The effect of intravitreal brolucizumab on choroidal thickness in patients with neovascular age-related macular degeneration

www.nature.com/scientificreports OPEN The effect of intravitreal brolucizumab on choroidal thickness in patients with neovascular age‑related macular degeneration Ki Woong Bae 1, Dong Ik Kim 1 & Daniel Duck‑Jin Hwang 1,2* In this study we evaluated the effect of intravitreal brolucizumab injections on choroidal thickness in patients with neovascular age-related macular degeneration (nAMD) who previously showed an incomplete response to anti-vascular endothelial growth factor treatment. A total of thirty-four eyes from 34 patients were included in this study. The patients received an average of 2.4 ± 1.1 brolucizumab injections with the mean follow-up period of 4.9 ± 2.0 months. After their first brolucizumab treatment, the central foveal thickness (CFT) and subfoveal choroidal thickness (SFCT) were significantly decreased from 431.6 ± 190.0 μm and 193.9 ± 75.1 μm to 274.6 ± 109.4 μm (P < 0.001) and 169.4 ± 71.1 μm (P < 0.001), respectively. However, there were no improvements in visual acuity. Patients were divided into three subgroups according to the number of brolucizumab treatments: one, two, and three or more injections. In all three subgroups, the CFT and SFCT were significantly reduced compared to baseline at all time points of brolucizumab injections. In conclusion, choroidal thickness was significantly reduced after intravitreal brolucizumab injections as a switching treatment in patients with nAMD. Age-related macular degeneration (AMD) is one of the leading cause of blindness worldwide1. Neovascular AMD (nAMD) is characterized by retinal vascular leakage and fluid accumulation associated with choroidal neovascularization (CNV)2. To date, various treatment modalities have been attempted to inhibit CNV-induced exudation. Currently, intravitreal injection of anti-vascular endothelial growth factor (VEGF) agents is the firstline treatment for nAMD. Brolucizumab is the most recently developed anti-VEGF agent used for n AMD3. Brolucizumab is the smallest molecules among the available anti-VEGF drugs and can be administered at higher concentrations than other anti-VEGF agents such as ranibizumab or aflibercept4. According to two pivotal clinical trials, including HAWK and HARRIER, brolucizumab was not inferior to aflibercept in terms of visual outcomes and demonstrated more favorable anatomical effects in post hoc a nalyses3,5,6. Intravitreal injections of anti-VEGF agents may affect choroidal thickness. It has been reported that aflibercept reduced choroidal thickness to a greater extent than r anibizumab7–9. Koizumi et al. showed that the decrease in choroidal thickness from aflibercept treatment was associated with better visual and anatomic outcomes at one year10. However, a thinner choroid may be related to macular atrophy in long-term follow-up, which could result in severe vision loss11,12. Therefore, it is important to monitor the change of choroidal thickness during anti-VEGF treatment. Some case series studies found that intravitreal brolucizumab injection reduced choroidal t hickness12–15. However, little is known about the change in choroidal thickness of patients with nAMD who have already been treated with other anti-VEGF agents and switched to brolucizumab. Therefore, we evaluated temporal changes of subfoveal choroidal thickness (SFCT) in patients with nAMD who were treated with brolucizumab as a switching therapy due to an incomplete response to previous treatment. 1 Department of Ophthalmology, Hangil Eye Hospital, #35 Bupyeong‑Daero, Bupyeong‑Gu, Incheon 21388, Korea. 2Department of Ophthalmology, Catholic Kwandong University College of Medicine, Incheon, Korea. *email: Scientific Reports | (2022) 12:19855 | https://doi.org/10.1038/s41598-022-23392-6 1 Vol.:(0123456789) www.nature.com/scientificreports/ Age (years) 70.6 ± 6.9 (range, 56–85) Sex, male: female 27:7 Type of AMD (N, %) PCV: typical AMD: RAP 26 (76.5), 6 (17.6), 2 (5.9) Previous number of intravitreal injections 17.8 ± 10.1 (range, 3–40) Injection number of brolucizumab 2.4 ± 1.1 (range, 1–4) Adverse events (N, %) 5 (14.7) Mean follow up period (months) 4.9 ± 2.0 (range, 1.8–8.0) Hypertension (N, %) 14 (41.2) Diabetes mellitus (N, %) 7 (20.6) Spherical equivalent (diopters) + 0.44 ± 1.35 (range,− 3.00 − + 2.75) Corrected visual acuity (logMAR) 0.42 ± 0.27 (range, 0.05–0.82) IOP (mmHg) 14.2 ± 2.5 Table 1.  Demographic and baseline characteristics (n = 34). Values are presented as N (percentage) or mean ± standard deviation. AMD age-related macular degeneration; PCV polypoidal choroidal vasculopathy; RAP retinal angiomatous proliferation; logMAR logarithm of the minimal angle of resolution; IOP intraocular pressure. Results Baseline characteristics. The baseline characteristics of the 34 patients with nAMD are summarized in Table 1. Among them, 27 were male (79.4%) and the mean age was 70.6 ± 6.9 years. Polypoidal choroidal vasculopathy (PCV) was the most frequent AMD subtype (26 eyes, 76.5%), followed by typical AMD (6 eyes, 17.6%) and retinal angiomatous proliferation (RAP) (2 eyes, 5.9%). The mean number of brolucizumab injections was 2.4 ± 1.1, ranged 1–4 times. All eyes were non-treatment-naïve, and the mean number of previous anti-VEGF (non-brolucizumab) injections was 17.8 ± 10.1 (range, 3–40). The mean follow-up period was 4.9 ± 2.0 months (range, 1.8–8.0). Visual outcomes and central foveal thickness (CFT) after intravitreal brolucizumab injec‑ tion. At the baseline, the average best corrected visual acuity (BCVA), converted to the logarithm of the minimal angle of resolution (logMAR), was 0.42 ± 0.27 (range 0.05–0.82) and 0.42 ± 0.32 (range 0.05–1.30) (P = 0.921) one month after the first injection. There was no significant change in vision, even after additional brolucizumab treatment. Among the 34 study eyes, the initial CFT was 431.6 ± 190.0 μm, which significantly decreased to 274.6 ± 109.4 μm (P < 0.001) after the first brolucizumab treatment. The contralateral 17 eyes that had no retinal pathology including epiretinal membrane, age-related macular degeneration, macular hole, or history of vitrectomy, had an average initial CFT of 286.2 ± 52.6 μm and SFCT of 246.5 ± 65.3 μm during the same period with no significant change at one month follow up. The temporal changes in retinal thickness are presented in Figs. 1, 2, and 3. The CFT was significantly decreased after additional brolucizumab injections compared to baseline CFT; after the second and third brolucizumab injections, the CFTs were 256.8 ± 106.4 μm (n = 19, P < 0.001) and 338.8 ± 115.4 μm (n = 9, P = 0.015), respectively. Temporal changes in subfoveal choroidal thickness after intravitreal brolucizumab injec‑ tion. For 34 eyes, the mean SFCT before brolucizumab treatment was 193.9 ± 75.1 μm which decreased 12.7% from the baseline to 169.4 ± 71.1 μm (P < 0.001) after the first injection. The SFCT was significantly decreased after additional brolucizumab injections compared to (...truncated)