Old Problem in a New Guise: Retinal Pigment Epithelium Tear after Intravitreal Faricimab (Vabysmo^®) Injection

Abstract

This case report describes a 78-year-old patient who developed a tear of the retinal pigment epithelium (RPE) during faricimab (Vabysmo^®) therapy. After three consecutive intravitreal aflibercept (Eylea^®) injections with persistent disease activity, therapy was switched to faricimab. The patient experienced a tear in the RPE 4 weeks postinjection. We report the first published case of RPE tear development after intravitreal faricimab injection in neovascular age-related macular degeneration. Faricimab has a new target structure in the angiopoietin-2 receptor in addition to VEGF. Patients at risk for RPE rupture were excluded from pivotal studies. Further investigation is needed to understand the effect of faricimab not only on visual acuity and intraretinal and subretinal fluid but also on mechanical stress on the RPE monolayer.

Introduction

Tears of the retinal pigment epithelium (RPE) are most commonly associated with vascularized pigment epithelial detachments (vPED) due to neovascular age-related macular degeneration (nAMD). RPE tears may occur in the natural course of a vPED with underlying macular neovascularization (MNV) or polypoidal choroidal vasculopathy. Since the beginning of intravitreal anti-VEGF therapies in patients with vPED due to nAMD, the incidence of RPE tears has increasingly been reported as a complication after anti-VEGF injection [1].

Faricimab (Vabysmo^®) is a combined-mechanism medication with simultaneous and independent binding on both vascular endothelial growth factor A (VEGF-A) and angiopoietin-2 (Ang-2) and was approved for the treatment of nAMD in January 2022 [2]. We report the first published case of RPE tear development after intravitreal faricimab injection in nAMD.

Case Report

A 78-year-old patient presented to our clinic for follow-up of the left eye in the context of anti-VEGF therapy for nAMD. Initially, a vPED was diagnosed, and the lesion was treated with three consecutive intravitreal aflibercept (Eylea^®) injections between August 2022 and October 2022. Visual acuity increased from 20/80 to 20/63. Despite treatment, the height of the PED increased from 402 µm to 608 µm, and the amount of subretinal fluid became more (Fig. 1a, b). Intravitreal medication was then switched from aflibercept to faricimab. Four weeks after receiving the injection, the patient developed an RPE tear (Fig. 1c–f). Visual acuity remained unchanged at 20/63.

Fig. 1.

Multimodal imaging before and after retinal pigment epithelium (RPE) tear. a, b Near-infrared image and optical coherence tomography (OCT) image prior to RPE tear development. OCT shows a wrinkled RPE band as response to intravitreal aflibercept treatment. Besides, OCT scan reveals a hyperreflective macular neovascularization (MNV) membrane underneath the RPE band and a sub-RPE cleft presenting as hypo-reflective space between the Bruch’s membrane and the MNV. c–f Multimodal imaging after intravitreal faricimab injection: color fundus photography shows a depigmented area corresponding to the exposed choroid (star) (c). d RPE tear area appears as sharp hyperreflectivity in near-infrared image (star). e OCT shows the retracted edge of torn RPE and the missing RPE band in the RPE tear area (arrowhead). f Correspondingly, the area of unilobular RPE tear exhibits a markedly reduced fundus autofluorescent signal as RPE cells with fluorescent lipofuscin are lost (arrowhead).

Discussion and Conclusion

In the TENAYA and LUCERNE phase-3 nAMD trials investigating the efficacy, safety, and durability of faricimab compared with on-label intravitreal aflibercept, a RPE tear occurred in 2.7%/3.0% in the faricimab groups as compared to 1.8%/0.9% in the aflibercept group [2]. In a retrospective analysis, data from three pivotal phase III trials of intravitreal ranibizumab in patients with nAMD (MARINA, ANCHOR, PIER) were pooled and found a rate of RPE tears of 1.8% in the 0.5 mg group [3].

In contrast to anti-VEGF monotherapy, the dual specificity of faricimab may contribute to increased vascular stability and reduced inflammation, resulting in less fibrosis and atrophy. Neutralizing both Ang-2 and VEGF-A may have a synergistic effect leading to stronger therapeutic results [4, 5]. To date, there is little data regarding RPE tear development under faricimab therapy in nAMD patients and particularly in the important subgroup of high-risk vPED patients. In this context, it must be noted that high-risk vPED patients with a MNV component area of less than 50% of the total lesion size on fluorescein angiography were excluded from the pivotal studies.

Faricimab belongs to a new generation of intravitreal drugs for treating nAMD. Unlike other drugs that target only VEGF, faricimab additionally targets the Ang-2 receptor, making it a new type of therapy. Further research is needed to examine the effects of targeting this new pathway, not only its impact on visual acuity and intraretinal and subretinal fluid but also with regards to mechanical stress on the RPE monolayer. As high-risk vPED patients are not included in regulatory studies, it is important to monitor these patients in real-world studies regarding the incidence of RPE tears. Similar to the approach with anti-VEGF monotherapies, it is important to keep an eye out for key markers that may indicate an impending RPE tear when using faricimab.

Patients with high-risk factors for RPE tears, such as a large height (>550 µm) [1] and diameter of PED lesions, the presence of hyperreflective lines in near-infrared images, and a small ratio of MNV to PED, should be clearly informed of this risk prior to treatment. To minimize the risk of a tear, it is also important to consider extending the intervals between injections. The CARE Checklist has been completed by the authors for this case report, attached as online supplementary material (for all online suppl. material, see https://doi.org/10.1159/000529930).

Statement of Ethics

Ethical approval is not required for this study in accordance with local guidelines. Written informed consent was obtained from the patient for publication of the details of their medical case and any accompanying images.

Conflict of Interest Statement

Author Christoph Clemens has received speaker honorarium from Heidelberg Engineering, Novartis, and Bayer. Author Florian Alten has received speaker honorarium from Bayer. Author Julian Zimmermann declares no conflict of interest. Author Nicole Eter has received research grants from Novartis and Bayer and has received a speaker honorarium from Heidelberg Engineering, Novartis, Bayer, Sanofi Aventis, Allergan, Bausch, and Lomb.

Funding Sources

No funding has been received for this study.

Author Contributions

Christoph Clemens and Florian Alten conceived, drafted, and wrote the article. Julian Zimmermann and Nicole Eter performed critical revisions of the article and approved the final version of the manuscript.

Funding Statement

No funding has been received for this study.

Data Availability Statement

All data generated or analyzed during this study are included in this article and its online supplementary material. Further inquiries can be directed to the corresponding author.