Efficacy of 2 mg vs. High-Dose 8 mg Aflibercept in Neovascular Age Related Macular Degeneration

Abstract

Purpose To investigate the efficacy of switching treatment from 2 mg aflibercept to high-dose 8 mg aflibercept in neovascular age-related macular degeneration (nAMD).

Methods The database was screened for eyes with nAMD switched from 2 mg to 8 mg aflibercept. Demographic data, multimodal imaging, treatment parameters and outcomes were recorded. Efficacy of 2 mg vs. 8 mg aflibercept was compared four injections prior to, and four injections after switching by analysing central subfield thickness (CST), subretinal fluid (SRF) and intraretinal fluid (IRF) as well as visual acuity (VA).

Results Sixteen consecutive eyes of 16 patients (mean age 78.5 ± 5.5 years) were identified. There were 13 women (81.3%) and 3 men (18.7%). Prior to switching, mean anti-vascular endothelial growth factor (VEGF) treatment duration for nAMD was 8.1 ± 2.1 years and pretreatment amounted to a mean of 27.8 ± 23.6 injections. Mean injection intervals were similar prior to and after switching (5.05 vs. 5.13 weeks; p = 0.76). CST remained stable before and after switching (p = 0.25). After switching, the percentage of eyes with a dry macula increased from 0% to 37.5% (p = 0.02) and the percentage of eyes with SRF decreased from 93.8% to 56.3% (p = 0.037). There was a trend, but no significant effect towards a reduction of IRF (18.8% to 6.3%, p = 0.60). Visual acuity remained stable irrespective of treatment (p = 0.78).

Conclusions Concerning CST on OCT, no clear advantage of high-dose 8 mg aflibercept over conventional 2 mg aflibercept was seen in this study. However, with high-dose 8 mg aflibercept the number of eyes with a dry macula increased, and the amount of eyes with SRF decreased significantly. In pretreated eyes, the analysis of macular fluid compartments (as compared to CST) might be more sensitive for comparing treatment effects between 2 mg and 8 mg aflibercept.

Zusammenfassung

Zielsetzung Untersuchung der Wirksamkeit eines Therapiewechsels von 2 mg Aflibercept auf hochdosierte 8 mg Aflibercept bei neovaskulärer altersbedingter Makuladegeneration (nAMD).

Methoden Die Datenbank wurde auf Augen mit nAMD durchsucht, bei denen von 2 mg auf 8 mg Aflibercept umgestellt wurde. Es wurden demografische Daten, multimodale Bildgebung, Behandlungsparameter und Therapieergebnisse erfasst. Die Wirksamkeit von 2 mg vs. 8 mg Aflibercept wurde jeweils über 4 Injektionen vor und nach dem Wechsel verglichen, wobei die zentrale Netzhautdicke (CST), subretinale Flüssigkeit (SRF), intraretinale Flüssigkeit (IRF) sowie die Sehschärfe (VA) analysiert wurden.

Ergebnisse Es wurden 16 konsekutive Augen von 16 Patienten (Durchschnittsalter 78,5 ± 5,5 Jahre) identifiziert, darunter 13 Frauen (81,3%) und 3 Männer (18,7%). Vor dem Wechsel betrug die mittlere Behandlungsdauer mit antivaskulären endothelialen Wachstumsfaktor-Injektionen (VEGF-Injektionen) 8,1 ± 2,1 Jahre bei durchschnittlich 27,8 ± 23,6 vorherigen Injektionen. Die mittleren Injektionsintervalle waren vor und nach dem Wechsel vergleichbar (5,05 vs. 5,13 Wochen; p = 0,76). Die CST blieb vor und nach dem Wechsel stabil (p = 0,25). Nach dem Wechsel stieg der Anteil an Augen mit trockener Makula von 0% auf 37,5% (p = 0,02) und der Anteil an Augen mit SRF sank signifikant von 93,8% auf 56,3% (p = 0,037). Es zeigte sich ein Trend zu einer Reduktion von IRF (18,8% auf 6,3%), der jedoch nicht signifikant war (p = 0,60). Die Sehschärfe blieb unabhängig von der Behandlung stabil (p = 0,78).

Schlussfolgerung Bezüglich der CST in der OCT zeigte sich in dieser Studie kein eindeutiger Vorteil von hochdosiertem 8 mg Aflibercept gegenüber der konventionellen 2 mg-Dosierung. Mit 8 mg Aflibercept konnte jedoch der Anteil an Augen mit trockener Makula signifikant gesteigert und der Anteil an Augen mit SRF signifikant reduziert werden. Bei vorbehandelten Augen könnte die Analyse der Flüssigkeitskompartimente in der Makula (im Vergleich zur CST) sensitiver für den Vergleich von Behandlungseffekten zwischen 2 mg und 8 mg Aflibercept sein.

Conclusion Box

Already known:

• High-dose aflibercept (8 mg) has been shown in randomized clinical trials to be safe and potentially more durable compared to the standard 2 mg formulation.

• Quantitative OCT parameters such as CST are widely used to assess treatment efficacy, but may not always capture subtle changes in macular fluid compartments.

• It remained unclear whether switching pretreated and therapy-resistant nAMD eyes from aflibercept 2 mg to 8 mg would improve fluid control in a real-world setting.

Newly described:

• In this real-world cohort, switching from aflibercept 2 mg to 8 mg significantly increased the proportion of eyes achieving a dry macula.

• Subretinal fluid decreased markedly after the switch, while CST values remained stable without significant change.

• The study highlights that qualitative OCT fluid analysis may be more sensitive than CST for detecting treatment effects of high-dose aflibercept in heavily pretreated nAMD eyes.

Keywords

aflibercept - intravitreal injections - nAMD

Schlüsselwörter

Retina - Aflibercept - altersbedingte Makuladegeneration - intravitreale Injektionen

Publication History

Received: 01 August 2025

Accepted: 24 November 2025

Accepted Manuscript online:
15 December 2025

Article published online:
18 February 2026

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