Short-term outcomes of intravitreal brolucizumab for treatment-naïve neovascular age-related macular degeneration with type 1 choroidal neovascularization including polypoidal choroidal vasculopathy

www.nature.com/scientificreports OPEN Short‑term outcomes of intravitreal brolucizumab for treatment‑naïve neovascular age‑related macular degeneration with type 1 choroidal neovascularization including polypoidal choroidal vasculopathy Hidetaka Matsumoto*, Junki Hoshino, Ryo Mukai, Kosuke Nakamura & Hideo Akiyama We evaluated the efficacy and safety of loading phase treatment with intravitreal brolucizumab for neovascular age-related macular degeneration (nAMD) with type 1 choroidal neovascularization (CNV). We analyzed consecutive 42 eyes of 40 patients with treatment-naïve nAMD associated with type 1 CNV. Three monthly injections of brolucizumab were completed in 36 eyes (85.7%). In those cases, best-corrected visual acuity (BCVA) was 0.24 ± 0.27 at baseline and improved significantly to 0.12 ± 0.23 after 3 months (P < 0.001). Central macular thickness was 301 ± 110 µm at baseline and decreased significantly to 160 ± 49 µm after 3 months (P < 0.001). Dry macula was achieved in 34 eyes (94.4%) after the loading phase. Central choroidal thickness was 264 ± 89 µm at baseline and decreased significantly to 223 ± 81 µm after 3 months (P < 0.001). Indocyanine green angiography after the loading phase revealed complete regression of polypoidal lesions in 15 of the 19 eyes (78.9%) with polypoidal lesions. Non-infectious intraocular inflammation (IOI) was observed in 8 of 42 eyes (19.0%) during the loading phase, while showing amelioration in response to combination therapy with topical and subtenon injection of steroids. In these eyes, BCVA after 3 months had not deteriorated as compared to that at baseline. These results indicate that loading phase treatment with intravitreal brolucizumab might be effective for improving visual acuity and reducing exudative changes in eyes with nAMD associated with type 1 CNV. Moreover, polypoidal lesions appear to frequently regress after this treatment. However, we must monitor patients carefully for brolucizumab-related IOI, and administer steroid therapy promptly. Age-related macular degeneration (AMD) is a leading cause of visual impairment in developed countries1. Late AMD is divided into two subtypes: geographic atrophy and neovascular AMD (nAMD)2. nAMD is usually associated with choroidal neovascularization (CNV) and progresses more rapidly than geographic atrophy. CNV is divided into types 1 and 2 depending on its histopathological l ocation3. Type 1 CNV grows beneath the retinal pigment epithelium (RPE). On the other hand, type 2 CNV grows into the subretinal space, thereby penetrating the RPE. Retinal angiomatous proliferation is a specific type of nAMD associated with intraretinal neovascularization, recently called type 3 n eovascularization4. nAMD with type 1 CNV accompanied by polypoidal lesions is categorized as polypoidal choroidal vasculopathy (PCV)5. The prevalence of PCV in nAMD patients is higher in Asian than in Caucasian p opulations6. In eyes with PCV, massive submacular hemorrhage can occur due to bleeding from polypoidal lesions, leading to significant visual d eterioration7,8. Department of Ophthalmology, Gunma University Graduate School of Medicine, 3‑39‑15 Showa‑machi, Maebashi, Gunma 371‑8511, Japan. *email: Scientific Reports | (2021) 11:6759 | https://doi.org/10.1038/s41598-021-86014-7 1 Vol.:(0123456789) www.nature.com/scientificreports/ Intravitreal injection of anti-vascular endothelial growth factor (VEGF) is the first line therapy for nAMD. Ranibizumab and aflibercept are anti-VEGF agents approved for ophthalmic use. In vitro studies have shown that aflibercept has higher anti-VEGF efficacy than r anibizumab9. Moreover, compared to ranibizumab, aflibercept is more effective for achieving regression of CNV beneath the RPE and polypoidal lesions as well as reducing choroidal thickness10–12. However, more than a few cases with type 1 CNV require frequent intravitreal injections of aflibercept to halt the development of CNV a ctivity13. Recently, brolucizumab was approved as a new anti-VEGF agent for the treatment of nAMD based on HAWK and HARRIER, worldwide phase 3 clinical t rials14,15. These trials proved q12/q8 week dosing intervals for intravitreal brolucizumab to be effective for improving and maintaining visual acuity for 96 weeks, results not inferior to those of a q8 week dosing interval for intravitreal aflibercept. Moreover, intravitreal brolucizumab provided better control of intraretinal, subretinal, and sub-RPE fluid than intravitreal aflibercept. These results indicate that brolucizumab might be the most effective approach to treating nAMD with type 1 CNV among the anti-VEGF agents approved for ophthalmic use. Nevertheless, there are significant concerns about intraocular inflammation (IOI), including retinal occlusive vasculitis, after intravitreal brolucizumab which can result in permanent loss of vision16. In this study, we evaluated efficacy and safety in the loading phase with intravitreal injections of brolucizumab for treatment-naïve nAMD with type 1 CNV. Results The subjects analyzed in this study included consecutive 42 eyes of 40 patients (35 eyes of 33 men; 7 eyes of 7 women) with treatment-naïve nAMD associated with type 1 CNV. Mean patient age was 74.9 ± 8.6 years. Twentythree eyes (54.8%) showed type 1 CNV with polypoidal lesions. Three monthly injections of brolucizumab as a loading phase treatment were completed in 36 eyes (85.7%). In these cases, best-corrected visual acuity (BCVA) at baseline, after 1 month, 2 months, and 3 months were 0.24 ± 0.27, 0.17 ± 0.24 (P < 0.01), 0.14 ± 0.24 (P < 0.001), and 0.12 ± 0.23 (P < 0.001), respectively. BCVA showed significant improvement after the first injection of brolucizumab (Fig. 1). Central macular thickness (CMT) at baseline, after 1 month, 2 months, and 3 months were 301 ± 110 µm, 187 ± 71 µm (P < 0.001), 166 ± 53 µm (P < 0.001), and 160 ± 49 µm (P < 0.001), respectively. CMT was significantly decreased after the first intravitreal brolucizumab administration (Fig. 2). Dry macula was achieved in 17 eyes (47.2%) after 1 month, in 31 eyes (86.1%) after 2 months, and in 34 eyes (94.4%) after 3 months. Central choroidal thickness (CCT) at baseline, after 1 month, 2 months, and 3 months were 264 ± 89 µm, 236 ± 86 µm (P < 0.001), 227 ± 83 µm (P < 0.001), and 223 ± 81 µm (P < 0.001), respectively. CCT was significantly decreased after the first brolucizumab injection (Fig. 3). The 3 monthly injections of brolucizumab were completed in 19 of 23 eyes with polypoidal lesions; ICGA after the loading phase then revealed complete regression of the polypoidal lesions in 15 of these 19 eyes (78.9%). A representative case is shown in Fig. 4. Brolucizumab-related IOI was observed in 8 of 42 eyes (19.0%) during the loading phase; 3 eyes (37.5%) after the first injection of brolucizumab, 3 eyes (37.5%) after the second injection, and 2 eyes (25.0%) after the third injection. Iritis, vitritis, retinal vasculitis, retinal vascular occlu (...truncated)