaluated biomarkers that are related to cardiovascular disease.

Effect of intravitreal injection of aflibercept on blood coagulation parameters in patients with age-related macular degeneration.

Purpose:Treatment with intravitreal injections of anti-vascular endothelial growth factor agents has been associated with an increased risk of arterial thromboembolic events. The aim of the present pilot study was to assess the effect of a single intravitreal injection of aflibercept on coagulation.Methods:Treatment-naïve patients with age-related macular degeneration (n = 47), who were scheduled to undergo treatment with intravitreal injections of aflibercept, were enrolled. None of the included patients received any anticoagulation therapy or had a history of a recent arterial thromboembolic event. Blood samples were collected before the first intravitreal injection, and at 7 and 30 days after aflibercept administration. We evaluated coagulation parameters, such as platelet count and plasma fibrinogen and D-dimer levels; functional clotting parameters, such as prothrombin time, international normalized ratio, and activated partial thromboplastin time; and anticoagulant parameters, such as the levels of Proteins S and C.Results:The levels of all of the evaluated biomarkers were within the normal range at baseline and at both the time points throughout the study. No statistically significant changes were observed in any of the measured parameters at 1 week and 1 month after aflibercept administration.Conclusion:A single intravitreal injection of aflibercept in treatment-naïve patients with exudative age-related macular degeneration has no statistically significant effect on blood coagulation parameters for up to 1 month after aflibercept administration. Our results also provide an explorative statistical data, and further studies are required to evaluate any significant clinical effects of aflibercept on blood coagulation parameters.ClinicalTrials.gov ID:NCT03509623.

Effect of intravitreal aflibercept on corneal endothelial cells: a 6-month follow-up study.

PurposeTo determine the effect of intravitreal aflibercept injection on the corneal endothelium in patients with diabetic or cystoid macular edema caused by retinal vein occlusion.Material and methodsForty-six eyes of 44 consecutive patients (27 men, 17 women; age range: 55–88 years) were evaluated. All participants initially received a single intravitreal injection of aflibercept (2 mg in 0.05 mL), followed by pro re nata use and underwent central corneal specular microscopy before the injection and at 1, 3 and 6 months after the first injection during a 6-month follow-up period. The endothelial cell density (ECD), average cell size (AVG), standard deviation of cell size (SD), coefficient of variation of cell size (CoV), maximum of cell size (MAX), minimum of cell size (MIN) and percentage of hexagonal cells (Hex%) were analyzed and the central corneal thickness (CCT) was measured.ResultsNo significant differences in the ECD, AVG, SD, CoV, MIN, Hex% and CCT were observed between measurements obtained before and 1, 3 and 6 months after the first injection. However, the MAX measured before injection differed significantly from the values measured at 1, 3 and 6 months after the first injection (P=0.033). An average of 1.43±0.58 intravitreal aflibercept injections were administered per patient.ConclusionThese study findings indicate that the intravitreal administration of aflibercept (2 mg) might very slightly alter the corneal endothelium within 6 months of the first injection.

Novel Predictors of Visual Outcome in Anti-VEGF Therapy for Myopic Choroidal Neovascularization Derived Using OCT Angiography

To explore novel prognostic factors associated with visual function and number of anti-vascular endothelial growth factor (VEGF) treatments in eyes with active myopic choroidal neovascularization (mCNV) using OCT angiography (OCTA). Prospective case series. Twenty-eight treatment-naïve eyes with active mCNV from 27 consecutive patients (mean age, 64.4 ± 11.1 years). All eyes received through injection a single loading dose of intravitreal aflibercept (IVA), followed byadditional IVA on a pro re nata (PRN) basis during the subsequent 12 months. At baseline, OCTA images of a 3× 3-mm macular cube were acquired using an OCTA scanner. On binarized and skeletonized OCTA images of the outer retinal layer, OCTA-derived baseline parameters of mCNV-including lesion size, vessel density, vessel length density (VLD), vessel diameter index, and fractal dimension (FD)-were measured and evaluated for correlation with 12-month best-corrected visual acuity (BCVA) and number of additional injections. The primary and secondary outcomes were BCVA 12 months after initial treatment and number of additional injections, respectively. There was no significant difference between baseline and 12-month BCVA (0.37 ± 0.30 and 0.30 ± 0.35 logarithm of the minimal angle of resolution, respectively; P=0.23). The number of additional injections was 0.93 ± 1.02 (mean ± standard deviation). Baseline VLD, FD, and BCVA were correlated with 12-month BCVA (P= 0.02, r= 0.46; P= 0.02, r= 0.46; and P= 0.02, r= 0.45, respectively), and VLD also was correlated with the number of additional injections (P= 0.03, r= 0.42). Exuberant mCNV, which is characterized by high VLD and FD derived using OCTA, is a predictor of poor visual outcomes after a single IVA injection followed by a PRN regimen. Only baseline VLD was correlated with the number of additional IVA injections, which indicates that this parameter could help to determine the optimal anti-VEGF treatment regimen for individual eyes with mCNV.

Effects of Intravitreal Aflibercept on Galectin-1 and Vascular Endothelial Growth Factor-A Plasma Levels in Patients with Diabetic Retinopathy

ABSTRACTPurpose: To analyze the interaction between aflibercept and galectin-1 and evaluate the plasma levels of galectin-1 and vascular endothelial growth factor (VEGF)-A after intravitreal injection of aflibercept in patients with diabetic retinopathy (DR).Methods: Interaction of galectin-1 with aflibercept was determined via immunoprecipitation. Seventeen patients with type 2 diabetes and diabetic macular edema (DME) were each treated with a single intravitreal injection of aflibercept (2.0 mg, 50 µL) monthly for three consecutive months. Plasma galectin-1 and VEGF-A levels were measured just before an injection was administered, 1 week after the first injection, and 2 months after the last injection. Nineteen age- and sex-matched healthy participants served as controls.Results: Irrespective of the tested galectin-1 concentration, 24% of added galectin-1 was precipitated by aflibercept. Baseline plasma concentrations of galectin-1 were 22.0 and 23.0 ng/mL in the control and aflibercept-treated groups, respectively. Systemic galectin-1 levels increased to 27.0 and 24.0 ng/mL at 7 days and 4 weeks, respectively, after treatment. At week 8, plasma galectin-1 levels significantly increased to 36.0 ng/mL. This level persisted for 20 weeks. Systemic VEGF-A levels significantly reduced to below the minimum detectable dose in 16 DME patients at 7 days after treatment. This level persisted for 4 weeks. Plasma VEGF-A levels were reduced at weeks 8 (p = 0.099) and 20 (p = 0.023). Decreased plasma VEGF-A levels were observed in all patients after treatment.Conclusion: We confirmed that physiological aflibercept levels precipitate galectin-1 in in vitro assays. Additionally, systemic upregulation of galectin-1 might be induced by intravitreal aflibercept, which may be relevant in the clinical outcomes of DR treatment.

Effect of intravitreal aflibercept (Eylea®) on retrobulbar hemodynamics in patients with neovascular age-related macular degeneration.

To investigate the short-term effect of single intravitreal aflibercept injection on retrobulbar blood flow in patients with neovascular age-related macular degeneration (nAMD). Twenty eyes of 20 patients with nAMD scheduled for single intravitreal aflibercept (Eylea®) injection and 20 fellow eyes (uninjected) were enrolled in this prospective interventional study. The hemodynamic parameters of the ophthalmic artery (OA), central retinal artery (CRA) and posterior ciliary artery (PCA) comprising peak systolic velocity (PSV), end-diastolic velocity (EDV), and resistive index (RI) were measured by using color Doppler ultrasonography (CDU) in both injected and uninjected fellow eyes at baseline and 1week after the injection. The measured first-week values of PSV and EDV in the CRA, OA and PCA showed a statistically significant reduction when comparing baseline values in both injected and uninjected fellow eyes (p=0.0001). Also, it was found a significant increase in the post-injection RI values of all the CRA, OA, PCA in injected eye and OA in the uninjected eye (p=0.0001). There was any significant difference between pre- and post-injection RI values of the CRA and PCA in the fellow eyes (p=0.137, p=0.736, respectively). Single intravitreal administration of aflibercept alters retrobulbar blood flow velocities (BFVs) in both injected and uninjected fellow eyes in the short-term period.

Single intravitreal aflibercept injection for unilateral acute nonarteritic ischemic optic neuropathy.

Acute nonarteritic ischemic optic neuropathy (ANAION) is the most common optic neuropathy in the elderly population without a well-established treatment. A 67-year-old man with a sudden painless visual loss in his left eye of one-day duration was diagnosed to have left ANAION. Next day, 2 mg aflibercept injection was injected intravitreally in OS. Visual acuity improved to 7/10 from 1/10 a week after the injection. Mean retinal nerve fiber layer thickness (RNFLT) was reduced to 159,7 μm from 182,4 μm at the first week. Visual fields improved dramatically during the follow-up of three months. The aim of this study is to present a case having ANAION treated with a single intravitreal aflibercept injection and discuss the place of intravitreal anti-VEGF injections in the treatment of armamentarium of ANAION.

Effects of a single intravitreal injection of aflibercept and ranibizumab on glomeruli of monkeys.

PurposeIt is known that endothelial cells in the kidney are also strongly VEGF-dependent. Whether intravitreal drugs can be detected within the glomeruli or affect VEGF in glomerular podocytes is not known. Therefore, the aim of this pilot study was to investigate the effects of a single intravitreal injection of aflibercept and ranibizumab on glomeruli of monkeys.MethodsThe kidneys of eight cynomolgus monkeys, which were intravitreally injected either with 2 mg of aflibercept or with 0.5 mg of ranibizumab, were investigated one and seven days after injection. Two animals served as controls. The distribution of aflibercept, ranibizumab and VEGF was evaluated using anti-Fc- or anti-F(ab)-fragment and anti-VEGF antibodies respectively. The ratio of stained area/nuclei was calculated using a semi-quantitative computer assisted method. Glomerular endothelial cell fenestration was quantified in electron microscopy using a systematic uniform random sampling protocol and estimating the ratio of fenestrae per µm.ResultsCompared to the controls, the anti-VEGF stained area/nuclei ratio of the ranibizumab-treated animals showed no significant changes whereas the stained areas of the aflibercept-treated monkeys showed a significant decrease post-treatment. Immune reactivity (IR) against aflibercept or ranibizumab was detected in aflibercept- or ranibizumab treated animals respectively. The number of fenestrations of the glomerular endothelial cells has shown no significant differences except one day after aflibercept injection in which the number was increased.ConclusionSurprisingly, both drugs could be detected within the capillaries of the glomeruli. After a single intravitreal injection of aflibercept, VEGF IR in the podocytes was significantly reduced compared to controls. Ranibizumab injection had no significant effect on the glomeruli's VEGF level. Whether this is caused by aflibercept's higher affinity to VEGF or because it is used in a higher stoichiometric concentration compared to ranibizumab remains to be investigated.

Evaluation of Very High- and Very Low-Dose Intravitreal Aflibercept in Patients with Neovascular Age-Related Macular Degeneration

To determine bioactivity and duration of effect of intravitreal aflibercept injection (also known as vascular endothelial growth factor Trap-Eye) for neovascular age-related macular degeneration (AMD). In this double-masked, phase 1 study, 28 patients with lesions ≤12 disc areas, ≥50% active choroidal neovascularization (CNV), and best corrected visual acuity (BCVA) ≤20/40 were randomized 1:1 to a single intravitreal injection of aflibercept 0.15 or 4 mg. The primary end point was the change from baseline in central retinal/lesion thickness (CR/LT) at week-8. Secondary outcomes were the change from baseline BCVA, the change in CNV lesion size and area of leakage, and proportion of patients requiring repeat injection at 8 weeks. Mean percent decrease in CR/LT for the 4-mg and 0.15-mg groups was, respectively, 34.2 versus 13.3 at week 4 (P=0.0065), 23.8 versus 5.9 at week 6 (P=0.0380), and 25.2% versus 11.3% at week 8 (P=0.150). The 4-mg group gained a mean of 4.5 letters in BCVA (6/14 patients gaining ≥10 letters) versus 1.1 letters in 0.15-mg group (1/14 gaining ≥10 letters) at week 8. Fewer patients needed retreatment in the 4-mg group at week 8. No serious adverse event or ocular inflammation was reported in either group. Intravitreal aflibercept 4 mg had a safety profile similar to that of the very low dose 0.15 mg, and was well-tolerated. The 4-mg dose significantly reduced foveal thickening at weeks 4 and 6, significantly improved BCVA at weeks 6, and reduced the need for repeat injection after 8 weeks compared with intravitreal aflibercept 0.15 mg in neovascular AMD patients.