The clinical introduction of faricimab as a novel treatment for nAMD is of particular interest in ophthalmology [13]. This study confirms that patients inadequately managed with ranibizumab and aflibercept for nAMD can benefit from switching treatment to faricimab to improve CST and maintain, or even slightly improve SFCT.
In this study, an inadequate response to anti-VEGF treatment was defined as persistent fluid in spite of 4-weekly dosing, or the inability to extend treat & extend intervals beyond 4 or 6 weeks. In real life studies with ranibizumab and aflibercept, continuous treatment intervals of 4 weeks were shown to be needed in 19–27% of eyes [14, 15], indicating a large population of patients possibly benefitting from treatment switches to newer, longer-lasting anti-VEGF agents.
To this end, novel anti-VEGF molecules as well as bispecific approaches have been investigated. Faricimab as a bispecific antibody against VEGF-A and the Ang2/Tie-2 pathway raised promising expectations in preclinical evidence in terms of vascular stability and reducing leakage [16] which were confirmed in large phase III clinical trials [7, 9].
To our knowledge, only a few trials have been conducted to investigate the efficacy of faricimab in a real-world setting since its approval [13, 17, 18]. These few published studies are mainly related to therapy-naïve patients, and there is little data on the outcome of faricimab therapy after pretreatment with other intravitreal drugs. Aim of the present study was to evaluate the short term response after switching to faricimab treatment following prior anti-VEGF treatment.
In the current study we focused on the morphological outcomes in OCT during loading phase of faricimab. OCT allows for a fast, accurate and quantitative assessment of nAMD and has established itself as an effective diagnostic standard in AMD [5, 19]. CST is one of the main CNV activity markers, it provides a good readily comparable reference point [5]. Beside CST being an OCT progression marker, SFCT should also be of interest. Growth of choroidal vessels is affected by the retinal pigment epithelium mediated by VEGF [16, 20, 21]. There are controversial findings in literature, however VEGF inhibition can lead to a SFCT thinning by inducing vasoconstriction and reduction of choriocapillaris endothelial cell fenestrations. Additionally SFCT thinning could also be secondary to suppression of the CNV activity [22]. Not only VEGF receptors are expressed in the choroid, furthermore Ang1/Tie2 receptors, maintain the choroidal vessels [23]. As faricimab affects both receptors, its impact could be greater than anti-VEGF inhibitors.
Although all eyes in the present study had a long history of pretreatment, having received on average 38.4 ± 26.7 anti-VEGF injections before starting faricimab, the clinical response was only limited. In spite of the heavy pretreatment, faricimab nevertheless allowed for improvements in CST. Additionally, limited effects on SFCT were observed. SFCT, representing the perfusion origin of MNV, has been shown to influence anti-VEGF outcomes in nAMD eyes, especially those with a thick-choroid phenotype, e.g. PCV [24]. As this study presents the short-term effects after the loading phase, further studies assessing the possibility of treatment interval extension based on these
Tenaya and Lucerne as phase 3 clinical studies compared faricimab to aflibercept in treatment naïve eyes. Faricimab provided equal functional and morphological outcomes with an interval of up to sixteen weeks [9]. This phase 3 studies were conducted with treatment naïve eyes, so a greater improvement in VA and CST in comparison with pre-treated eyes is expected [13]. Despite these results raising promising expectations, the effect of faricimab in clinical practice now needs to be verified in treatment naïve and pretreated patients. In this context, our data present real-world outcomes of treatment switch in pretreated eyes. Our findings correlate well with other studies on the subject. Stanga et al. evaluated VA and CST in 11 eyes early on after approval. Follow up time was only four weeks in this early published study. Both VA and CST improved [17]. Although those first and early results seemed to be promising, follow up time was short and cohort size small. Two Japanese studies of 2023 showed a decrease in central foveal and choroidal thickness, as well as an increase in VA within the first three month of faricimab loading in treatment naïve patients [18, 23]. Overall, the morphological outcomes after faricimab were comparable to those after aflibercept treatment [23]. Even in treatment resistant AMD, faricimab can lead to an improved CST and VA even in treatment resistant AMD [13, 25]. Kichi et al found a decrease in CST without an improvement in VA, however treatment intervals could be prolongated [26]. Consistent with existing studies, we could verify these results in the documented CST decrease.
Interestingly, improvements were readily seen after the first faricimab injection. However, subsequent injections maintained this effect but did not significantly improve it. The effect power of 0,4 corresponds to a medium sized effect. Among patients receiving ranibizumab therapy immediately before the switch, the effect was greater compared to patients previously receiving aflibercept. On the other hand, not every eye showed a favorable response to faricimab. As shown in Fig. 2, eyes with a weak faricimab response do exist and reswitching to prior treatment should be considered.
As a limitation, the present study focuses on morphological results of OCT measurements, whereas subjective visual improvement, metamorphopsia and visual acuity are not assessed. When assessing the OCT results, it should be noted that the automatic segmentation of the Heidelberg Explorer fails in a number of cases when images are captured with IRF or SRF. The measurement accuracy of SFCT is limited by person-dependent manual measurement. The entire OCT evaluation and measurement of the SFCT was performed by the same person and the automatic segmentation was checked.
In conclusion, our data support the efficacy of switching treatment in eyes with nAMD not adequately responding to older anti-VEGF agents. Future studies should observe not only the ability to extend treatment intervals, but also the the long-term course both functionally and morphologically.