One-year results of intravitreal injections of brolucizumab in patients with polypoidal choroidal vasculopathy
We studied the 1-year outcomes of IVBr injections in treatment-naïve Japanese PCV patients and found that BCVA improved significantly during the follow-up period. CMT and CCT also decreased significantly after 1 year. Polypoid lesions completely regressed after 1 year in 93.3% of eyes. To our knowledge, no previous study has assessed the regression rate of polypoid lesions regarding outcomes at 1 year after IVBr injections for patients with PCV.
In a sub-analysis of the HAWK study, Ogura et al.17 reported the efficacy of brolucizumab in Japanese patients with PCV. They reported that brolucizumab (n=39) was as effective as aflibercept (n=30) in improving vision. Yamamoto et al.12 conducted a multicenter study and reported outcomes at 1 year in 90 PCV-naïve eyes treated with fortnightly intravitreal aflibercept and reported a mean improvement in BCVA of 0.31 to 0.17 logMAR. The average number of injections during the first year was 7.1. Morimoto et al.18 reported outcomes at 2 years in 58 PCV treatment naïve eyes with a good baseline BCVA treated with intravitreal aflibercept using a treatment and extension regimen (TAE) and found a mean improvement in BCVA of 0.27 to 0.12 logMAR in the first year. The average number of injections during the first year was 7.72. In the current study, mean BCVA improved from 0.28 to 0.13 logMAR. The number of injections was 6.4. Although a direct comparison between our study and previous results is difficult, our visual results with brolucizumab appear favorable, with fewer injections compared to aflibercept in Japanese patients with PCV.
In the current study, CCT decreased significantly from 226 to 181 µm (19.9% decrease from baseline) at 1 year. We have previously reported outcomes at 1 year in treatment-naïve PCVs treated with fortnightly intravitreal aflibercept who had a mean decrease in CCT from 265 to 231 µm (12.8% decrease from baseline)11. Koizumi et al.19 also reported changes in subfoveal choroidal thickness after intravitreal injections of aflibercept in 86 patients with PCV at 1 year and reported a mean decrease in CCT from 270 to 234 µm (13.3% decrease per compared to inclusion). Therefore, the reduction in choroidal thickness in PCV patients treated with IVBr injections tended to be greater than that achieved with aflibercept. Kim et al.20 reported a decrease in choroidal thickness after anti-VEGF therapy for PCV. Choi et al.21 studied 88 patients with PCV who received anti-VEGF injections and reported that faster growth of chorioretinal atrophy (CRA) was significantly related to decreased choroidal thickness. A greater decrease in choroidal thickness could be a risk factor for the long-term development of ARC in patients with PCV. Thinning of the choroid could affect ARC in the longer term and ARC may be linked to BCVA. Therefore, it is necessary to determine whether IVBr injections affect VA over a longer follow-up period.
In the current study, 60.0% of patients with PCV completed injections at 12-week intervals for 1 year. A dry macula was obtained in 73.3% after 1 year. Ogura et al.17 reported the efficacy of brolucizumab in Japanese patients with PCV in a sub-analysis of the HAWK study. The authors reported that the probability of injections at 12-week intervals after a 48-week loading phase was 76%, which was similar to our result. Injections at 12-week intervals were the longest intervals in the TAE regimen, which is widely used around the world. The persistence of brolucizumab could be due to its strong affinity for VEGF. Its low molecular weight allows for greater drug delivery by injection compared to other available anti-VEGFs and offers the potential for more efficient tissue penetration and increased duration of action14. Therefore, brolucizumab could reduce the treatment burden for patients with PCV.
In the current study, complete regression of polypoid lesions at 12 months was achieved in 93.3% of cases. Matsumoto et al.22 and Fukuda et al.23 reported the short-term results of IVBr for PCV. In these two reports, the regression rates of polypoid lesions after quarterly injections of IVBr were 78.9% (15 eyes out of 19 eyes) and 78.6% (11 eyes out of 14 eyes). There were no previous studies that reported the regression rate of polypoid lesions regarding outcomes at 1 year. In our previous study, when aflibercept intraocular monotherapy was used to treat PCV, complete regression of polypoid lesions was achieved in 48.0% with a twice-monthly fixed regimen and in 52.9% with an as-needed regimen. .11. In the EVEREST II study8, which compared the efficacy between ranibizumab monotherapy and combined photodynamic therapy (PDT), the 12-month rates were 69.3% in patients treated with intravitreal PDT/ranibizumab and 34.7% in patients treated with intravitreal ranibizumab as monotherapy. In another of our previous studies, regression rates of polypoid lesions in patients treated with combination therapy with intravitreal ranibizumab or intravitreal aflibercept were higher (78.2% and 78.9%) than either or the other monotherapies with these drugs.24. In the current study, the regression rate of polypoid lesions with IVBr injections was much higher than with ranibizumab or aflibercept monotherapy or in combination with PDT, which may explain why 73.3% of patients had a dry macula at 1 year.
However, brolucizumab-related IOI is a major adverse event associated with intravitreal brolucizumab. In the current study, two (11.8%) of 17 eyes had IOI. The frequency of IOIs was about the same compared to a sub-analysis of the HAWK study that Ogura et al. reported (15.4%)15,16,17. Although IVBr injections for PCV are effective, we must be cautious of IOI and treat promptly if brolucizumab-related IOI develops.
This study had some limitations, one of the main ones being the retrospective design. The second limitation was the small sample size. A large randomized study should confirm the current results. Also, the long-term results are not known. The results of this study should be evaluated with a longer follow-up period.
In conclusion, IVBr injections effectively improved vision and exudative changes in PCV patients over a one-year follow-up, as well as a higher resolution rate of polypoid lesions as seen in the ICGA. The results of this analysis suggest that brolucizumab may be useful for treating PCV with a lower treatment burden.