Aflibercept as Adjunctive Treatment for Filtration Surgery in Neovascular Glaucoma

Objective: To investigate intravitreal aflibercept (IVA) injection as an adjunctive treatment to trabeculectomy with mitomycin C (TMC) and panretinal photocoagulation (PRP) for neovascular glaucoma (NVG).Materials and Methods: PRP and IVA (2 mg/0.05 ml) injection were given, and TMC was performed within 2weeks after IVA. Additional PRP, laser suture lysis, subconjunctival 5-fluorouracil injection, and bleb needlingwere performed after TMC if indicated. Best corrected visual acuity (BCVA), intraocular pressure (IOP), surgicalcomplications, and number of anti-glaucoma medications were collected.Results: Five eyes from 5 consecutive patients were included. Two eyes had proliferative diabetic retinopathy (PDR), 2 central retinal vein occlusion, and 1 ocular ischemic syndrome (OIS) (mean initial IOP: 46.8±6.8 mmHg). NVI regression occurred in one eye after PRP alone, and in one eye after PRP and IVA resulting in a good IOP control with topical medical therapy. The other 3 underwent TMC. The preoperative IOP was 34 (OIS), 54 (PDR), and 50 (PDR) mmHg. The 3-month postoperative IOP decreased to 8, 8, and 4 mmHg, respectively, and to 21, 10, and 6 mmHg, respectively, at the last visit. Only the one OIS eye required postoperative topical IOP-lowering medications. Final BCVA was improved, unchanged, and decreased in 2, 2, and 1 eye, respectively. No intraoperative/postoperative complications or NVI recurrence were observed (mean follow-up: 10.7 months).Conclusion: Intravitreal aflibercept was shown to be a potentially effective additional treatment to PRP and TMC in patients with NVG.

Effects of Intravitreal Aflibercept on the Systemic Insulin-like Growth Factor-I and Vascular Endothelial Growth Factor-A in Patients with Diabetic Retinopathy and Age-Related Macular Degeneration

Purpose. To analyze the effect of intravitreal aflibercept injections on systemic levels of insulin-like growth factor-1 and vascular endothelial growth factor-A in patients with diabetic retinopathy and age-related macular degeneration. Methods. Vascular endothelial growth factor-A and insulin-like growth factor-1 levels were determined before and one week and four weeks after intravitreal injection of aflibercept (2.0 mg/50 μl) for 19 patients with age-related macular degeneration (mean age, 76 ± 11 years) and 18 patients with diabetic retinopathy (mean age, 64 ± 14 years). Twenty-two healthy individuals were enrolled as controls. Results. A significant decline in systemic vascular endothelial growth factor-A level, from 43 (30–57) pg/ml at baseline to 8 (8–8) pg/ml ( p < 0.001 ) at week one and 17 (8–25) pg/ml ( p = 0.0054 ) at week four, was observed in the age-related macular degeneration group. In the diabetic retinopathy group, vascular endothelial growth factor-A levels declined from 53 (35–117) pg/ml to 2 (1–5) pg/ml ( p < 0.0001 ) one week after injection and 16 (13–22) pg/ml four weeks after injection ( p = 0.0327 ). At baseline, systemic insulin-like growth factor-1 concentration was higher in the diabetic retinopathy group (57 [37–99] pg/ml) than in the age-related macular degeneration group (35 [24–51] pg/ml) ( p = 0.0056 ). A subgroup analysis showed that patients in the proliferative diabetic retinopathy subgroup had significantly higher systemic insulin-like growth factor-1 concentrations (71 [44.7–243] pg/ml) than those in the nonproliferative diabetic retinopathy subgroup (43 [29–66] pg/ml) ( p = 0.0048 ). Conclusions. The difference between the baseline systemic insulin-like growth factor-1 levels of the age-related macular degeneration and diabetic retinopathy groups and the higher insulin-like growth factor-1 levels in the proliferative diabetic retinopathy subgroup one week after aflibercept therapy suggest that insulin-like growth factor-1 may play a role in the pathomechanism of diabetic retinopathy.

The Aflibercept-Induced MicroRNA Profile in the Vitreous of Proliferative Diabetic Retinopathy Patients Detected by Next-Generation Sequencing

Purpose: Vascular endothelial growth factor-A (VEGF-A) is an important pathogenic factor in proliferative diabetic retinopathy (PDR), and aflibercept (Eylea) is one of the widely used anti-VEGF agents. This study investigated the microRNA (miRNA) profiles in the vitreous of 5 idiopathic macular hole patients (non-diabetic controls), 5 untreated PDR patients (no-treatment group), and 5 PDR patients treated with intravitreal aflibercept injection (treatment group).Methods: Next-generation sequencing was performed to determine the miRNA profiles. Deregulated miRNAs were validated with quantitative real-time PCR (qRT-PCR) in another cohort. The mRNA profile data (GSE160310) of PDR patients were retrieved from the Gene Expression Omnibus (GEO) database. The function of differentially expressed miRNAs and mRNAs was annotated by bioinformatic analysis and literature study.Results: Twenty-nine miRNAs were significantly dysregulated in the three groups, of which 19,984 target mRNAs were predicted. Hsa-miR-3184-3p, hsa-miR-24-3p, and hsa-miR-197-3p were validated to be remarkably upregulated in no-treatment group versus controls, and significantly downregulated in treatment group versus no-treatment group. In the GSE160310 profile, 204 deregulated protein-coding mRNAs were identified, and finally 179 overlapped mRNAs between the 19,984 target mRNAs and 204 deregulated mRNAs were included for further analysis. Function analysis provided several roles of aflibercept-induced miRNAs, promoting the alternation of drug sensitivity or resistance-related mRNAs, and regulating critical mRNAs involved in angiogenesis and retinal fibrosis.Conclusion: Hsa-miR-3184-3p, hsa-miR-24-3p, and hsa-miR-197-3p were highly expressed in PDR patients, and intravitreal aflibercept injection could reverse this alteration. Intravitreal aflibercept injection may involve in regulating cell sensitivity or resistance to drug, angiogenesis, and retinal fibrosis.

Intravitreal aflibercept following treat and extend protocol versus fixed protocol for treatment of neovascular age-related macular degeneration

Background To assess the morphological and functional outcome of intravitreal aflibercept following the treat and extend protocol compared to the fixed protocol for treatment of eyes with neovascular age-related macular degeneration. Methods This retrospective study included 126 eyes of 113 patients with primary onset neovascular age-related macular degeneration who were followed for 12 months. All eyes were treated with 2 mg/0.05 mL aflibercept. All eyes received an upload with three monthly aflibercept injections. We subsequently studied two groups of eyes. For group 1, 54 eyes were treated following the treat and extend protocol. For group 2, 72 eyes were treated following the fixed protocol (fixed 2-monthly interval). Main outcome measures included: best corrected visual acuity (BCVA), central macular thickness (CMT) and number of injections. Results BCVA (logMAR) in group 1 vs group 2 was (0.61 ± 0.3 vs 0.72 ± 0.3, p = 0.09) before treatment and (0.48 ± 0.3 vs 0.51 ± 0.3, p = 0.6) after one year of treatment. CMT in group 1 vs group 2 was (371 ± 101 μm vs 393 ± 116 μm, p = 0.5) before treatment and (284 ± 60 μm vs 290 ± 67 μm, p = 0.1) after one year of treatment. Number of injections/eye in group 1 vs group 2 was (8.5 ± 2.2 vs 7.0 ± 0, p < 0.001). Conclusions Significant differences regarding BCVA and central macular thickness were not found between both treatment protocols during the first year of treatment using aflibercept. However, a significantly higher number of injections was needed for eyes in the treat and extend group during the first year of treatment. This might suggest that aflibercept should better not be extended past an 8 weeks interval during the first year of treatment. Study registration This study was approved by the Ethics Committee of the Medical Association of Saarland, Germany (Nr. 123/20, Date: 16.06.2020). All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. This article does not contain any studies with animals performed by any of the authors.

The 2-Year Leakage Index and Quantitative Microaneurysm Results of the RECOVERY Study: Quantitative Ultra-Widefield Findings in Proliferative Diabetic Retinopathy Treated with Intravitreal Aflibercept

Eyes with proliferative diabetic retinopathy (PDR) have been shown to improve in the leakage index and microaneurysm (MA) count after intravitreal aflibercept (IAI) treatment. The authors investigated these changes via automatic segmentation on ultra-widefield fluorescein angiography (UWFA). Forty subjects with PDR were randomized to receive either 2 mg IAI every 4 weeks (Arm 1) or every 12 weeks (Arm 2) through Year 1. After Year 1, Arm 1 switched to quarterly IAI and Arm 2 to monthly IAI through Year 2. By Year 2, the Arm 1 leakage index decreased by 43% from Baseline (p = 0.03) but increased by 59% from Year 1 (p = 0.04). Arm 2 decreased by 61% from Baseline (p = 0.008) and by 31% from Year 1 (p = 0.12). Both cohorts exhibited a significant decline in MAs from Baseline to Year 2 (871 to 410; p < 0.001; 776 to 207; p < 0.001, respectively). Subjects with an improved leakage and MA count showed a more significant improvement in the Diabetic Retinopathy Severity Scale (DRSS) score. Moreover, central subfield thickness (CST) was positively associated with changes in the leakage index. In conclusion, the leakage index and MA counts significantly improved from Baseline following IAI treatment, and monthly injections provided a more rapid and sustained reduction in these parameters compared with quarterly injections.

Combined therapy with intravitreal aflibercept and subtenon corticosteroids in eyes with severe diabetic papillopathy: two case reports

Background Diabetic papillopathy is a rare diagnosis of exclusion characterized by unilateral or bilateral optic disc edema with variable degrees of visual loss. Although the visual prognosis has been generally reported as favorable, the presence of severe disc edema associated with macular edema prompts the need for treatment. We present a specific and unreported therapeutic approach consisting of intravitreal aflibercept and subtenon triamcinolone acetonide injections in two patients with evidence of diabetic papillopathy and macular edema. Case presentation In the first case, a 60-year-old Caucasian woman affected by type II diabetes mellitus presented with fundoscopic evidence of sequential bilateral optic disc edema associated with acute severe visual loss in both eyes. The second patient, a diabetic 57-year-old Caucasian male, presented with sudden painless visual loss in his left eye. Multimodal imaging and systemic findings correlated towards an infrequent diagnosis of diabetic papillopathy. In a period of 5–7 weeks after treatment, both patients experienced almost full visual and anatomical recovery. A steady situation was observed at 12 months of follow-up. Conclusions Both our cases displayed a severe grade of optic disc edema, which was optimally reversed with intravitreal aflibercept and subtenon triamcinolone acetonide leading to a relatively rapid and safe improvement in visual acuity.

Association between Vortex Vein Engorgement and Treatment Outcomes of Intravitreal Aflibercept for Polypoidal Choroidal Vasculopathy

Purpose: To investigate the influence of the number of engorged vortex veins on treatment outcomes in eyes with treatment-naïve polypoidal choroidal vasculopathy (PCV) undergoing intravitreal aflibercept monotherapy.Methods: The medical charts of 65 patients with PCV who underwent intravitreal aflibercept injection were reviewed retrospectively. The number of quadrants of vortex vein engorgement was evaluated in the middle phase of ultra-widefield indocyanine green angiography, which was classified as extended engorgement if the dilated choroidal vessels expanded the macula. Associations between treatment outcomes with age, subfoveal choroidal thickness (SFCT), central retinal thickness, and vortex vein engorgement were investigated using univariate and multivariate analyses.Results: There were no significant differences in best-corrected visual acuity (BCVA), SFCT, and central retinal thickness at baseline and 12 months, according to the number of vortex vein engorgement. However, an increase in the number of vortex vein engorgement extending to the macula was associated with a thick SFCT (p = 0.038), a greater number of injections (p = 0.041), low BCVA at 12 months (p = 0.038), and a less dry macula at 12 months (p = 0.026). In the multivariate analysis, the number of quadrants with vortex vein engorgement extending to the macula was significantly associated with BCVA changes at 12 months, total number of injections, and a dry macula at 12 months (p = 0.030, p = 0.030, p = 0.020, respectively).Conclusions: More quadrants with vortex vein engorgement extending to the macula in PCV was associated with unfavorable visual outcomes, a less dry macula at 12 months, and a greater number of injections at 1 year after intravitreal aflibercept injection. Clinicians should keep in mind that vortex vein engorgement extending to the macula may be a new biomarker in predicting treatment outcomes in PCV.