Intravitreal Aflibercept Injection Research Articles

Intravitreal Aflibercept vs Laser Therapy for Retinopathy of Prematurity

Prospective long-term data after retinopathy of prematurity (ROP) treatment with anti-vascular endothelial growth factor injections vs laser therapy are scarce. The FIREFLEYE (Aflibercept for ROP IVT Injection vs Laser Therapy) next trial is prospectively evaluating the long-term efficacy and safety outcomes following ROP treatment with intravitreal aflibercept vs laser therapy. To evaluate 2-year ophthalmic and safety outcomes after 0.4-mg aflibercept injection or laser therapy in the 24-week randomized (2:1) FIREFLEYE trial (FIREFLEYE outcomes previously reported). This prospective nonrandomized controlled trial performed in 24 countries in Asia, Europe, and South America (2020-2025) follows up participants treated in the FIREFLEYE randomized clinical trial (2019-2021) through 5 years of age. Participants included children born very or extremely preterm (gestational age ≤32 weeks) or with very or extremely low birth weight (≤1500 g) who were previously treated with a 0.4-mg injection of aflibercept compared with laser therapy for severe acute-phase ROP. Data for the present interim analysis were acquired from March 18, 2020, to July 25, 2022. Complications of ROP treated at investigator discretion (no study treatment). Efficacy end points included ROP status, unfavorable structural outcomes, ROP recurrence, treatment for ROP complications, completion of vascularization, and visual function. Safety end points included adverse events and growth and neurodevelopmental outcomes. Overall, 100 children were enrolled (median gestational age, 26 [range, 23-31] weeks; 53 boys and 47 girls). Of these, 21 were Asian, 2 were Black, 75 were White, and 2 were of more than 1 race. At 2 years of age, 61 of 63 children (96.8%) in the aflibercept group vs 30 of 32 (93.8%) in the laser group had no ROP. Through 2 years of age, 62 of 66 (93.9%) in the aflibercept group and 32 of 34 (94.1%) in the laser group had no unfavorable structural outcomes. No new retinal detachment occurred during the study. Four children in the aflibercept group (6.1%) were treated for ROP complications before 1 year of age (2 had preexisting end-stage disease and total retinal detachment; 1 had reactivated plus disease; and 1 had recurrent retinal neovascularization not further specified). Most children were able to fix and follow a 5-cm toy (aflibercept group, 118 of 122 eyes [96.7%] among 63 children; laser group, 62 of 63 eyes [98.4%] among 33 children). High myopia was present in 9 of 115 eyes (7.8%) among 5 children in the aflibercept group and 13 of 60 eyes (21.7%) among 9 children in the laser group. No relevant differences in growth and neurodevelopmental outcomes by Bayley Scales of Infant and Toddler Development, Third Edition and Vineland Adaptive Behavior Scales, Second Edition were identified. In this nonrandomized follow-up of a randomized clinical trial comparing treatment of severe acute-phase ROP with 0.4-mg injection of aflibercept and laser, disease control was stable and visual function was appropriate in children through 2 years of age. No adverse effects on safety, including growth and neurodevelopment, were identified. These findings provide clinically relevant long-term information on intravitreal aflibercept injection therapy for ROP. ClinicalTrials.gov Identifier: NCT04015180.

Treatment Effects of Switching to Faricimab in Eyes with Diabetic Macular Edema Refractory to Aflibercept

Background and Objectives: Faricimab is a vascular endothelial growth factor A and angiopoietin-2 bispecific antibody. It is a novel therapeutic approach distinct from previous anti-vascular endothelial growth factor agents. This study aimed to evaluate the efficacy of switching from aflibercept to faricimab in the treatment of diabetic macular edema (DME) refractory to aflibercept, with a specific focus on the resolution of macular edema. Materials and Methods: The medical records of 29 eyes of 21 patients with DME that were refractory to intravitreal injections of aflibercept (IVAs) and who had completed the clinical follow-up of at least four intravitreal injections of faricimab (IVFs) were reviewed. The central retinal thickness (CRT), best-corrected visual acuity (BCVA), and the mean period (weeks) until the next injection were measured after the second-to-last IVA, first-to-last IVA, last IVA, and first to fourth IVFs following the transition to IVF. Results: The mean time from the first IVF to the assessment of effectiveness was significantly shorter than the time to the last IVA; however, no significant difference was found in the time from the second, third, and fourth IVFs to the assessment. The mean CRTs after the first and second IVFs were not significantly different from the CRT after the last IVA, but the mean CRT after the third and fourth IVFs was significantly thinner than that after the last IVA (p = 0.0025 and p = 0.0076, respectively). The mean BCVAs after the third and fourth IVFs significantly improved compared with that after the last IVA (p = 0.0050 and p = 0.0052, respectively). Conclusions: When switching the treatment to IVF for eyes with IVA-resistant DME, better treatment outcomes are achieved if IVF is performed three or more times.

Proteomic study of vitreous in proliferative diabetic retinopathy patients after treatment with aflibercept: a quantitative analysis based on 4D label-free technique.

To identify different metabolites, proteins and related pathways to elucidate the causes of proliferative diabetic retinopathy (PDR) and resistance to anti-vascular endothelial growth factor (VEGF) drugs, and to provide biomarkers for the diagnosis and treatment of PDR. Vitreous specimens from patients with diabetic retinopathy were collected and analyzed by Liquid Chromatography-Mass Spectrometry (LC-MS/MS) analyses based on 4D label-free technology. Statistically differentially expressed proteins (DEPs), Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway representation and protein interactions were analyzed. A total of 12 samples were analyzed. The proteomics results showed that a total of 58 proteins were identified as DEPs, of which 47 proteins were up-regulated and 11 proteins were down-regulated. We found that C1q and tumor necrosis factor related protein 5 (C1QTNF5), Clusterin (CLU), tissue inhibitor of metal protease 1 (TIMP1) and signal regulatory protein alpha (SIRPα) can all be specifically regulated after aflibercept treatment. GO functional analysis showed that some DEPs are related to changes in inflammatory regulatory pathways caused by PDR. In addition, protein-protein interaction (PPI) network evaluation revealed that TIMP1 plays a central role in neural regulation. In addition, CD47/SIRPα may become a key target to resolve anti-VEGF drug resistance in PDR. Proteomic analysis is an approach of choice to explore the molecular mechanisms of PDR. Our data show that multiple proteins are differentially changed in PDR patients after intravitreal injection of aflibercept, among which C1QTNF5, CLU, TIMP1 and SIRPα may become targets for future treatment of PDR and resolution of anti-VEGF resistance.

The Reinforced Treat-and-Extend Protocol for Exudative Age-Related Macular Degeneration: Retrospective Assessment of 24-Month Real-World Outcomes in France.

The aim of this work is to evaluate the real-world outcomes of the reinforced treat-and-extend (RTE) protocol for the treatment of exudative age-related macular degeneration with intravitreal injections of aflibercept or ranibizumab (anti-vascular endothelial growth factor therapies). This was a retrospective review of patients from two tertiary ophthalmology centers in France initiating the RTE protocol between February 2018 and June 2021. The primary outcome was change in best-corrected visual acuity (BCVA) after 24months. Secondary outcomes were change in central retinal thickness (CRT), recurrence, and management-related factors (injection interval, number of injections/consultations). Outcomes were additionally evaluated after protocol changes (strict versus modified RTE protocol groups). Sixty-eight patients (72 eyes) were included (68% females; mean age 82.2 ± 7.8years). After 24months, mean BCVA significantly improved (65.22 ± 14 vs. 71.96 ± 13 Early Treatment Diabetic Retinopathy Study letters; p < 0.001) and CRT significantly decreased (388.6 ± 104 vs. 278.8 ± 51μM; p < 0.001) with 21% of eyes showing signs of exudation. Over the 24months, a mean total of 14.9 ± 4.0 injections and 8.6 ± 1.4 consultations were performed. Mean 24-month injection interval was 7.9 ± 2.3weeks. Initial and 24-month ophthalmic outcomes for eyes in the strict (47%) versus modified (53%) groups were not significantly different, but mean time interval to first recurrence of disease activity was significantly shorter for the modified group (7.3 ± 2.4 vs. 9.9 ± 2.5weeks; p < 0.001). Patients in the strict RTE group received significantly less injections (13.9 ± 3.6 vs. 16.5 ± 3.9; p = 0.006) and mean 24-month injection interval was significantly longer (9.5 ± 2.7 vs. 6.5 ± 2.1weeks; p < 0.001). Consultation number was similar (8.5 ± 1.9 vs. 8.8 ± 1.6; p = 0.93). Treatment with aflibercept versus ranibizumab did not influence ophthalmic or management outcomes. The RTE protocol, even when modified, reduced consultations but improved ophthalmic outcomes. The RTE protocol could reduce hospital visits and overall burden while also encouraging better patient compliance. Video Abstract available for this article. Vincent Soler and François-Philippe Roubelat summarize the Reinforced Treat-and-Extend Protocol and main results (MP4 225022 KB).

Psychophysical, electrofunctional, and morphological evaluation in naïve neovascular AMD patients treated with intravitreal anti‐VEGF

AbstractObjectivesThe aim of this study was to investigate the retinal morpho‐functional characteristics of patients with neovascular wet age‐related macular degeneration (nAMD) treated with intravitreal injection (IV) of aflibercept (AFL).MethodsThe study was conducted on 35 patients previously diagnosed with type 1 nAMD who received a fixed‐dosing regimen of aflibercept injections over 12 months. The goal was to assess trends in visual abilities over time by measuring visual acuity (VA), contrast sensitivity (CS), visual evoked potentials (VEPs), and spectral domain‐optical coherence tomography (SD‐OCT). The same psychophysical, electro‐functional, and morphological tests administered at baseline (T0) were repeated 4 to 8 weeks after the last aflibercept injection (Tn), resulting in a total of six examinations.ResultsAt Tn, all subjects exhibited improved VA for both far and near distances compared to values detected at T0. Similarly, VEP amplitude and latency values at Tn showed a greater P100 improvement than those observed at T0. Additionally, the CS examination at Tn demonstrated improvement, particularly at high spatial stimulation frequencies. The Tn SD‐OCT results highlighted a reduction in macular thickness compared to T0 values.ConclusionsThis exploratory research indicates that intravitreal injections of AFL, following a fixed‐dosing regimen, represent a valuable therapeutic approach for enhancing visual performance. This conclusion is supported by comprehensive statistical analysis of psychophysical, electro‐functional, and morphological examinations within the same group of patients with nAMD, as demonstrated for the first time.

Effect of anti-VEGF on retinal blood flow in diabetic mice using laser speckle flowgraphy.

To assess intra- (repeatability) and inter-observer (reproducibility) variability of laser speckle flowgraphy (LSFG) for retinal blood flow (RBF) measurement in 20 eyes of wild type (C57BL/6J) mice and effect of intravitreal Aflibercept on RBF in optic nerve head (ONH) region of 10 eyes of Ins2 (Akita) diabetic mice. 'Mean blur rate (MBR)' was measured for all quadrants of tissue area (MT), vessel (MV) and total area (MA) of ONH region. Changes in MT were analysed at each timepoint. Repeatability was evaluated by measuring MBR variability without changing mouse head position, and reproducibility after resetting mouse head position by another operator. Coefficient of repeatability (CR) through Bland-Altman plot method coefficient of variation (COV) and Intraclass correlation coefficient (ICC) was calculated. Intravitreal Aflibercept (1 μg) was administered to Akita eyes and intraocular pressure (IOP) was measured using a tonometer at baseline, day 7, 14, 21 and 28 post-injection. Hurvich and Tsai's criterion was used. Coefficient of repeatability values of repeatability and reproducibility for all quadrants were within limits of agreement. Reliability was excellent (ICC 0.98-0.99) and reproducibility was moderate to excellent (ICC 0.64-0.96). There was a non-significant IOP increase in all Akita eyes at Day 28 (p > 0.05), and significant increase in MT in all quadrants at Day 21 and superior, inferior and temporal quadrants at Day 28 (p < 0.05). Laser speckle flowgraphy demonstrates excellent repeatability and moderate to excellent reproducibility in measuring RBF. Intravitreal Aflibercept injection results in a significant increase in MT up to 28 days post-injection without significant increase in IOP.

Клинико-лабораторные факторы риска рецидива (реактивации) ретинопатии недоношенных после интравитреального введения афлиберцепта

Purpose. To study the causes of reactivation of retinopathy of prematurity (ROP) after intravitreal aflibercept injections. Material and methods. This study was carried out at V.F. Voino-Yasenetsky Scientific and Practical Center for Specialized Medical Care in Children from September 2021 to February 2023. The study included 101 premature infants (202 eyes) with retinopathy of prematurity who received intravitreal administration of aflibercept. The patients were divided into two groups: the control group included patients who received a single intravitreal injection of a VEGF inhibitor (aflibercept) with a positive effect. The main group included children who received two or more intravitreal injections of VEGF inhibitors (aflibercept) after reactivation of ROP. All patients were monitored for reactivation of retinopathy of prematurity after intravitreal injection of aflibercept. Results. The study noted a statistically significant difference in blood pH levels, stage of ROP, and APROP. In the group with reactivation ROP, APROP was noted 2 times more often (48.94% versus 27.78% in the control group). The group with more intravitreal aflibercept injections had lower blood pH levels (7.348±0.044 versus 7.372±0.030 in the control group). Conclusion. The study showed that clinical and paraclinical risk factors for the development of recurrent (reactivation) of ROP after intravitreal treatment with aflibercept are: severe eye disease (stage of ROP, aggressive posterior ROP), a change in the acid-base balance of the blood towards increased acidity. Blood acidity reflects a generalized process of impaired angiogenesis throughout the body. The more severe the patient’s initial eye condition, the higher the incidence of reactivation of ROP. Key words: recurrence, reactivation, retinopathy of prematurity, risk factor, clinical and paraclinical, aflibercept

Частота рецидивов ретинопатии недоношенных после введения ингибиторов ангиогенеза (афлиберцепта) в зависимости от массы тела ребенка

Purpose. To study the effectiveness of treatment and the causes of reactivation of retinopathy (ROP) in premature children after aflibercept injection. Material and methods. This study was conducted at the V.F. Voino-Yasenetsky Scientific and Practical Center for Specialized Medical Care in Children from September 2021 to February 2023. The study included 122 premature infants (244 eyes) with ROP who received intravitreal administration of aflibercept. Patients were divided into two groups: the main group (reactivation group) consisted of children who received two or more intravitreal injections of VEGF inhibitors (aflibercept) and the control group consisted of children who received a single intravitreal injection of VEGF inhibitor (aflibercept) with a positive effect. In addition, 3 subgroups were identified depending on birth weight: 37 children had a birth weight of less than 900 g (1st subgroup), 41 children weighed from 900 to 1200 g (2nd subgroup), and 44 children weighed more than 1200 g (3rd subgroup). All patients were monitored for reactivation of ROP after intravitreal injection of aflibercept. Results. Since 2010, we have been using angiogenesis inhibitors in the treatment of ROP. The effectiveness of one dose of aflibercept (0,5 mg/0,0125 ml) is 84,84%. Repeated injections are easily tolerated by patients and increase the effectiveness of treatment to 99,76%. The work is devoted to the analysis of reactivation of ROP after one injection of aflibercept and the study of the reasons for repeated injections. 37/244 eyes (15,16%) showed reactivation of ROP after one injection. Factors influencing the reactivation of retinopathy of prematurity after intravitreal injection of aflibercept include: gestational age, postconceptual age at the 1st injection, birth weight, weight at the 1st injection, birth height, newborn head circumference, head circumference at the 1st injection, newborn chest circumference, history of blood transfusions, body mass index (BMI) at the 1st injection, nuchal cord complications. A large dependence of the reactivation rate on the child’s weight was noted. The birth weight subgroup of less than 900 g had a recurrence rate of 28,38%, followed by the average birth weight subgroup (12,20%) and the subgroup weighing more than 1200 g (6,82%). The reactivation time in the three subgroups of patients was 9,82±5,76, 10,20±3,27 and 12,33±9,24 weeks, respectively. The time of reactivation was also determined by the child’s weight. Reactivation occurred earlier in children with lower weight: in three subgroups of patients, 9.82±5.76, 10.20±3.27 and 12.33±9.24 weeks, respectively. Conclusion. Based on our research, the frequency of reactivation of ROP depends on the weight of the premature baby. A change in weight, even by 100 grams, changes the course of ROP. The lower the birth weight is, the higher the reactivation rate of ROP becomes. Reactivation of ROP occurs 4 times more often (in every 3–4 children) in children with very low birth weight (less than 900 g). The frequency of reactivation is also determined by the weight of the child during the first injection of an angiogenesis inhibitor. Weight also determines the time of reactivation, occurring in children weighing less than 900 or 9–10 weeks after the first injection. If there are risk factors, it is advisable to: carry out simultaneous injections in both eyes, which will increase the dose of aflibercept in total, carefully monitor them in the first 2 months with examination of the fundus, or increase the dose of the drug. Effectiveness can be enhanced by ingesting synergists or impact of physiotherapy. Key words: recurrence, reactivation, retinopathy of prematurity, risk factor, birth weight, intravitreal injection, aflibercept, vascular endothelial growth factor

Aflibercept Off-Target Effects in Diabetic Macular Edema: An In Silico Modeling Approach.

Intravitreal aflibercept injection (IAI) is a treatment for diabetic macular edema (DME), but its mechanism of action (MoA) has not been completely elucidated. Here, we aimed to explore IAI's MoA and its multi-target nature in DME pathophysiology with an in silico (computer simulation) disease model. We used the Therapeutic Performance Mapping System (Anaxomics Biotech property) to generate mathematical models based on the available scientific knowledge at the time of the study, describing the relationship between the modulation of vascular endothelial growth factor receptors (VEGFRs) by IAI and DME pathophysiological processes. We also undertook an enrichment analysis to explore the processes modulated by IAI, visualized the effectors' predicted protein activity, and specifically evaluated the role of VEGFR1 pathway inhibition on DME treatment. The models simulated the potential pathophysiology of DME and the likely IAI's MoA by inhibiting VEGFR1 and VEGFR2 signaling. The action of IAI through both signaling pathways modulated the identified pathophysiological processes associated with DME, with the strongest effects in angiogenesis, blood-retinal barrier alteration and permeability, and inflammation. VEGFR1 inhibition was essential to modulate inflammatory protein effectors. Given the role of VEGFR1 signaling on the modulation of inflammatory-related pathways, IAI may offer therapeutic advantages for DME through sustained VEGFR1 pathway inhibition.

Wide-Field Choroidal Thickness Analysis after Half-Fluence Photodynamic Therapy Combined with Intravitreal Aflibercept Injection in Pachychoroid Neovasculopathy.

Background: Pachychoroid neovasculopathy (PNV) is a pachychoroid-spectrum disease. As blood circulation throughout the choroid may be involved in PNV pathogenesis, analysis using ultra-wide-field (UWF) fundus imaging is crucial. We evaluated choroidal thickness after half-fluence photodynamic therapy (PDT) combined with intravitreal aflibercept injection for PNV using UWF swept-source optical coherence tomography. Methods: Seventeen eyes with PNV that underwent half-fluence PDT with an adjuvant single intravitreal aflibercept injection were analyzed. To compare choroidal thicknesses in the central and peripheral choroids, we set subfields <3, <9, and 9-18 mm from the fovea. The <9 and 9-18 mm subfields were divided into four quadrants. Results: Choroidal thickness in each subfield decreased significantly after half-fluence PDT (p < 0.001); this reduction was more pronounced in the central area. We also investigated the relationship between the dominant side of the deep choroidal veins that harbor choroidal vein efflux from the macula. When choroidal thickness in the supratemporal and infratemporal 9 mm subfields were evaluated, the ratio of choroidal thickness reduction was not significantly different between the dominant and non-dominant sides. The dominant side was not associated with the extent of choroidal thickness reduction in PNV. Conclusions: Half-fluence PDT caused thinning of the entire choroid, especially in the central area, in PNV.

Comparative analysis of the anterior chamber changes after intravitreal injections of aflibercept and brolucizumab

BACKGROUND: Currently, the information is insufficient about the effect of multiple intravitreal injections (IVI) of brolucizumab in comparison with aflibercept on the parameters of iridolenticular diaphragm.&#x0D; AIM: The aim of this study is using optical coherence tomography of the anterior segment (AS-OCT) to evaluate changes in the parameters of the anterior chamber in patients with multiple intravitreal injections of aflibercept and brolucizumab in the treatment of the neovascular form of age-related macular degeneration (nAMD).&#x0D; MATERIALS AND METHODS: In total, 60 patients (60 eyes) were included into the study. The follow-up period duration was 12 months. Patients were divided into 2 groups: group 1 — 30 patients receiving intravitreal injections of aflibercept, group 2 — 30 patients receiving intravitreal injections of brolucizumab. Using a Revo NX tomograph, AS-OCT was performed, the depth of the anterior chamber and the dimensions of the anterior chamber angle were examined. The measurement was performed before intravitreal injections, one month after the first, one month after the third intravitreal injections, and one year after treatment.&#x0D; RESULTS: In both groups, a shift of the iridolenticular diaphragm was noted according to AS-OCT data — a significant decrease in depth of the anterior chamber, anterior chamber angle parameters before treatment and after 4 months of treatment, as well as after a year of treatment. In group 1, in contrast to group 2, a greater number of intravitreal injections led to a greater decrease in the depth of the anterior chamber (rxy = 0.415, p = 0.02) and to a greater narrowing of the anterior chamber angle on the nasal and temporal sides (rxy = 0.37, p = 0.049 and rxy = 0.424, p = 0.02, respectively).&#x0D; CONCLUSIONS: For the first time, changes of the anterior chamber of the eye were determined against the background of multiple intravitreal injections of aflibercept and brolucizumab in the treatment of the neovascular form of age-related macular degeneration using AS-OCT.

Perifoveal retinal thickness changes after intravitreal aflibercept injection for choroidal neovascularization in age-related macular degeneration

ObjectiveThere has been some concern that anti-vascular growth factor treatment accelerates the development of macular atrophy in eyes with neovascular age-related macular degeneration. During the treatment with aflibercept, the thickness of choroid may decrease. This may lead to photoreceptor death. The rod cells are more susceptible to atrophic changes than cones during the disease. We aimed to find any thickness changes in the perifoveal outer nuclear layer, where the highest density of rods is found, during the aflibercept intravitreal injection therapy. Materials and MethodsRetrospectively, forty-two patients who were treated for age-related macular degeneration with choroidal neovascularization were included in the study. After the first three loading doses, intravitreal injections were repeated every two months. Outer nuclear layer thicknesses were measured 2000 µm away from the center of the fovea with OCT, at a total of 20 points, located at 180 and 90°. The mean of these measurements was obtained before the treatment and 1 year after the therapy. Results were compared by using the Wilcoxon Rank Test. ResultsThe mean visual acuity was 1,11±0,287 logMAR at the beginning and increased to 0,53±0,32 LogMAR after. Perifoveal thickness was significantly reduced when compared with the thickness before the treatment (p = 0.039, p < 0.05). This result was also significantly lower than the control group thicknesses (p = 0.035, p < 0.05). ConclusionAnti-VEGFs can cause loss of phagocytic functions of RPE. The mechanism of the observed thinning of the ONL may be described as follows: VEGF emitted by the RPE normally helps to maintain the choriocapillaris. Thus, injecting an anti-VEGF intravitreally causes RPE atrophy, which leads to a decrease in the choroidal vascular index. This in turn causes first the rods, and later the cones, that are part of the outer nuclear layer, to start to die and disappear, hence the thinning of this layer. As aflibercept consists of parts of the extracellular domain of both the VEGFR1 and VEGFR2 receptors, that are held together by a human IgG1 backbone, this makes the binding of aflibercept to VEGF-A and VEGF-B stronger as compared to the binding of the previously used ranibizumab or bevacizumab (by nearly a factor 100 in the case of the most abundant isoform VEGF-A 165). Besides, aflibercept also binds very well to placental growth factor (PIGF), which is also associated with several ocular diseases.

INCIDENCE AND CHARACTERISTICS OF NEOVASCULAR AGE-RELATED MACULAR WITH OVER A 12-MONTH REMISSION AFTER THREE MONTHLY AFLIBERCEPT ADMINISTRATION: 60 Months Results of a Pro Re Nata Regimen.

To investigate the characteristics of patients with over a 12-month remission after 3 monthly intravitreal aflibercept injections followed by a pro re nata regimen for exudative age-related macular degeneration (AMD). One hundred forty-four eyes with exudative AMD were included. All patients received 3 monthly intravitreal aflibercept injections as a loading dose, followed by an as-needed regimen for 60 months. Patients were classified into the remission and recurrence groups depending on the presence or absence of a 12-month remission. ARMS2 A69S and CFH I62V were genotyped in all cases. During the study, 82 eyes (56.9%) showed 12 months or more remission at least once. The cumulative incidence rate of a 12-month remission showed a plateau pattern and converged to 60% (y = -166.26x-2.172 + 0.6, R2 = 0.8168). Patients in the remission group were younger than those in the recurrence group (P < 0.001) and had less risk allele frequency of the ARMS2 gene than the recurrence group (P < 0.001). The longer the remission interval was prolonged, the better visual acuity was achieved at the 60-month visit (P < 0.001). Fifty-seven percent of patients showed a 12-month remission or more at least once during a 60-month follow-up, suggesting that patients with no reactivation can prolong the treatment interval.

OCT Biomarkers and Visual Acuity in the Treatment of Diabetic Macular Edema

At baseline, visual acuity and the extent of vertical intraretinal fluid were predictive of better visual outcomes for 196 patients with diabetic macular edema who received tightly controlled treatment with 2mg intravitreal aflibercept injections.

Intravitreous aflibercept or vitrectomy for initial treatment of diabetic vitreous hemorrhage? A Systematic Review of Current Evidence

Introduction &amp; Objectives : To assess the efficacy and safety of intravitreous aflibercept versus vitrectomy in patients with diabetic vitreous hemorrhage (VH)&#x0D; Methods : Cochrane Central Register of Controlled Trials, MEDLINE, and EMBASE database were searched. No constraints based on language or publication date were applied. Only randomized controlled trials (RCTs) comparing intravitreal aflibercept injection with vitrectomy procedure were included. Search results were screened independently by two authors. Data extraction and synthesis were performed according to The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. The primary outcome measures were best-corrected visual acuity obtained at least 6 months following interventions, rate of recurrent hemorrhage, and periprocedural ocular adverse events. The quality of evidence was assessed using the GRADE tools.&#x0D; Results : Two clinical trials that randomized 239 eyes were included in this review. There was no evidence ofa difference in primary outcome of mean visual acuity at six months between randomized groups. However, patients receiving intravitreous aflibercept were more likely to experience recurrent VH than those undergoing vitrectomy (RR 3.12 95% CI 1.95 - 4.99, absolute effect of 32 more people with recurrent VH per 100 people treated with aflibercept). Rates of periprocedural ocular complications were similar in both groups.&#x0D; Conclusion : Intravitreous aflibercept safety and efficacy appear to be non-inferior compared to vitrectomy for initial management of diabetic VH. Further well-designed studies are needed to investigate the long- term effects of treatments.

Triple Gram-negative bacterial endophthalmitis following intravitreal injection

PurposeTo describe a puzzling case of endophthalmitis caused by three unusual bacteria after intravitreal injection, its outcome, and underlying questions.FindingsA 70-year-old female patient was diagnosed with acute endophthalmitis following intravitreal aflibercept injection for age-related macular degeneration. A standard tap and inject procedure was performed. Microbiological analyses on the anterior chamber and vitreous samples yielded the presence of three non-fermenting Gram-negative rods: Pseudomonas stutzeri, Stenotrophomonas maltophilia, and Ochrobactrum anthropi. The outcome was favorable after intravitreal injections of vancomycin and ceftazidime, with an almost complete recovery of the visual acuity to its baseline level. No potential source of infection was identified.ConclusionEndophthalmitis following intravitreal injection can be caused by a wide variety of bacteria, including some rare Gram-negative species. They can sometimes co-exist in a single patient, but their virulence may vary greatly. Due to the variable antibiotic susceptibility and frequent multiresistance associated with non-fermenting Gram-negative rods, a prompt microbiological approach is required. Favorable outcome can be achieved with standard management.

Retracted: Clinical Comparative Study of Intravitreal Injection of Triamcinolone Acetonide and Aflibercept in the Treatment of Diabetic Retinopathy Cystoid Macular Edema.

[This retracts the article DOI: 10.1155/2022/1348855.].

Effect of polyp regression and reduction on treatment efficacy in polypoidal choroidal vasculopathy treated with aflibercept

Intravitreal injection of aflibercept (IVA) has successfully treated polypoidal choroidal vasculopathy (PCV), and polyp morphology is an important indicator of treatment efficacy. However, many studies have not reported the presence or absence of polyp regression and treatment outcomes, and few studies have reported polyp reduction and treatment outcomes in cases with residual polyps. We retrospectively measured the polyp area on indocyanine green angiography images before and after the IVA loading phase and investigated the regression and reduction of polyps and treatment outcomes of 81 eyes with PCV treated with IVA. We investigated the relationship between the presence or absence of complete regression of polyps and the percentage change in the polyp area and treatment outcomes. Eyes with complete polyp regression had significantly better visual acuity improvements compared with baseline at 12 months (P = 0.0108), fewer treatments (P = 0.0024), fewer recurrences during 12-months follow-up (P = 0.0010), and more “dry maculas” at 3 months (P = 0.0048) than eyes in which polyp regression did not occur. A significant correlation was seen only between the percentage of polyp regression and visual acuity at 3 months (P = 0.0395). Regarding IVA therapy for PCV, the presence or absence of complete polyp regression at the end of the loading phase affected the treatment outcome, whereas the degree of polyp reduction in cases of residual polyps had no effect.

Clinical Outcomes of Topical Bromfenac Combined with Intravitreal Aflibercept Injection for Exudative Age-related Macular Degeneration

Purpose: To evaluate the efficacy of topical bromfenac combined with intravitreal aflibercept (IVA) injection in the treatment of exudative age-related macular degeneration over a 2-year period.Methods: We retrospectively studied 43 patients (43 eyes) with exudative age-related macular degeneration. Patients were included if they received IVA injections under an as-needed protocol and had &gt; 2 years of follow-up. Among the 43 eyes, 25 received only IVA (IVA group), whereas 18 received a combination of IVA and topical bromfenac (bromfenac group). The primary outcome measure was the total number of IVA injections administered over 2 years from the initial injection compared between groups. We also compared changes in best-corrected visual acuity (BCVA) and central retinal thickness (CRT) between groups.Results: The bromfenac group received a significantly lower number of IVA injections over 2 years (7.4 ± 1.0), compared with the IVA group (9.0 ± 1.9) (&lt;i&gt;p&lt;/i&gt; &lt; 0.01). Both groups showed improvements in BCVA and CRT after 2 years compared with their baseline values. However, changes in BCVA and CRT at 2 years did not significantly differ between groups (&lt;i&gt;p&lt;/i&gt; = 0.786 and &lt;i&gt;p&lt;/i&gt; = 0.905, respectively).Conclusions: Among patients with exudative age-related macular degeneration, the total number of IVA injections over 2 years was lower in the bromfenac group than in the IVA group. More studies are needed to confirm the efficacy of topical bromfenac in a combined treatment regimen.

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

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