Initial Monthly Injections Research Articles

Evaluation of the First-Dose Anti-VEGF Anatomical Response in Polypoidal Choroidal Vasculopathy Patients: Correlation with the Third-Dose Response and Risk Factor Analysis

Introduction: The aims of the study were to investigate whether first-dose efficacy can predict third-dose anatomical response and analyze the risk factors for first-dose response of polypoidal choroidal vasculopathy (PCV) patients. Methods: We retrospectively reviewed patients’ medical records from 27 centers of China PCV Research Alliance. PCV patients treated with intravitreal injections of conbercept (IVC) based on the 3+ pro re nata regimen (three initial monthly injections, followed by injections as needed) with complete 3-month injection data were included. Response correlations, risk factor associations, changes in central macular thickness (CMT) or best-corrected visual acuity (BCVA), and number of injections in the first year of follow-up were evaluated separately in the pachy-PCV and non-pachy-PCV phenotypes. Results: Overall, 165 eligible patients were included. There was a significant correlation between first-dose and third-dose anatomical response in pachy-PCV or non-pachy-PCV patients (rs = 0.611, p < 0.001; rs = 0.638, p < 0.001). Multivariate analysis revealed associations of good first-dose anatomical response in pachy-PCV patients with baseline CMT with a predicted area under the curve (AUC) of 0.847, while a good response in non-pachy-PCV patients was associated with baseline BCVA, baseline CMT, pigment epithelial detachment (PED) height, higher proportion of intraretinal fluid, and lower PED minimum diameter with a predicted AUC of 0.940. CMT in the good first-dose response group was significantly decreased from baseline at all first-year follow-up visits in both groups (p < 0.001), and mean BCVA was improved in the good versus poor first-dose anatomical response group (5.4 vs. 1.6 ETDRS letters in pachy-PCV, 10.6 vs. 7.4 letters in non-pachy-PCV) after the third injection. No significant difference was observed in the number of injections in the first year of follow-up between different response groups. Conclusion: In PCV patients receiving IVC, the first- and third-dose responses are significantly correlated, and different factors influence the first-dose response in different subtypes of PCV.

Evaluation of standard-of-care intravitreal aflibercept treatment practices in patients with diabetic macular oedema in the UK: DRAKO study outcomes

Background/ObjectivesDRAKO (NCT02850263) was a 24-month, prospective, non-interventional, multi-centre cohort study enrolling patients with diabetic macular oedema (DMO) including central involvement. The study evaluated UK standard-of-care intravitreal aflibercept (IVT-AFL) treatment. This analysis describes the treatment pathway and service provision for the anti–vascular endothelial growth factor (VEGF) treatment-naïve (C1) and non-naïve patients (C2) who received prior anti-VEGF treatment for DMO other than IVT-AFL.MethodsMean changes in best-corrected visual acuity and central subfield thickness were measured and stratified by baseline factors, including ethnicity and administration of five initial monthly injections within predefined windows. Clinic visits were classified as treatment only (T1), monitoring assessment only (T2), combined visits (T3) or post-injection visits with no treatment or assessment (T4).ResultsMedian time from decision to treat to treatment was 6 days. As a percentage of total visits, T1, T2, T3 and T4 were 7%, 42%, 48% and 3% for C1 and 11%, 39%, 48% and 2% for C2. Most IVT-AFL injections were administered by healthcare professionals (HCPs) other than doctors (C1, 57.4%; C2, 58.5%). The percentage of treatments associated with a procedure-related adverse event where at least 75% of injections were completed by the same injector role were similar for doctors and other HCPs (C1, 1.1% and 0.8%; C2, 0.7%, and 1.0%).ConclusionsResults indicate that upon DMO diagnosis, patients were treated promptly, and most visits were combined (treatment and assessment) or monitoring only. Most IVT-AFL was administered by non-physicians with a similar treatment-related safety profile as IVT-AFL administered by physicians.

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.

Macular Sensitivity after Intravitreal Ranibizumab Injection for Macular Edema in Central Retinal Vein Occlusion: One versus Three Initial Monthly Injections

Background: We aimed to compare the macular sensitivity after one initial intravitreal injection of an anti-vascular endothelial growth factor (VEGF) agent followed by pro re nata (PRN) dosing with that after three initial monthly injections followed by PRN dosing in patients with central retinal vein occlusion (CRVO) and macular edema. Methods: We included 20 eyes of 20 patients with treatment-naïve macular edema in CRVO and followed them for 12 months after intravitreal ranibizumab injection (IRI). Before and 1, 3, 6, and 12 months after IRI, macular sensitivity within the central 1 mm, 3 mm, and 6 mm fields was measured with an MP3 microperimeter and best-corrected visual acuity (BCVA) was assessed. Eleven eyes received one initial IRI (1 + PRN group), and nine received three initial monthly IRIs (3 + PRN group). PRN injections were performed when fovea exudative changes were evident. Results: Mean macular sensitivity within the central 1 mm, 3 mm, and 6 mm fields significantly improved from baseline to month 12 in all treated eyes. We found no significant differences in macular sensitivity in the central 1 mm, 3 mm, or 6 mm fields between the two groups at month 1, 3, 6, or 12. The choice of treatment regimen (1 + PRN or 3 + PRN) showed no association with either macular sensitivity in the central 1 mm, 3 mm, and 6 mm fields or BCVA at month 12. Conclusions: These findings suggest that a 1 + PRN regimen improves macular sensitivity to a similar extent as a 3 + PRN regimen.

Monthly Alternating Injections of Aflibercept and Bevacizumab for Neovascular Age-Related Macular Degeneration.

We investigated the efficacy of monthly alternating injections of aflibercept and bevacizumab (MAAB) for maintenance treatment in patients with neovascular age-related macular degeneration (AMD) who showed improvement with the initial monthly injections but presented with rapid worsening after conversion to bimonthly injections. We included 72 patients with neovascular AMD who showed improvement with loading injections of aflibercept. For maintenance treatment, bevacizumab was administered every alternate month between the bimonthly aflibercept injections in 24 (33.3%) eyes showing worsening (MAAB group). The other eyes were treated with aflibercept (BiA group) bimonthly. Baseline low retinal thickness, thick choroid, and presence of intraretinal fluid were associated with worsening after extending the injection intervals. Visual improvement was lower in the MAAB group than in the BiA group, but the final visual outcomes were comparable. Additional bevacizumab stabilized the early fluctuation of retinal thickness, thus maintaining long-term visual stability without increasing the risk of geographic atrophy or disciform scar until the second year. Previously treated eyes or those with polypoidal choroidal vasculopathy responded less to the initial loading doses and showed worsening under the bimonthly regimen. MAAB was effective in preventing anatomical and functional deterioration when bimonthly aflibercept proved insufficient for the maintenance treatment of neovascular AMD.

A Comparative Study of Ranibizumab and Aflibercept for Neovascular Age-Related Macular Degeneration: 12-Month Outcomes of Polish Therapeutic Program in Non-Tertiary Institution.

IntroductionThis single-center study aimed to compare the 12-month treatment outcomes of ranibizumab with that of aflibercept in routine clinical practice.MethodsCohort of patients diagnosed with treatment-naïve neovascular age-related macular degeneration (AMD), treated using either ranibizumab (n = 33 eyes) or aflibercept (n = 44 eyes) monotherapy over a 12-month follow-up period was analyzed. Anonymous data were extracted from the electronic database dedicated to the drug program.ResultsIn the ranibizumab group, there were no statistically significant changes in best-corrected visual acuity (BCVA) (Early Treatment Diabetic Retinopathy Study [ETDRS] letters) and central retina thickness (CRT) (µm), between baseline (67.9 ± 8.6 & 384.9 ± 97.9) and at 12 months (67.9 ± 12.1 & 398.9 ± 127.1; P = 0.372 & P = 0.884, respectively). In the aflibercept, there was an improvement in BCVA and reduction in CRT between baseline (64.2 ± 8.1 & 414.3 ± 97.8) and at 12 months (70.7 ± 7.4 & 342.3 ± 71.6; P < 0.001 & P < 0.001, respectively). There was no difference in BCVA between the two groups at either diagnosis (P = 0.101) or 12 months (P = 0.917). Mean number of injections in the ranibizumab group was significantly lower (4.9 ± 1.5) than in the aflibercept group (6.7 ± 1; P < 0.001).Conclusions One initial injection of ranibizumab and then pro re nata (PRN) regimen resulted in stabilization of disease progression. Drug selection and treatment scheme could influence twelve-months outcomes. In the aflibercept group, three initial monthly injections and then every two months provided both significant BCVA improvement and CRT reduction at 12 months of treatment.

Retinal Fluid Volatility Associated With Interval Tolerance and Visual Outcomes in Diabetic Macular Edema in the VISTA Phase III Trial

To describe longitudinal retinal fluid dynamics on spectral domain OCT and to identify imaging biomarkers that predict the worsening of DME with interval extension during anti-vascular endothelial growth factor (VEGF) therapy. A post hoc sub-analysis of phase III, VISTA-DME study. Eyes received either intravitreal aflibercept injection 2 mg every 4 weeks (2q4) or every 8 weeks after 5 initial monthly injections (2q8), and eyes imaged with the Cirrus HD-OCT system were included. The macular cube was analyzed for 10 time-points from baseline through week 100. Retinal OCT images were evaluated using a novel software platform to extract retinal fluid features for calculation of volumetric fluid parameters, including the retinal fluid index (RFI): the percentage of retinal volume that was occupied by intraretinal fluid. Fifty-five eyes were included in the 2q4 group, and 58 eyes were included in the 2q8 group. Early RFI volatility with a central macular RFI increase by ≥5 points from week 4 to 8 (P = .004, odds ratio [OR] 31.3, 95% confidence interval [CI] 3.0 to 329) and cumulative RFI volatility with an aggregate increase in macular RFI by ≥10 points from those timepoints with increased RFI between baseline to week 20, P = .005, OR 10.2, 95% CI 2.1 to 51.3) were both significant predictors for the worsening of DME and visual acuity when the treatment interval was extended to 8 weeks in the 2q8 group. Early fluid dynamics as measured by (1) early RFI volatility and (2) cumulative RFI instability with aggregate increased RFI were associated with intolerance of interval extension.

Intravitreal Aflibercept Treatment Strategies in Routine Clinical Practice of Neovascular Age-Related Macular Degeneration in Belgium: A Retrospective Observational Study.

IntroductionSTELLAR was a Belgian, multicentre, retrospective, observational chart review that described the utilization (number of injections and treatment regimen) and effectiveness of intravitreal aflibercept (IVT-AFL) in patients with anti-vascular endothelial growth factor (VEGF) treatment-naïve neovascular age-related macular degeneration (nAMD) during the first 12 months of IVT-AFL treatment.MethodsPatients initiating IVT-AFL between July 2013 and July 2017 were included in STELLAR. Primary endpoints were number of visits and IVT-AFL injections, and number of patients who received ≥ 7 versus < 7 IVT-AFL injections during the first 12 months of treatment.ResultsA total of 337 patients completed ≥ 12 months of IVT-AFL treatment. The mean number of visits and mean number of injections during the first 12 months was 9.8 and 7.1 injections, respectively (64% received ≥ 7 injections). Overall, 96% of patients received ≥ 3 initial monthly injections. Of the 337 patients, 180 received VT-AFL as needed (pro re nata), 141 received it as treat-and-extend dosing and 16 received it as fixed dosing. The proportion of patients who received treat-and-extend dosing increased year-on-year. Mean best-corrected visual acuity (BCVA) (± standard deviation) was 61.6 (± 14.9) Early Treatment Diabetic Retinopathy Study (ETDRS) letters at baseline and improved by + 3.9 and + 5.7 ETDRS letters at 3 and 12 months, respectively. Mean BCVA improvement was numerically greater in patients who received ≥ 7 versus < 7 injections during the first 12 months 7 (+ 6.5 vs. + 4.4 ETDRS letters) and in patients who received ≥ 3 versus < 3 initial monthly injections (+ 5.2 vs. − 0.25 ETDRS letters [3 at months]; + 5.9 vs + 1.2 ETDRS letters [at 12 months]). No specific adverse events were reported.ConclusionMost patients in this Belgian study received ≥ 7 IVT-AFL injections during a mean of 9.8 visits over the 12 months assessed. IVT-AFL was an effective treatment for nAMD in clinical practice, with numerically higher BCVA gains in patients receiving ≥ 7 versus < 7 injections over the first 12 months and ≥ 3 versus < 3 injections in the first 3 months.Electronic supplementary materialThe online version of this article (10.1007/s40123-020-00300-7) contains supplementary material, which is available to authorized users.

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...

Macular Atrophy in Neovascular Age-Related Macular Degeneration: A Randomized Clinical Trial Comparing Ranibizumab and Aflibercept (RIVAL Study)

To investigate differences in the development of macular atrophy (MA) over 24 months between treat-and-extend (T&E) ranibizumab and aflibercept in patients with neovascular age-related macular degeneration (nAMD). A phase 4 randomized, partially masked, multicenter study. Individuals 50 years of age or older diagnosed with active, treatment-naïve subfoveal choroidal neovascularization secondary to nAMD with baseline best-corrected visual acuity (BCVA) of 23 logarithm of minimum angle of resolution letters or more. Patients were randomized 1:1 to receive either intravitreal injections of ranibizumab 0.5 mg or aflibercept 2.0 mg and were treated according to the same reading center-guided T&E regimen after 3 initial monthly injections. The primary outcome was mean change in square root area of MA from baseline to month 24. Key secondary outcomes included number of injections and mean change in BCVA from baseline to months 12 and24. Two hundred seventy-eight patients were included in the analysis (ranibizumab 0.5 mg, n= 141; aflibercept 2.0 mg, n= 137). Mean change in square root area of MA from baseline to month 24 was+0.36 mm (95% confidence interval [CI], 0.27-0.45 mm) for ranibizumab and+0.28 mm (95% CI, 0.19-0.37 mm) for aflibercept (treatment difference,+0.08 mm [95% CI,-0.05 to 0.21 mm]; P= 0.24). The proportion of patients with MA increased from 7% (10/141) to 37% (43/117) for ranibizumab and from 6% (8/137) to 32% (35/108) for aflibercept from baseline to month 24. The average number of injections received per year was similar between both groups: 9.6 (95% CI, 9.2-10.0) for ranibizumab and 9.5 (95% CI, 9.1-9.9) for aflibercept. The mean change in BCVA from baseline to month 24 was+6.6 letters (95% CI,4.7-8.5 letters) for the ranibizumab group and+4.6 letters (95% CI, 2.7-6.6 letters) for the aflibercept group (P= 0.15). Rates of adverse events (AEs) were similar between both groups. No significant differences in the rate of development or growth of MA over 24 months were observed between ranibizumab and aflibercept in nAMD patients treated using an identical T&E regimen.

Intravitreal Aflibercept for Retinal Angiomatous Proliferation: Results of a Prospective Case Series at 96 Weeks

Introduction: Retinal angiomatous proliferation (RAP) is a subtype of neovascular age-related macular degeneration (nAMD). Untreated, the lesions are thought to be aggressive and lead to a poor visual outcome. Despite some limitations, studies reporting the treatment of RAP lesions with the intravitreal anti-VEGF drugs ranibizumab and bevacizumab have demonstrated variable but generally favourable responses. More recently, aflibercept has been licensed for the treatment of nAMD and may offer some advantages over other agents. We present the visual and anatomical outcomes at 96 weeks of patients with RAP lesions who were treated with intravitreal aflibercept, according to the pivotal VIEW study nAMD treatment protocol. Methods: This is a prospective study of treatment-naïve patients with Reading Centre-graded RAP lesions. The patients received aflibercept every 8 weeks, after 3 initial monthly injections, up to and including week 48. During weeks 52–96, patients received injections at least every 12 weeks, with monthly evaluations for interim injections if they fulfilled the retreatment criteria. At each visit, best-corrected visual acuity (BCVA) and optical coherence tomography (OCT) central macular thickness (CMT) were measured. Results: Forty-six patients reached study completion at week 96. Mean BCVA had improved by 6.0 (standard deviation [SD] 7.9) and 4.8 (SD 7.4) ETDRS letters at 52 (p = 0.003) and 96 (p = 0.02) weeks, respectively, from a baseline of 57.3 (SD 12.0) letters. At 52- and 96-week time points, 45/46 (98%) and 41/46 (89%) of patients, respectively, had maintained their vision (<15 letters of BCVA lost). At the 96-week time point, 13/46 (28%) of patients had gained ≥15 letters and also demonstrated a mean reduction in CMT of 162 μm (SD 106) (p = <0.0001), with 72% of maculae being fluid-free. Using univariate analysis, we found no significant difference between any of the visual outcome measures in this study and the pivotal VIEW study; the mean number of injections required and change in CMT were also similar. Conclusions: In this study, we present the 96-week results, of the largest series to date, of patients treated prospectively with aflibercept for RAP using the VIEW protocol. We show that they benefited from treatment to a degree similar to those with type 1 and 2 nAMD.

Branch Retinal Vein Occlusion: Treatment Outcomes According to the Retinal Nonperfusion Area, Clinical Subtype, and Crossing Pattern

This prospective study examined 58 eyes with branch retinal vein occlusion (BRVO) to investigate the effects of the nonperfusion area (NPA), clinical subtype, and crossing pattern on the 2-year outcomes of ranibizumab therapy for the macular edema (ME). All eyes received three initial monthly injections, followed by additional pro re nata (PRN) injections. The final best corrected visual acuity (BCVA) and ranibizumab injection number were not associated with the macular NPA or total NPA at baseline or month 12, and they showed no significant differences between the clinical subtypes. However, the incidence of neovascular changes was higher in the major BRVO group than in the macular BRVO group (P = 0.030). Twelve and 19 of the 34 eyes with major BRVO exhibited arterial overcrossing and venous overcrossing, respectively. At baseline, the total NPA did not differ according to the crossing pattern, however, the total NPA was significantly larger in the venous overcrossing group at month 12 (P = 0.047). At month 24, the incidence of neovascular changes was higher in the venous overcrossing group (P = 0.030). Following ranibizumab therapy for BRVO-associated ME, the clinical subtype and the arteriovenous crossing pattern may be associated with neovascular changes.

Effect of Ranibizumab and Aflibercept on Best-Corrected Visual Acuity in Treat-and-Extend for Neovascular Age-Related Macular Degeneration

To our knowledge, this is the first randomized clinical trial to compare visual outcomes and injection loads between ranibizumab and aflibercept using an identical treat-and-extend (TE) regimen for neovascular age-related macular degeneration (nAMD). To report the results of the preplanned 12-month interim analysis of 2 predefined secondary efficacy end points of a randomized clinical trial. The Comparison of Ranibizumab and Aflibercept for the Development of Geographic Atrophy in (Wet) AMD Patients (RIVAL) trial was conducted in 24 sites in Australia and included 281 treatment-naive eyes from 281 participants with active choroidal neovascularization secondary to nAMD and a visual acuity letter score of 23 or greater who were recruited between April 11, 2014, and October 31, 2015. A preplanned interim analysis was performed at month 12. Best-corrected visual acuity (BCVA) assessors and the central reading center, which determined treatment intervals, were masked to treatment assignments. Participants were randomized (1:1) to receive intravitreal injections of 0.5 mg of ranibizumab or 2.0 mg of aflibercept. After receiving 3 initial monthly injections, participants entered the TE phase. Mean change in BCVA and the number of injections from baseline to month 12. Of 281 participants, 148 (52.7%) were women and the mean (SD) age was 77.7 (8.1) years. The baseline mean BCVA letter score (approximate Snellen equivalent) was 65.3 (20/50) in the ranibizumab arm and 65.1 (20/50) in the aflibercept arm. One hundred twenty-seven ranibizumab participants (90.1%) and 121 aflibercept participants (88.3%) completed month 12 with a mean (SD [Snellen equivalent]) BCVA letter score of 72.9 (15.5 [20/32]) and 70.5 (14.6 [20/40]), respectively. The mean change in BCVA letter scores from baseline to month 12 was 7.2 (95% CI, 5.5-8.9) for ranibizumab and 4.9 (95% CI, 3.1-6.6) for aflibercept (letter score difference, 2.3; 95% CI, -0.1 to 4.7; P = .06). The mean number of injections from baseline to month 12 was 9.7 in both the ranibizumab (SD, 2.8) and aflibercept (SD, 2.6) arms with a rate ratio of 1.00 (95% CI, 1.0-1.1; P = .86). Our findings suggest that neither aflibercept nor ranibizumab for nAMD are superior to the other regarding the average visual acuity gains and number of injections during 1 year in a TE regimen. Further follow-up to 2 years may determine if advantages of one over the other can be identified. Clinicaltrials.Gov identifier: NCT02130024.

Intravitreal Ranibizumab Therapy for Diabetic Macular Edema in Routine Practice: Two-Year Real-Life Data from a Non-interventional, Multicenter Study in Germany.

IntroductionThe prospective, non-interventional OCEAN study examined the use of intravitreal ranibizumab injections for the treatment of diabetic macular oedema (DME) in a real-world setting in Germany.MethodsAdults with DME receiving ≥ 1 ranibizumab (0.5 mg) injections were recruited by 250 ophthalmologists. Best-corrected visual acuity (VA) testing, imaging and treatments were performed according to the investigators’ routine practice and documented over 24 months.ResultsThe full analysis set included 1226 participants. Mean baseline VA was 60.6 [95% CI: 59.7; 61.5] Early Treatment Diabetic Retinopathy Study letters. VA improved by ≥ 15 letters in 21.5% and 23.5% of the participants at 12 months and 24 months, respectively. They received a mean number of 4.42 [95% CI: 4.30; 4.54] injections in the first year and 5.52 [95% CI: 5.32; 5.73] injections over 24 months, which was markedly lower than in clinical trials. Only 33.4% of the participants received an upload with four initial monthly injections as recommended by the German ophthalmologic societies. Time-to-event analyses that account for missing data inherent to a non-interventional study design demonstrated that participants receiving ≥ 7 injections in the first year had a faster response, but the duration of the response was shorter compared to the subgroups receiving 1–3 and 4–6 injections. Serious adverse events were reported for 143/1250 (11.4%) participants in the safety population.ConclusionUnder-treatment is a major problem of DME anti- vascular endothelial growth factor therapy under real life conditions. Despite fewer injections given compared to randomised controlled trials with a consequently reduced overall mean visual gain, a profound functional improvement (≥ 15 letters) was achieved over 2 years in 23.5% of eyes with DME.Trial Registration NumberNCT02194803, ClinicalTrials.gov.FundingNovartis Pharma GmbH, Nuremberg, Germany.Electronic supplementary materialThe online version of this article (10.1007/s13300-018-0513-2) contains supplementary material, which is available to authorized users.

Anti-Vascular Endothelial Growth Factor Therapy for Macular Edema following Central Retinal Vein Occlusion: 1 Initial Injection versus 3 Monthly Injections

Purpose: To compare the 12-month efficacy of 1 initial intravitreal injection of an anti-vascular endothelial growth factor (VEGF) agent followed by pro re nata (PRN) dosing with that of 3 initial monthly injections followed by PRN dosing in patients with macular edema (ME) after central retinal vein occlusion (CRVO). Methods: Twenty-nine eyes received 1 initial injection (1+PRN group) and 20 received 3 monthly injections (3+PRN group). Results: At month 12, changes in logMAR visual acuity from baseline were -0.172 ± 0.372 and -0.142 ± 0.317 in the 1+PRN and 3+PRN groups, respectively; the difference was not significant (p = 0.769). The number of anti-VEGF injections administered in the 3+PRN group (5.9 ± 2.1) was significantly greater than that in the 1+PRN group (4.1 ± 2.8; p = 0.022). Conclusion: When used for ME after CRVO, a 1+PRN regimen achieved 12-month outcomes similar to those of a 3+PRN regimen with fewer injections.

Intravitreal Aflibercept Versus Photodynamic Therapy in Chinese Patients with Neovascular Age-Related Macular Degeneration: Outcomes of the SIGHT Study

Purpose: SIGHT compared intravitreal aflibercept injections (IAI) with photodynamic therapy (PDT) in Chinese patients with predominantly classic choroidal neovascularization (CNV) secondary to neovascular age-related macular degeneration (nAMD).Methods: Patients were randomized 3:1 to IAI (2 mg every 8 weeks after 3 initial monthly injections)/sham PDT or active PDT/sham IAI (with switch to IAI at week 28). We report the primary outcome (mean change in best-corrected visual acuity [BCVA] at week 28) and final 52-week outcomes.Results: Patients were randomized to IAI (n = 228) or PDT (n = 76) (mean age: 65.1 years). Mean BCVA change was +14.0 (IAI) versus +3.9 letters (PDT→IAI) (week 28) and +15.2 versus +8.9 letters (between-group difference: 6.2 letters; P = 0.0009) (week 52); mean reduction in central retinal thickness was −189.6 versus −170.0 μm (week 52). The greatest improvements in BCVA with IAI were in youngest patients (<65 years), and in those with a smaller active component of the CNV lesion (<50% of lesion size). The most common ocular treatment-emergent adverse events (study eye; IAI vs. PDT→IAI) were macular fibrosis (11.8% vs. 6.6%) and visual acuity reduced (6.6% vs. 21.1%). Three treatment-emergent Antiplatelet Trialists' Collaboration-defined arterial thromboembolic events were observed but none was considered drug related.Conclusions: IAI demonstrated superiority over PDT in Chinese nAMD patients. The benefits of IAI were maintained through week 52 in all patients, including subgroups, and in patients who switched from PDT to IAI. The incidence of adverse events was consistent with the known safety profile of IAI. Trial registration number NCT01482910.

Retinal Vein Occlusion - Which Treatment When?

According to the latest findings, macular oedema due to retinal vein occlusion is best treated safely and effectively with near-term intravitreal anti-VEGF therapy (aflibercept, bevacizumab [off label], ranibizumab). After an initial upload of 3monthly injections of anti-VEGF, the decision on re-injection should be based on OCT (rather than on visual acuity). After initial monthly injections, the "pro-re-nata" (PRN) and the "treat-and-extend" regimens have been predominantly used in the further course of therapy. Taking into account the side effect spectrum (in particular cataract progression, increased intraocular pressure), intravitreal therapy with a dexamethasone implant may be a reasonable alternative. The prognosis for visual acuity and the decline in macular oedema depend on starting treatment early and continuing it consistently. Before starting treatment, as well as during treatment, fluorescein angiography is necessary to detect ischemic retinal areas. There is evidence that early targeted laser coagulation of ischemic retina may reduce the frequency of necessary injections and improve the response of the oedema to therapy. Significant retinal ischemia may lead to proliferations, rubeosis iridis and secondary glaucoma and therefore requires laser treatment.

Cost-effectiveness of intravitreal aflibercept versus other treatments for wet age-related macular degeneration in Japan

Objective: This analysis estimated the cost-effectiveness of intravitreal aflibercept injection(s) (IAI) for wet age-related macular degeneration (wAMD) compared with other treatments in Japan.Methods: This was a cost-utility analysis based on published data. A state-transition cohort model was constructed with six health states based on best-corrected visual acuity in the better-seeing eye. The cycle time was 4 weeks, and the time horizon was 12 years. The model compared IAI 2 mg every 8 weeks (2q8) for 2 years after three initial monthly injections, ranibizumab as needed, ranibizumab 0.5 mg every 4 weeks (0.5q4), pegaptanib sodium 0.3 mg every 6 weeks, verteporfin photodynamic therapy (PDT), and best supportive care, assumed to include medical management and monitoring, but no active therapy. Costs (expressed as Japanese yen [JPY]) and quality-adjusted life years (QALYs) gained were estimated for each treatment and discounted at 2.0%. Input data were obtained from clinical studies, the Japanese drug tariff and social insurance reimbursement schedule, and expert opinion. The analysis was conducted from the societal perspective, including medical costs as well as costs of blindness.Results: IAI 2q8 was dominant (i.e. more effective in terms of QALYs and less costly) to all other comparators (ranibizumab as needed, ranibizumab 0.5q4, pegaptanib sodium, PDT, and best supportive care), as shown by the incremental cost-utility ratio (i.e. cost per QALY gained).Limitations: The strengths of the analysis include the wide range of comparators evaluated and the use of Japanese-specific utility data. The limitations include the use of one eye, inclusion of published data up to 2 years only, and assumptions on disease course over 5 years.Conclusions: IAI 2q8 was more effective in terms of QALYs and less costly compared with other treatments for wAMD in Japan.

Differential Response to Anti-VEGF Regimens in Age-Related Macular Degeneration Patients with Early Persistent Retinal Fluid

To compare the effect of intravitreal aflibercept or ranibizumab drug type and frequency on visual acuity outcomes in eyes with neovascular age-related macular degeneration (NVAMD) and early persistent retinal fluid after 3 initial monthly injections. A post hoc analysis of eyes enrolled in VIEW 1 and VIEW 2, 2 similarly designed, randomized, phase 3 trials. A total of 1815 eyes with NVAMD from VIEW 1 and VIEW2. Analyses included patients with known fluid status at baseline and weeks 4, 8, and 12 in 3 treatment groups: ranibizumab 0.5 mg every 4 weeks (Rq4) (n= 595), intravitreal aflibercept injection (IAI) 2 mg every 4 weeks (2q4) (n= 613), and IAI 2 mg every 8 weeks (2q8) after 3 monthly injections (n= 607). Mean best-corrected visual acuity (BCVA) change from baseline over weeks 16 to 52 and the proportion of eyes that gained ≥15 letters or lost ≥5 letters were evaluated in eyes with and without persistent fluid (cystic intraretinal or subretinal fluid at all 4 initial visits). Visual outcomes also were assessed in eyes with persistent fluid by fluid type (intraretinal and subretinal fluid). The proportions of eyes with persistent fluid were 29.4%, 18.8%, and 20.3% in the Rq4, 2q4, and 2q8 groups, respectively. In these eyes, mean BCVA gain from baseline to week 52 was greater with 2q4 compared with Rq4 (P < 0.01) and 2q8 (P < 0.05), whereas it was similar with Rq4 and 2q8 (P= 0.294). At week 52, similar proportions of eyes gained ≥15 letters (31.5%-35.2%), whereas fewer eyes lost ≥5 letters with 2q4 compared with Rq4 and 2q8 (6.5% vs. 16.6% and 16.2%). The pattern of visual outcomes was similar regardless of fluid type. In eyes without persistent fluid, BCVA changes were similar across treatment groups. In patients with early persistent fluid, 2q4 may provide additional clinical benefit over 2q8 or Rq4.