Monthly Intravitreal Aflibercept Injections Research Articles

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.

Final 4-year results of the RAINBOW real-world study: intravitreal aflibercept dosing regimens in France in treatment-naïve patients with neovascular age-related macular degeneration

PurposeThe purpose of this study is to evaluate real-world treatment outcomes in patients with neovascular age-related macular degeneration (nAMD) treated with intravitreal aflibercept (IVT-AFL) in routine clinical practice in France.MethodsRAINBOW (NCT02279537) was an ambispective, observational, 4-year study assessing IVT-AFL effectiveness, treatment patterns, and safety in patients with nAMD in France. Treatment-naïve patients prescribed IVT-AFL and treated according to local practice (pro re nata or treat-and-extend) were eligible. Three treatment cohorts were retrospectively identified based on their treatment pattern within the first 12 months: regular (3 initial monthly IVT-AFL injections received within 45–90 days after the first injection in month 0 and followed by injections every 2 months), irregular with the initial monthly injections, and irregular without the initial monthly injections. The primary endpoint was mean change in best-corrected visual acuity (BCVA) from baseline to month 12. The 48-month results are described here.ResultsOverall, the study included 516 patients (each with one study eye), and 30.2% of patients completed 48 months of IVT-AFL treatment. Mean change in BCVA from baseline (56.5 letters) to month 48 for patients with an assessment at both time points was + 1.1 (regular cohort, n = 47), + 0.1 (irregular cohort with initial monthly injections, n = 115), and − 1.3 letters (irregular cohort without initial monthly injections, n = 26), representing a decrease from the gains achieved at month 12. Mean number of IVT-AFL injections received by month 48 in the treatment cohorts was 14.9, 13.7, and 11.9, respectively. The safety profile of IVT-AFL was consistent with previous studies.ConclusionIn RAINBOW, the 48-month results demonstrate a lack of long-term effectiveness of IVT-AFL treatment of nAMD due to progressive undertreatment in routine clinical practice in France. These real-world findings highlight the importance of 3 initial monthly IVT-AFL injections followed by continuous proactive treatment beyond the first year to achieve optimal functional outcomes.Trial registration numberClinicalTrials.gov Identifier: NCT02279537.

OCTA changes following loading phase with intravitreal aflibercept for DME

ObjectifMesurer les variations observées à l'angiographie-tomographie par cohérence optique (OCTA) à la suite de l'administration intravitréenne d'anti-VEGF (facteur de croissance endothélial vasculaire) dans le traitement de l’œdème maculaire diabétique (OMD), et évaluer le lien entre les paramètres mesurés à l'OCTA avant le traitement et les résultats visuels. NatureÉtude de cohorte prospective. MéthodesUn groupe de 29 patients présentant un OMD ont reçu 5 injections intravitréennes mensuelles d'aflibercept. On a eu recours au test de Wilcoxon pour observations appariées afin de comparer les données mesurées à l'OCTA au départ et après 6 mois. Au nombre des paramètres mesurés à l'OCTA, citons l'aire de la zone fovéale avasculaire (ZFA), le périmètre de la ZFA, la circularité de la ZFA, la densité vasculaire du plexus vasculaire superficiel (segmenté conformément à la cartographie de l’étude ETDRS [Early Treatment of Diabetic Retinopathy Study], soit zone centrale, zone interne, zone externe et zone complète). Une sous-analyse a permis de séparer les patients en 2 groupes : sujets qui ont répondu au traitement (réduction de l’épaisseur du sous-champ central > 50 µm pendant le traitement) et sujets qui n'ont pas répondu au traitement. Une régression linéaire multiple et une régression logistique ont servi à déterminer les liens entre les paramètres mesurés à l'OCTA avant le traitement et les résultats en matière d'acuité visuelle. RésultatsUn total de 29 patients ont été inclus: 25 patients (86,2 %) présentaient une rétinopathie diabétique non proliférante et 4 (13,8 %), une rétinopathie diabétique proliférante. La densité vasculaire a diminué dans les zones centrale (p = 0,004) et interne (p = 0,013) selon la cartographie de l’étude ETDRS. Cet effet n’était significatif que chez les patients qui ont répondu au traitement (zone centrale; p = 0,002; zone interne; p = 0,017). Les paramètres OCT et OCTA mesurés avant le traitement n'ont pas influé sur les résultats ultimes en matière d'acuité visuelle. ConclusionOn a noté, après l'administration intravitréenne d'aflibercept dans le traitement de l'OMD, une diminution significative de la densité vasculaire du plexus vasculaire superficiel dans les zones centrale et interne selon la cartographie de l'ETDRS. Ce phénomène s'est produit exclusivement chez les patients qui ont répondu au traitement. Nos observations tiennent vraisemblablement aux limites de la technologie de l'OCTA elle-même, en ce sens que la densité vasculaire avant le traitement a potentiellement été surestimée par la présence d'artéfacts, soit quelques particules en suspension en mouvement. Les paramètres mesurés à l'OCTA avant le traitement n'ont pas pu servir de biomarqueurs permettant de prévoir les résultats visuels après l'administration d'un anti-VEGF.

Baseline Characteristics and Outcomes After Anti–Vascular Endothelial Growth Factor Therapy for Macular Edema in Participants With Hemiretinal Vein Occlusion Compared With Participants With Central Retinal Vein Occlusion

Intravitreal anti-vascular endothelial growth factor (VEGF) injections are commonly used to treat eyes with macular edema secondary to hemiretinal vein occlusion (HRVO) or central retinal vein occlusion (CRVO). Information on whether differences exist in outcomes after anti-VEGF therapy can help guide treatment for each of the different disease types. To compare baseline characteristics, treatment burden, and outcomes of macular edema treatment in participants with HRVO with those of participants with CRVO. This post hoc outcome analysis from the Study of Comparative Treatments for Retinal Vein Occlusion 2 randomized clinical trial included 362 participants with macular edema caused by HRVO or CRVO treated at 66 US sites. Randomization began in September 2014, and the last month 24 follow-up visit occurred in February 2018. Data were analyzed from April 2020 to May 2021. Eyes were initially randomized to 6 monthly intravitreal injections of aflibercept or bevacizumab and were treated according to protocol between months 6 to 12 depending on 6-month outcome. After month 12, patients were treated per investigator discretion and observed through month 60. Mean visual acuity letter score (VALS). Of 362 included patients, 157 (43.4%) were female, and the mean (SD) age was 68.9 (12.0) years. Outcome data were analyzed up to month 24 owing to substantial missing data at later visits. A significantly greater proportion of participants with HRVO than those with CRVO were Black (37% vs 11%). Treatment rates between months 12 to 23 were 0.36 (95% CI, 0.32-0.40) injections per month for patients with CRVO and 0.28 (95% CI, 0.19-0.36) for patients with HRVO (P = .11). The mean VALS from months 1 to 24 of an HRVO study eye exceeded that of a CRVO study eye by 5.5 (95% CI, 1.5-9.5; P = .01), consistent with the magnitude of the VALS difference between eyes with CRVO and HRVO at baseline. Eyes with CRVO presented at baseline with more macular edema than eyes with HRVO (difference in central subfield thickness [CST], 86 μm; 95% CI, 48-124; P < .001), with no difference in CST between the groups throughout months 1 to 24. Black race was more prevalent among participants with HRVO than CRVO, and no differences were observed in the frequency of treatments for macular edema between eyes with CRVO and HRVO. Although eyes with CRVO presented with worse visual acuity and more macular edema on average than did eyes with HRVO, the magnitude of VALS improvement, central retinal thickness in response to anti-VEGF therapy, and treatment burden were similar between the groups.

Intraocular Pressure–Related Events After Anti–Vascular Endothelial Growth Factor Therapy for Macular Edema Due to Central Retinal Vein Occlusion or Hemiretinal Vein Occlusion

Intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections are used to treat a variety of posterior segment conditions, including some associated with glaucoma, such as macular edema due to central retinal vein occlusion (CRVO). Therefore, information regarding intraocular pressure (IOP)-related events associated with anti-VEGF therapies is important to help balance the risks and benefits over the course of therapy. To investigate IOP-related events among participants in the Study of Comparative Treatments for Retinal Vein Occlusion 2 (SCORE2). Secondary analysis of a randomized clinical trial that included 312 participants with macular edema secondary to CRVO or hemiretinal vein occlusion (HRVO) who were not taking IOP-lowering medications at baseline. First randomization occurred on September 14, 2014, and contained data through data freeze on April 1, 2020. Analysis took place from April 2020 through December 2020. Study participants were initially randomized to 6 monthly intravitreal injections of aflibercept or bevacizumab. At month 6, protocol-defined good responders were rerandomized to continued monthly or treat-and-extend dosing of their originally assigned study drug, and protocol-defined poor or marginal responders were switched to alternative treatment. After month 12, participants were treated as per investigator discretion. Three different outcomes: (1) IOP elevation more than 10 mm Hg from baseline, (2) IOP to a level higher than 35 mm Hg, and (3) IOP-lowering incisional or laser surgery. Of the 312 participants meeting inclusion criteria (138 [44.2%] were female; mean [SD] age, 67.8 [12.1] years), 25 (8.0%) had IOP elevation more than 10 mm Hg over baseline through month 60, and 5 (1.6%) had IOP higher than 35 mm Hg. The 60-month Kaplan-Meier cumulative incidence of IOP elevation more than 10 mm Hg over baseline was 0.13 (95% CI, 0.08-0.19), and the 60-month Kaplan-Meier cumulative incidence of IOP higher than 35 mm Hg was 0.02 (95% CI, 0.01-0.06), and did not differ among participants initially randomly assigned to receive aflibercept or bevacizumab. Three participants (1.0%) underwent IOP-lowering incisional surgery, and 3 participants (1.0%) underwent IOP-lowering glaucoma laser surgery. Intravitreal anti-VEGF injections are used to treat some conditions associated with glaucoma, such as macular edema due to CRVO, and the rates of IOP-related events in this trial support monitoring IOP in eyes treated with anti-VEGF therapy for macular edema associated with CRVO or HRVO for up to 60 months. ClinicalTrials.gov Identifier: NCT01969708.

Improvements of Retinal Sensitivity after Intravitreal Injection of Aflibercept in Eyes with Neovascular Age-Related Macular Degeneration with or without Polypoidal Choroidal Vasculopathy

Purpose: We aim to determine the effects of intravitreal aflibercept (IVA) on the mean sensitivity (MS) of the central retina, best-corrected visual acuity (BCVA), and central foveal thickness (CFT) in eyes with neovascular age-related macular degeneration (nAMD) with or without polypoidal choroidal vasculopathy (PCV). Methods: This was a prospective, interventional study. All eyes were treatment-naive with nAMD with or without PCV. Each eye received 3 monthly IVA injections followed by an IVA injection every 2 months for 12 months. The primary outcome was the change in the MS within the central 2°. The secondary outcomes were the changes in BCVA, CFT, greatest linear dimension (GLD), and percentage of eyes with a dry macula. Results: Thirty-seven eyes of 37 patients were studied. A significant improvement of the MS (dB) was observed +4.9 ± 4.6 dB (mean ± standard deviation) at 3 M (p < 0.001), +5.5 ± 4.9 dB at 6 (p < 0.001), and +7.0 ± 3.4 dB at 12 M (p < 0.001) compared to the baseline in all eyes. The MS of the eyes with non-PCV was not significantly different from that of eyes with PCV (p = 1.00, 1.00, 1.00, and 0.76 at baseline, 3, 6, and 12 M, respectively). The MS of 11 patients whose BCVA remained unchanged was significantly improved by +6.5 ± 2.8 dB at 3 M (p < 0.001), +6.1 ± 4.3 dB at 6 M (p < 0.001), and +6.4 ± 4.8 dB at 12 M (p = 0.003) compared to the baseline. The mean BCVA was significantly improved from the baseline to 3 M (p < 0.001), 6 M (p = 0.027), and 12 M (p = 0.003) in all eyes. The BCVA was improved or maintained in 97% of the patients at 12 M. The mean CFT and GLD were significantly reduced at 12 M (p < 0.001). Twenty-two eyes (71%) had a dry macula at 12 M. Conclusions: IVA administered by a fixed dosing regimen led to significant improvements of the central MS, BCVA, and macular morphology at 1 year in eyes with nAMD with or without PCV. These results were not significantly different between eyes with non-PCV and with PCV. The improvements of the MS of the retina of the central 2° in a subgroup whose BCVA remained unchanged through the 12-month experimental period was also significant. We conclude that the MS of the central 2° might be a better marker than the BCVA in determining the effectiveness of IVA treatments and might be helpful in determining early effects on the retina before BCVA changes can be detected.

Efficacy and safety of intravitreal aflibercept in ranibizumab-refractory patients with neovascular age-related macular degeneration

BackgroundAnti–vascular endothelial growth factor (anti-VEGF) agents have become the standard of care in neovascular age-related macular degeneration (nAMD). Despite generally excellent response rates to anti-VEGF therapy, some patients do not respond or may respond suboptimally. In the case of refractory or rapidly recurring fluid in nAMD, clinicians may switch to another anti-VEGF agent. TITAN was an observational study that assessed the effectiveness and safety of intravitreal aflibercept (IVT-AFL) in patients with nAMD refractory to ranibizumab who switched to IVT-AFL after less than 12 months of ranibizumab treatment in routine clinical practice in France.MethodsTITAN was an observational, retrospective and prospective 12-month study conducted at 28 centres in France. Patients with nAMD refractory to ranibizumab were enrolled. Patients who were switched from ranibizumab to IVT-AFL were followed for 12 months. Data were obtained from medical records for retrospectively included patients, and at routine follow-up visits for those included prospectively. The main outcome measure was percentage of patients who achieved treatment success (gain of ≥1 Early Treatment Diabetic Retinopathy Study letters in best-corrected visual acuity [BCVA] and/or any reduction in central retinal thickness [CRT]) from baseline to 12 months after switching. A sample size of 225 patients was determined based on a 2-sided 95% confidence interval with a width equal to 0.12 when the sample proportion was 0.70.ResultsWe analysed safety data (N = 217) and clinical outcomes from patients in the per-protocol population (n = 125). The mean (standard deviation) number of IVT-AFL injections was 7.5 (2.6). Treatment success was achieved in 68.8% of patients. Mean BCVA change from baseline to Month 12 was + 1.5 letters (P = 0.105) and the mean CRT change was − 45.0 μm (P < 0.001). In a subgroup analysis, in patients who received three initial monthly IVT-AFL injections, mean BCVA gain was 3.3 letters at Month 12 (P = 0.015). Excluding lack of efficacy and inappropriate scheduling of drug administration, the most common adverse event was eye pain (2.3%).ConclusionsSwitching ranibizumab-refractory patients with nAMD to IVT-AFL may improve visual outcomes in some patients, particularly those who receive three initial monthly injections.Trial registrationClinicalTrials.gov, NCT02321241. First posted: December 22, 2014; Last update posted: July 2, 2018

Effects of Intravitreal Aflibercept on Retinal Function and Improvement of Macular Edema Associated With Diabetic Retinopathy.

PurposeTo determine the effectiveness of intravitreal aflibercept (IVA) on the retinal function in eyes with diabetic macular edema (DME).MethodsTwenty-five eyes of 25 patients with DME were treated with three consecutive monthly IVA injections. The retinal sensitivities (RS) within the central 10° were determined by microperimetry (MP). The central subfield macular thickness (CMT) was determined by optical coherence tomography, and the implicit times (IT) and amplitudes (Amp) of the flicker electroretinograms (ERGs) were determined from the ERGs elicited and recorded by the RETeval. The number of microaneurysms (MAs) was counted in the fundus photographs. The assessments were made before the IVA injections (pre-IVA) and one week after the IVA injections (post-IVA). The correlations between the reduction ratio of the MA numbers/CMT and RS/IT/Amp were evaluated.ResultsThe mean RS improved from 19.9 ± 5.9 dB to 22.0 ± 5.8dB, the CMT decreased from 485.7 ± 90.6 µm to 376.9 ± 81.6 µm, and the number of MAs decreased from 49.6 ± 33.2 to 24.8 ± 18.1 after the IVA injection (all P < 0.01). The changes in the IT from 31.3 ± 3.3 ms to 31.5 ± 3.1 ms and the Amp from 12.2 ± 5.5 µV to 11.3 ± 6.1µV post-IVA were not significant. A significant correlation was found between the relative changes in the CMT and RS (r = −0.43; P = 0.02), the MAs and RS (r = −0.38; P = 0.03). No significant correlation was observed between the relative changes of the number of MAs/CMT and IT/Amp.ConclusionsIVA can improve both central retinal function and anatomical conformation.Translational RelevanceA new aspect of aflibercept will be useful for DME treatment.

Title: Pachydrusen in Fellow Eyes Predict Response to Aflibercept Monotherapy in Patients with Polypoidal Choroidal Vasculopathy.

We investigated whether responses to as-needed intravitreal aflibercept injections (IAIs) for polypoidal choroidal vasculopathy (PCV) differed among patients based upon drusen characteristics in fellow eyes. 110 eyes from 110 patients with PCV received 3 monthly IAI and thereafter Pro re nata (PRN) IAI over 12 months. Patients were classified into 4 groups depending on fellow eye findings. Group 1 (n = 16): pachydrusen; Group 2 (n = 45): no drusen; Group 3 (n = 35): soft drusen; Group4 (n = 14) PCV/scarring. Best-corrected visual acuity improved at 12 months in all groups, but not significantly in Group 1 and Group 4; however, visual improvement was similar among the groups after adjusting baseline confounders. Group 1 had a significantly lower percentage of eyes needing retreatment (all p < 0.001; Group 1: 16.7%; Group 2: 50.8%; Group 3: 80%; Group 4: 85.7%). The mean number of retreatments was least in Group 1 among the groups (all p-value < 0.003; Group 1: 0.50 ± 1.32; Group 2: 1.73 ± 2.08; Group 3:2.71 ± 1.99; Group 3: 2.71 ± 2.16). Patients with pachydrusen in fellow eyes were less likely to require additional IAI following the loading dose and may be ideal candidates for aflibercept monotherapy in their first year.

Changes in Aqueous Cytokine Levels Following Intravitreal Aflibercept in Treatment-Naive Patients with Diabetic Macular Edema.

Purpose: To investigate the changes in aqueous humor cytokine levels in response to short-term aflibercept therapy in treatment-naive patients with center-involving diabetic macular edema (DME). Methods: This is a prospective cohort study that included patients with treatment-naive DME with central subfield macular thickness ≥310 μm on optical coherence tomography from July 2015 to May 2017. Patients received 3 monthly intravitreal aflibercept injections. Aqueous samples for cytokine analysis were obtained before the first and third injections. Levels of various cytokines were measured using multiplex immunoassay. Main outcome measures were changes in aqueous cytokine levels from baseline to month 2. Results: A total of 17 patients were enrolled and 16 completed the study. The mean age was 57.2 ± 8.1 years. The following cytokines were significantly higher at month 2 versus baseline: transforming growth factor-beta (TGF-β)1 (P = 0.004), TGF-β2 (P = 0.017), inducible protein (IP)-10 (P = 0.011), and hepatocyte growth factor (HGF) (P = 0.02). There were significant reductions in the levels of vascular endothelial growth factor (VEGF) (P < 0.001), placental growth factor (PlGF) (P = 0.028), interleukin (IL)-6 (P = 0.011), and platelet-derived growth factor-AA (PDGF-AA) (P = 0.003). Conclusions: In treatment-naive patients with DME, short-term aflibercept therapy not only results in VEGF and PlGF suppression, but also leads to reduced levels of IL-6 and PDGF-AA and higher concentrations of TGF-β1, TGF-β2, HGF, and IP-10.

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

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

Impact of intravitreal aflibercept dosing regimens in treatment-naïve patients with neovascular age-related macular degeneration in routine clinical practice in France: results from the RAINBOW study

ObjectiveTo evaluate 12-month outcomes in treatment-naïve patients with neovascular (wet) age-related macular degeneration (AMD) stratified by intravitreal aflibercept (IVT-AFL) regimen.Methods and analysisPatients included in the 12-month interim analysis of Real...

Two-Year Outcomes of Treat-and-Extend Intravitreal Aflibercept for Exudative Age-Related Macular Degeneration: A Prospective Study

To report the 2-year outcomes of intravitreal aflibercept injections (IAIs) in Japanese patients with neovascular age-related macular degeneration (AMD) using a 1-month adjusted treat-and-extend (TAE) regimen. Multicenter, prospective, nonrandomized, interventional study. Ninety-seven eyes of 97 patients with treatment-naive AMD were studied at 3 tertiary ophthalmological institutions. The patients were treated with 3 consecutive monthly IAIs followed by the TAE regimen with a 1-month adjustment for a maximum of 3 months. Our TAE regimen allowed us to shorten and extend the treatment intervals even after a 3-month or 1-month treatment interval, or both, were reached. Best-corrected visual acuity (BCVA), central retinal thickness (CRT), and subfoveal choroidal thickness (SCT) were analyzed. The mean changes in the BCVA, CRT, and SCT from the baseline to 2 years after initiating the treatment were determined. In addition, the number of injections also was determined. The mean BCVA significantly improved from 0.27 logarithm of the minimum angle of resolution (logMAR) units to 0.14 logMAR at 2 years (P < 0.01). The mean CRT decreased significantly from 307±132 μm to 202±76 μm at 2 years (P < 0.01). The mean SCT decreased significantly from 247±106 μm to 203±96 μm at 2 years (P < 0.01). Seventy eyes (72.2%) showed a dry macula at 2 years. The treatment interval at 2 years was 1 month in 20 eyes (20.6%), 2 months in 18 eyes (18.6%), and 3 months in 59 eyes (60.8%). In 49 (50.5%) eyes with a 3-month treatment interval immediately after the loading phase, no fluid was seen in 25 eyes (51.0%) for the duration of this study. The rest had switched to a more frequent scheme. The mean number of injections during the 2-year period was 13.0±3.9. Intravitreal aflibercept injections with a 1-month adjusted TAE regimen significantly improved the BCVA and CRT with a reduced number of injections at 2 years. The treatment interval was adjusted to extend to 3 months in 60% and to shorten to 1 month in 20% of the eyes at 2 years.

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

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

Treatment of large avascular retinal pigment epithelium detachments in age-related macular degeneration with aflibercept, photodynamic therapy, and triamcinolone acetonide.

PurposeTo evaluate the use of aflibercept, triamcinolone acetonide, and photodynamic therapy (PDT) in the treatment of avascular pigment epithelium detachments (aPEDs).Patients and methodsPatients with treatment-naïve aPEDs ≥1,500 µm in diameter were randomized to treatment or observation. Treatment consisted of 6 monthly intravitreal injections of aflibercept. If the aPED persisted, the patients were treated with half-fluence PDT in combination with intravitreal triamcinolone acetonide and aflibercept. The primary outcome was change of best-corrected visual acuity (BCVA) after 24 months of follow-up. Secondary outcomes were changes in pigment epithelium volume, height and diameter, central retinal thickness, and number of patients developing choroidal neovascularization or geographic atrophy (GA).ResultsTreatment and inclusion of patients were stopped after an interim analysis of 6-month data because 75% of the aPEDs were in different stages of GA. Nine patients with aPED were included in the study, of these one patient was excluded because of bilateral central serous chorioretinopathy. The remaining eight had drusenoid aPEDs. After 24 months of follow-up, estimated means of BCVA decreased by 4.2 and 20.8 letters in the treatment and observation group, respectively. This decrease over time was not significantly different between groups (P=0.140, 95% CI −5.3, 38.6). Estimated means of PED volume, height, diameter, and central retinal thickness were not significantly different between groups. Choroidal neovascularization and retinal pigment epithelium tear developed in one patient in the treatment group. One patient in the treatment group and two patients in the observation group progressed to complete retinal pigment epithelium and outer retinal atrophy. A decrease in PED volume was associated with the development of complete retinal pigment epithelium and outer retinal atrophy (P=0.029).ConclusionThis small trial indicates that multitargeted, primarily antiangiogenic therapy does not favorably alter the natural course of drusenoid aPEDs.

Intravitreal aflibercept for exudative age-related macular degeneration with good visual acuity: 2-year results of a prospective study.

PurposeWe report the 2-year outcomes of intravitreal aflibercept (IVA) for exudative age-related macular degeneration (AMD) with good visual acuity (VA) and examine the baseline factors associated with good visual outcome.Materials and methodsThis multicenter, prospective study evaluated 39 eyes (39 AMD patients) enrolled from August 2013 to August 2014 at 12 and 24 months. Only patients with initial best-corrected VA (BCVA) >0.3 logarithm of the minimum angle of resolution (20/40 Snellen) were eligible. Three consecutive monthly IVA injections were followed by 2 monthly injections for 12 months. Thereafter, patients received injections on a treat- and-extend regimen for up to 24 months. Outcome measures included BCVA and central macular thickness (CMT) at 12 and 24 months. Post hoc analysis, BCVA, and CMT were evaluated by AMD types (typical AMD [tAMD], type 1, and type 2 polypoidal choroidal vasculopathy [PCV]). Baseline characteristics and BCVA associations were evaluated with linear regression analysis and Student’s t-test.ResultsMean age was 69 years and 26 of 39 eyes were male. tAMD, type 1 and type 2 PCV occurred in 18, 12, and 9 eyes, respectively. Baseline mean BCVA was 0.097 logarithm of the minimum angle of resolution (20/25 Snellen) and showed significant improvement to 0.058 (20/22 Snellen, P=0.03) at 12 months and 0.066 (20/23) at 24 months. CMT improved significantly from 320 (99) µm (mean [SD]) to 250 (93) µm (P=0.002) at 12 months and 240 (93) µm (P=0.0005) at 24 months. BCVA and CMT were not significantly different among the three groups. Only subretinal hemorrhage (SRH) was significantly associated with improved BCVA. BCVA change from baseline was −0.12 with SRH and −0.011 without SRH (P=0.017) at 12 months.ConclusionIVA showed good efficacy for exudative AMD with good VA at 24 months. tAMD and type 1 and 2 PCV showed similar prognosis. Baseline SRH predicted favorable long-term vision in AMD with good VA.

Choroidal Changes After Suprachoroidal Injection of Triamcinolone Acetonide in Eyes With Macular Edema Secondary to Retinal Vein Occlusion

To evaluate choroidal and suprachoroidal changes following suprachoroidal injection of triamcinolone acetonide injectable suspension (CLS-TA), in eyes with macular edema due to retinal vein occlusion (RVO). Prospective cohort study within a randomized, controlled phase 2 clinical trial. Enhanced depth imaging optical coherence tomography (EDI-OCT) images were analyzed from 38 eyes of 38 treatment-naïve patients with macular edema due to RVO, enrolled in the prospective Suprachoroidal Injection of Triamcinolone Acetonide with Intravitreal Aflibercept in Subjects with Macular Edema Due to Retinal Vein Occlusion (TANZANITE) study who received either a suprachoroidal injection of CLS-TA with an intravitreal injection of aflibercept (combination arm) or only an intravitreal injection of aflibercept (monotherapy arm), followed by monthly intravitreal aflibercept injections in both arms based on pro re nata criteria. Macular choroidal thickness measured to the outer choroidal vessel lumen (vascular choroidal thickness, VCT), outer choroid stroma (stromal choroidal thickness, SCT), or inner scleral border (total choroidal thickness, TCT) showed no significant changes over 3months in both study arms (P= .231-.342). Eyes that received combination therapy showed a trend toward thickening of the suprachoroidal space (SCS) compared with monotherapy alone (13.4μm vs 5.3μm at 3months; P= .077). In the 15 eyes that demonstrated a visible SCS at baseline, the SCS expanded significantly after suprachoroidal CLS-TA injection (16.2μm to 27.8μm at 3months; P= .033). Suprachoroidal injection of CLS-TA does not alter choroidal thickness in eyes with macular edema due to RVO, but may result in expansion of the SCS.

Treat-and-Extend Regimen with Aflibercept for Neovascular Age-Related Macular Degeneration: Efficacy and Macular Atrophy Development

To evaluate the effects of intravitreal injection of aflibercept using a treat-and-extend dosing regimen on treatment-naïve neovascular age-related macular degeneration (AMD) and the development of macular atrophy. Retrospective, interventional case series. Eyes (n = 137) with treatment-naïve neovascular AMD, including 18 eyes with typical AMD with classic choroidal neovascularization (CNV), 44 eyes with typical AMD with occult CNV, 58 eyes with polypoidal choroidal vasculopathy, and 17 eyes with retinal angiomatous proliferation (RAP). Clinical records of eyes with neovascular AMD that underwent 3 consecutive monthly intravitreal injections of aflibercept followed by a treat-and-extend dosing regimen were reviewed, and the corresponding imaging studies were analyzed. Changes in best-corrected visual acuity (BCVA), central macular thickness (CMT), central choroidal thickness (CCT), and the extent of macular atrophy in the macular area during a 2-year follow-up period. In all subtypes after 1 and 2 years, CMT and CCT were reduced significantly, whereas macular atrophy showed significant enlargement. At baseline, the extent of macular atrophy was greater in RAP than other subtypes; after 2 years, the macular atrophy enlargement was also greatest in RAP and correlated negatively with CCT (rs=-0.72; P < 0.01). Best-corrected visual acuity showed significant improvement after 1 and 2 years in all subtypes other than RAP. In RAP, BCVA was improved significantly after 1 year, but the magnitude of this improvement lost statistical significance after 2 years. Treat-and-extend with intravitreal aflibercept may be effective for improving BCVA and ameliorating exudative changes in neovascular AMD. However in RAP, choroidal thinning during the treatment regimen may accelerate enlargement of macular atrophy, thereby diminishing the improvement in BCVA after 2 years.

Changes in retinal vessel diameters after intravitreal aflibercept in patients with diabetic macular edema

PurposeTo evaluate changes in retinal vessel diameters after loading doses with intravitreal aflibercept in patients with diabetic macular edema (DME).MethodsThis was a three months prospective, interventional study. We included 17 patients with DME, central retinal thickness &gt;300 μm and no active proliferative diabetic retinopathy. Previous treatment with any intravitreal vascular endothelial growth factor inhibitor was not allowed within 4 months prior to inclusion. All patients received 3 monthly intravitreal injections of aflibercept, and vessel diameters were evaluated at baseline and four weeks after the last injection. Retinal arterial and venous diameters were measured in 50‐degree disc‐centered images using the Oxymap model T1 (Oxymap, Reykjavik, Iceland) as the average diameter of the four major arterioles and venules from the four quadrants. Paired t‐test was used to test for differences in mean oxygen saturations from baseline to follow‐up.ResultsMedian age and duration of diabetes were 59.5 and 2.6 years at baseline. Median HbA1c and CRT were 65 mmol/mol and 336 μm, respectively, and 23.5% were women. Venous diameter decreased from baseline to follow‐up (157.9 μm vs. 153.2 μm, p = 0.03), whereas arterial diameter was unchanged (115.4 μm vs. 116.1, p = 0.70).ConclusionsRetinal venous diameter decreased after treatment with 3 monthly intravitreal injections of aflibercept in patients with DME, whereas no difference was found in the retinal arterial diameter. As previous studies have demonstrated that retinal venules dilate with increasing severity of diabetic retinopathy, our results suggest that treatment with intravitreal aflibercept causes positive changes to retinal vessel geometry.

Comparison of pro re nata versus Bimonthly Injection of Intravitreal Aflibercept for Typical Neovascular Age-Related Macular Degeneration

Purpose: The aim of this study was to clarify the 1-year outcomes of pro re nata (PRN) and bimonthly intravitreal injections of aflibercept (IVA) for typical neovascular age-related macular degeneration (tAMD) after the initial 3 monthly IVA. Methods: We conducted a prospective, interventional study. Fifty-eight treatment-naïve patients with tAMD were randomly assigned to the PRN (30 patients) or the bimonthly (28 patients) treatment group. Both groups initially received 3 monthly IVA. Visual acuity, central macular retinal thickness (CRT), and central choroidal thickness (CCT) were evaluated at 12 months. Subanalysis was performed to identify factors associated with the best-corrected visual acuity (BCVA). Results: BCVA was significantly improved only in the bimonthly group at 12 months. CRT and CCT were significantly decreased in both groups. Subanalysis showed that the only factor associated with BCVA improvement at 12 months was the existence of pigment epithelial detachment at baseline. Conclusions: BCVA showed significant improvement only in the bimonthly group but not in the PRN group at 12 months.