Search

Abstract Background Intravitreal faricimab, a bispecific antibody targeting both angiopoietin-2 (Ang-2) and vascular endothelial growth factor-A (VEGF-A), was recently introduced for the treatment of neovascular age-related macular degeneration (nAMD), diabetic macular oedema and cystoid macular oedema secondary to retinal vein occlusion. The aim of our study was to assess the efficacy, safety and durability of intravitreal faricimab in a real-world cohort of treatment-naïve patients with nAMD. Methods Single-centre, prospective cohort study of 21 eyes from 19 treatment-naïve nAMD patients who were treated with intravitreal faricimab from October 2022 to April 2024. Patients underwent a loading dose (LD) of 4 monthly faricimab injections followed by a treat-and-extend regimen. Primary outcomes included best-corrected visual acuity (BCVA) and structural parameters from spectral-domain optical coherence tomography (SD-OCT). Secondary outcomes included the proportion of eyes achieving a dry macula, maximal fluid-free interval and intended interval at last follow-up. Results The study included 21 eyes of 19 patients (mean age 83.1 years). After LD, 93.3% of eyes achieved a dry macular SD-OCT scan within a median time of 8 weeks. At the first extension, 53% of eyes remained dry, while 47% showed fluid recurrence. Long-term analysis (n = 14) revealed significant reductions in macular volume (MV), central subfield thickness (CST), and pigment epithelial detachment (PED) height over a median follow-up of 64.9 weeks, with sustained visual and anatomical improvements. Median BCVA, CST, and MV at the final follow-up were significantly improved from baseline (p

Purpose: To evaluate 12-month clinical outcomes of a treat-and-extend regimen with intravitreal aflibercept injections in patients with occult (type 1) choroidal neovascularization (CNV) secondary to chronic central serous chorioretinopathy (CSC). Methods: This was a prospective observational single-center study involving 24 patients (24 eyes) with occult (type 1) CNV secondary to chronic CSC. All patients received three initial loading doses of intravitreal 2 mg (0.05 ml) aflibercept at 4-weekly intervals, followed by a treat-and-extend protocol. The primary outcome was best-corrected visual acuity (BCVA) at 12 months. Statistical analyses were conducted and graphs were created using Statistica 10.0 software. Results: Mean BCVA increased significantly from 0.44 ± 0.35 at baseline to 0.58 ± 0.3 at month 12 (р = 0.01). At month 12, complete resolution of SRF was observed in 18 eyes (75%). The mean number of intravitreal aflibercept injections over 12 months was 7.5 ± 1.4. Conclusion: Treat-and-extend intravitreal aflibercept is an effective and safe approach for managing patients with occult (type 1) CNV secondary to chronic CSC.

Abstract Introduction Anti-vascular endothelial growth factor (VEGF) is generally given using pro re nata or “treat-and-extend” (T&E) regimens for neovascular age-related macular degeneration (nAMD). Randomized clinical trials have reported that T&E is superior to Pro re nata (PRN), but results from clinical trials may not always be replicated in clinical practice. Real-world data comparing T&E and PRN regimens for nAMD are limited. The objective of this work was to report 24-month outcomes of PRN versus T&E regimens for ranibizumab and aflibercept to treat nAMD in routine clinical practice. Methods We conducted a retrospective analysis of data from a prospectively designed observational outcomes registry, the Fight Retinal Blindness! Project (FRB). Treatment-naïve eyes starting nAMD treatment with at least three injections using a T&E or PRN regimen were tracked by using the FRB. The primary outcome was the mean change in visual acuity (VA) measured by the number of letters read on a logarithm of the minimum angle of resolution chart at 2 years versus baseline. The secondary outcome was the number of injections at 2 years. Results From January 1, 2015 to January 31, 2019, 3313 eyes from 2948 patients with nAMD were included: 1243 eyes from 1065 patients were classified as PRN and 2070 eyes from 1935 patients started a T&E regimen. At 24 months, patients on the T&E regimen experienced significantly greater mean (95% confidence interval) improvement in VA than those on PRN (+ 4.2 [3.1, 5.2] vs. + 1.3 [0.1, 2.6] letters; p

Background: Intravitreal faricimab, a bispecific antibody targeting both angiopoietin-2 (Ang-2) and vascular endothelial growth factor-A (VEGF-A), was recently introduced for the treatment of neovascular age-related macular degeneration (nAMD), diabetic macular oedema and cystoid macular oedema secondary to retinal vein occlusion. The aim of our study was to assess the efficacy, safety and durability of intravitreal faricimab in a real-world cohort of treatment-naïve patients with nAMD. Methods: Single-centre, prospective cohort study of 21 eyes from 19 treatment-naïve nAMD patients who were treated with intravitreal faricimab from October 2022 to April 2024. Patients underwent a loading dose (LD) of 4 monthly faricimab injections followed by a treat-and-extend regimen. Primary outcomes included best-corrected visual acuity (BCVA) and structural parameters from spectral-domain optical coherence tomography (SD-OCT). Secondary outcomes included the proportion of eyes achieving a dry macula, maximal fluid-free interval and intended interval at last follow-up. Results: The study included 21 eyes of 19 patients (mean age 83.1 years). After LD, 93.3% of eyes achieved a dry macular SD-OCT scan within a median time of 8 weeks. At the first extension, 53% of eyes remained dry, while 47% showed fluid recurrence. Long-term analysis (n = 14) revealed significant reductions in macular volume (MV), central subfield thickness (CST), and pigment epithelial detachment (PED) height over a median follow-up of 64.9 weeks, with sustained visual and anatomical improvements. Median BCVA, CST, and MV at the final follow-up were significantly improved from baseline (p < 0.01). The intended interval between injections was ≥ 12 weeks in 42.86% of eyes. No cases of intraocular inflammation were observed, although 10% experienced retinal pigment epithelial tears. Conclusions: Intravitreal faricimab demonstrated favourable efficacy, safety, and durability outcomes in a real-world cohort of treatment-naïve nAMD patients. [ABSTRACT FROM AUTHOR]

Introduction: Anti-vascular endothelial growth factor (VEGF) is generally given using pro re nata or "treat-and-extend" (T&E) regimens for neovascular age-related macular degeneration (nAMD). Randomized clinical trials have reported that T&E is superior to Pro re nata (PRN), but results from clinical trials may not always be replicated in clinical practice. Real-world data comparing T&E and PRN regimens for nAMD are limited. The objective of this work was to report 24-month outcomes of PRN versus T&E regimens for ranibizumab and aflibercept to treat nAMD in routine clinical practice. Methods: We conducted a retrospective analysis of data from a prospectively designed observational outcomes registry, the Fight Retinal Blindness! Project (FRB). Treatment-naïve eyes starting nAMD treatment with at least three injections using a T&E or PRN regimen were tracked by using the FRB. The primary outcome was the mean change in visual acuity (VA) measured by the number of letters read on a logarithm of the minimum angle of resolution chart at 2 years versus baseline. The secondary outcome was the number of injections at 2 years. Results: From January 1, 2015 to January 31, 2019, 3313 eyes from 2948 patients with nAMD were included: 1243 eyes from 1065 patients were classified as PRN and 2070 eyes from 1935 patients started a T&E regimen. At 24 months, patients on the T&E regimen experienced significantly greater mean (95% confidence interval) improvement in VA than those on PRN (+ 4.2 [3.1, 5.2] vs. + 1.3 [0.1, 2.6] letters; p < 0.001), with more injections (14.9 standard deviation(SD) 4.3) vs. 9.8(SD 4.3); p < 0.001). Conclusions: Eyes treated with a T&E regimen had better VA outcomes from VEGF inhibitors than eyes treated PRN. This large real-world data assessment supports previous data from randomized clinical trials that the T&E regimen delivers better outcomes than PRN. Plain Language Summary: This study focused on comparing two methods of treating neovascular age-related macular degeneration, a common eye condition. The treatments used were ranibizumab and aflibercept. We looked at the reactive "pro re nata" method, where treatment is given sporadically and only when the condition reactivates, and the proactive "treat-and-extend" method, which aims to keep the disease inactive with the fewest treatments at regular intervals. The main aim was to determine which method provides the best vision outcomes over a 24-month period and the frequency of treatment required. We found that the treat-and-extend method resulted in a greater improvement in vision than the pro re nata method, although it did require more injections. This study highlights the effectiveness of the treat-and-extend method for neovascular age-related macular degeneration, suggesting it gets better outcomes despite requiring more injections. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate 12-month clinical outcomes of a treat-and-extend regimen with intravitreal aflibercept injections in patients with occult (type 1) choroidal neovascularization (CNV) secondary to chronic central serous chorioretinopathy (CSC). Methods: This was a prospective observational single-center study involving 24 patients (24 eyes) with occult (type 1) CNV secondary to chronic CSC. All patients received three initial loading doses of intravitreal 2 mg (0.05 ml) aflibercept at 4-weekly intervals, followed by a treat-and-extend protocol. The primary outcome was best-corrected visual acuity (BCVA) at 12 months. Statistical analyses were conducted and graphs were created using Statistica 10.0 software. Results: Mean BCVA increased significantly from 0.44 ± 0.35 at baseline to 0.58 ± 0.3 at month 12 ( = 0.01). At month 12, complete resolution of SRF was observed in 18 eyes (75%). The mean number of intravitreal aflibercept injections over 12 months was 7.5 ± 1.4. Conclusion: Treat-and-extend intravitreal aflibercept is an effective and safe approach for managing patients with occult (type 1) CNV secondary to chronic CSC [ABSTRACT FROM AUTHOR]

Background/aims: To evaluate the efficacy, safety and durability of intravitreal faricimab in patients with neovascular age-related macular degeneration (nAMD) with unsatisfactory response to traditional anti-vascular endothelial growth factor (anti-VEGF) agents. Methods: Single-centre, prospective cohort study of all consecutive patients with nAMD who were switched to intravitreal faricimab from intravitreal ranibizumab or aflibercept, due to unsatisfactory treatment response (maximal fluid-free interval ≤ 8 weeks). Intravitreal faricimab was administered with a loading dose of four 4-weekly injections, followed by an 8-week extension. A treat and extend (T&E) regime was adopted thereafter. Primary outcome was the difference between the maximal fluid-free interval achieved with faricimab, and the one achieved before the switch. Morpho-functional outcomes were also assessed. Secondary outcome was accordance with clinical management when applying faricimab pivotal trial criteria versus our real-world T&E protocol, measured as a proportion. Results: Twenty-six eyes of 26 patients with a median age of 82 years (range 77–85) were included. Patients were followed for 30.2 weeks (range 26.3–33.1). Maximal fluid-free interval after switch to faricimab (Mdn = 6.0 weeks; IQR = 4–8) was longer than the maximum interval before the switch (Mdn = 4.0 weeks; IQR = 4–4), p < 0.001. Comparing real-world T&E protocol with pivotal trial criteria, 8 (30.8%) eyes received the same clinical management while 18 (69.2%) eyes were kept at a shorter interval when following our T&E protocol. No serious adverse events were recorded. Conclusions: Faricimab appears to increase the fluid-free interval and allow extension of dosing interval in patients with nAMD poorly responsive to traditional anti-VEGF drugs. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate 1-year outcomes of loading phase treatment followed by maintenance therapy using a treat-and-extend (TAE) regimen with intravitreal faricimab for neovascular age-related macular degeneration (nAMD). Study design: Retrospective, interventional case series. Methods: We retrospectively studied 40 eyes of 38 consecutive patients with treatment-naïve nAMD, assessing best-corrected visual acuity (BCVA), foveal thickness, central choroidal thickness (CCT), total number of injections over 1 year, and intended injection interval at the last visit. Results: Thirty eyes (75.0%) had completed the 1-year intravitreal faricimab treatment. Their BCVA showed significant improvement, with significant reductions in foveal thickness and CCT. The total number of injections during the 1-year treatment period was 6.6 ± 0.7. The intended injection interval at the last visit was 12.7 ± 3.3 weeks. Of the 10 eyes (25.0%) failing to complete the 1-year faricimab treatment, 1 eye developed intraocular inflammation after the loading phase treatment but showed no recurrence of exudative changes, and no further treatment was required. Moreover, 5 eyes switched to intravitreal brolucizumab injection due to persistent exudative changes with an 8-week interval of faricimab injections. The remaining 4 eyes either dropped out or the patient died. Conclusions: A loading phase treatment followed by a TAE regimen with intravitreal faricimab appears to be generally safe and effective for improving visual acuity and ameliorating exudative changes in eyes with nAMD. However, there might be cases in which exudative changes cannot be adequately controlled with injections of faricimab every 8 weeks in the maintenance phase. [ABSTRACT FROM AUTHOR]

Introduction: AZURE was a 76-week, randomized, open-label, parallel-group, phase IIIb noninferiority study comparing the efficacy and safety of intravitreal aflibercept (IVT-AFL) in a treat-and-extend (T&E) regimen with fixed dosing in patients with neovascular age-related macular degeneration (nAMD) previously receiving IVT-AFL for ≥ 1 year. Methods: Patients were aged ≥ 51 years and had completed ≥ 1 year of IVT-AFL treatment prior to enrollment (IVT-AFL once per month [– 1 or + 2 weeks] for 3 months followed by IVT-AFL every 2 months [6–12 weeks]). Patients were randomly assigned (1:1) to receive IVT-AFL 2 mg in either a T&E (minimum treatment interval of 8 weeks with no upper limit, adjusted according to functional and anatomic outcomes, as assessed by the investigator; n = 168), or a fixed dosing regimen (treatment every 8 weeks [± 3 days]; n = 168). The primary endpoint was best-corrected visual acuity (BCVA) change from baseline to week (W) 52. The key secondary endpoint was the proportion of patients maintaining vision (< 15-letter loss) at W52. Results: The full analysis set comprised 332 patients (T&E: n = 165; fixed dosing: n = 167). Mean BCVA change (baseline to W52) was − 0.3 ± 7.5 vs. − 0.5 ± 8.4 letters (T&E vs. fixed dosing; least-squares mean difference [95% CI]: 0.22 [− 1.51 to 1.96] letters; P < 0.0001 for noninferiority test [5-letter margin]). From baseline to W52, 95.2% (T&E) and 94.0% (fixed dosing) of patients maintained vision. Mean central subfield thickness change from baseline to W52 was − 24 ± 55 (T&E) and − 33 ± 47 (fixed dosing) µm. Last treatment interval to W76 was ≥ 12 weeks for 37.0% of T&E patients. No new safety signals were identified. Conclusion: IVT-AFL T&E can achieve similar functional and anatomic outcomes to fixed dosing every 8 weeks over 52 weeks in patients with nAMD who have completed ≥ 1 year of treatment, while reducing treatment burden. Trial Registration: ClinicalTrials.gov Identifier: NCT02540954. [ABSTRACT FROM AUTHOR]

Purpose. To evaluate long-term results of anti-VEGF therapy performed in a modified “treat-and-extend” regimen in macular edema secondary to central retinal vein occlusion.Material and methods. The prospective study included 29 patients (16 men and 13 women) aged 24–81. The median follow-up period was 36 months [24; 60]. 20 patients underwent ranibizumab monotherapy, 3 patients – aflibercept monotherapy, while 6 patients received a combination of the two drugs following the modified regimen, which allowed terminating anti-VEGF treatment when macular edema remission was achieved.Results. Macular edema completely resolved in 27 out of 29 patients (93.1%) by the end of the second year, while the remaining 2 patients showed the complete resolution during the third year. 18 patients (62.1%) could terminate anti-VEGF therapy during the first 6 months, whereupon they received 3 to 5 monthly injections with no macular edema relapse over the subsequent 21–22 months of the follow-up. 11 patients continued anti-VEGF therapy and averagely received 7.09 ± 1.14, 5.09 ± 2.34 and 2.18 ± 2.36 injections with individually determined intervals at years 1, 2 and 3, respectively. On the whole, 22 patients (75.9%) terminated anti-VEGF therapy and transferred to drugless observation at the end of year 2, while 5 other patients (17.2%) terminated anti-VEGF therapy during year 3. As a result of the treatment, the maximum BCVA improved from 0.15 [0.07; 0.3] to 0.7 [0.4; 0.9] by the end of year 1 (Z = -4.69; p = 0.0000027) and remained stable during the rest of the follow-up.Conclusion. Anti-VEGF therapy in modified treat-and-extend regimen is effective in macular edema secondary to central retinal vein occlusion. and results in a significant and sustainable visual acuity gain and complete resolution of macular edema with a minimum quantity of injections in most patients.

There remains limited agreement regarding the efficacy and safety of different antivascular endothelial growth factor (anti-VEGF) agents for the management of polypoidal choroidal vasculopathy (PCV). Our meta-analysis compares different anti-VEGF agents for PCV treatment. Ovid MEDLINE, EMBASE, and Cochrane Library were systematically searched from January 2000 to July 2022. We included articles comparing the efficacy and safety of different anti-VEGF agents, specifically bevacizumab (BEV), ranibizumab (RAN), aflibercept AFL), and brolucizumab (BRO), for patients with PCV. 10,440 studies were identified, 122 underwent full-text review, and seven were included. One study was a randomized trial, and six were observational studies. Ranibizumab and aflibercept were associated with a similar best-corrected visual acuity (BCVA) at the last visit in three observational studies (P = 0.10), similar retinal thickness at the last visit in two observational studies (P = 0.85). One observational study comparing BEV versus RAN found comparable outcomes for final BCVA, retinal thickness, and polyp regression. One randomized trial on BRO versus AFL found comparable outcomes for improvement in BCVA, while anatomical outcomes favored BRO. The available evidence suggests that final BCVA is comparable across different anti-VEGF agents, however, further investigation is warranted due to paucity of evidence. [ABSTRACT FROM AUTHOR]

PurposeThis article describes treatment patterns and visual outcomes for central retinal vein occlusion (CRVO) in the antivascular endothelial growth factor (anti-VEGF) era.MethodsA retrospective cohort study of eyes diagnosed with CRVO between 2009 and 2016 was conducted. Treatment history and visual acuity (VA) measurements were abstracted from medical records and analyzed.ResultsA total of 476 eyes of 476 patients (median age 67 years, median follow-up 25.4 months) were included. Optical coherence tomography was obtained in 93.9% and fluorescein angiography in 80% of cases on presentation. Mean VA at presentation and final visit was 20/60 and 20/94, respectively, for eyes with nonischemic CRVO, whereas that of ischemic cases remained worse than 20/800 at final follow-up. Intravitreal bevacizumab was the most common first treatment (42.2%). Intravitreal steroid was the first treatment in 3.6% and ultimately administered in 11.3% of eyes. In the first year, an average of 5.2 ± 3.6 and 2.2 ± 3.4 anti-VEGF injections were given in treatment-naive and nontreatment-naive eyes, respectively.ConclusionsIn our real-world cohort, anti-VEGF injection burden and frequency are lower than in published clinical trials. Visual outcomes in both ischemic and nonischemic eyes with CRVO are poorer than expected and worse than those recorded in controlled trial settings.

Tomoko Miyakubo, Ryo Mukai, Hidetaka Matsumoto, Masahiro Morimoto, Maki Takahashi, Kazuki Nagai, Kosuke Nakamura, Junki Hoshino, Hideo Akiyama Department of Ophthalmology, Gunma University, Graduate School of Medicine, Maebashi, Gunma, JapanCorrespondence: Ryo Mukai, Department of Ophthalmology, Gunma University Graduate School of Medicine, 3-39-15 Showa-machi, Maebashi, Gunma, 371-8511, Japan, Tel +81-27-220-8338, Fax +81-27-233-3841, Email rmukai@gunma-u.ac.jpPurpose: To compare the efficacies of photodynamic therapy (PDT) combined with intravitreal aflibercept (IVA) injections and IVA monotherapy using a treat-and-extend regimen (TAE) for treatment-naïve polypoidal choroidal vasculopathy (PCV).Patients and Methods: One hundred and nine eyes treated with PDT combined with IVA (PDT+IVA group: 51 eyes) or IVA monotherapy (IVA group: 58 eyes) were assessed for 2 years. The main outcome measures included best-corrected visual acuity (BCVA), central macular thickness (CMT), central choroidal thickness (CCT), number of IVA injections, and macular atrophy (MA). Polypoidal lesions before and after the loading phase were assessed using indocyanine green angiography.Results: In both groups, BCVA significantly improved after the loading phase and was maintained for 2 years. CMT and CCT were significantly reduced in both groups, without significant differences after 2 years between the groups (P=0.2708). The mean number of IVA injections in the IVA and PDT+IVA groups during the 2 years were 13.2± 3.3 and 12.7± 1.8, respectively, without a significant difference (P=0.06). The frequencies of MA expansion in the IVA and PDT+IVA groups during the 2 years were 25.9% and 33.4%, respectively, with no significant difference in the incidence (odds ratio: 1.40, P=0.4253). The ratios of polyp regression after the loading phase in the IVA and PDT+IVA groups were 55.2% and 94.1%, respectively, with a significant difference (P< 0.0001).Conclusion: PDT combined with IVA injections using a TAE regimen is effective for anatomical and visual function improvement, without a significant difference as compared to IVA monotherapy. It can facilitate complete regression of polyps with higher odds.Keywords: polypoidal choroidal vasculopathy, aflibercept, photodynamic therapy, treat-and-extend, macular atrophy

Purpose: To compare a treat‐and‐extend (TAE) strategy with a fixed dosing regimen of intravitreal conbercept (IVC) for the management of treatment‐naïve polypoidal choroidal vasculopathy (PCV) patients. Methods: 249 patients with treatment‐naïve PCV were randomized 1:1 to fixed dosing regimen with injections every 12 weeks (3 + Q12W) group or treat‐and‐extend regimen(3 + TAE) group. Patients received 3 monthly intravitreal injections of 0.5 mg conbercept as loading dose in both groups. The 3 + Q12W patients were monitored monthly and received mandated injections every 12 weeks; the 3 + TAE patients were monitored and treated monthly until the resolution of exudative disease activity; the interval between visits was then individualized according to study protocol. Visual and anatomical outcomes were compared between the two groups. Results: At 48 weeks, there was no significant difference between the 3 + Q12W group and 3 + TAE group in mean BCVA improvement (p = 0.421), mean changes in central retinal thickness (CRT) (p = 0.818), maximum retinal thickness (MRT) (p = 0.448), pigment epithelial detachment (PED) height (p = 0.221), PED volume (p = 0.076), branching vascular network (BVN) area (p = 0.615), polypoidal lesion number (p = 0.701), polypoidal lesion area (p = 0.424), rates of patients who avoided vision loss of ≥15 ETDRS letters (p = 0.397) or complete polypoidal lesion regression rate (43.8% vs. 41.8%, p = 0.814). The 3 + Q12W group had more decreased retinal haemorrhage area (p = 0.014) and fewer mean numbers of injections comparing with 3 + TAE group (6.6 vs. 9.4, p < 0.001). Mean maximum extension interval between injections after loading injections was 9.6 ± 2.0 weeks for 3 + TAE group, with 27.8% of patients achieving an extension interval of 12 weeks and 61.1% patients 8 weeks or more. Conclusions: Both 3 + Q12W and 3 + TAE regimens of IVC could result in improvement in visual and anatomical outcomes in PCV patients. [ABSTRACT FROM AUTHOR]

Introduction: There are no guidelines on the optimal anti-vascular endothelial growth factor (anti-VEGF) monotherapy regimen for patients with polypoidal choroidal vasculopathy (PCV). In this study, we aimed to assess the comparative safety and efficacy of different treatment regimens of anti-VEGF monotherapy for PCV. Methods: We conducted a systematic literature search on Ovid MEDLINE, Embase, and Cochrane Library from January 2000 to May 2023 for comparative articles reporting on different treatment regimens of anti-VEGF agents in PCV. Our primary outcomes were the final best-corrected visual acuity (BCVA) and the change in BCVA from baseline. Secondary outcomes were the final retinal thickness (RT), the change in RT from baseline, the rate of polyp closure, and the incidence of adverse events. Results: A total of 10,440 studies were screened, and seven studies reporting on 636 eyes with PCV at baseline were included in this systematic review. One RCT of 53 eyes found a similar final BCVA, change in BCVA from baseline, final RT, and complete polyp closure rate between a treat-and-extend (T&E) regimen and a bimonthly fixed-dosing regimen of aflibercept. This trial also found superiority of T&E for change in RT from baseline. One observational study of 33 eyes found a similar BCVA at last study observation between a pro re nata (PRN) regimen and bimonthly fixed-dosing regimen of aflibercept. One observational study of 42 eyes found a similar change in BCVA from baseline and complete polyp closure rate between a PRN regimen and bimonthly fixed-dosing regimen of aflibercept. One RCT of 249 eyes found a similar change in BCVA and RT from baseline, as well as polyp closure, between a T&E regimen and fixed 12-week dosing regimen of conbercept. One observational study of 30 eyes found a superiority of T&E aflibercept for change in BCVA and risk of polyp recurrence, compared to a PRN regimen. Conclusion: Overall, there is a paucity of evidence comparing various treatment regimens of anti-VEGF therapy in patients with PCV. This limited evidence suggests that current treatment regimens are similarly efficacious, though T&E aflibercept achieved superior outcomes when compared to bimonthly dosing or PRN in some individual studies. Further trials are needed to confirm or refute these findings. [ABSTRACT FROM AUTHOR]

We aimed to investigate whether a treat-and-extend regimen of intravitreal brolucizumab (6.0 mg/0.05 mL) is effective for eyes with exudative age-related macular degeneration (AMD) refractory to aflibercept for 12 months. Sixty eyes from 56 patients receiving brolucizumab for exudative AMD refractory to aflibercept were included. Patients received a mean of 30.1 aflibercept administrations for a mean 67.9-month follow-up. All patients exhibited exudation on optical coherence tomography (OCT) despite regular 4–8 weeks of aflibercept administration. Visit 1 was scheduled at the same interval from the last aflibercept injection to the baseline. The treatment interval was extended or shortened by 1–2 weeks depending on the presence or absence of exudation on OCT. After switching to brolucizumab, the follow-up interval significantly extended at 12 months (before switching: 7.6 ± 3.8 weeks vs. at 12 months: 12.1 ± 6.2 weeks, p = 1.3 × 10−7). Forty-three percent of the eyes achieved a dry macula at 12 months after switching. However, the best-corrected visual acuity did not improve at any visit. Morphologically, the central retinal thickness and subfoveal choroidal thickness significantly decreased from baseline at 12 months (p = 3.6 × 10−3 and 1.0 × 10−3, respectively). Switching to brolucizumab can be considered to extend the treatment interval in eyes with exudative AMD refractory to aflibercept. [ABSTRACT FROM AUTHOR]

In 2022, the Taiwan, China fundus disease expert group issued the Consensus on the Optimal Treat-and-Extend Regimens for Neovascular Age-Related Macular Degeneration. The following explanations are given to help Chinese ophthalmologists better to refer to and use the Consensus. The main contents are as follows: The treat-and-extend(T& E)regimen of anti-vascular endothelial growth factor(VEGF)treatment in patients with neovascular age-related macular degeneration(nARMD)should aim at maintaining long-term vision and reducing the number of injections. We can start the treatment by injecting once a month for consecutive 3mo. After the initial treatment, the treatment interval of patients with stable conditions can be gradually extended(2 or 4wk each time)until 16wk. If the disease is still steady after injecting 2 or 3 times at the most prolonged interval, we can suspend the treatment, and then the patient needs to be rechecked every 3-4mo; If the disease is active again, the treatment interval needs to be shortened and can be extended again after controlling the disease. We can adopt a relatively conservative approach for patients with apparent negative recovery factors. Complications such as subconjunctival hemorrhage, macular fibrosis and macular atrophy deserve our attention during treatment. In the future, we can explore the best injection scheme for nARMD patients with different subtypes and baseline conditions to realize personalized therapy.

Introduction: The Canadian Treat-and-Extend Analysis Trial with Ranibizumab (CANTREAT) was a 2-year, multicentred, randomized clinical trial to evaluate treat-and-extend (T&E) relative to monthly administration of ranibizumab in neovascular age-related macular degeneration (nAMD). This post hoc analysis of the CANTREAT trial explores the relationship between the maximal extension interval tolerated by patients receiving T&E ranibizumab and visual acuity outcomes. Methods: Treatment-naïve patients with nAMD were randomized to receive either a once-monthly dosing or T&E regimen of ranibizumab across 27 treatment centres in Canada and were followed for 24 months. For this post hoc analysis, patients in the T&E cohort were subdivided into the following groups based on maximum extension interval: 4 weeks, 6 weeks, 8 weeks, 10 weeks, and 12 weeks. The primary outcome was the change in ETDRS best-corrected visual acuity (BCVA) from baseline to month 24 while secondary outcomes included change in central retinal thickness (CRT). All results were reported using descriptive statistics. Results: A total of 285 participants undergoing T&E were enrolled in this post hoc analysis. At month 24, the change in BCVA from baseline was +8.5 ± 9.3, +7.7 ± 13.8, +4.4 ± 9.6, +4.4 ± 18.5, and +7.8 ± 14.8 letters in the 4-, 6-, 8-, 10-, and 12-week cohorts, respectively. The change in CRT at month 24 was −79.2 ± 95.0, −143.9 ± 128.9, −97.7 ± 101.1, −120.9 ± 105.3, and −133.2 ± 108.8 μm in the 4-, 6-, 8-, 10-, and 12-week cohorts, respectively. Conclusion: The capacity to extend does not necessarily associate with improved visual acuity outcomes, with the poorest change in BCVA seen in those extended 8–10 weeks. The highest change in BCVA and lowest decrease in CRT was in the group maximally extended for 4 weeks. There was a correlation between change in BCVA and change in CRT for other extension groups. Future studies should establish the predictive factors for successful extension in patients undergoing T&E in nAMD. [ABSTRACT FROM AUTHOR]

Introduction: The aim of this study was to evaluate the effect of initial treatment regimen individualization (pro re nata or treat-and-extend [TAE]), according to macular neovascularization (MNV) subtype, on the functional and anatomical response in neovascular age-related macular degeneration (nAMD). The secondary objective was to compare the treatment burden between each MNV subtype. Methods: Consecutive treatment-naïve nAMD patients were retrospectively included. MNV subtype was graded by 2 independent blinded investigators on multimodal imaging. Functional and anatomical outcomes were analysed according to treatment regimen and MNV subtypes. Results: A total of 281 eyes from 243 patients were included in the study. According to the treatment regimen, there was no significant difference in best-corrected visual acuity gain within the first 2 years of treatment for type 1 (p = 0.106) and type 3 MNV (p = 0.704). Conversely, there was a significant difference in favour of TAE regimen for type 2 (p = 0.017) and type 4 MNV (p = 0.047). Type 1 MNV had a higher proportion of visits with subretinal fluid (p = 0.0007) but not with intraretinal fluid (p = 0.22). The mean interval between the last 2 injections was significantly shorter for type 1 MNV (p = 0.0045). Conclusion: The individualization of the initial treatment protocol according to MNV subtype can improve the functional outcome and may decrease the treatment burden. [ABSTRACT FROM AUTHOR]

Abstract The management of neovascular age-related macular degeneration (nAMD) has taken a major stride forward with the advent of anti-VEGF agents. The treat-and-extend (T&E) approach is a refined management strategy, tailoring to the individual patient’s disease course and treatment outcome. To provide guidance to implementing anti-VEGF T&E regimens for nAMD in resource-limited health care systems, an advisory board was held to discuss and generate expert consensus, based on local and international guidelines, current evidence, as well as local experience and reimbursement policies. In the experts’ opinion, treatment of nAMD should aim to maximize and maintain visual acuity benefits while minimizing treatment burden. Based on current evidence, treatment could be initiated with 3 consecutive monthly injections. After the initial period, treatment interval may be extended by 2 or 4 weeks each time for the qualified patients (i.e. no BCVA loss ≥5 ETDRS letters and dry retina), and a maximum interval of 16 weeks is permitted. For patients meeting the shortening criteria (i.e. any increased fluid with BCVA loss ≥5 ETDRS letters, or presence of new macular hemorrhage or new neovascularization), the treatment interval should be reduced by 2 or 4 weeks each time, with a minimal interval of 4 weeks. Discontinuation of anti-VEGF may be considered for those who have received 2–3 consecutive injections spaced 16 weeks apart and present with stable disease. For these individuals, regular monitoring (e.g. 3–4 months) is recommended and monthly injections should be reinstated upon signs of disease recurrence.

Introduction: The aim of this post hoc analysis of the ARIES study is to explore the requirement for intravitreal aflibercept (IVT-AFL) treatment intervals of < 8 weeks (w) in patients with neovascular age-related macular degeneration (nAMD), and to assess vision and anatomic outcomes in such patients who require more intensive treatment. Methods: ARIES was a multicenter, randomized, phase 3b/4 study that investigated the efficacy of two IVT-AFL proactive, individualized, treat-and-extend regimens over 2 years in treatment-naïve patients with nAMD. Patients were determined as injection-intensive if the study investigator identified that a treatment interval of < 8 w was needed and if they had ≥ 1 interval of < 8 w after three initial monthly doses. Treatment intervals could be extended subsequently if extension criteria were met. This is a post hoc analysis of patients enrolled in ARIES and statistical analysis is descriptive. Results: Of 269 patients in the combined treatment arms, 23.0% (n = 62) were injection-intensive (Year 1: 13.8% [n = 37]; Year 2: 9.3% [n = 25]). Time from IVT-AFL initiation to injection-intensive determination varied (range, 16–100 w; median: 43.2 w). Mean treatment interval was 8.4 w before and 6.1 w after injection-intensive determination. Overall, 59.7% achieved treatment intervals of ≥ 8 w following injection-intensive determination. Vision improvements from baseline to Week 104 were smaller for injection-intensive patients than non–injection-intensive patients (mean [SD] best-corrected visual acuity change: + 2.3 [15.6] vs. + 5.9 [12.3] letters). Anatomic outcomes were similar between injection-intensive and non–injection-intensive patients (central retinal thickness change from baseline to Week 104: − 160 [154] vs. − 167 [136] µm). Conclusions: In ARIES, 23% of treatment-naïve patients with nAMD experienced at least one treatment interval of < 8 w. Injection-intensive patients showed improved vision and anatomic outcomes. For most, treatment intervals could be extended to ≥ 8 w following injection-intensive determination. ClinicalTrials.gov Identifier: NCT02581891. [ABSTRACT FROM AUTHOR]

Abstract Purpose To investigate the visual and anatomical outcomes associated with treat-and-extend (TAE) regimen of intravitreal (IVT) aflibercept in eyes with treatment naïve neovascular age-related macular degeneration (nvAMD). Methods A retrospective chart review of eyes that underwent IVT aflibercept injections for nvAMD between May 2014 and March 2018 was performed. The primary outcome was the change in best corrected visual acuity (BCVA) at 12 months. Secondary outcomes included the change in central retinal thickness (CRT), subretinal fluid (SRF) and intraretinal fluid (IRF). Results Data from 213 eyes of 213 patients (138 female, 65%) met the inclusion criteria. The mean (SD) age of the patients was 80.4 (± 9.2) years. The mean baseline BCVA (0.92 ± 0.50 logMAR, improved by 0.20 (± 0.40) logMAR units at 12 months (p < 0.001). Seventy-two (34%) eyes gained ≥ 0.3 logMAR and 47 (22%) eyes achieved BCVA ≤ 0.3 logMAR at 12 months. Baseline BCVA, patient age, and the number of aflibercept injections received were predictors of the change in BCVA at 12 months. Mean CRT improved from 347 (± 117) µm at baseline to 246 (± 55) µm at 12 months (p < 0.001). The percentage of eyes with SRF and IRF on SD-OCT declined from 63 to 21% and from 60 to 26% at 12 months, respectively. Conclusion A TAE regimen of IVT aflibercept in treatment naïve nvAMD is associated with good visual and anatomical outcomes in routine clinical practice. Resolution of exudation occurred in about half of nvAMD cases at 12 months. Individualized administration of IVT aflibercept may reduce injection burden.

We aimed to investigate whether a treat-and-extend regimen of intravitreal brolucizumab (6.0 mg/0.05 mL) is effective for eyes with exudative age-related macular degeneration (AMD) refractory to aflibercept for 12 months. Sixty eyes from 56 patients receiving brolucizumab for exudative AMD refractory to aflibercept were included. Patients received a mean of 30.1 aflibercept administrations for a mean 67.9-month follow-up. All patients exhibited exudation on optical coherence tomography (OCT) despite regular 4–8 weeks of aflibercept administration. Visit 1 was scheduled at the same interval from the last aflibercept injection to the baseline. The treatment interval was extended or shortened by 1–2 weeks depending on the presence or absence of exudation on OCT. After switching to brolucizumab, the follow-up interval significantly extended at 12 months (before switching: 7.6 ± 3.8 weeks vs. at 12 months: 12.1 ± 6.2 weeks, p = 1.3 × 10−7). Forty-three percent of the eyes achieved a dry macula at 12 months after switching. However, the best-corrected visual acuity did not improve at any visit. Morphologically, the central retinal thickness and subfoveal choroidal thickness significantly decreased from baseline at 12 months (p = 3.6 × 10−3 and 1.0 × 10−3, respectively). Switching to brolucizumab can be considered to extend the treatment interval in eyes with exudative AMD refractory to aflibercept.

Introduction: Recently, there has been growing interest in exploring the relationship between visual acuity and fluid localization in different retinal compartments. This post hoc analysis of the ARIES study explores the relationship between the presence of intraretinal fluid (IRF) and subretinal fluid (SRF), both at baseline and throughout treatment, and best-corrected visual acuity (BCVA) in patients with neovascular age-related macular degeneration (nAMD) treated with intravitreal aflibercept (IVT-AFL) in a treat-and-extend regimen. Methods: ARIES (NCT02581891) was a multicenter, randomized, phase 3b/4 study comparing the efficacy of two IVT-AFL treat-and-extend regimens over 2 years in patients with treatment-naïve nAMD. This post hoc analysis explores the relationship between the presence of SRF/IRF and absolute BCVA (letter score) at baseline and fixed visits. Results: In 210 patients (treat-and-extend treatment arms combined), SRF presence at baseline was associated at every time point with a numerically higher mean BCVA than if absent, with 10 more letters at week 104. IRF presence at baseline was associated at all but one time point with a numerically lower mean BCVA than if absent (week 104, 8-letter difference). Baseline SRF+IRF was associated with lower BCVA (week 104, 7-letter difference) than if only SRF was present, but higher BCVA (week 104, 8-letter difference) than if only IRF was present. Absence of SRF+IRF was not associated with better BCVA at any time point during the study. Conclusion: In ARIES, in patients with nAMD treated with IVT-AFL, the presence of SRF was associated with better visual acuity, whereas IRF was associated with poorer visual acuity. The findings of this post hoc analysis suggest that differentiating IRF from SRF may offer better prognostic value in guiding treatment-extension decisions than the use of combined or "any" IRF and SRF. Prospective trials are needed to validate these results and determine their clinical relevance. Trial registration number (ClinicalTrials.gov): NCT02581891. 2jEy9rDhgXKJkUVo9DzmZL Association between Visual Acuity and Fluid Compartments with Treat-and-Extend Intravitreal Aflibercept in Neovascular Age-Related Macular Degeneration: An ARIES Post Hoc Analysis: A Video Abstract (MP4 308264 KB) [ABSTRACT FROM AUTHOR]

Introduction: To explore the efficacy and safety of intravitreal aflibercept (IVT-AFL) proactive, individualized treat-and-extend (T&E) regimens in exudative age-related macular degeneration (AMD) in the subgroup of patients with polypoidal choroidal vasculopathy (PCV) enrolled in the ALTAIR study. Methods: This was a PCV subgroup analysis of ALTAIR, a 96-week, randomized, open-label, phase 4 study in treatment-naïve patients with exudative AMD in Japan. Following three initial monthly doses, patients received IVT-AFL at week 16 and were randomized 1:1 to T&E regimens with either 2-week (IVT-AFL-2W) or 4-week (IVT-AFL-4W) adjustments. The primary endpoint of ALTAIR was the mean change in best-corrected visual acuity (BCVA) from baseline to week 52. Endpoints were assessed at weeks 52 and 96. Safety analyses were conducted. Results: A total of 90 patients with PCV were included within the full analysis set. From baseline to week 52, mean [standard deviation (SD)] change in BCVA was + 7.5 (14.7) letters and + 8.2 (11.6) letters in the IVT-AFL-2W and IVT-AFL-4W groups, respectively. From baseline to week 96, 91.3% and 90.9% of patients maintained vision in the IVT-AFL-2W and IVT-AFL-4W groups, respectively. From baseline to week 52, mean (SD) change in central retinal thickness was − 153 (177) µm and −112 (122) µm in the IVT-AFL-2W and IVT-AFL-4W groups, respectively. Overall, 51.1% of patients (IVT-AFL-2W, 43.5%; IVT-AFL-4W, 59.1%) achieved a treatment interval of 16 weeks between weeks 16 and 96. The safety profile of IVT-AFL was consistent with previous studies. Conclusion: In treatment-naïve patients with PCV, IVT-AFL administered using two different T&E regimens improved and maintained functional and anatomic outcomes over 96 weeks while minimizing treatment burden. Trial registration: ClinicalTrials.gov identifier, NCT02305238. [ABSTRACT FROM AUTHOR]

Intravitreal injections (IVI) of anti-vascular endothelial growth factor (anti-VEGF) have become the standard of care for age-related macular degeneration (AMD). Although most pivotal trials have used monthly injections, alternative strategies that enable the injections to be administered on a more flexible schedule, including pro re nata (PRN) and treat-and-extend (T&E) regimens, are being applied more frequently. This review sought to provide further scientific evidence about the visual outcomes and treatment burden among the currently available anti-VEGF agents and regimens, including aflibercept, ranibizumab, abicipar and brolucizumab. To this end, a systematic review of published randomized studies was conducted from the MEDLINE and EMBASE databases and the Cochrane library, and a meta-analysis was applied to the obtained data using single-means modeling to compare the efficacy and maintenance among the different available treatments and regimens at Years 1 and 2. Quality analysis identified the best-informed data for modeling purposes. Overall, 47 relevant publications were retrieved for the analysis. Superior efficacy, meaning that there were observed improvements in visual acuity (VA) and central retinal thickness (CRT), occurred with monthly versus PRN regimens, yet a higher IVI number was also observed. Conversely, the T&E regimens displayed similar efficacy to the monthly regimens, but with a reduced IVI number. Aflibercept T&E exhibited similar efficacy to ranibizumab T&E, but with significantly lower IVI numbers at both Year 1 (p < 0.0001) and Year 2 (p = 0.0011). Though all of the regimens resulted in maintained efficacy between Years 1 and 2, the required IVI number varied. The retrieved data did not enable other regimens or newer anti-VEGF agents such as brolucizumab to be compared. In conclusion, the T&E regimens were shown to be the most efficient, optimizing durable effectiveness whilst minimizing the IVI number in newly diagnosed exudative AMD, with aflibercept requiring the lowest IVI number. [ABSTRACT FROM AUTHOR]

Introduction: Switching to an alternative anti-vascular endothelial growth factor (anti-VEGF) agent has been suggested for patients with neovascular age-related macular degeneration (nAMD) who have a suboptimal response to initial therapy. However, post hoc analyses of some studies have shown that continuation of initial anti-VEGF therapy is, in many cases, associated with stable visual outcomes or gradual gains. Methods: This ARIES (ClinicalTrials.gov Identifier: NCT02581891) post hoc analysis describes outcomes in patients with treatment-naïve nAMD receiving treat-and-extend intravitreal aflibercept (IVT-AFL) for 104 weeks, who were identified as meeting criteria for an early hypothetical switch. Patients were categorized retrospectively according to six criteria (presence of central intraretinal and/or subretinal fluid at week 8 or 24, with/without a next planned treatment interval ≤ 8 weeks, and with/without gains in best-corrected visual acuity [BCVA] ≤ 5 letters [with absolute BCVA < 70 letters]). Results: Hypothetical switch criteria were largely met due to the presence of central subretinal fluid rather than intraretinal fluid. Depending on the criterion, 8–46% of patients were considered to be hypothetical switchers. BCVA outcomes were not worse in the hypothetical switchers, irrespective of criteria. Using criteria of intraretinal/subretinal fluid at week 24 and a next planned treatment interval ≤ 8 weeks, mean changes in BCVA (letters) from baseline in hypothetical switchers and non-switchers were: + 6.1 (95% confidence interval [CI] 3.4, 8.8) and + 6.6 (95% CI 4.7, 8.6), respectively, at week 24; + 8.2 (95% CI 5.0, 11.3) and + 7.5 (95% CI 5.3, 9.7), respectively, at week 52; and + 5.7 (95% CI 1.3, 10.1) and + 3.4 (95% CI 0.1, 6.7), respectively, at week 104. Conclusions: In newly diagnosed nAMD, there appears little rationale for early switching from IVT-AFL since, with continuous proactive treatment, comparable visual gains can be achieved by patients meeting hypothetical switch criteria compared with those who initially respond well on a treat-and-extend regimen. However, further prospective studies are needed. Trial registration: ClinicalTrials.gov Identifier: NCT02581891. Video Summary: 49swg7LFcAwynzUPgPUQw7 Video summary of the ARIES Post Hoc Analysis "Hypothetical Switch of Anti-Vascular Endothelial Growth Factor in Neovascular Age-Related Macular Degeneration" (MP4 54283 KB) [ABSTRACT FROM AUTHOR]

Purpose: To compare two aflibercept treatment regimens and the electrophysiological outcome concerning cone and rod function in age-related macular degeneration (nAMD) over 18 months. Methods: 41 patients with treatment-naïve nAMD were randomized 1:1 to either arm 1 or 2. Arm 1 received three consecutive monthly aflibercept injections, followed by bimonthly treatment until week 52. Thereafter, a treat-and-extend (TAE) regimen was applied. Arm 2 was treated according to a TAE protocol throughout the 18-month follow-up. We assessed visual acuity (VA), central retinal thickness (CRT), injection rate and interval, and evaluated cone and rod function with full-field and multifocal electroretinography (ffERG, mERG). Results: There were no statistically significant differences in mean baseline VA, lesion type, age, gender, or symptom duration between the two arms. During the 18-month follow-up, mean VA improved in arm 1 (n = 19) from 63.5 ± 10.5 to 69.1 ± 9.2 letters; p = 0.098; and in arm 2 (n = 20) from 66.8 ± 13.6 to 73.9 ± 9.0 letters; p =.002. In both arms, mean CRT was significantly reduced; p < 0.000. At month 18, we found no significant difference in the number of injections or injection intervals between groups. Arm 1 had received 11.3 ± 1.7 injections vs. 10.9 ± 2.0 in arm 2. The mean injection interval was 9.2 ± 3.4 weeks vs. 9.5 ± 3.1, with 52% (n = 10) on the maximum 12-week interval in arm 1, and 50% (n = 10) in arm 2. The combined rod-cone a-wave amplitude significantly decreased over time; p = 0.043. The isolated rod b-wave amplitude showed a statistically significant decline; p = 0.026. The overall mERG amplitude and implicit time remained unchanged over time; p = 0.878 vs. p = 0.922. The central ring 1 mERG amplitude improved; p = 0.041, with an unaffected implicit time. Conclusions: After 18 months, both treatments arms have received a similar number of injections at comparable intervals. Electrophysiological evaluation shows no signs of toxicity concerning cone function. But ffERGs for the combined and isolated rod response have declined, possibly reflecting either toxic effects of the drug to rods or the natural course of the disease itself. [ABSTRACT FROM AUTHOR]

PurposeTo compare the efficacy and safety of conbercept using a treat-and-extend (T&E) regimen vs. a pro re nata (PRN) regimen in Chinese patients with neovascular age-related macular degeneration (nAMD).MethodsThis was a randomized, multicenter, non-inferiority study. After an initial loading phase of three consecutive monthly intravitreal injections of 0.5 mg Conbercept, the patients were treated to PRN or T&E regimen. The prespecified retreatment criteria was defined as a more than 5-letter decrease in BCVA from the previous visit or any evidence of new retinal hemorrhages, or the presence of any IRF and any SRF of more than 200 μm in height at the sub-foveal center. The primary outcome was the mean change in best-corrected visual acuity (BCVA) from baseline to 24 months, with a prespecified non-inferiority limit of −5 letters.ResultsFrom July 2016 through August 2018, 141 participants were allocated and treated (T&E, n = 69; PRN, n = 72). About one fifth of the overall participants were dropped out during the 12-month follow-up (28/141, 19.9%), and about one thirds of the overall participants were lost during the 24-month follow-up (51/141, 36%). At 2 years, mean BCVA letter improvement was + 4.0 in the T&E group vs. + 5.1 in the PRN group, and T&E regimen was not non-inferior to PRN regimen [difference, −1.169 letters; 95% confidence interval (CI): −6.864 ∼ 4.526]. Subgroup analyses also demonstrate the similar results in PCV patients, naive patients and no-naive patients. The mean decrease in central subfield thickness were 180 ± 165 μm in the T&E group and 247 ± 230 μm in the PRN group, respectively. The patients in the PRN group had required significantly fewer injections than those in the T&E group (12.4 vs. 14.6 injections, P = 0.041). The types and rates of adverse events were comparable in the two treatment groups.ConclusionThese findings suggest that the T&E regimen was not non-inferior to the PRN regimen in patients with nAMD in terms of BCVA outcomes through 24 months.Clinical Trial RegistrationClinicalTrials.gov, identifier NCT02802657.

Abstract Background To evaluate the three-year outcome after intravitreal aflibercept injection (IAI) for neovascular age-related macular degeneration (nAMD). Methods Forty-nine treatment-naïve nAMD patients (50 eyes) were enrolled in this prospective study. The eyes received IAI at two-month intervals in the first year. The treatment regimen was changed to IAI based on a treat-and-extend approach in the second and third years. Results Twenty-nine eyes of 28 patients were successfully followed up over 36 months. The nAMD subtypes included 15 eyes with typical AMD and 14 eyes with polypoidal choroidal vasculopathy. The number of IAIs performed over the 3 years was 17.2 ± 3.1 (mean ± standard deviation). The mean logMAR, which was 0.42 at baseline, improved to 0.19 (P = 0.001) at 12 months, and 0.26 (P = 0.049) at 36 months. The central retinal thickness (CRT) was 329 ± 120 μm at baseline, 151 ± 38 μm (P

Takeshi Joko,1 Yoshimi Nagai,2 Ryusaburo Mori,3 Koji Tanaka,3 Yuji Oshima,4 Yusuke Hikichi,5 Tetsushi Komori,6 Joao Carrasco,7 Martine C Maculaitis,8 Oliver Will,8 Kathleen Beusterien,8 Kanji Takahashi2 1Department of Ophthalmology, Matsuyama Red Cross Hospital, Matsuyama, Ehime, Japan; 2Department of Ophthalmology, Kansai Medical University, Hirakata, Osaka, Japan; 3Division of Ophthalmology, Department of Visual Sciences, Nihon University of School of Medicine, Chiyoda-ku, Tokyo, Japan; 4Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; 5Department of Market Access, Bayer Yakuhin, Ltd., Chiyoda-ku, Tokyo, Japan; 6Department of Research & Product Development, Bayer Yakuhin, Ltd., Kita-Ku, Osaka, Japan; 7Department of Market Access, Bayer Consumer Care AG, Basel, Canton of Basel-Stadt, Switzerland; 8Health Division, Kantar, New York, NY, USACorrespondence: Takeshi JokoDepartment of Ophthalmology, Matsuyama Red Cross Hospital, 1 Bunkyocho, Matsuyama, Ehime 790-8524, JapanTel +81 89 924 1111Email takeshijoko@matsuyama.jrc.or.jpBackground: In Japan, intravitreal anti-vascular endothelial growth factor (anti-VEGF) dosing regimens for wet age-related macular degeneration (wAMD) include pro re nata, every 2 months, and treat-and-extend, resulting in different outcomes and patient burden. Although reflecting patient preferences in treatment decision-making is desirable, few studies have examined this in Japan. This study assessed the patients willingness to trade-off between different dosing regimens.Patients and Methods: Patients with wAMD were recruited from four Japanese university hospitals to complete a face-to-face cross-sectional survey. In a discrete choice experiment, patients were asked to choose their preferred option from two anti-VEGF treatment profiles shown side-by-side across a series of choice tasks. The profiles varied on four attributes: number of injections in 12 months, number of physician consultations in 12 months, chance of 1-year visual acuity (VA) improvement, and chance of 2-year VA maintenance. Preference weights were estimated using hierarchical Bayes’ models.Results: Overall, 120 patients (30 treatment naïve and 90 anti-VEGF experienced) completed the survey. Patients were willing to accept an increase from three to approximately eight injections in 12 months to increase the chance of 1-year VA improvement from 25% to 40%. They would be willing to accept 11 injections in 12 months if the chance of 2-year VA maintenance increased from 80% to 96%. The most valued attributes were increasing the chance of 2-year VA maintenance and reducing the number of injections in 12 months, which were each about twice as important as decreasing physician consultations in 12 months and increasing the chance of 1-year VA improvement (p< 0.001). Among the dosing regimens, patients most preferred treat-and-extend because of its higher chance of 2-year VA maintenance.Conclusion: Informing patients with wAMD about the likelihood of long-term VA maintenance when selecting treatment may increase the acceptance of an optimal treatment regimen and number of injections.Keywords: wet age-related macular degeneration, patient preference, anti-vascular endothelial growth factor treatment, dosing regimen, treat-and-extend

Purpose. To evaluate the economic and clinical results of the aflibercept and ranibizumab angiogenesis inhibitors in the treat-and-extend regimen in patients with the “wet” form of age-related macular degeneration (wAMD). Materials and methods. We analyzed cost minimization, impact on the budget and “missed opportunities” for the treatment of patients with wAMD using intravitreal injections (IVI) of aflibercept compared to ranibizumab in the “treat-and-extend” regimen (T & E). Costs were calculated with regard to the budget of the system of compulsory health insurance. To calculate the number of IVI, network meta-analysis data (P. Lanzetta, et al., 2019), including a matching-adjusted indirect comparison of aflibercept and ranibizumab in wAMD patients in the T & E regimen, were taken into account. The budget impact analysis involved a cohort of 1,000 wAMD patients. To assess the stability of the results, a one-factor multicomponent sensitivity analysis was used. Results. Network meta-analysis data showed that aflibercept and ranibizumab used in the T & E regimen revealed comparable changes in the maximum corrected visual acuity; however, the use of aflibercept required a significantly lower (by 6 procedures in two years) number of IVI compared to ranibizumab. Analysis of cost minimization showed that the use of aflibercept can reduce costs by 36 % in two years compared to ranibizumab in the T & E regimen. The use of aflibercept in the T & E regimen with wAMD will reduce the cost of compulsory medical insurance by 281 million rubles in two years of therapy per 1,000 patients. The analysis of “missed opportunities” showed that budget savings of the compulsory medical insurance as a result of transferring 1,000 patients from ranibizumab to aflibercept will allow an additional 563 patients to be treated in two years. A sensitivity analysis confirmed the robustness of the study results. Conclusion. Treating wAMD with aflibercept in the T & E regimen saves a significant part of health protection resources compared to using ranibizumab in the same regimen.

Abstract Background To evaluate the safety and efficacy of a treat-and-extend protocol of aflibercept for cystoid macular oedema (CMO) secondary to central retinal vein occlusion (CRVO). Methods Twenty patients with CMO secondary to CRVO were included in this prospective cohort study. After 3 loading 4-weekly injections, treatment intervals were increased by 2 weeks if there was no clinical activity, to a maximum of 12 weeks. If clinical activity recurred or persisted, the interval between injections was shortened by 2 weeks, to a minimum of 4 weeks. Main outcome measures were change in visual acuity and the proportion of patients gaining 15 or more Early Treatment of Diabetic Retinopathy Study (ETDRS) letters from baseline at 6, 12 and 18 months. Results Mean BCVA gain from baseline was 19.7 ± 13.8, 22.2 ± 13.9 and 21.9 ± 15.8 ETDRS letters at 6, 12 and 18 months, respectively. Sixty-five percent of patients gained 15 or more ETDRS letters at 6 months, increasing to 70.6% at 12 and 18 months. Patients received 5.0 [4.0 to 6.0], 8.5 [8.0 to 10.3] and 11.0 [9.0 to 12.5] injections by 6, 12 and 18 months, respectively. Conclusions The visual outcomes achieved with a treat-and-extend protocol in this study were similar to the pivotal trials of aflibercept for CMO secondary to CRVO, which used monthly and then as-needed protocols. Trial registration Australian and New Zealand Clinical Trials Registry, registration number ACTR N12615000417583 , 01/05/2015.

Purpose: To compare 1-year outcomes of eyes with diabetic macular edema (DME) treated in routine clinical practice based on the proportion of visits where intravitreal VEGF inhibitor injections were delivered., Design: Cohort study., Participants: There were 2288 treatment-naive eyes with DME starting intravitreal VEGF inhibitor therapy from October 31, 2015 to October 31, 2021 from the Fight Retinal Blindness! international outcomes registry., Methods: Eyes were grouped according to the proportion of visits at which an injection was received, Group A with less than the median of 67% (n = 1172) versus Group B with greater than the median (n = 1116)., Main Outcome Measures: Mean visual acuity (VA) change after 12 months of treatment., Results: The mean (95% confidence interval [CI]) VA change after 12 months of treatment was 3.6 (2.8-4.4) letters for eyes in Group A versus 5.2 (4.4-5.9) letters for eyes in Group B (P = 0.005). The mean (95% CI) central subfield thickness (CST) change was -69 (-76 to -61) μm and -85 (-92 to -78) μm for eyes in Group A versus Group B, respectively (P = 0.002). A moderate positive correlation was observed between the number of injections received over 12 months of treatment and the change in VA (P < 0.001). Additionally, eyes that received more injections had a moderately greater CST reduction., Conclusions: This registry analysis found that overall VA and anatomic outcomes tended to be better in DME eyes treated at a greater proportion of visits in the first year of intravitreal VEGF inhibitor therapy., Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (Copyright © 2024 American Academy of Ophthalmology. All rights reserved.)

Purpose: To assess the effect of fluid status at baseline (BL) and at the end of the loading phase (LP) of three different ranibizumab regimens: treat‐and‐extend (T&E), fixed bimonthly (FBM) injections and pro re nata (PRN), in patients with neovascular age‐related macular degeneration (nAMD). Design: Post hoc analysis of the In‐Eye study (phase IV clinical trial). Methods: Patients were randomized 1:1:1 to the three study arms and were treated accordingly. The presence and type of fluid, intraretinal fluid (IRF) or subretinal fluid (SRF) and the anatomical and visual outcomes were analysed. Main outcome measures: Best‐corrected visual acuity (BCVA), the mean change from baseline BCVA (BL BCVA), and the proportion of eyes gaining more than 15 letters or losing more than five letters were analysed. Morphological characteristics including the subtype of choroidal neovascular membrane and the development of atrophy and fibrosis were also evaluated. Results: Patients with SRF at LP had better visual outcomes than patients with IRF. The persistence of SRF did not affect the mean change from BL BCVA among the three treatment regimens. However, in patients with IRF mean change from BL BCVA was significantly lower in the FBM group. The presence of IRF at BL and at the end of the loading phase was associated with the development of fibrosis at the end of the study; this result was contrary to that observed for patients with SRF. Conclusions: While SRF is compatible with good visual and anatomical outcomes, IRF leads to worse results in patients with nAMD; our results suggest that patients with IRF have better outcomes when individualized treatment regimens are used (PRN or T&E) in contrast with a FBM regimen. [ABSTRACT FROM AUTHOR]

Purpose: To assess vision, injection quantity, initial lesion size, and final anatomic status in patients with nAMD completing the treat-extend-stop (TES) protocol. Methods: Patients with nAMD received ≥ 3 monthly anti-VEGF injections followed by 1–2 week injection interval extensions, with intra/subretinal fluid resolution on SD-OCT, to 12 weeks. With quiescent disease, and 2 quarterly injections, patients were monitored alone beginning at 4 weeks extending by 1–2 week intervals until quarterly monitoring. Results: Eighty-eight of 143 eyes with nAMD completed the TES protocol without disease recurrence. Sixteen (18.2%) developed sub-foveal geographic atrophy (GA), 25 (28.4%) developed fibrovascular scarring (FV) and 47 (53.4%) developed regressed choroidal neovascularization (rCNV) with 16.9 ± 13.3 average injections between the 3 groups which was not statistically significant. Average treatment time was 30.3 ± 26.1 months and subsequent follow-up was 23.2 ± 19.8 months. Average lesion size for FV was 18.77 ± 10.8mm2 vs. GA at 12.00 ± 9.99mm2 vs. regressed CNV at 7.12 ± 6.5mm2 (p < 0.05). Pre, post, and final vision for GA was 39.6 letters (20/160) vs. 32.7 letters (20/200 + 2, p = 0.4725) vs. 25.0 letters (20/320, p = 0.0865); FV was 22.4 letters (20/400 + 2) vs. 11.6 letters (20/640, p = 0.0351) vs. 11.0 letters (20/640 + 1, p = 0.0226), and rCNV was 56.4 letters (20/80 + 1) vs. 69.5 letters (20/40, p < 0.001) vs. 67.3 letters (20/40–2, p = 0.0016). In the rCNV group, 17/46 eyes gained ≥ 3 lines and 30/46 eyes achieved ≥ 20/40 vision. Non-central GA expanded 0.226 ± 0.126 mm vs. 0.225 ± 0.098 mm during and after treatment completion over 24 months (p = 0.99). Conclusions: Central GA or FV portends worse visual outcomes vs. rCNV after cessation of therapy. Anti-VEGF therapy may not affect the rate of GA expansion. Final anatomic character and location are key determinants of final vision. [ABSTRACT FROM AUTHOR]

Purpose: To explore the relationship between retinal fluid status and best-corrected visual acuity (BCVA) in patients treated with intravitreal aflibercept (IVT-AFL) treat-and-extend (T&E) in the ALTAIR study. Methods: Outcomes were investigated according to overall fluid status at week 16 (predefined) and the relationship between any fluid, intraretinal fluid (IRF), subretinal fluid (SRF), or pigment epithelial detachment with BCVA at baseline, and weeks 16, 52, and 96 (post-hoc). The analyses involved treatment-naïve patients (N = 246) with exudative age-related macular degeneration (AMD), aged ≥ 50 years with BCVA of 73–25 Early Treatment Diabetic Retinopathy Study letters, who participated in the ALTAIR study. Results: The mean (standard deviation) change in BCVA from baseline to week 52 was + 10.6 (10.9) and + 6.5 (16.0) letters in patients without and with fluid at week 16, respectively; and to week 96 was + 9.1 (14.3) and + 4.3 (16.1) letters in patients without and with fluid at week 16, respectively. The last injection interval was 16 weeks in 33.6% and 2.0% (week 52), and 62.9% and 17.6% (week 96) of patients without or with fluid at week 16, respectively. At baseline, 35.7% of patients had IRF and 85.2% of patients had SRF, which decreased to 11.8% (IRF) and 31.7% (SRF) of patients, 8.5% (IRF) and 18.7% (SRF), and 6.5% (IRF) and 20.7% (SRF) at weeks 16, 52, and 96, respectively. Presence of IRF at all timepoints was associated with poorer BCVA than if IRF was absent, while the presence of SRF was not associated with poorer BCVA compared with the absence of SRF. Conclusion: IVT-AFL T&E dosing was effective at clearing fluid regardless of fluid type in ~ 80% of patients with exudative AMD. Patients without fluid at week 16 had numerically better BCVA than those with fluid at week 16. Over 60% of patients without fluid at week 16 achieved the maximum treatment interval of 16 weeks by study end, compared with < 20% of patients with fluid at week 16. IRF (weeks 16, 52, 96), although evident in a small number of patients, was associated with poorer BCVA, whereas SRF was not. Trial registration: ClinicalTrials.gov Identifier: NCT02305238 [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the functional and anatomical outcomes of a treat-and-extend (TAE) regimen with aflibercept for treatment-naive macular edema (ME) secondary to branch retinal vein occlusion (BRVO). Methods: This was a prospective, multicenter, noncomparative, open-label clinical trial. Forty-eight eyes of 48 patients received three monthly intravitreal aflibercept injections prior to the TAE regimen. However, if the best-corrected visual acuity (BCVA) was ≥ 20/20 and the central macular thickness (CMT) was < 250 μm during the loading phase, the patient immediately proceeded to the TAE regimen. The treatment interval was adjusted by 4 weeks based on changes in CMT. The primary outcome was the mean change in BCVA from baseline to 52 weeks. Results: The mean change in BCVA was 23.6 ± 14.2 letters. The proportion of patients with BCVA gain ≥ 15 letters was 77.1% at 24 weeks and 72.9% at 52 weeks. The mean reduction in CMT was 326.2 ± 235.6 μm at 24 weeks and 324.2 ± 238.0 μm at 52 weeks. The mean number of injections was 6.7 ± 1.2 (range: 6–11, all patients received three monthly intravitreal aflibercept injections) over 52 weeks, and 34 patients (70.8%) reached the maximal extension interval of 16 weeks at 52 weeks. Conclusions: The TAE regimen using aflibercept for ME secondary to BRVO, which has a treatment interval of up to 16 weeks, showed comparable efficacy to the fixed-dosing regimen along with reduced treatment burden. [ABSTRACT FROM AUTHOR]

The use of anti-vascular-endothelial growth factor agents for neovascular age-related macular degeneration (nAMD) in different treatment schemes is widely common in clinical practice. However, there is currently limited data on the long-term outcomes of a strict treat-and-extend regimen (TER) and imaging biomarkers to predict both functional outcome and the potential for a TER exit due to success. In this retrospective study we followed treatment-naïve subjects with nAMD starting treatment with either ranibizumab or aflibercept in a TER without loading dose but with predefined exit criteria for up to 8 years. We evaluated both the functional outcome and several spectral-domain optical coherence tomography parameters in a follow-up mode using a standardized protocol. Within the 211 eyes followed for a mean of 60.3 ± 20.9 months, follow-up adherence was high with major part of discontinuations of TER being due to success. Mean best-corrected visual acuity (BCVA) increased from initially 63.9 ± 15.5 ETDRS letters to 70.0 ± 14.7 after 1 year (+6.1 letters, p < 0.001) and to 68.5 ± 18.1 (+4.6 letters, p = 0.028) at 5 years. A worse BCVA (p = 0.001) and a better external limiting membrane (ELM) disruption score at baseline predicted (p = 0.019) BCVA gain at 5 years. The probability of reaching the exit criteria was significantly associated with a better ELM disruption score (p = 0.044) and the absence of a central pigment epithelial detachment (PED) (p = 0.05) at baseline. Significant visual gains were sustained in a long-term TER in a real-world setting. Integrity of ELM at baseline predicted BCVA gain at 5 years and the potential for TER exit due to success.

Purpose: To investigate the visual and anatomical outcomes associated with treat-and-extend (TAE) regimen of intravitreal (IVT) aflibercept in eyes with treatment naïve neovascular age-related macular degeneration (nvAMD). Methods: A retrospective chart review of eyes that underwent IVT aflibercept injections for nvAMD between May 2014 and March 2018 was performed. The primary outcome was the change in best corrected visual acuity (BCVA) at 12 months. Secondary outcomes included the change in central retinal thickness (CRT), subretinal fluid (SRF) and intraretinal fluid (IRF). Results: Data from 213 eyes of 213 patients (138 female, 65%) met the inclusion criteria. The mean (SD) age of the patients was 80.4 (± 9.2) years. The mean baseline BCVA (0.92 ± 0.50 logMAR, improved by 0.20 (± 0.40) logMAR units at 12 months (p < 0.001). Seventy-two (34%) eyes gained ≥ 0.3 logMAR and 47 (22%) eyes achieved BCVA ≤ 0.3 logMAR at 12 months. Baseline BCVA, patient age, and the number of aflibercept injections received were predictors of the change in BCVA at 12 months. Mean CRT improved from 347 (± 117) µm at baseline to 246 (± 55) µm at 12 months (p < 0.001). The percentage of eyes with SRF and IRF on SD-OCT declined from 63 to 21% and from 60 to 26% at 12 months, respectively. Conclusion: A TAE regimen of IVT aflibercept in treatment naïve nvAMD is associated with good visual and anatomical outcomes in routine clinical practice. Resolution of exudation occurred in about half of nvAMD cases at 12 months. Individualized administration of IVT aflibercept may reduce injection burden. [ABSTRACT FROM AUTHOR]

Purpose: To assess disease stability (absence of intra- and/or subretinal fluid) and the portion of eyes being capable to extend their treatment interval to ≥ 12 weeks in exudative age-related macular degeneration (AMD). Methods: A systematic literature search was performed in NCBI, PubMed, CENTRAL, and ClinicalTrials.gov to identify clinical studies reporting treatment outcomes for ranibizumab, aflibercept, and brolucizumab in exudative AMD under a treat-and-extend protocol and a follow-up of ≥ 12 months. Weighted mean differences and subgroup comparisons were used to integrate the different studies. Results: This meta-analysis refers to 29 published series, including 27 independent samples and 5629 patients. In the pooled group, disease stability was reported in 62.9% and 56.0%, respectively, after 12 and 24 months of treatment, whereas treatment intervals were extended to ≥ 12 weeks in 37.7% and 42.6%, respectively. Ranibizumab, aflibercept, and brolucizumab differed regarding their potential to achieve disease stability (56.3%, 64.5%, and 71.5% after 12, and 50.0%, 52.7% and 75.7% after 24 months; p = < 0.001) and to allow an interval extension to ≥ 12 weeks (28.6%, 34.2%, and 53.3% after 12, and 34.2%, 47.7%, and 41.7% after 24 months; p = < 0.001). Conclusion: The portion of eyes achieving disease stability regressed in the second year, whereas the portion of eyes under a ≥ 12-week interval increased. This discrepancy may reflect the challenges in balancing between under-treatment and a reduced treatment burden. [ABSTRACT FROM AUTHOR]

Justus G Garweg1,21Swiss Eye Institute, Rotkreuz, and Berner Augenklinik Am Lindenhofspital, Bern, Switzerland; 2Department of Ophthalmology, Inselspital, University of Bern, Bern, SwitzerlandPurpose: To review published evidence for a treatment interval extension to ≥12-weeks in neovascular macular degeneration treated with intravitreal Aflibercept.Methods: A systematic search was performed in the NCBI/PubMed database to identify pro- and retrospective studies retrieved by the key terms or and or AND AND and included all papers that used a treat-and-extend (T&E) protocol including a loading phase of 3 intravitreal anti-VEGF injections and a minimal follow-up of 2 years. Disease stability was defined as the absence of any intraocular and absence or stability of subretinal fluid and pigment-epithelial detachment.Results: Four studies were identified that reported information pertaining to disease stability or treatment extension beyond 12 weeks under intravitreal Aflibercept therapy including 1,102 eyes in total. Following a T&E protocol, a mean of 62.9% achieved disease stability and a 6.9 letter gain based on 11.9 injections over 24 months of Aflibercept treatment. As much as 43.0% of all eyes or 64.1% of the eyes with stable disease were maintained on ≥12-weekly injection intervals.Conclusions: A consequent treatment with a null tolerance for intraretinal fluid is prerequisite to induce stability and maintain visual gain after the loading phase. Using Aflibercept in a T&E protocol, disease stability and interval extension to ≥12 weeks were reported in 43% of the eyes by end of the second year with less injections, but similar results as under fix dosing. A lower treatment burden strongly argues for an individualized proactive treatment regimen.Keywords: neovascular age-related macular degeneration, AMD, Aflibercept, intravitreal anti-VEGF injections, treat-and-extend, proactive treatment, long-term outcome, review

Copyright of Der Ophthalmologe is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Purpose: To investigate the efficacy and safety of a treat-and-extend (T&E) regimen using aflibercept (Eylea) for diabetic macular edema (DME). Study design: Prospective, open-label, multicenter, single-arm, nonblinded clinical study. Methods: Forty eyes of 40 patients with DME received a T&E regimen of intravitreal aflibercept injection (IAI) with the longest treatment interval set to 16 weeks and adjunct focal/grid laser for 1 year. An intent-to-treat analysis was performed using the same last-observation-carried-forward method. A per-protocol analysis was also performed for patients who completed a 1-year T&E regimen. The primary endpoints were mean changes in best-corrected visual acuity (BCVA) and central subfield macular thickness (CST) from baseline. Secondary endpoints included IAI-interval extension and resultant IAI numbers and the association between an early response to IAI and final BCVA gain at 1 year. Results: Thirty-one patients (77.5%) completed the 1-year aflibercept T&E regimen. In these per-protocol participants, the mean CST improvement/reduction was 187.3 ± 145.0 µm (P <.001), but the mean BCVA gain was limited to 4.3 ± 12.2 letters (P =.782). Subanalysis revealed that eyes that gained ≥ 4 letters (median at week 12) after the initial 3 consecutive IAIs (induction phase) achieved greater vision improvement (13.8 ± 9.5 letters) than did the residual eyes (− 4.3 ± 9.2 letters) at 1 year (P <.001). Treatment intervals were extended to 12 and 16 weeks in 16.1% (5/31) and 45.2% (14/31) of the patients, respectively. The mean IAI number was 7.0 ± 1.1. Conclusions: The results of this study suggest that although the BCVA improvement might be somewhat less than that of frequent treatment, a T&E aflibercept regimen with the longest treatment interval set to 16 weeks is a realizable rational strategy for DME treatment over 1 year. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the 4-year outcome of aflibercept treatment using a treat-and-extend (TAE) regimen for recurrent neovascular age-related macular degeneration (AMD). Study design: Retrospective observational study. Methods: Data of eyes with recurrent AMD previously treated with anti-vascular endothelial growth factor agents or photodynamic therapy and had started aflibercept treatment using a TAE regimen for the first time were collected. Best-corrected visual acuity (BCVA), intervals of treatments, the presence of exudation, central foveal thickness (CFT), and central choroidal thickness (CCT) were analyzed. Results: Of 47 consecutive eyes, 30 of the 47 eyes completed a 4-year follow-up. The mean BCVA (logMAR) was sustained over the 4 years (0.37 at baseline, 0.36 at 1 year, 0.36 at 2 years, 0.41 at 3 years, and 0.43 at 4 years, P = 0.21). Of the 30 eyes that completed the follow-up, BCVA of two eyes deteriorated by 0.3 logMAR or more at 4 years. At 4 years, 67% of eyes had extended treatment intervals to > 8 weeks, and 47% of eyes had extended intervals to > 12 weeks. Exudative changes in the macula, seen in all eyes at baseline, were only seen in 50% of the eyes at 4 years. The mean CFT and CCT decreased significantly at 4 years from 332 μm to 248 μm and from 218 μm to 183 μm, respectively. Conclusion: In clinical settings, aflibercept treatment using a TAE regimen may successfully maintain visual acuity for up to 4 years even in recurrent cases of AMD. [ABSTRACT FROM AUTHOR]

Purpose: To assess the noninferiority of the treat‐and‐extend (T&E) and fixed bimonthly regimens of 0.5 mg intravitreal ranibizumab as compared with the pro re nata (PRN) in naïve patients with neovascular age‐related macular degeneration (nAMD). Methods: Phase IV, randomized, 12‐month, multicentre trial. Patients aged ≥50 years with nAMD and visual impairment [best‐corrected visual acuity (BCVA) between 23 and 78 Early Treatment Diabetic Retinopathy Study (ETDRS) letters] were eligible. Patients (one eye per patient) were randomized to bimonthly, n = 103, T&E, n = 99 or PRN, n = 104. Noninferiority was established at five letters ETDRS. Results: The mean (95% CI) difference in BCVA at 12 months was 7.2 (4.2–10.2), 6.4 (2.9–9.8), and 8.0 (51.1–11.0) in the bimonthly, T&E and PRN, respectively. The bimonthly or T&E regimens were not inferior to the PRN scheme. All regimens were associated with a significant reduction of central subfield thickness and volume. The mean (95% CI) number of injections in the bimonthly regimen (7.6, 7.5–7.7) was similar as compared with the PRN regimen (7.4, 6.7–8.0) (p = 0.159) but lower than in the T&E regimen (9.3, 8.9–9.7) (p < 0.001). Conclusion: At 12 months, bimonthly and T&E ranibizumab were noninferior to PRN in naïve nAMD. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the physiology of the macular and whole retina after intravitreal aflibercept (IVAs) injections in patients with macular edema associated with a central retinal vein occlusion (CRVO) by electroretinography (ERG). Methods: We studied 20 eyes of 20 patients with non-ischemic CRVO (72.0 ± 9.2 years). All patients were treated with monthly injections of IVA for the initial 3 months and then treated by the treat-and-extend (TAE) regimen for 12 months. The best-corrected visual acuity (BCVA), optical coherence tomographic images, focal macular ERGs (fmERGs), and full-field ERGs recorded before and after the treatment were compared. The fmERGs were elicited by a 15° white stimulus spot centered on the fovea. The full-field ERGs were recorded by a protocol recommended by International Society for Clinical Electrophysiology of Vision. The amplitudes and implicit times determined before and after the IVA were compared. Results: The foveal thickness was significantly reduced accompanied by improvement of the BCVA after the treatments, and the improvements were maintained for at least 12 months. The amplitudes and implicit times of the fmERGs improved continuously for the 12 months. On the other hand, the reduced amplitudes of the full-field ERG, summed oscillatory potentials, and the photopic negative responses remained unchanged for the 12-month period. However, the implicit times of the maximum and cone responses were significantly shortened after the IVA. Conclusions: IVA injections by the TAE regimen led to a continuous improvement of the macular function in patients with ME associated with a CRVO. However, the function of the whole retina changed differently than the macula after the treatment. [ABSTRACT FROM AUTHOR]

Background: To evaluate the three-year outcome after intravitreal aflibercept injection (IAI) for neovascular age-related macular degeneration (nAMD).Methods: Forty-nine treatment-naïve nAMD patients (50 eyes) were enrolled in this prospective study. The eyes received IAI at two-month intervals in the first year. The treatment regimen was changed to IAI based on a treat-and-extend approach in the second and third years.Results: Twenty-nine eyes of 28 patients were successfully followed up over 36 months. The nAMD subtypes included 15 eyes with typical AMD and 14 eyes with polypoidal choroidal vasculopathy. The number of IAIs performed over the 3 years was 17.2 ± 3.1 (mean ± standard deviation). The mean logMAR, which was 0.42 at baseline, improved to 0.19 (P = 0.001) at 12 months, and 0.26 (P = 0.049) at 36 months. The central retinal thickness (CRT) was 329 ± 120 μm at baseline, 151 ± 38 μm (P < 0.001) at 12 months, and 143 ± 61 μm (P < 0.001) at 36 months. The mean subfoveal choroidal thickness (SFCT) was 288 ± 97 μm at baseline, 243 ± 82 μm (P < 0.001) at 12 months, and 208 ± 63 μm (P < 0.01) at 36 months. The changes in logMAR, CRT, and SFCT over the study period did not differ between typical AMD and PCV.Conclusion: Long-term aflibercept injection can achieve visual improvement and reduce the thickness of the retina and choroid in nAMD. Morphological improvement of these tissues may not be sufficient to sustain earlier visual improvement over the long-term. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate efficacy and safety of intravitreal injections of aflibercept (IVT-AFL) treat-and-extend (T&E) dosing regimens in treatment-naïve patients with exudative age-related macular degeneration (AMD).Methods: Adults aged at least 50 years old with exudative AMD and best-corrected visual acuity (BCVA) of 73-25 Early Treatment Diabetic Retinopathy Study (ETDRS) letters were included. Patients received three monthly doses of IVT-AFL 2 mg. At week 16, patients were randomized 1:1 to IVT-AFL T&E with either 2- or 4-week adjustments. The primary endpoint was mean change in BCVA from baseline to week 52. Outcomes were assessed at weeks 52 and 96.Results: Baseline characteristics were comparable between the groups (n = 123 each). Over 52 weeks, mean number of injections was 7.2 and 6.9 and mean last injection interval was 10.7 and 11.8 weeks, for the 2- and 4-week groups, respectively. From baseline, mean change in BCVA was + 9.0 and + 8.4 letters (week 52) and + 7.6 and + 6.1 letters (week 96); mean change in central retinal thickness was - 134.4 µm and - 126.1 µm (week 52) and - 130.5 µm and - 125.3 µm (week 96). Last injection interval before week 52 was at least 12 weeks in 42.3% and 49.6% of patients and 56.9% and 60.2% before week 96. Over 96 weeks, mean number of injections was 10.4 (both groups). The safety profile of IVT-AFL was consistent with previous reports.Conclusions: IVT-AFL administered using two different T&E regimens for treatment-naïve exudative AMD improved functional and anatomic outcomes at week 52 and outcomes were maintained to week 96. Outcomes were similar between the 2- and 4-week groups.Trial Registration: ClinicalTrials.gov identifier, NCT02305238. [ABSTRACT FROM AUTHOR]

Background: To evaluate the safety and efficacy of a treat-and-extend protocol of aflibercept for cystoid macular oedema (CMO) secondary to central retinal vein occlusion (CRVO).Methods: Twenty patients with CMO secondary to CRVO were included in this prospective cohort study. After 3 loading 4-weekly injections, treatment intervals were increased by 2 weeks if there was no clinical activity, to a maximum of 12 weeks. If clinical activity recurred or persisted, the interval between injections was shortened by 2 weeks, to a minimum of 4 weeks. Main outcome measures were change in visual acuity and the proportion of patients gaining 15 or more Early Treatment of Diabetic Retinopathy Study (ETDRS) letters from baseline at 6, 12 and 18 months.Results: Mean BCVA gain from baseline was 19.7 ± 13.8, 22.2 ± 13.9 and 21.9 ± 15.8 ETDRS letters at 6, 12 and 18 months, respectively. Sixty-five percent of patients gained 15 or more ETDRS letters at 6 months, increasing to 70.6% at 12 and 18 months. Patients received 5.0 [4.0 to 6.0], 8.5 [8.0 to 10.3] and 11.0 [9.0 to 12.5] injections by 6, 12 and 18 months, respectively.Conclusions: The visual outcomes achieved with a treat-and-extend protocol in this study were similar to the pivotal trials of aflibercept for CMO secondary to CRVO, which used monthly and then as-needed protocols.Trial Registration: Australian and New Zealand Clinical Trials Registry, registration number ACTRN12615000417583, 01/05/2015. [ABSTRACT FROM AUTHOR]