Intravitreal Aflibercept Injection Research Articles

XTEND: Two-Year Results from a Global Observational Study Investigating Proactive Dosing of Intravitreal Aflibercept in Neovascular Age-Related Macular Degeneration.

XTEND (NCT03939767) is a multicenter, observational, prospective study of patients with treatment-naïve neovascular age-related macular degeneration (nAMD) in routine clinical practice. The study aims to examine treatment outcomes of proactive intravitreal aflibercept (IVT-AFL) treatment regimens (fixed dosing or treat-and-extend) according to local marketing labels. Study eyes received IVT-AFL injections as per the local label. The mean changes in best-corrected visual acuity (BCVA) and central subfield thickness (CST) from baseline to month (M) 12 and M24 were measured and stratified by baseline factors. Treatment exposure and safety data were evaluated. Statistical analysis was descriptive. Overall, 1466 patients from 17 countries were treated. For the overall population, the mean ± standard deviation (SD) age was 78.7 ± 8.5 (range 50-100)years, and 891 patients (60.8%) were female. The mean ± SD baseline BCVA was 54.3 ± 20.3 letters and CST was 374 ± 126µm. At M12 and M24, mean (95% confidence interval [CI]) BCVA change was + 4.3 (3.4, 5.3) and + 2.3 (1.3, 3.3) letters, respectively. Mean (95% CI) CST was - 106 (- 114, - 99) μm and - 109 (- 117, - 102) μm at M12 and M24, respectively. At M24, 41.5% of patients had a BCVA ≥ 70 letters. Patients received a mean ± SD of 7.7 ± 2.7 injections by M12 and 10.8 ± 5.0 injections by M24 (3.1 injections between M12 and M24). Adverse events were consistent with the known safety profile of IVT-AFL. The 24-month results indicate that, in routine clinical practice, a proactive IVT-AFL regimen achieves functional improvements in patients with treatment-naïve nAMD. The proportion of patients achieving ≥ 70 letters at M24 increased, and patients with baseline BCVA ≥ 70 letters maintained vision regardless of the followed IVT-AFL label. ClinicalTrials.gov identifier: NCT03939767. A video abstract is available for this article. Supplementary file2 (MP4 364624 KB).

Effect of Vitreous Reflux after Intravitreal Aflibercept Injection for Macular Edema with Branch Retinal Vein Occlusion: A Real-World Study.

This study aimed to evaluate the therapeutic effect of vitreous reflux (VR) after intravitreal aflibercept injection (IVAI) for macular edema (ME) following naïve branch retinal vein occlusion (BRVO). Eighty patients with ME following BRVO were divided into three groups according to the conjunctival bleb diameter after IVAI as follows: group A (no VR), group; B (<3 mm VR), and group C (>3 mm VR). Each patient received single IVAI. The treatment response was evaluated with the best-corrected visual acuity (BCVA) and optical coherence tomography measurements of the retinal foveal thickness (RFT) before treatment and 1 month after the first injection. RFT >375 μm was defined as recurrence and received additional IVAI. The recurrence rate of ME and total numbers of IVAI were investigated at 12 months. The BCVA values at 1 month were 0.17 ± 0.29 in group A (n = 41), 0.18 ± 0.17 in group B (n = 18), and 0.19 ± 0.26 in group C (n = 21). The RFT at 1 month were 270 ± 45 μm in group A, 279 ± 24 μm in group B, and 290 ± 43 μm in group C, respectively. ME recurred in 29 out of 41 patients in group A, 15 out of 18 in group B, and 14 out of 21 in group C. The total numbers of IVAI were 2.50 ± 1.24 in group A, 2.59 ± 1.06 in group B, and 2.29 ± 1.27 in group C, respectively. In the above mentioned comparisons, no significant differences were found following an IVAI (P > 0.05). VR after IVAI did not affect the therapeutic effect in patients with ME following BRVO. Thus, we do not need to pay excess attention to VR in the case of IVAI.

Aflibercept or ranibizumab for diabetic macular edema.

Vascular endothelial growth factor (VEGF) is the primary substance involved in retinal barrier breach. VEGF overexpression may cause diabetic macular edema (DME). Laser photocoagulation of the macula is the standard treatment for DME; however, recently, intravitreal anti-VEGF injections have surpassed laser treatment. Our aim was to evaluate the efficacy of intravitreal injections of aflibercept or ranibizumab for managing treatment-naive DME. This single-center, retrospective, interventional, comparative study included eyes with visual impairment due to treatment-naive DME that underwent intravitreal injection of either aflibercept 2 mg/0.05 mL or ranibizumab 0.5 mg/0.05 mL at Al-Azhar University Hospitals, Egypt between March 2023 and January 2024. Demographic data and full ophthalmological examination results at baseline and 1, 3, and 6 months post-injection were collected, including the best-corrected distance visual acuity (BCDVA) in logarithm of the minimum angle of resolution (logMAR) notation, slit-lamp biomicroscopy, dilated fundoscopy, and central subfield thickness (CST) measured using spectral-domain optical coherence tomography. Overall, the 96 eyes of 96 patients with a median (interquartile range [IQR]) age of 57 (10) (range: 20-74) years and a male-to-female ratio of 1:2.7 were allocated to one of two groups with comparable age, sex, diabetes mellitus duration, and presence of other comorbidities (all P >0.05). There was no statistically significant difference in baseline diabetic retinopathy status or DME type between groups (both P >0.05). In both groups, the median (IQR) BCDVA significantly improved from 0.7 (0.8) logMAR at baseline to 0.4 (0.1) logMAR at 6 months post-injection (both P = 0.001), with no statistically significant difference between groups at all follow-up visits (all P >0.05). The median (IQR) CST significantly decreased in the aflibercept group from 347 (166) µm at baseline to 180 (233) µm at 6 months post-injection, and it decreased in the ranibizumab group from 360 (180) µm at baseline to 190 (224) µm at 6 months post-injection (both P = 0.001), with no statistically significant differences between groups at all follow-up visits (all P >0.05). No serious adverse effects were documented in either group. Ranibizumab and aflibercept were equally effective in achieving the desired anatomical and functional results in patients with treatment-naïve DME in short-term follow-up without significant differences in injection counts between both drugs. Larger prospective, randomized, double-blinded trials with longer follow-up periods are needed to confirm our preliminary results.

Potential Risk Factors for Ocular Pain in Patients Undergoing Multiple Intravitreal Injections of Anti-Vascular Endothelial Growth Factor.

To assess ocular pain in patients undergoing multiple intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF) who have previous factors that may influence pain sensitivity. This is a prospective, observational, case series study involving patients who underwent multiple (≥3) pro re nata intravitreal injections of ranibizumab or aflibercept to treat any cause of chorioretinal vascular disease. Ocular pain was assessed by the numerical analog scale during intravitreal injection. For this study, the main variable was ocular pain and the secondary variables included age, sex, previous history of glaucoma, primary retinal vascular disease, severe dry eye history, trigeminal pain, scleral buckle surgery, collagen diseases, fibromyalgia, severe migraine history, pars plana vitrectomy, scleral thickness measurements, and type of anti-VEGF. In a total of 894 patients, 948 eyes (4822 intravitreal injections), 793 patients (88.6%) had ocular pain sensitivity between no pain to mild pain, 80 patients (8.9%) had moderate ocular pain, 15 patients (1.6%) had severe ocular pain, and 6 patients (0.7%) had extremely severe ocular pain. Patients with severe dry eye (p = 0.01) and previous history of scleral buckle surgery (p = 0.01) showed a significant correlation with ocular pain during intravitreal injection. Pars plana scleral thickness (>550 um) and diabetic neuropathy were associated with ocular pain but did not meet the criteria for statistical significance (p = 0.09 and p = 0.06, respectively). Dry eye and prior scleral buckle surgery may contribute to pain associated with intravitreal injection. These issues should be taken into consideration in patients undergoing multiple intravitreal injections.

Местные факторы, определяющие ответ на антиангиогенную терапию препаратами первой линии при макулярной неоваскуляризации

Background: the prevalence of macular neovascularization (MNV) is on the rise. However, fundamental data on systemic and local factors determining response to the treatment of MNV have not yet been studied. Aim: to analyze baseline intraocular pressure (IOP) and mean ocular perfusion pressure (mOPP) in patients with MNV in association with the response to antiangiogenic therapy. Patients and Methods: this retrospective cohort study included 84 patients (29 men, 55 women; 92 eyes) with newly diagnosed MNV and signs of disease activity. The age of the patients ranged from 52 to 97 years (mean age 73.4±8.5 years). In 18 (19.5%) patients, MNV was bilateral. IOP and mOPP were measured in all patients with MNV who received fixed-interval intravitreal injections of aflibercept. Treatment results were evaluated clinically and morphometrically by optical coherence tomography. Patients were allocated into five subgroups based on treatment response. A correlation analysis was performed between IOP and mOPP, on the one hand, and treatment outcomes, on the other hand. Results: improvement of MNV activity markers in the setting of treatment manifested as reduction in area and height of subretinal fluid (k=0.9432, p&lt;0.01, and k=0.58959, p&lt;0.001), reduction in height and area of retinal pigment epithelium (RPE) detachment (k=0.82808, p&lt;0.05; k=0.50221, p&lt;0.05) and reduction in sub-RPE fluid (k=0.84515, p&lt;0.05) were strongly directly correlated with baseline IOP. The correlation between IOP and central retinal thickness was negative (k=-0.27266, p&lt;0.05). The biomarker associated with the ideal response was IOP levels of 12.6 mmHg, the balance point, where the sensitivity and specificity of poor response approximately coincided. At this IOP, the sensitivity of poor response was 0.603 and the specificity was 0.737. The IOP was found to be below 12.6 mm Hg in 40% of non-responders and 74% of responders. The 95% confidence interval limits did not overlap, thereby illustrating the reliability of the results (p=0.00784, p&lt;0.01). The range of recommended IOP level for a good treatment response was determined as 11–21 mm Hg. Conclusions: the identification of modifiable risk factors is of paramount importance in the field of practical ophthalmology, as it increases the likelihood of a favorable outcome. Further studies are necessary to investigate the potential for modifying IOP through IOP-lowering therapy prior to intravitreal injection. KEYWORDS: macular neovascularization, antiangiogenic therapy, risk factor, intraocular pressure, mean ocular perfusion pressure. FOR CITATION: Likhvantseva V.G., Kapkova S.G., Tretyak E.B., Rychkova S.I., Gevorkyan A.S., Borisenko T.E. Local factors determining the response to antiangiogenic therapy with first-line drugs in macular neovascularization. Russian Journal of Clinical Ophthalmology. 2024;24(2):69–77 (in Russ.). DOI: 10.32364/2311-7729-2024-24-2-5.

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&gt;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.

Частота рецидивов ретинопатии недоношенных после интравитреальной инъекции афлиберцепта в зависимости от гестационного возраста

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 retinopathy of prematurity who received intravitreal administration of aflibercept. All patients were divided into 3 groups depending on gestational age, including a group of patients with a gestational age of less than 27 weeks (70 eyes), a group of patients with a gestational age of 27 to 29 weeks (106 eyes) and a group of patients with a gestational age of from 29 weeks (68 eyes). All patients were monitored for reactivation of retinopathy of prematurity after intravitreal aflibercept injection. Results. The overall relapse rate after treatment was 37/244 eyes (15.16%); The reactivation rate of the gestational age &gt;29 weeks group was 5.88% of the middle gestational age group – 9.43% and the low gestational age group (&lt;27 weeks) – 32.86% respectively. The reactivation time in the three groups of patients was 10.75±5.03 weeks for the low gestational age group, 7.40±4.04 weeks for the middle gestational age group, and 15,00±11,31 weeks for the high gestational age group. Conclusion. Intravitreal injection of aflibercept is an effective treatment for ROP. The younger the gestational age, the more often and faster reactivation of ROP occurs after injections of angiogenesis inhibitors. Key words: recurrence, reactivation, retinopathy of prematurity, risk factor, gestational age, intravitreal injection, aflibercept, vascular endothelial growth factor, angiogenesis inhibitors

Evaluation of Physician Knowledge of Safety and Safe Use Information for Intravitreal Aflibercept Injection in Europe: A Second Survey of Physicians Following Dissemination of Updated Risk-Minimization Materials.

Materials have been distributed in the European Union to inform physicians on the safe use of intravitreal aflibercept (IVT-AFL) as part of the risk-minimization plan for IVT-AFL. We aimed to measure physician knowledge and understanding of key safety information for IVT-AFL. The current study was a follow-up cross-sectional survey ('wave 2') to an earlier survey ('wave 1') examining the effectiveness of the IVT-AFL educational materials by assessing physician knowledge of the key safety information. Based on wave 1 results, the educational materials were revised to focus more on items of key concern (e.g.,use in women of childbearing potential, procedural information); physicians in France, Germany, Italy, Spain, and the UK completed a questionnaire to evaluate their knowledge of key safety information in the revised educational materials. Among 454 physician respondents (of 4715 invited; response rate 9.6%), most reported having received the IVT-AFL Summary of Product Characteristics (SmPC; 89%) and Prescriber Guide (82%). More than half reported receiving the Injection Procedure Video (54%) and Patient Booklet (65%). The highest percentage of correct answers was observed for questions concerning procedural steps, the most important risks, and safe use as emphasized by the educational materials and the SmPC. Physician knowledge and understanding of safe use of IVT-AFL, including for questions that prompted revisions to the educational materials, suggests the need to reconsider methods for developing educational materials to follow best practices (e.g., focusing on only key messages and pretesting with end users).

Volume-rendering three-dimensional image analysis of macular neovascularization in age-related macular degeneration.

To visualize and investigate the three-dimensional (3D) images of macular neovascularization (MNV) in eyes with neovascular age-related macular degeneration using optical coherence tomography angiography (OCTA) according to the treatment response to intravitreal aflibercept injection (IVI). OCTA images at baseline and 12 weeks (after three loading IVIs) were retrospectively reconstructed as 3D images for patients with type 1 and 2 MNV treated with the "pro-re-nata" regimen. The fluid-free and persistent fluid groups were divided according to the presence of subretinal and intraretinal fluid at 12 weeks after treatment. Using reconstructed 3D images of MNV, the volume, average volume per slice, and z-axis of the volumetric structure were evaluated. Twenty-three and nine were classified into the fluid-free and persistent fluid groups, respectively. The MNV volume decreased significantly from baseline to 12 weeks in the fluid-free group (p = 0.005), not in the persistent fluid group (p = 0.250). The average volume of MNV per slice at 12 weeks correlated with the persistent fluid group in both the univariate and multivariate analyses (p = 0.034, p = 0.039, Exp [B] = 14.005). This study may provide a perspective on vascular volumetric changes of MNV according to treatment response.

Outcomes of Treatment-Resistant Neovascular Age-Related Macular Degeneration Switched from Aflibercept to Faricimab

PurposeWhile previous studies have demonstrated the efficacy of Faricimab in treatment-naïve nAMD patients, its outcomes in patients switched from Aflibercept are less understood. This study aimed to assess real world anatomical and functional outcomes of switching to Faricimab in patients undergoing Aflibercept intravitreal injections for nAMD with sub-optimal response. DesignRetrospective case series. SubjectsPatients with nAMD at a single tertiary care center who were switched from Aflibercept to Faricimab due to persistent suboptimal response. MethodsPatients had received a minimum of 6 consecutive intravitreal injections of aflibercept and showed persistent presence of intraretinal or subretinal fluid on OCT despite receiving aflibercept at 4 or 6-weekly intervals at the time of the switch. Patients receiving 4-weekly aflibercept were either switched with 2 or 3 loading doses of 4-weekly Faricimab injections.. Regression models were used to identify predictors of clinical outcomes. Main Outcome MeasuresVisual acuity, central macular thickness, and OCT parameters were assessed pre- and post-switch ResultsEighty-one eyes of 68 patients were included. The mean age was 79.1 years (SD: 8.9), and females constituted 53% of cases. A statistically significant reduction in central macular thickness was observed post-switch (p<0.0001). The proportion of cases with intraretinal (p=0.0219) and subretinal fluid (p<0.000) decreased significantly. Overall clinical improvement on OCT was noted in 80% of patients. No significant improvement in ETDRS vision was observed. There was no evidence that switching regimen (2 vs. 3 loading doses) had an independent effect on clinical outcomes. ConclusionAmongst patients with treatment-resistant nAMD, switching from Aflibercept to Faricimab may serve as a safe and effective option. Significant anatomical improvements were observed, with a trend towards visual stability. The loading regimen with two Faricimab injections appeared to be sufficient for non-naïve patients. However, a longer follow-up and larger studies are warranted to confirm these findings.

Subclinical Ocular Changes after Intravitreal Injections of Different Anti-VEGF Agents for Neovascular Age-Related Macular Degeneration

Intraocular inflammations (IOIs) have been reported to occur after intravitreal injections of brolucizumab, and one of their causes has been suggested to be drug-specific features. We evaluated the anterior chamber by the aqueous flare value (AFV) and the retina by flicker electroretinography (ERG) after the initial intravitreal injection of aflibercept (IVA), brolucizumab (IVBr), or faricimab (IVF) for neovascular age-related macular degeneration (nAMD). The AFV and flicker ERGs were determined before, 2 weeks after, and 4 weeks after the injections in 14 eyes of 14 patients for each drug. After the injections, none of the patients had an IOI, but the AFV increased significantly in the IVA and IVF groups. The increase in the IVF group was +4.6 photon count/ms, which was significantly greater than in the other groups, but was not clinically significant. The implicit time was significantly prolonged in the IVBr group but unchanged in the IVA and IVF groups. These results suggest that brolucizumab, administered at high molar doses, may cause transient retinal disturbances that are not detectable by general ophthalmologic examinations but affect the implicit ERG times.

The Impact of Diabetic Retinopathy on the Choriocapillaris in Neovascular AMD.

To investigate the impact of diabetic retinopathy (DR) on morphological choriocapillaris (CC) modifications in eyes with type 1 macular neovascularization (MNV) secondary to AMD using optical coherence tomography angiography (OCTA). Eyes with AMD-related type 1 MNV with and without DR were prospectively included. We performed 3 × 3mm OCTA scans at two visits: before the loading phase of intravitreal injections of aflibercept (T1) and 1month after the last injection (T2). OCTA En face flow images of the CC were analyzed for flow deficit percentage (FD%), FD average area and FD number in a 500-µm-wide ring surrounding the dark halo (DH) around type 1 MNV. A total of 65 eyes, out of which 30 eyes had mild DR, were included. In the group without diabetes, there was a gradual reduction in FD% in the CC ring around the DH after antiangiogenic therapy, indicating reperfusion of the CC (P = 0.003). However, in the DR group, there were no significant changes in CC parameters between the two study visits. Specifically, the FD% in the CC ring around the DH did not show a significant reduction at T2 compared with T1 values (P > 0.05). Furthermore, the comparison of the variation in FD% between the two groups was statistically significant. The nondiabetic group exhibited a gradual CC reperfusion after the loading phase of aflibercept, whereas the diabetic eyes did not show significant changes (P = 0.029). The CC surrounding the DH associated to type 1 MNV exhibited greater hypoperfusion in diabetic eyes compared with eyes without diabetes, both before starting therapy and after the loading phase. Hence, DR may be a potential risk factor in the development and progression of late-stage AMD and may also influence the response to antiangiogenic therapy.

Pharmacogenetic Association between Allelic Variants of the Autophagy-Related Genes and Anti-Vascular Endothelial Growth Factor Treatment Response in Neovascular Age-Related Macular Degeneration.

Age-related macular degeneration (AMD) is the leading cause of late-onset blindness in elderly. The occurrence and development of AMD is a multifactorial complex process where autophagy plays an important role. The first-line drugs for neovascular AMD (nAMD) are inhibitors of VEGF, with up to 30% of patients having an incomplete response to treatment. Genetic factors may influence the response to anti-VEGF therapy and explain treatment outcome variability. We aimed to estimate the role of polymorphic markers of the MTOR (rs1064261, rs1057079, rs11121704, rs2295080), SQSTM1 (rs10277), ULK1 (rs11246867, rs3088051), MAP1LC3A (rs73105013) and ATG5 (rs573775) genes in the development of nAMD and the efficacy of anti-VEGF therapy response. Genotyping by allele-specific PCR was performed in 317 controls and 315 nAMD patients in the Russian population. Of them, 196 treatment-naive nAMD patients underwent three monthly intravitreal injections (IVIs) of aflibercept. Genotypic frequencies were compared with OCT markers of therapy effectiveness and best-corrected visual acuity (BCVA) measures. The main outcomes were the BCVA gain and decrease in central retinal thickness (CRT). MTOR-rs1057079-C, MTOR-rs11121704-C and MTOR-rs2295080-G alleles were associated with an increased risk of nAMD. The BCVA was increased in 117 (59.7%) patients by 10 [5-20] letters, did not changed in 59 (30.1%), and was decreased in 20 (10.2%) patients. ULK1-rs3088051 was associated with BCVA change. Among patients with the TT and CT genotypes for ULK1-rs3088051, an improvement in visual acuity was noted in 67.6% and 53.8% of cases, while in patients with the CC genotype, an increase in BCVA was recorded in 37.5% of cases (p = 0.01). The decrease in CRT was associated with SQSTM1-rs10277 (p = 0.001): it was significantly higher in TT (93 [58-122] mkm) and CT (66 [30-105] mkm) carriers compared to the CC genotype (47 [24-68] mkm). Other SNPs did not show significant associations with the outcome of anti-VEGF treatment. MTOR gene polymorphisms are moderately associated with the risk of nAMD. SQSTM1-rs10277 and ULK1-rs3088051 may influence short-term response to intravitreal anti-VEGF treatment. The results suggest that autophagy could be a target for future drugs to overcome resistance to anti-VEGF therapy.

Correlations between subfoveal choroidal thickness, macular thickness, and visual outcome in neovascular age-related macular degeneration using swept source OCT: insights from intravitreal aflibercept treatment

BackgroundAge-related macular degeneration (AMD) is a leading cause of visual impairment among individuals aged 50 and above, often resulting in irreversible vision loss (1). Currently, antiangiogenic therapy is the primary treatment approach for neovascular AMD (2). The choroid has gained significant attention in recent years due to its involvement in various ocular pathologies (7). The objective of this study was to evaluate visual acuity and correlate pre-treatment variables, such as foveal thickness and choroidal thickness, with post-treatment outcomes.Materials and MethodsThis study was designed as a prospective interventional study to investigate the changes in choroidal and macular thickness in patients with neovascular AMD who received intravitreal aflibercept injections. The study utilized medical records and employed Swept Source Optical Coherence Tomography (OCT-SS) for evaluation. The data was collected from patients treated in Presidente Prudente, Brazil, during a three-month load dose period.ResultsThe best-corrected mean visual acuity significantly improved from 1.0 logarithm of the minimum resolution angle (logMAR) units to 0.55 logMAR after treatment with aflibercept (p < 0.001). Patients undergoing treatment exhibited a significant decrease in average macular thickness from 323 μm to 232 μm (p = 0.001), as well as a reduction in choroidal thickness from 206 μm to 172 μm (p = 0.031), while maintaining intraocular pressure within the normal range (p = 0.719) without significant variation. Statistically significant associations were found between the difference in pre- and post-treatment choroidal thickness and the pretreatment values of macular thickness (p = 0.005) and choroidal thickness (p = 0.013). There was also a statistically significant correlation between the difference in pre- and post-treatment macular thickness and the pretreatment macular thickness value (p < 0.001).ConclusionIn this study, aflibercept exhibited remarkable effectiveness in reducing macular and choroidal thickness, as evaluated using OCT-SS, and significantly improved visual acuity in patients with neovascular AMD. The assessment of both choroidal and macular changes, as well as their correlations, can provide valuable insights for clinicians, enabling them to make well-informed therapeutic decisions and effectively monitor treatment outcomes. Notably, this study contributes to the existing body of literature as the first to establish a correlation between pretreatment foveal thickness, variation in choroidal thickness, and post-treatment choroidal thickness.

Complete resolution of subretinal fluid of the fellow eye following aflibercept injection in wet AMD

Abstract Purpose: To present a case of a patient with bilateral wet age-related macular degeneration (AMD) who was unilaterally treated with intravitreal aflibercept injections (IAIs) and the disease status in the fellow eye ameliorated after an IAI. Methods: Retrospective case report. Results: A 72-year-old woman was diagnosed with wet and dry AMD in her right (OD) and left (OS) eye, respectively. In OD, treatment strategy comprised 3 monthly IAIs, followed by re-injections according-to-need, while optical coherence tomography (OCT) scans were performed before IAIs. One month after the second IAI, subretinal fluid developed in OS. One week later, an IAI was applied in OD; two days later the disease status in OS was assessed by fluorescein angiography and OCT. Surprisingly, in OS subretinal fluid completely resolved and fluorescein angiography did not detect leakage, highlighting the absence of an active choroidal neovascularization. The short interval between IAI and the resolution of exudative phenomena in the other eye is suggestive of a beneficial effect in the contralateral eye. Conclusion: Herein we showed that an IAI had an effect to the fellow untreated eye. Our observation is consistent with active aflibercept in the systemic circulation. To the best of our knowledge, no other report in literature has demonstrated this effect of aflibercept in wet AMD.

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.

Modified early intensive and treat-and-extend regimen of anti-vascular endothelial growth factor for diabetic macular edema in Taiwan

Given the rising prevalence of patients with diabetes and increasing treatment burden for patients with vision-threatening diabetic macular edema (DME), we aimed to explore the efficacy of modified early intensive and treat-and-extend regimen of anti-vascular endothelial growth factor (VEGF) therapy under the Taiwan National Insurance Bureau reimbursement policy. We obtained data on 69 eyes treated with initial 4-monthly intravitreal injections of aflibercept or ranibizumab, plus individualized treat-and-extend regimen. At 12 months, the mean (SD) change in LogMAR best corrected visual acuity from baseline was − 0.28 (0.31) in all eyes, while that in the aflibercept and ranibizumab groups were − 0.30 (0.34) and − 0.25 (0.28), respectively. Central retinal thickness decreased by 137.2 (122.4) in all eyes, 138.1 (134.2) in the aflibercept group, and 136.2 (110.9) in the ranibizumab group. Additionally, the aflibercept group had a lower mean number of injections than the ranibizumab group (8.5 vs. 8.7). The last extended dosing interval of > 12 weeks was 31.0% and 16.7% of the eyes in the aflibercept and ranibizumab groups, respectively. The modified anti-VEGF regimens effectively managed DME in terms of functional and anatomical outcomes, and efficiently reduced the healthcare burden by reducing the number of injections and extending treatment intervals within 12 months.

Ocular and Systemic Risk Factors for Disease Worsening Among Patients with NPDR: Post Hoc Analysis of the PANORAMA Trial

PurposeIdentify baseline systemic and ocular characteristics associated with nonproliferative diabetic retinopathy (NPDR) worsening, and the impact of intravitreal aflibercept injection (IAI) on these associations. DesignPost hoc analysis of PANORAMA. ParticipantsPatients with moderately severe to severe NPDR enrolled in the prospective PANORAMA phase 3 trial. MethodsAssociations between baseline systemic and ocular factors with events indicative of NPDR worsening at Week 100 were evaluated by multivariable analysis in sham-treated eyes. NPDR worsening was defined as development of (1) vision-threatening complications (VTCs; comprising PDR and/or anterior segment neovascularization), (2) center-involved diabetic macular edema (CI-DME), or (3) ≥ 2-step Diabetic Retinopathy Severity Scale (DRSS) worsening. Impact of IAI on identified baseline factors was evaluated using univariable analysis in combined IAI groups. Main Outcomes MeasuresBaseline systemic and ocular factors associated with events indicative of NPDR worsening at Week 100. The cumulative incidence and risk of developing such events at Week 100 among sham versus IAI-treated eyes. ResultsUsing multivariable analyses among sham-treated eyes, 5 baseline factors associated with increased risk of NPDR worsening were identified: fluorescein leakage, retinal nonperfusion area, thicker central subfield thickness, eosinophil level, and proteinuria. Considering baseline fluorescein leakage area as a prognostic indicator in detail, the risk of developing VTCs alone, VTCs and/or CI-DME, or ≥ 2-step DRSS worsening increased with increasing fluorescein leakage area in the sham group (all P < 0.05). Considering baseline retinal nonperfusion area as a prognostic indicator in detail, the risk of developing VTCs alone, CI-DME alone, or VTCs and/or CI-DME increased with increasing baseline retinal nonperfusion area in the sham group (all P < 0.05). In contrast, among IAI-treated eyes, increasing baseline fluorescein leakage or retinal nonperfusion areas did not increase the risks of NPDR worsening. ConclusionsWithin the PANORAMA trial, increased areas of fluorescein leakage and retinal nonperfusion at baseline were identified as key ocular biomarkers associated with events indicative of NPDR worsening among sham-treated patients. IAI treatment appeared to mitigate the effect of these baseline risk factors and reduced the likelihood of NPDR worsening.

Risk of transient vision loss after intravitreal aflibercept using vial-prepared vs. the novel prefilled syringe formulation.

To compare the risk of transient vision loss (TVL) probably attributable to a severe intraocular pressure spike after intravitreal aflibercept application using the novel prefilled syringe (PFS) vs. the established vial system (VS). Datasets of the intravitreal injection service of the Ludwig Maximilians-University Munich and the Technical University Munich, Germany, were screened for documentation of TVL after intravitreal injection of aflibercept. The observation period included two full months prior to the introduction of the novel PFS and two months afterwards. TVL was defined as loss of perception of hand motion for a duration of >30 s. Over a period of four months, 1720 intravitreal injections of aflibercept were administered in 672 patients. There were 842 injections with the old VS, and 878 injections using the novel PFS. Using the VS, TVL was noted during two injections (0.24%) in two patients, as compared to 11 cases of TVL (1.25%) in 10 patients with the PFS (p = 0.015). Using the PFS, patients had a 5.3-fold risk of TVL as compared to the VS (OR: 5.33; 95% CI: 1.2-24.1; p = 0.0298). There was a more than five-fold risk of TVL using the novel pre-filled aflibercept syringe as compared to the established vial system. During informed consent, this risk should be discussed.

Effect of Prefilled vs Vial-Drawn Syringes on Sustained Increases in Intraocular Pressure in Patients Treated With Aflibercept.

Purpose: To evaluate the effect of syringe type on developing sustained intraocular pressure (IOP) increases. Methods: This retrospective cohort study included patients in a single academic center receiving antivascular endothelial growth factor (anti-VEGF) injections from 2012 to 2022 for various indications. Patients were grouped by anti-VEGF treatment of either vial-drawn or prefilled syringe delivery. Trends in IOP were recorded for 1 year after treatment began. Development of sustained IOP increase, ocular hypertension, and glaucoma was recorded. Sustained IOP increase was defined as ≥5 mm Hg above baseline for at least 4 weeks. Results: Of 257 total patients, 6 (2.3%) developed sustained IOP increases throughout the study's duration. No significant differences were noted with respect to prefilled versus vial-drawn syringe status on the development of sustained IOP increases or incident glaucoma (IOP: 1.8% vs 2.7%, respectively, P = .65; glaucoma: 0.0% vs 2.0%, respectively, P = .14). Patients treated with prefilled syringes were significantly less likely to develop ocular hypertension (2.8% vs 8.8%, P < .05). Conclusions: This study found that aflibercept intravitreal injection with prefilled syringes was not associated with a significant increase in IOP-related adverse effects when compared with those treated with vial-drawn syringes.