Effective response to intravitreal faricimab in a patient with myopic neovascular membrane resistant to aflibercept

Summary

A 56-year-old woman with pathological myopia and macular neovascularization in the right eye was treated with 20 intravitreal injections of aflibercept following a treat-and-extend protocol, with no significant clinical improvement. A single intravitreal injection of faricimab was administered, after which the patient showed complete resolution of subretinal fluid and reduced neovascular lesions. Her visual acuity improved from 20/200 to 20/80 in the right eye, and she remained stable for 9 months without further signs of neovascular activity. Faricimab, which targets both VEGF-A and Ang-2, may be an effective alternative in myopic neovascular membranes resistant to aflibercept. Larger studies are needed to explore the long-term efficacy of faricimab in treating pathological myopia.

Introduction

Approximately 24% of adults over 40 years of age have myopia. Some of these patients may develop degenerative changes in the fundus of the eye, leading to pathological myopia (PM).1,2 Secondary macular neovascular membrane can occur in any degree of myopia, affecting up to 11% of patients with PM.1,2 Symptoms usually include metamorphopsia, central scotoma and visual distortion.1,2

Subretinal neovascularization is one of the main causes of progressive and irreversible loss of central vision, significantly compromising quality of life.3 Intravitreal injections of antiangiogenic drugs such as aflibercept are widely used in treating macular neovascularization, with proven efficacy in improving visual acuity and reducing retinal thickness.4,5 We present the case of a 56-year-old woman with myopic neovascular membrane whose condition failed to improve after 20 applications of aflibercept. She subsequently responded to a single dose of intravitreal faricimab.

Case Report

A 56-year-old woman with high myopia presented at Clinica Promedica (Indaiatuba, SP, Brazil) in May 2018 with sudden low visual acuity in the right eye. The patient had no history of systemic diseases or comorbidities. She had previously undergone phacoemulsification surgery with intraocular lens implantation in both eyes, with a presurgical refraction of −12 D sphere.

On initial evaluation, corrected visual acuity was 20/200 in the right eye and 20/25 in the left eye. Biomicroscopy showed transparent corneas, large and formed anterior chambers, trophic irides, intraocular lenses, and the absence of posterior capsule opacity. Retinal mapping revealed macular subretinal hemorrhage involving the foveal region, with rarefaction of the retinal pigment epithelium and choroidal thinning in the right eye. The left eye did not show significant alterations in the macular region, except for a reduction in choroidal thickness. No abnormalities were observed in the inner or outer retinal layers, and there were no signs of macular neovascularization in this eye. Optical coherence tomography (OCT) with Spectralis (Heidelberg Engineering Inc, Heidelberg, Germany) revealed a subretinal neovascular membrane in the right eye, with no changes in the left eye (Figure 1).

Figure 1.

Optical coherence tomography (OCT) of the right eye at baseline showing hyperreflective material in the subfoveal region and the presence of subretinal fluid.

Treatment was initiated, with administration of 3 monthly doses of aflibercept without satisfactory response. Despite the suboptimal anatomical response, a treat-and-extend approach was adopted to stabilize the lesion and reduce the treatment burden. Other anti-VEGF agents were not employed initially due to limitations in availability and local regulatory approvals. Between November 2018 and October 2023, 20 applications of aflibercept were performed in the right eye, without significant clinical improvement (Figure 2). Because of the poor response to aflibercept in December 2023, a single application of faricimab was performed in the right eye. The post-application examination showed complete resolution of the subretinal fluid and reduction of the neovascular lesion (Figure 3). The patient has remained stable through December 2025, with no signs of neovascular membrane activity, maintaining a visual acuity of 20/80 in the right eye and 20/25 in the left eye.

Figure 2.

OCT of the right eye showing presence of intraretinal fluid and presence of hyperreflective material in the subfoveal region after 19 doses of intravitreal aflibercept.

Figure 3.

OCT of the right eye showing no intraretinal fluid but persistence of hyperreflective material after a single dose of intravitreal faricimab.

Discussion

Aflibercept is a vascular endothelial growth factor (VEGF) inhibitor widely used in treating ocular neovascularizations, including those associated with pathological myopia. The MYRROR Study (2015) demonstrated an average gain of 12.1 letters in corrected visual acuity at 24 weeks and a significant reduction in central retinal thickness. However, there are cases of resistance to aflibercept treatment, as evidenced by the present case.4

Potential causes of failure to respond to aflibercept include anomalies in vascular morphology, such as arteriolar neovascularization, which is less responsive to treatment.6 Another possible cause of resistance is choroidal vascular hyperpermeability, observed in studies on age-related macular degeneration, a condition that shares pathological features with myopic choroidal neovascularization (MCN).7 Serous detachment of the pigment epithelium (DEP) has also been associated with non-responsiveness to aflibercept in patients with diabetic macular edema (DME), suggesting that this condition may influence treatment response in MCN.8 None of these factors associated with reduced responsiveness to aflibercept were not present in our patient, who displayed a thin choroid and lacked other high-risk features.

Increased choroidal thickness may also contribute to anti-VEGF treatment failure, because patients with higher choroidal thickness tend to be less responsive. While most of this evidence comes from studies on DME, these factors are also thought to play a role in patients with MCN.9

Faricimab is an innovative therapy that simultaneously blocks VEGF-A and angiopoietin-2 (Ang-2). By inhibiting these two pathways, faricimab has the potential to offer a therapeutic advantage in aflibercept-resistant cases. Ang-2, by interacting with the Tie-2 receptor, contributes to vascular instability and increased permeability, exacerbating neovascularization. Clinical studies, such as TENAYA and LUCERNE, conducted on patients with age-related macular degeneration, have shown that faricimab offers comparable efficacy to aflibercept, with longer intervals between injections.10 Although Ang-2 has not been directly associated with resistance to aflibercept, its inhibition may explain the limited response to aflibercept and the observed improvement with faricimab in this case.

Faricimab is still in the early stages of evaluation for MCN, but its bispecific mechanism of action may represent an effective approach for patients who do not respond adequately to other anti-VEGF therapies. More studies are needed to confirm the efficacy of faricimab in this context; nevertheless, this case provides early evidence that the drug may be a viable alternative. to aflibercept.