Full-Thickness Macular Hole After Faricimab Treatment for Branch Retinal Vein Occlusion-Associated Macular Edema with Vitreomacular Traction: A Case Report

Introduction

The treatment strategy for vitreomacular traction (VMT) is generally straightforward; however, the optimal timing of vitrectomy varies depending on the severity of visual symptoms, including decreased visual acuity or metamorphopsia [1]. When cystoid macular edema (CME) develops during observation for VMT, the appropriate sequence of interventions becomes less clear [2]. Although anti-vascular endothelial growth factor (VEGF) therapy is often used for CME secondary to branch retinal vein occlusion (BRVO), its effect on tractional components such as VMT is unpredictable. Recent evidence indicates that vitreoretinal interface abnormalities can occur in retinal vein occlusion; VMT is present in approximately 3% of eyes and epiretinal membrane (ERM) manifests in about 18% [3]. According to the International Vitreomacular Traction Study Group, vitreomacular adhesion refers to persistent vitreous attachment without retinal distortion; VMT denotes such attachment accompanied by morphologic changes without a full-thickness defect; and a macular hole represents a full-thickness foveal defect [4].

Here, we describe a patient with VMT under observation who developed BRVO, received anti-VEGF therapy, and subsequently formed a full-thickness macular hole (FTMH) that required vitrectomy. This case is notable because FTMH formation after anti-VEGF therapy for BRVO with preexisting VMT has rarely been reported. The presence of subtle optical coherence tomography (OCT) features, such as vertical hyperreflective lines, may provide insight into early structural stress at the fovea. Recognition of such atypical progression may aid clinical decision-making and improve monitoring strategies in similar cases.

Case Report

A 72-year-old woman had been under observation at a referring eye clinic for approximately 1 year concerning VMT with a lamellar macular hole (LMH) detected on OCT (Figure 1A, 1B). She later developed BRVO with CME, prompting referral to our hospital. The best-corrected visual acuity (BCVA) at presentation was 20/22. Fundus photography revealed intraretinal hemorrhages in the superonasal macula (Figure 1C). OCT showed CME with coexisting VMT, an ERM, an LMH, and a vertical hyperreflective line at the fovea (Figures 1D, 1E, 2A, 2B). One week after intravitreal faricimab injection, CME improved, but VMT persisted (Figure 1F–1H), and BCVA slightly declined to 20/25. OCT maps indicated partial reduction of edema, particularly in the superior parafoveal region (Figure 2C, 2D).

Four weeks after injection, BCVA further decreased to 20/33. OCT revealed a stage 2 FTMH at the site of the previously observed hyperreflective line (Figure 1I–1K), with persistent but reduced macular edema (Figure 2E, 2F). Given the progressive visual decline and anatomical confirmation of FTMH with residual traction, anti-VEGF therapy was discontinued, and surgical intervention was deemed necessary. Age-related lens opacity was also noted.

Two weeks later, the patient underwent combined cataract extraction and pars plana vitrectomy with internal limiting membrane (ILM) peeling stained using indocyanine green, followed by 20% sulfur hexafluoride (SF6) gas tamponade. A circular ILM area centered on the fovea (approximately 2 disc diameters in size) was peeled without use of an inverted flap or other modified techniques. One week postoperatively, fundus imaging confirmed gas tamponade and residual hemorrhage (Figure 3A); OCT demonstrated successful FTMH closure without clinically significant residual edema (Figure 3B, 3C). Compared with preoperative findings, the macular thickness map showed decreased thickening in the superior region (Figure 3D, 3E).

Three weeks postoperatively, intraretinal hemorrhages had partially resolved; however, OCT demonstrated recurrent CME with cystoid spaces, particularly in the inner nuclear layer (Figure 3F–3H). Macular thickness maps confirmed increased thickness in the superior subfield (Figure 3I, 3J). Six weeks postoperatively, CME worsened further (Figure 4A–4E) despite the maintenance of FTMH closure. A second faricimab injection was administered. One week after reinjection, OCT revealed substantial resolution of CME (Figure 4F–4H); macular maps confirmed substantial normalization of thickness in the central and superior subfields (Figure 4I, 4J). BCVA improved to 20/22.

Discussion

FTMH is a rare but recognized complication after intravitreal anti-VEGF therapy and is most frequently reported in eyes with neovascular age-related macular degeneration (nAMD) [5–7]. Previous reports have described this complication after treatment with agents such as ranibizumab, aflibercept, and bevacizumab [5–9]. Such events are exceedingly rare in patients with BRVO, despite the widespread use of anti-VEGF agents for macular edema associated with this condition [8]. To our knowledge, this is the first reported case of FTMH formation after faricimab injection in a patient with BRVO-associated CME and coexisting VMT.

FTMH formation after intravitreal anti-VEGF therapy is thought to result from the rapid resolution of CME, which can abruptly alter vitreoretinal tractional forces in eyes with preexisting VMT or ERM [5–7]. In the present case, FTMH developed within 1 month of faricimab injection in an eye with focal VMT, supporting this mechanism. Whereas FTMH is more commonly reported in nAMD [5–7], its occurrence in BRVO is rare, likely reflecting a lower prevalence of vitreoretinal interface abnormalities in this population (relative to patients with nAMD) [2,3]. However, the presence of VMT – as demonstrated in the present case – may substantially increase this risk. A recent review by Rajeswaren et al identified VMT (36%), subretinal fluid (68%), and pigment epithelial detachment (68%) as key risk factors for macular hole formation after anti-VEGF therapy in nAMD, emphasizing the role of preexisting vitreoretinal interface pathology [10]. Furthermore, vitreomacular adhesion involving residual vitreous collagen and glial proliferation may generate focal stress points at the fovea, heightening susceptibility to structural failure during rapid anatomical changes [1,11].

Among anti-VEGF agents, faricimab is distinguished by its dual inhibition of VEGF-A and angiopoietin-2, which not only reduces vascular permeability but also enhances vascular stabilization [12]. This dual mechanism may promote faster and more pronounced resolution of macular edema relative to other agents. In eyes with preexisting VMT or ERM, such abrupt structural changes may destabilize the fovea and precipitate macular hole formation. In our case, faricimab was selected as the initial treatment to achieve a robust anatomical response with fewer injections, given the patient’s advanced age and limited ability to attend frequent follow-up visits. Although a definitive causal relationship could not be established, faricimab’s potent and rapid dual action may have acted as a precipitating factor for FTMH formation in an anatomically predisposed eye.

Notably, a vertical hyperreflective line was visible at the fovea on pretreatment OCT. This feature morphologically resembles the “foveal crack sign”, a potential predictive biomarker for macular hole formation in eyes with persistent vitreomacular adhesion [13]. Furashova and Matthe reported that eyes exhibiting both the foveal crack sign and vitreous adhesion had a 77% risk of developing FTMH, suggesting a strong predictive value for this OCT finding. Similarly, Scharf et al described hyperreflective stress lines as early indicators of foveal stress and Müller cell cone instability caused by tractional forces [14]. The same OCT feature was observed in the present case, supporting the interpretation of focal foveal stress before anti-VEGF therapy-induced anatomical changes.

In cases of coexisting CME and VMT, treatment selection requires careful consideration. Anti-VEGF agents are widely accepted as first-line therapy, although their efficacy may be limited in tractional cases. Gong et al demonstrated that eyes with diabetic macular edema and VMT exhibited less reduction in central macular thickness after anti-VEGF therapy relative to such eyes without VMT, suggesting that mechanical traction can diminish therapeutic response [2]. Corticosteroid therapy, such as dexamethasone intravitreal implants, has been shown to reduce macular edema in patients with BRVO; however, its effects on preexisting vitreoretinal interface abnormalities remain poorly characterized. Castro-Navarro et al reported anatomical improvement in BRVO-associated CME with dexamethasone implants, although VMT progression was not specifically assessed [15]. Bakri and Omar described a case in which VMT worsened after corticosteroid administration, underscoring the potential risk of unmasking or aggravating traction [16]. Furthermore, dexamethasone implants accelerate cataract formation, making them a less favorable option in phakic eyes [17].

Intriguingly, not all FTMHs occurring after anti-VEGF therapy require surgical intervention, given that spontaneous closure has been documented in some cases [18,19]. In such instances, dynamic changes in the vitreoretinal interface – such as recurrence of macular edema or centripetal contraction of the ERM – may approximate the macular hole edges and promote closure. In the present case, however, persistent VMT, the presence of an ERM, and a hyperreflective vertical line resembling the foveal crack sign on baseline OCT indicated preexisting focal foveal stress and an unfavorable biomechanical environment for spontaneous closure. These findings collectively suggest that the likelihood of spontaneous closure strongly depends on the preexisting condition of the vitreoretinal interface, rather than pharmacologic differences among anti-VEGF agents.

Considering these limitations, vitrectomy may be a valid therapeutic option in selected cases. Kimura et al reported favorable anatomical outcomes after vitrectomy with ILM peeling in eyes with nAMD refractory to anti-VEGF therapy and associated with VMT or ERM [20]. Similarly, Meyer et al demonstrated that relieving VMT through surgery may help prevent FTMH formation in high-risk eyes [21]. In the present case, residual CME persisted and worsened at 6 weeks postoperatively despite successful FTMH closure. A second intravitreal faricimab injection led to prompt resolution of CME and restoration of visual acuity to 20/22. This favorable response indicates that anti-VEGF therapy may remain effective even after surgical intervention, once tractional components have been eliminated.

No prospective studies have directly compared anti-VEGF therapy with early vitrectomy in eyes exhibiting VMT and CME of various etiologies. This case report is inherently limited by its single-patient design, which restricts generalizability. Although the observed anatomical progression and temporal association suggest a plausible causal relationship between faricimab injection and FTMH formation, the findings should be interpreted cautiously. Because such coexisting pathologies are uncommon, individual centers may lack sufficient case volumes to enable meaningful comparisons. Thus, collaborative multicenter studies are essential to establish optimal management strategies for these rare but clinically significant cases. Future research should examine the comparative efficacy of different treatment modalities – including anti-VEGF agents, corticosteroids, and early vitrectomy – and evaluate the prognostic value of imaging biomarkers (e.g., foveal crack sign) for identifying high-risk patients.

Conclusions

This case demonstrates that FTMH formation may occur after anti-VEGF therapy in eyes with preexisting VMT. The vitreoretinal interface should be carefully assessed before treatment, particularly in eyes with tractional components. These findings highlight the importance of individualized treatment planning and suggest that potent agents such as faricimab should be used cautiously in anatomically vulnerable eyes. Future studies should further investigate imaging biomarkers, including the foveal crack sign, to identify high-risk patients and guide therapeutic decisions. This case underscores the need for comprehensive evaluation of both anatomical and therapeutic factors to minimize traction-related complications.