Initial Pro Re Nata Brolucizumab for Exudative AMD: The PROBE Study

The present study aimed to determine the efficacy and safety of pro re nata (PRN) intravitreal brolucizumab therapy for neovascular age-related macular degeneration (AMD) without a loading dose in the real-world setting. The PROBE study (Pro Re Nata Brolucizumab for Exudative AMD) is a retrospective, observational, multicentric study that included 27 treatment-naïve patients (27 eyes) with neovascular AMD who received PRN brolucizumab therapy with the treatment interval being at least 8 weeks, should the need for a second consecutive injection arise. The primary outcome measure was changed to best-corrected visual acuity (BCVA) over time. Secondary outcome measures included the determination of change in central subfield thickness (CST) and complications. The mean follow-up was 11.2 ± 1.2 months. The mean baseline and final BCVA were 57.4 ± 4.5 letters and 65.3 ± 3.12 letters, respectively (p = 0.014). The mean gain in letters at the end of follow-up was 7.8 ± 3.5 letters. There was a significant decrease in CST at the end of the follow-up period (p = 0.013). Patients received a mean of 2.2 ± 0.9 injections (in addition to the first mandatory injection) during the follow-up period. There were no adverse events noted. In conclusion, initial PRN brolucizumab for exudative AMD without a loading dose demonstrated significant visual improvement and no adverse events.

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One-year outcome of intravitreal ziv-aflibercept therapy for non-responsive neovascular age-related macular degeneration

British Journal of Ophthalmology ◽

10.1136/bjophthalmol-2017-310318 ◽

2017 ◽

Vol 102 (1) ◽

pp. 91-96 ◽

Cited By ~ 8

Author(s):

Imoro Zeba Braimah ◽

Komal Agarwal ◽

Ahmad Mansour ◽

Jay Chhablani

Keyword(s):

Adverse Events ◽

Macular Degeneration ◽

Retinal Pigment ◽

Subretinal Fluid ◽

Age Related Macular Degeneration ◽

Secondary Outcome ◽

Free Interval ◽

Age Related ◽

Significant Difference ◽

The Mean

AimTo evaluate 12-month outcome of intravitreal ziv-aflibercept (IVZ) therapy in eyes with neovascular age-related macular degeneration (nAMD) that are non-responsive to bevacizumab and ranibizumab.MethodsThis retrospective study included 16 eyes (14 patients) with nAMD who were on prior treatment with bevacizumab and ranibizumab and were treated with as-needed IVZ (1.25 mg/0.05 mL) for 12 months. The primary outcome measure was the mean change in best corrected visual acuity (BCVA) and secondary outcome measures included mean change in central macular thickness (CMT), retinal pigment epithelial detachment (RPED) heights, longest treatment free interval, presence of subretinal fluid (SRF) and intraretinal fluid (IRF) and adverse events.ResultsThere was no change in the mean logarithm of minimum angle of resolution (logMAR) BCVA at baseline and following treatment with IVZ therapy (p=0.978). The mean number of IVZ injections during 12 months was 5.9±3.3, and the mean number of antivascular endothelial growth factors (VEGFs) injections prior to switching to IVZ was 8.4±4.7. The mean treatment free interval was longer during IVZ therapy (114.4±67.1 days) compared with 76.3±54.6 days before IVZ therapy (p=0.03). Five (31.25%) eyes had visual gains of at least 0.1 logMAR, 3 (18.75%) eyes had stable BCVA (within 0.1 logMAR) and 8 (50%) eyes had BCVA decline of at least 0.1 logMAR. There was no significant difference in the mean CMT, RPED heights and presence of IRF and SRF at 12 months compared with baseline. No adverse events were noted.ConclusionIVZ increased the treatment free interval in non-responders but no significant change in visual and anatomic outcomes.

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One-Year Outcomes of 1 Dose versus 3 Loading Doses Followed by Pro Re Nata Regimen Using Ranibizumab for Neovascular Age-Related Macular Degeneration: The ARTIS Trial

Journal of Ophthalmology ◽

10.1155/2019/7530458 ◽

2019 ◽

Vol 2019 ◽

pp. 1-6

Author(s):

Fenghua Wang ◽

Yuanzhi Yuan ◽

Ling Wang ◽

Xiaofeng Ye ◽

Jingke Zhao ◽

...

Keyword(s):

Visual Acuity ◽

Macular Degeneration ◽

Age Related Macular Degeneration ◽

Link Type ◽

Age Related ◽

The Mean ◽

Pro Re Nata ◽

One Year ◽

Number Of Injections

Purpose. To compare the functional and anatomical outcomes of one dose and three loading doses followed by the pro re nata (PRN) regimen in Chinese neovascular age-related macular degeneration (nvAMD) (including polypoidal choroidal vasculopathy (PCV)) patients. Methods. In this multicenter, prospective, open-label, controlled, 12-month study (ClinicalTrials.gov: NCT02810808), patients were randomized (1 : 1) to 1 dose + PRN (PRN group) or 3 loading doses + PRN (LD group) using intravitreal ranibizumab treatment. Best-corrected visual acuity (BCVA) and central retinal thickness (CRT) were evaluated. The main outcome was the change in BCVA. The noninferiority limit was 5 letters. Results. Forty-five patients in the PRN group and 49 patients in the LD group finished 12-month follow-up. Each group included 4 PCV patients. The mean change in BCVA from baseline was 7.8 letters in the PRN group, compared with 10.9 letters in the LD group (P=0.344). There were no significant differences between two groups in the mean change of CRT (−159.3 μm vs. −120.5 μm) at month 12. The mean number of injections during the 12-month follow-up was 6.0 in the PRN group and 6.8 in the LD group. The proportion of patients who gained an improvement in visual acuity by 15 or more letters was 28.9% in the PRN group and 44.9% in the LD group (P=0.066). Conclusion. One dose + PRN showed noninferior visual gains than 3 loading doses + PRN regimen using ranibizumab in Chinese nvAMD and PCV patients. Number of injections in the PRN group was similar as that in the LD group but remained a potential risk of vision instability during one-year follow-up using OCT-guided retreatment criteria. This trial is registered with NCT02810808.

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Real-World Experience with Brolucizumab in Wet Age-Related Macular Degeneration: The REBA Study

Journal of Clinical Medicine ◽

10.3390/jcm10132758 ◽

2021 ◽

Vol 10 (13) ◽

pp. 2758

Author(s):

Alper Bilgic ◽

Laurent Kodjikian ◽

Francesc March de Ribot ◽

Vaishali Vasavada ◽

Jesus H. Gonzalez-Cortes ◽

...

Keyword(s):

Macular Degeneration ◽

Real World ◽

Age Related Macular Degeneration ◽

Secondary Outcome ◽

The Real ◽

Switch Therapy ◽

Age Related ◽

Treatment Naïve ◽

The Mean

The aim of the present study was to determine the efficacy and safety of intravitreal brolucizumab therapy for neovascular age-related macular degeneration (AMD) in the real-world setting. The REBA study (real-world experience with brolucizumab in wet AMD) was a retrospective, observational, multicentric study that included 78 consecutive patients (105 eyes), with neovascular AMD, who received brolucizumab therapy. Both treatment-naive and switch-therapy patients were included. Switch therapy was based either on fluid recurrence, fluid recalcitrance, or inability to extend beyond q4/q6. All relevant data were collected. The primary outcome measure was change in best-corrected visual acuity (BCVA) over time. Secondary outcome measures included determination of change in central subfield thickness (CST) and complications. The mean baseline BCVA was 49.4 ± 5.4 letters and 40 ± 3.2 letters, and corresponding mean BCVA gain was +11.9 ± 3.9 letters (p = 0.011) and +10.4 ± 4.8 letters (p = 0.014) in the treatment-naive and switch-therapy groups, respectively. The change in CST was significantly decreased in the treatment-naive (p = 0.021) and the switch-therapy (p = 0.013) groups. The mean follow-up was 10.4 months in both groups. One patient in the switch-therapy group developed vascular occlusion and another a macular hole after the fifth brolucizumab injection. Both patients recovered uneventfully. In conclusion, patients showed a very good anatomical and functional response to brolucizumab therapy in the real world, regardless of prior treatment status, until the end of the follow-up period. Two significant untoward events were noted.

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Pro re Nata versus Bimonthly Regimen in Exudative AMD Treated with Aflibercept: 1-year Results

Ophthalmology Point of Care ◽

10.5301/oapoc.0000021 ◽

2017 ◽

Vol 1 (1) ◽

pp. oapoc.0000021

Author(s):

Jean-Julien Keppi ◽

Benjamin Wolff ◽

Laurent Castelnovo ◽

Guillaume Michel ◽

Claude Speeg-Schatz ◽

...

Keyword(s):

Visual Acuity ◽

Diabetic Retinopathy ◽

Age Related Macular Degeneration ◽

Newly Diagnosed ◽

Age Related ◽

Intravitreal Aflibercept ◽

The Mean ◽

Pro Re Nata ◽

Visual Results

Purpose To compare pro re nata (PRN) and bimonthly intravitreal aflibercept injection protocols in the treatment of neovascular age-related macular degeneration (nAMD). Methods This was a retrospective, observational, comparative study in 2 centers. All study patients presented with newly diagnosed nAMD and were treated as follows after an induction of 3 consecutive monthly loading doses: the bimonthly group was retreated every 2 months and followed up every 4 months while the PRN group was retreated in case of subretinal exudation or visual acuity decrease and followed up every month. A comprehensive ophthalmic examination was performed at each study visit. Results At 1 year, 34 eyes were analyzed. The 19 patients in the bimonthly group had a mean visual acuity improvement of +8.5 Early Treatment Diabetic Retinopathy Study (ETDRS) letters whereas stabilization was observed in the PRN group (-0.47 ETDRS letters; p = 0.027). All patients in the bimonthly group had 4 follow-up visits and 7.5 injections whereas the mean number of follow-up visits in the PRN group (15 patients) was 7.8 with 7.6 injections. Conclusions Our study suggests that a fixed bimonthly aflibercept retreatment protocol may provide better visual results than a PRN protocol.

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Aflibercept in real-life for the treatment of age-related macular degeneration using a treat and extend protocol: The Armada study

European Journal of Ophthalmology ◽

10.1177/11206721211005703 ◽

2021 ◽

pp. 112067212110057

Author(s):

Pierre Gascon ◽

Prithvi Ramtohul ◽

Charles Delaporte ◽

Sébastien Kerever ◽

Danièle Denis ◽

...

Keyword(s):

Macular Degeneration ◽

Real Life ◽

Age Related Macular Degeneration ◽

Cumulative Number ◽

Treat And Extend ◽

Treatment Interval ◽

Age Related ◽

Treatment Naïve ◽

The Mean

Purpose: To report the visual and anatomic outcomes in treatment-naïve neovascular age-related macular degeneration (nAMD) patients treated with aflibercept under a standardized Treat and Extend (T&E) protocol for up to 3 years of follow-up in “real-life” practice. Methods: This retrospective, observational, multicenter study included patients with treatment-naïve nAMD and at least 12 months of follow-up. T&E regimen adjustment was initiated after loading phase. At each visit best-corrected visual acuity (BCVA) and optical coherence tomography parameters were performed. Results: One hundred and thirty-six eyes of 115patients had at least 1 year of follow-up with 114 and 82 eyes completing at least 2 and 3 years of follow-up, respectively (mean follow-up duration: 2.7 ± 1.3 years). Mean age was 78.6 ± 8.6 years old and 52% were women. Mean BCVA increased from 60.6 ± 18.7 letters at diagnosis to 66.9 ± 16.2 letters at 1 year (+6.3 letters, p = 0.003) and remained stable throughout the follow-up period (63.1 ± 20.3 letters (+2.5, p = 0.1) and 64.0 ± 20.1 letters (+3.4, p = 0.27) at 2 and 3 years, respectively). The mean central retinal thickness decreased significantly from 358.2 ± 87.9 µm at baseline to 302 ± 71.7 µm at 12 months and maintained stable after 36 months of follow-up (297.1 ± 76 µm, p < 0.0001). Mean number of injections was 6.6 ± 2.2, 4.8 ± 1.9, and 5.6 ± 1.7 at 1, 2, and 3 years, respectively. Mean cumulative number of 16.4 ± 5.6 injections after 3 years. Mean treatment interval was 6.8 ± 2.5 weeks at 1 year. Eight-week and 12-week treatment interval were achieved in 59.5% and 19.1%, 65.8%, and 36.8% and 69.5% and 41.5% at 1, 2, and 3 years, respectively. Conclusions: Our study demonstrated that intravitreal injections of aflibercept initiated under a standardized T&E for patients with treatment-naïve nAMD allow for significant visual improvement at 12 months, which was maintained over a 3-year follow-up period.

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Association between Retinal Thickness Variability and Visual Acuity Outcome during Maintenance Therapy Using Intravitreal Anti-Vascular Endothelial Growth Factor Agents for Neovascular Age-Related Macular Degeneration

Journal of Personalized Medicine ◽

10.3390/jpm11101024 ◽

2021 ◽

Vol 11 (10) ◽

pp. 1024

Author(s):

Timothy Y. Y. Lai ◽

Ricky Y. K. Lai

Keyword(s):

Visual Acuity ◽

Retinal Thickness ◽

Age Related Macular Degeneration ◽

Vascular Endothelial ◽

Anti Vegf ◽

Age Related ◽

Thickness Variability ◽

The Mean ◽

Endothelial Growth Factor

Previous studies based on clinical trial data have demonstrated that greater fluctuations in retinal thickness during the course of intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy for neovascular age-related macular degeneration (nAMD) is associated with poorer visual acuity outcomes. However, it was unclear whether similar findings would be observed in real-world clinical settings. This study aimed to evaluate the association between retinal thickness variability and visual outcomes in eyes receiving anti-VEGF therapy for nAMD using pro re nata treatment regimen. A total of 64 eyes which received intravitreal anti-VEGF therapy (bevacizumab, ranibizumab or aflibercept) for the treatment of nAMD were evaluated. Variability in spectral-domain optical coherence tomography (OCT) central subfield thickness (CST) was calculated from the standard deviation (SD) values of all follow-up visits after three loading doses from month 3 to month 24. Eyes were divided into quartiles based on the OCT CST variability values and the mean best-corrected visual acuity values at 2 years were compared. At baseline, the mean ± SD logMAR visual acuity and CST were 0.59 ± 0.39 and 364 ± 113 µm, respectively. A significant correlation was found between CST variability and visual acuity at 2 years (Spearman’s ρ = 0.54, p < 0.0001), indicating that eyes with lower CST variability had better visual acuity at 2 years. Eyes with the least CST variability were associated with the highest mean visual acuity improvement at 2 years (quartile 1: +9.7 letters, quartile 2: +1.1 letters, quartile 3: −2.5 letters, quartile 4: −9.5 letters; p = 0.018). No significant difference in the number of anti-VEGF injections was found between the four CST variability quartile groups (p = 0.21). These findings showed that eyes undergoing anti-VEGF therapy for nAMD with more stable OCT CST variability during the follow-up period were associated with better visual outcomes. Clinicians should consider adopting treatment strategies to reduce CST variability during the treatment course for nAMD.

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Comparison of the Effectiveness and Prognostic Factors of Intravitreal Ranibizumab between Typical Neovascular Age-Related Macular Degeneration and Polypoidal Choroidal Vasculopathy over 24 Months of Follow-Up

Ophthalmologica ◽

10.1159/000431000 ◽

2015 ◽

Vol 234 (1) ◽

pp. 33-39 ◽

Cited By ~ 9

Author(s):

Wataru Matsumiya ◽

Shigeru Honda ◽

Keiko Otsuka ◽

Akiko Miki ◽

Takayuki Nagai ◽

...

Keyword(s):

Macular Degeneration ◽

Polypoidal Choroidal Vasculopathy ◽

Age Related Macular Degeneration ◽

Morphological Parameters ◽

Intravitreal Ranibizumab ◽

Corrected Visual Acuity ◽

Age Related ◽

The Mean ◽

Choroidal Vasculopathy

Purpose: To compare the response to ranibizumab between patients with typical neovascular age-related macular degeneration (tAMD) and those with polypoidal choroidal vasculopathy (PCV), and to determine the predictors for the outcomes. Methods: Fifty-nine eyes from 59 consecutive patients (tAMD: 27 eyes, PCV: 32 eyes) were treated with three monthly ranibizumab injections followed by as-needed retreatment. Best-corrected visual acuity (BCVA) and morphological parameters were evaluated over 24 months of follow-up. Results: The mean BCVA in tAMD and PCV patients was significantly improved at 3 months (-0.22 and -0.09 logMAR units, respectively). The improvement in BCVA was sustained up to 24 months in tAMD (p = 0.01) but not in PCV patients. The significant predictor for good response to ranibizumab in tAMD patients was the improvement of BCVA at 3 months, whereas that in PCV patients was the anatomical resolution at 3 months. Conclusions: Ranibizumab is an effective therapy for tAMD and PCV over 24 months. The predictors for good outcome might be different between tAMD and PCV.

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Real-World Results of Aflibercept versus Ranibizumab for the Treatment of Exudative AMD Using a Fixed Regimen

BioMed Research International ◽

10.1155/2018/9276580 ◽

2018 ◽

Vol 2018 ◽

pp. 1-7 ◽

Cited By ~ 2

Author(s):

Joana Providência ◽

Tiago M. Rodrigues ◽

Mariana Oliveira ◽

João Bernardes ◽

João Pedro Marques ◽

...

Keyword(s):

Real World ◽

Age Related Macular Degeneration ◽

Treatment Protocols ◽

Corrected Visual Acuity ◽

Age Related ◽

Significant Difference ◽

Clinical Practice Setting ◽

The Mean ◽

Endothelial Growth Factors

Intravitreal injections of antivascular endothelial growth factors have been considered a milestone in the treatment of neovascular age-related macular degeneration (nAMD). However, the increasing incidence of AMD and the burden of visits and injections overcharge both the patient and the healthcare systems. Real-world solutions depend on treatment protocols aimed at optimizing the number of clinical visits while guaranteeing good functional outcomes. We performed a retrospective analysis of 72 eyes from 63 naïve patients diagnosed with nAMD that underwent a fixed intravitreal protocol consisting of bimonthly injections after a three-month loading dose, with either Aflibercept or Ranibizumab (no predefined criteria for treatment selection). Best corrected visual acuity (BCVA) and optical coherence tomography were analyzed at baseline and during follow-up clinical visits (months 3, 6, 12, and 18). From the included participants, 42 followed a fixed regimen with Aflibercept and 30 with Ranibizumab. At the 12-month visit, there was not a statistically significant difference in the mean change of BCVA between the two groups (p=0.121); however, the mean difference in the central retinal thickness was significantly superior in the Aflibercept group (-142.2 versus -51.5, p=0.011). The described fixed regimen seems to be efficient in the treatment of nAMD in a clinical practice setting.

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Age-Related Macular Degeneration: Clinical Findings following Treatment with Antiangiogenic Drugs

Journal of Ophthalmology ◽

10.1155/2014/346360 ◽

2014 ◽

Vol 2014 ◽

pp. 1-6 ◽

Cited By ~ 7

Author(s):

Ricardo Casaroli-Marano ◽

Roberto Gallego-Pinazo ◽

Clemencia Torrón Fernández-Blanco ◽

Marta S. Figueroa ◽

Begoña Pina Marín ◽

...

Keyword(s):

Macular Degeneration ◽

Clinical Findings ◽

Age Related Macular Degeneration ◽

Close Monitoring ◽

Loading Dose ◽

Vegf Inhibitors ◽

Age Related ◽

Antiangiogenic Drugs ◽

Antiangiogenic Drug

Purpose. To survey the management of patients with neovascular age-related macular degeneration (nvAMD) in Spain.Methods. An observational retrospective multicenter study was conducted. The variables analyzed were sociodemographic characteristics, foveal and macular thickness, visual acuity (VA), type of treatment, number of injections, and the initial administration of a loading dose of an antiangiogenic drug.Results. 208 patients were followed up during 23.4 months in average. During the first and second years, patients received a mean of4.5±1.8and1.6±2.1injections of antiangiogenic drugs, and5.4±2.8and3.6±2.2follow-up visits were performed, respectively. The highest improvement in VA was observed at 3 months of follow-up, followed by a decrease in the response that stabilized above baseline values until the end of the study. Patients who received an initial loading dose presented greater VA gains than those without.Conclusions. Our results suggest the need for a more standardized approach in the management and diagnosis of nvAMD receiving VEGF inhibitors. To achieve the visual outcomes reported in pivotal trials, an early diagnosis, proactive approach (more treating than follow-up visits), and a close monitoring might be the key to successfully manage nvAMD.

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Limited Treatment Response during Follow-up after Switching to Aflibercept in Neovascular Age-related Macular Degeneration

Journal of the Korean Ophthalmological Society ◽

10.3341/jkos.2021.62.9.1218 ◽

2021 ◽

Vol 62 (9) ◽

pp. 1218-1226

Author(s):

Gon Soo Choe ◽

Jong Woo Kim ◽

Chul Gu Kim ◽

Jae Hui Kim

Keyword(s):

Visual Acuity ◽

Retrospective Study ◽

Macular Degeneration ◽

Treatment Response ◽

Visual Outcome ◽

Age Related Macular Degeneration ◽

Neovascular Amd ◽

Age Related ◽

The Mean

Purpose: To investigate the limited response to aflibercept after switching to aflibercept in neovascular age-related macular degeneration (AMD). Methods: This retrospective study included 70 eyes with neovascular AMD that were initially treated with ranibizumab and then switched to aflibercept. The incidence and timing of the limited response to aflibercept were identified and visual outcome was compared between eyes with and without limited response. In addition, factors predictive of limited response were analyzed. Results: A limited response to aflibercept was noted in approximately 1/5 of the patients who underwent switching to aflibercept in neovascular AMD. Switching to aflibercept was performed at a mean of 16.2 ± 12.7 months after diagnosis. During the mean 34.7 months of follow-up after switching, limited response was noted in 15 eyes (21.4%) at a mean of 22.0 ± 13.9 months after switching. The degree of reduction in visual acuity was mean logMAR 0.34 ± 0.41 in eyes with limited response and mean 0.06 ± 0.20 in eyes without (p = 0.002). In addition, the duration between the diagnosis and the switching was shorter (p = 0.012), and the number of ranibizumab injections before switching was lower (p = 0.016) in eyes with limited response than in eyes without. Conclusions: Patients who showed limited response to aflibercept after switching to aflibercept showed a worse visual outcome. The probability of having a limited response is higher when the switching is performed earlier.

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