Brolucizumab for Treating Recalcitrant Neovascular Age-Related Macular Degeneration and Polypoidal Choroidal Vasculopathy

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Pfister, Andreas Weinberger, Justus G. Garweg This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7357019/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Purpose To report the anatomical and functional outcomes after switching to brolucizumab in patients with recalcitrant neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV). Methods This retrospective case series assessed the impact of switching to brolucizumab on disease activity over 12 months in patients with recalcitrant nAMD and PCV. The data are presented as mean ± SD. Results Of the 27 eyes, 16 (59.3%) presented with recalcitrant nAMD and 11 (40.7%) presented with PCV. Patients with nAMD were older (81.4 ± 5.7 vs. 74.7 ± 7.7 years; p = 0.016 ) and had less fluid (central retinal thickness: nAMD: 349.3 ± 95.3 µm, PCV: 597.1 ± 348.4 µm; p = 0.005 ), which was explained by different pigment epithelial detachment heights (nAMD: 176.5 ± 102.6 µm, PCV: 384.6 ± 284.6 µm; p = 0.023 ). Twelve months after switching to bro (159 injections), the treatment interval increased from 5.6 ± 1.8 to 10.5 ± 4.5 weeks ( p = 0.01 ). Visual gains after switch were maintained in two out of three patients with intraocular inflammation (IOI). Conclusions PCV is remarkably overrepresented in the group of eyes with recalcitrant nAMD. Despite the risk of IOI, the strong drying potential of brolucizumab justifies its use in eyes requiring anti-VEGF treatment intervals of six weeks or less. Health sciences/Diseases Health sciences/Medical research Recalcitrant neovascular age-related macular degeneration (nAMD) polypoidal choroidal vasculopathy (PCV) anti-VEGF brolucizumab intraocular inflammation disease control Figures Figure 1 Figure 2 Precis PCV is overrepresented in the group of eyes with recalcitrant nAMD. Despite the risk of intraocular inflammation, the strong drying potential of brolucizumab justifies its consideration in anti-VEGF treatment intervals of six weeks or less. Introduction Clinically, advanced neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV) share remarkable similarities, such as a similar genetic background. However, there are also relevant discrepancies. 1 – 3 Patients with PCV tend to be younger and respond less reliably to anti-vascular endothelial growth factor (anti-VEGF) agents, including a high proportion of eyes that do not respond well and require frequent treatment. 4 , 5 Conversely, eyes with PCV may experience greater visual improvement and favorable long-term anatomical stability. 6 , 7 These differences may be related to their pathophysiology: nAMD results from subretinal neovessel formation that does not respect tissue boundaries. In response to treatment, these neovascular membranes undergo an endothelial-mesenchymal transition, resulting in a fibrovascular scar. 8 The pathophysiology of PCV is not fully understood. Polypoidal changes in the choroidal vasculature have been linked to pachychoroid changes in the larger choroidal vasculature, yet they do not evoke endothelial cell proliferation or vascular spreading. Therefore, they may regress without fibrovascular scarring upon anti-VEGF treatment. Both diseases respond well to anti-VEGF therapy once disease activity is under control. 9 , 10 However, up to half of eyes with nAMD fail to achieve complete disease stability and require frequent intravitreal anti-VEGF treatments at intervals of 10 weeks or less to maintain functional stability. 11 Virtually no information is available about the proportion of these eyes that meet imaging criteria for PCV. 12 Intravitreal brolucizumab (Bro) has a strong effect on recalcitrant nAMD, 13 , 14 with or without pigment epithelial detachment, and on incompletely responsive PCV. It achieves higher rates of polypoidal regression than other anti-VEGF agents (78%-93% vs. 42%-56% after 3–12 months). 10 , 15 – 17 . However, brolucizumab carries a significant risk of intraocular inflammation (IOI; 4%-21%), which can be severe and require systemic and local corticosteroid treatment to prevent severe vision loss. 13 , 15 , 16 , 18 – 22 Therefore, its use has been restricted to difficult-to-treat cases. In our institution, brolucizumab has been used as a rescue therapy for eyes unresponsive to other anti-VEGF agents, aiming to improve disease activity control. 18 , 23 In clinical practice, PCV is significantly underdiagnosed in Caucasian patients if indocyanine green angiography (ICGA) is not performed. 6 , 24 , 25 Therefore, we assumed an increased prevalence, particularly in recalcitrant nAMD requiring treatment escalation to brolucizumab. To test this hypothesis, we retrospectively reassessed the imaging data of patients who received intravitreal brolucizumab as a rescue treatment for nAMD that did not respond well to treatment. We looked for signs of PCV using non-ICGA-based imaging criteria. 6 , 12 This explorative analysis aimed to report the functional and anatomical outcomes of brolucizumab as a third-line therapy in eyes with recalcitrant nAMD and PCV. Patients and Methods In this retrospective, consecutive case series, we included patients with recalcitrant nAMD, with or without imaging criteria favoring PCV, who received brolucizumab as a third-line treatment to control disease activity. All patients gave their general consent to use their coded data for quality control and clinical research purposes after this study was approved by the Bern Institutional Cantonal Ethics Committee (registration number 2020 − 01847). The study complied with Swiss federal laws, the International Council for Harmonization E6 Good Clinical Practice Guideline, and the Declaration of Helsinki, latest version. "Recalcitrant nAMD" was defined as persistent intraretinal and/or subretinal fluid on spectral-domain optical coherence tomography (SD-OCT) after at least six months of monthly anti-VEGF treatment or a maximum treatment interval of less than ten weeks following a treat-and-extend protocol. 26 PCV was defined in a non-ICGA-based manner, as described by Cheung et al., based on color fundus photography and OCT features. 12 The following inclusion criteria were applied: active nAMD or PCV, as defined by the presence of retinal fluid requiring intravitreal therapy with brolucizumab as a third-line treatment; Snellen best-corrected visual acuity at or above 0.1 at diagnosis; prior treatment with ranibizumab, aflibercept, or faricimab (switching between agents was permitted); and written consent to further use of coded data. Exclusion criteria included: Refusal to grant consent for the use of the patient’s coded data; subretinal bleeding greater than one optic nerve head (ONH) diameter at diagnosis; pretreatment with photodynamic therapy; and preexisting structural damage to the macula for any reason other than nAMD without functional potential. Any systemic comorbidities that interfere with treatment outcomes were also excluded, namely any local or systemic rheumatoid diseases and/or vasculitis requiring topical, intravitreal, or systemic treatment. Any opacifications in the optic axis that prohibit ocular imaging and fundoscopy were excluded, as were any intraocular surgeries and/or laser treatments (except YAG laser capsulotomy) within three months prior to inclusion. Eyes switched to bro did not receive formal loading but were initially maintained at the same interval as before the switch. Data were collected retrospectively from electronic medical records at the following prespecified time points: at diagnosis, prior to the first anti-VEGF treatment (baseline), after the loading phase, six months before switching to bro, before the last anti-VEGF treatment prior to switching, at the time of switching, after the first bro injection, after three bro injections, and after six and twelve months of bro treatment. At each time point, Snellen best-corrected visual acuity (BCVA) was recorded. For statistical use, Snellen VA was converted to ETDRS letter scores (BCVA of 1.0 is defined as 85 ETDRS letters). Intraocular pressure, optical coherence tomography (OCT) imaging data (using a Heidelberg Spectralis device and HRA-2 software, Heidelberg, Germany), including center point retinal thickness (CRT), central subfield thickness (CST), maximal PED height in the central 3 mm around the foveola (ETDRS grid), and the presence of subretinal fluid (SRF) and/or intraretinal fluid (IRF) were recorded, as well as adverse events. CRT and CST measurements were assessed according to a standard operating procedure after manually correcting the segmentation, if necessary. The primary outcome measures were the changes in BCVA, morphological parameters (CST, CRT, and PED height), and treatment intervals (i.e., comparing the injection intervals before and after switching). Secondary outcomes included the total number of injections per eye before switching and the number of injections in the first year after switching. The proportion of eyes that switched to another drug and clinically relevant side effects of interest, e.g., signs of intraocular inflammation (IOI), with or without retinal vasculitis (RV) or retinovascular occlusion (RO), were recorded. Data from patients who switched to another anti-VEGF drug were censored after the switch and were no longer included in the evaluation. Statistical Analysis Descriptive statistics and subgroup comparison analyses were performed. According to the Shapiro-Wilk test, most of the data were not normally distributed. Therefore, the data are presented as the mean ± standard deviation (SD), as well as the median and interquartile range (IQR: 25%-75%). A t-test was applied to group comparisons when the data were normally distributed, and a nonparametric Mann-Whitney U test was used when the data were not normally distributed. The Wilcoxon signed-rank test was used to analyze longitudinal changes in functional and morphological parameters, and the Friedman test for dependent samples was used to compare multiple time points in longitudinal analyses. A p-value of ≤ 0.05 was considered statistically significant. All statistical analyses were performed using the SPSS software package, version 27 (SPSS, Inc., Chicago, Illinois, USA), and R, version 4.4.2 (R: A language and environment for statistical computing; R Foundation for Statistical Computing, Vienna, Austria, 2024). Results Patients Twenty-seven eyes from 27 patients were included, with a mean age of 78.7 ± 7.2 years (12 females [44.4%] and 15 males [55.6%]). Sixteen eyes were diagnosed with "typical" nAMD (59.3%), and according to imaging findings, eleven were categorized as PCV (40.7%). Subgroup analysis revealed that patients with nAMD were older than those with PCV (81.4 ± 5.7 years vs. 74.7 ± 7.7 years, respectively; p = 0.016 ), though no differences were observed for other baseline parameters, including gender, BCVA, and CST, besides age and CRT (Table 1 ). Both groups showed similar improvements in BCVA, CRT, and CST after switching to bro (Table 2 ). Table 1 Baseline demographic findings Baseline characteristics nAMD PCV pooled p-value (nAMD vs. PCV) Participants (= number of eyes), n (%) 16 (59.3) 11 (40.7) 27 (100) Females, n (%) 5 (31.3) 7 (63.6) 12 (44.4) 0.13 Age at baseline, (years (SD)) 81.4 (5.7) 74.7 (7.7) 78.7 (7.2) 0.016 Best-corrected visual acuity (ETDRS letters (SD)) 65.7 (13.8) 64.8 (18.0) 65.3 (15.2) 1.0 Central retinal thickness (µm (SD)) 349.3 (95.3) 597.1 (348.4) 435.5 (242.8) 0.005 Central subfield thickness, (µm (SD)) 384.5 (78.9) 569.6 (326.8) 448.9 (214.7) 0.12 Table 2 Evolution of functional and anatomical outcomes nAMD PCV pooled p-value (nAMD vs. PCV) Best-corrected visual acuity (ETDRS letters (SD); median; IQR At baseline (diagnosis) 65.7 (13.8) 69.9; 56.5–75.0 64.8 (18.0) 69.9; 62.0–75.0 65.3 (15.2) 69.9; 60.3–75.0 1.0 End of loading 67.2 (15.3) 73.9; 57.6–75.0 72.6 (15.6) 80.2; 69.9–80.2 69.1 (15.2) 74.4; 69.9–80.2 0.31 At switch to bro 59.9 (15.8) 60.3; 51.3–69.9 66.8 (11.5) 69.9; 60.3–75.0 62.7 (14.4) 65.1; 58.9–73.9 0.23 12 months after switch 67.4 (16.8) 72.5; 55.9–80.2 75.7 (4.7) 73.9; 73.9–78.9 71.5 (12.7) 73.9; 69.9–80.2 0.57 p-value (longitudinal) Baseline – end of loading 0.14 0.046 0.012 0.08 Baseline – switch to bro 0.10 0.80 0.17 0.14 At switch – 12 months 0.89 0.07 0.23 0.15 Central retinal thickness µm (SD) median; IQR Baseline (diagnosis) 349.3 (95.3) 315; 279–381 597.1 (348.4) 487; 354–691 435.5 (242.8) 365; 305–480 0.005 End of loading 314.8 (89.1) 295; 230–414 520.3 (393.9) 450; 281–527 383.3 (248.1) 336; 244–438 0.13 At switch to bro 479.5 (306.6) 366; 329–523 512.6 (209.7) 465; 366–580 493.0 (267.2) 414; 331–555 0.27 12 Months after switch 336.9 (105.6) 297; 256–443 433.9 (140.1) 435; 306–556 388.2 (131.1) 345; 275–523 0.11 p-value (longitudinal) Baseline – end of loading 0.30 0.60 0.052 0.27 Baseline – switch to bro 0.033 0.16 0.42 0.12 Switch – 12 months 0.025 0.14 0.006 0.60 Central subfield thickness, µm (SD) median; IQR At baseline (diagnosis) 384.5 (78.9) 374; 312–405 569.6 (326.8) 423; 367–679 448.9 (214.7) 395; 348–445 0.12 End of loading 343.7 (71.3) 341; 275–424 506.4 (367.6) 396; 266–524 398.0 (223.7) 342; 275–442 0.44 At switch to bro 443.1 (105.5) 390; 364–495 539.0 (181.2) 530; 372–564 483.7 (147.3) 457; 368–563 0.15 12 Months after switch 369.4 (90.3) 370; 284–427) 442.2 (94.2) 450; 345–530 407.9 (97.0) 401; 327–505 0.17 p-value (longitudinal) Baseline – end of loading 0.10 0.034 0.013 0.29 Baseline – switch to bro 0.035 0.58 0.37 0.13 Switch – 12 months 0.069 0.008 0.001 0.54 In the pooled cohort, BCVA increased from diagnosis to the end of the loading phase, then decreased until the switch to BRO. After switching, mean BCVA recovered over 12 months (Fig. 1 ). The mean baseline CRT was higher in the PCV group (nAMD: 349.3 ± 95.3 µm; PCV: 597.1 ± 348.4 µm; p = 0.005 ), while the CST was comparable in both groups (nAMD: 384.5 ± 78.9 µm; PCV: 569.6 ± 326.8 µm; p = 0.12 ; see Table 2 ). During the loading phase, CRT improved in the pooled cohort to 383.3 ± 248.1 µm (-52.2). Thereafter, it increased to 493.0 ± 267.2 µm (+ 57.5 µm). Twelve months after the switch, the CRT improved to 388.2 ± 131.1 (–104.8) µm ( p = 0.006 ; Fig. 2 ). Similarly, CST decreased after the loading phase but increased again in both groups until the switch to BRO (Table 2 ). After that, CST decreased again until 12 months after the switch (-75.8 µm; p = 0.001 ). Pooled data indicate an increase in the prevalence of PED from 23 patients (85.2%) to 25 patients (92.6%) after switching to BRO. Twelve months after the switch, two nAMD eyes (12.5%) were completely dry. Persistent PED was observed in six eyes (37.5%), while none of the PCV eyes were completely dry and ten (81.8%) showed persistent PED. The number of injections and treatment intervals before and after the switch are displayed in Tables 3 and 4 . Pooled data showed an increase in treatment intervals after switching to Bro after the third injection, accompanied by a decrease in the annual number of injections in the year after switching to Bro compared to the year before switching to Bro (Tables 3 and 4 ). Bro treatment had to be discontinued due to IOI in three cases (11.1%). No systemic adverse events (AEs) were reported (Table 5 ). Table 3 Treatment intervals Treatment intervals (weeks (SD)) nAMD PCV pooled p -value (nAMD vs. PCV) Last prior to switch 5.7 (1.8) 5.5 (1.9) 5.6 (1.8) 0.81 after third bro injection 8.8 (3.5) 7.8 (1.9) 8.4 (3.0) 0.75 after fifth bro injection 10.4 (3.2) 7.3 (1.2) 8.8 (2.8) 0.038 12 months after switch to brolucizumab 12.6 (5.1) 8.0 (1.5) 10.5 (4.5) 0.040 p-value (longitudinal) Last prior to switch - after third bro injection 0.004 0.035 < 0.001 0.75 Last prior to switch - after fifth bro injection 0.012 0.11 0.003 0.07 Last prior to switch − 12 months after switch to bro 0.012 0.018 0.001 0.054 Table 4 Treatment demand (number of injections) Number of injections n (SD) median; IQR nAMD PCV pooled Intergroup p-value (nAMD vs. PCV) prior to switch) baseline to switch to bro) 32.6(25.6) 28; 12–46 39.5 (32.4) 30; 14–78 35.4 (27.7) 30; 12–47 0.65 12 months prior to switch to bro 8.9 (1.9) 9.0; (7–10) 10.5 (2.0) 11.0; (9–12) 9.6 (2.0) 10.0; 8–11 0.039 12 months after switch to bro 7.3 (2.1) 7; 6–9 8.0 (1.2) 8; 7–9 7.6 (1.7) 7; 7–9 0.41 p-value (longitudinal) 12 months prior to switch – 12 months after switch N/A 0.027 0.032 - Table 5 Treatment discontinuation due to intraocular inflammation (IOI) Patients who discontinued treatment due to IOI Pathology/Complication Number of bro before IOI BCVA prior to IOI BCVA after completion of anti-inflammatory therapy intraocular pressure > 21 mmHg Treatment 1 Anterior uveitis with papillitis and vasculitis 5 0.25 0.25 no Solumedrol intravenously followed by prednisone orally. Topical therapy: Prednisolone acetate 2 severe uveitis/occlusive retinal vasculitis 2 0.5 0.6 no Solumedrol intravenously followed by prednisone orally. Topical therapy: none 3 arteriovenous occlusion 5 0.32 0.16 no Acetylsalicylate Discussion The prevalence of PCV in our series was fivefold higher than expected in European cohorts of treatment-naïve patients with nAMD. 28 , 29 PCV generally responds well to anti-VEGF treatment in Caucasians, 30 but complete drying of the macula is less common compared to Asian cohorts. 23 Consequently, treatment in these eyes may be challenging. Nevertheless, eyes with PCV appear to respond similarly to bro as eyes with recalcitrant nAMD (Figs. 1 and 2 ). Although polyp regression is likely in both Asian and Caucasian populations, 31 , 32 recurrence within one year is expected with as-needed (PRN) treatment. 32 None of the difficult-to-treat eyes with PCV and nAMD in our series qualified for PRN treatment or treatment interruption before switching. A reduced probability of complete polyp regression has been reported previously in Caucasians. 33 This deserves to be confirmed independently while explaining the overrepresentation of PCV in our series. Despite the limited sample size, the decrease in central retinal thickness (CRT) and central subfield thickness (CST) after switching to bro (Table 2 ) indicates that bro may be more effective than previous anti-VEGF agents in treating recalcitrant nAMD and PCV. Published evidence strongly supports this, as bro has been shown to be highly effective in reducing retinal fluid and CRT. 13 , 34 – 36 However, a strong anatomic response after switching does not necessarily lead to significant visual improvement in pretreated nAMD. 37 In contrast, our PCV patients experienced a remarkable functional response in addition to a twofold increase in treatment intervals and a significant reduction in the number of injections after switching (Tables 2 – 4 ) which adds to published evidence. 38 , 39 The fact that three of our patients (11%) experienced intraocular inflammation (IOI) after switching to bro (requiring systemic corticosteroid treatment in two instances to maintain the visual function achieved prior to IOI) is understandable given the inadequate pre-switch control of disease activity and the absence of other therapeutic options. Nevertheless, this must be discussed critically with treatment-experienced patients, who may accept this additional risk and report any post-injection irregularity immediately. An obvious limitation of our study is its small sample size. This is due to the strict selection of patients who demanded treatment of six weeks or less during the 12 months prior to switching to bro and who had a minimum follow-up period of 12 weeks. On the other hand, the robustness of our findings is consistent with a majority of recent reports. 13 , 16 , 18 , 33 , 35 , 37 , 38 , 40 In conclusion, PCV is overrepresented in the group of eyes with recalcitrant nAMD. After other anti-VEGF agents failed to control disease activity, switching to bro extended the treatment interval from 5.6 to 10.5 weeks for PCV as for other types of macular neovascularization. Despite the inherent risk of IOI in response to brolucizumab, these results justify considering switching to brolucizumab in eyes requiring anti-VEGF treatment intervals of six weeks or less. Declarations Author contributions: JS: data collection, writing of manuscript, preparation of tables and figures; IP: data collection and analysis, preparation of tables and figures; AW: data collection; JGG: data collection, writing and revising the manuscript Financial disclosures: JS: none; IP: none;AW: AW acts for several pharmaceutical companies (Roche, Bayer, Apellis, AbbVie, Novartis,) as an advisor. JGG acts as an advisor for several pharmaceutical companies (AbbVie, Bayer, Novartis, Roche) and has received research funding from Bayer and Roche. None of the authors received financial support for the undertaking of the present study or have conflicts of interest with the data that are presented in this report. Funding : This study did not receive any external funding Data availability statement: The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request. References Fenner, B. J. et al. Evolving treatment paradigms for PCV. Eye (London England) . 36 , 257–265. 10.1038/s41433-021-01688-7 (2022). Pan, Y. et al. Exploring the contribution of ARMS2 and HTRA1 genetic risk factors in age-related macular degeneration. Prog. Retin. Eye Res. 97 , 101159. 10.1016/j.preteyeres.2022.101159 (2023). Laude, A. et al. Polypoidal choroidal vasculopathy and neovascular age-related macular degeneration: same or different disease? Prog. Retin. Eye Res. 29 , 19–29. 10.1016/j.preteyeres.2009.10.001 (2010). Cho, M., Barbazetto, I. A. & Freund, K. B. Refractory neovascular age-related macular degeneration secondary to polypoidal choroidal vasculopathy. Am. J. Ophthalmol. 148 , 70–78e71. 10.1016/j.ajo.2009.02.012 (2009). 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Z. fur Augenheilkunde . 240 , 208–212. 10.1159/000488808 (2018). Chaikitmongkol, V. et al. Recurrent polypoidal lesions after achieving inactive polypoidal choroidal vasculopathy following 1-year fixed-dosing aflibercept treatments. Asia-Pacific J. Ophthalmol. (Philadelphia Pa) . 14 , 100176. 10.1016/j.apjo.2025.100176 (2025). Kimura, M. & Sakurada, Y. Association of Polyp Regression after Loading Phase with 12-Month Outcomes of Eyes with Polypoidal Choroidal Vasculopathy. 17 , (2024). 10.3390/ph17060687 Nguyen, Q. D. et al. Brolucizumab: Evolution through Preclinical and Clinical Studies and the Implications for the Management of Neovascular Age-Related Macular Degeneration. Ophthalmology 127 , 963–976. 10.1016/j.ophtha.2019.12.031 (2020). Rossi, S. et al. Treatment of neovascular age-related macular degeneration: one year real-life results with intravitreal Brolucizumab. Front. Med. 11 , 1467160. 10.3389/fmed.2024.1467160 (2024). Dugel, P. U. et al. Brolucizumab Versus Aflibercept in Participants with Neovascular Age-Related Macular Degeneration: A Randomized Trial. Ophthalmology 124 , 1296–1304. 10.1016/j.ophtha.2017.03.057 (2017). Bilgic, A. et al. Real-world experience with brolucizumab in neovascular age-related macular degeneration over 2 years: the REBA extension study. Graefe's archive Clin. experimental Ophthalmol. = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie . 262 , 1161–1167. 10.1007/s00417-023-06329-1 (2024). Nam, S. W., Byun, Z., Ham, D. I. & Kong, M. Response to brolucizumab treatment for refractory serous pigment epithelial detachment secondary to polypoidal choroidal vasculopathy. BMC Ophthalmol. 22 , 485. 10.1186/s12886-022-02711-5 (2022). Ueda-Consolvo, T. et al. Switching to brolucizumab from aflibercept in age-related macular degeneration with type 1 macular neovascularization and polypoidal choroidal vasculopathy: an 18-month follow-up study. 261 , 345–352, (2023). 10.1007/s00417-022-05793-5 Kamao, H. et al. Punctate Hyperfluorescence as a Favorable Predictive Factor for Treatment Response Following a Switch to Brolucizumab for Patients with Aflibercept-Refractory Neovascular Age-Related Macular Degeneration. 14 , (2025). 10.3390/jcm14145141 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7357019","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":505521499,"identity":"71e1de59-3beb-47ed-8844-0d0b48f31606","order_by":0,"name":"Jan Spindler","email":"","orcid":"","institution":"Berner Augenklinik","correspondingAuthor":false,"prefix":"","firstName":"Jan","middleName":"","lastName":"Spindler","suffix":""},{"id":505521500,"identity":"cc821892-4ff4-439e-b22e-8e52879e39ab","order_by":1,"name":"Isabel B. Pfister","email":"","orcid":"","institution":"Swiss Eye Institute","correspondingAuthor":false,"prefix":"","firstName":"Isabel","middleName":"B.","lastName":"Pfister","suffix":""},{"id":505521501,"identity":"d3f70f47-f174-42b8-b3f3-a938ee20a39e","order_by":2,"name":"Andreas Weinberger","email":"","orcid":"","institution":"Pallas Kliniken AG, Pallas Klinik Olten","correspondingAuthor":false,"prefix":"","firstName":"Andreas","middleName":"","lastName":"Weinberger","suffix":""},{"id":505521502,"identity":"62618b66-52b4-4119-bb46-106e9a4c6b17","order_by":3,"name":"Justus G. Garweg","email":"data:image/png;base64,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","orcid":"","institution":"University of Bern","correspondingAuthor":true,"prefix":"","firstName":"Justus","middleName":"G.","lastName":"Garweg","suffix":""}],"badges":[],"createdAt":"2025-08-12 14:53:14","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7357019/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7357019/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":90309523,"identity":"c29b419c-2e8e-4a3f-b4dd-b1d327c2ebe3","added_by":"auto","created_at":"2025-09-01 09:39:16","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":42356,"visible":true,"origin":"","legend":"\u003cp\u003eEvolution of best-corrected visual acuity (BCVA)\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-7357019/v1/03556def03286c581fc3dc51.png"},{"id":90307346,"identity":"3aa67799-173d-42f4-a62e-76c08686154b","added_by":"auto","created_at":"2025-09-01 09:31:16","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":42977,"visible":true,"origin":"","legend":"\u003cp\u003eEvolution of central retinal thickness (CRT)\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-7357019/v1/c3b192f965ccdc79aa2410f0.png"},{"id":91027133,"identity":"e8c9357b-de81-4f7f-9528-c6ba82df3a8d","added_by":"auto","created_at":"2025-09-10 21:01:20","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1186291,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7357019/v1/130d4ed7-26f3-486f-8427-336de971c435.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Brolucizumab for Treating Recalcitrant Neovascular Age-Related Macular Degeneration and Polypoidal Choroidal Vasculopathy","fulltext":[{"header":"Precis","content":"\u003cp\u003ePCV is overrepresented in the group of eyes with recalcitrant nAMD. Despite the risk of intraocular inflammation, the strong drying potential of brolucizumab justifies its consideration in anti-VEGF treatment intervals of six weeks or less.\u003c/p\u003e"},{"header":"Introduction","content":"\u003cp\u003eClinically, advanced neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV) share remarkable similarities, such as a similar genetic background. However, there are also relevant discrepancies.\u003csup\u003e\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e Patients with PCV tend to be younger and respond less reliably to anti-vascular endothelial growth factor (anti-VEGF) agents, including a high proportion of eyes that do not respond well and require frequent treatment. \u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e,\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e Conversely, eyes with PCV may experience greater visual improvement and favorable long-term anatomical stability.\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e,\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e These differences may be related to their pathophysiology: nAMD results from subretinal neovessel formation that does not respect tissue boundaries. In response to treatment, these neovascular membranes undergo an endothelial-mesenchymal transition, resulting in a fibrovascular scar.\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e The pathophysiology of PCV is not fully understood. Polypoidal changes in the choroidal vasculature have been linked to pachychoroid changes in the larger choroidal vasculature, yet they do not evoke endothelial cell proliferation or vascular spreading. Therefore, they may regress without fibrovascular scarring upon anti-VEGF treatment. Both diseases respond well to anti-VEGF therapy once disease activity is under control.\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e,\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eHowever, up to half of eyes with nAMD fail to achieve complete disease stability and require frequent intravitreal anti-VEGF treatments at intervals of 10 weeks or less to maintain functional stability.\u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e Virtually no information is available about the proportion of these eyes that meet imaging criteria for PCV.\u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eIntravitreal brolucizumab (Bro) has a strong effect on recalcitrant nAMD,\u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e,\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e with or without pigment epithelial detachment, and on incompletely responsive PCV. It achieves higher rates of polypoidal regression than other anti-VEGF agents (78%-93% vs. 42%-56% after 3\u0026ndash;12 months).\u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e,\u003cspan additionalcitationids=\"CR16\" citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e. However, brolucizumab carries a significant risk of intraocular inflammation (IOI; 4%-21%), which can be severe and require systemic and local corticosteroid treatment to prevent severe vision loss.\u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e,\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e,\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e,\u003cspan additionalcitationids=\"CR19 CR20 CR21\" citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u003c/sup\u003e Therefore, its use has been restricted to difficult-to-treat cases. In our institution, brolucizumab has been used as a rescue therapy for eyes unresponsive to other anti-VEGF agents, aiming to improve disease activity control.\u003csup\u003e\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e,\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eIn clinical practice, PCV is significantly underdiagnosed in Caucasian patients if indocyanine green angiography (ICGA) is not performed.\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e,\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e,\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u003c/sup\u003e Therefore, we assumed an increased prevalence, particularly in recalcitrant nAMD requiring treatment escalation to brolucizumab. To test this hypothesis, we retrospectively reassessed the imaging data of patients who received intravitreal brolucizumab as a rescue treatment for nAMD that did not respond well to treatment. We looked for signs of PCV using non-ICGA-based imaging criteria.\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e,\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eThis explorative analysis aimed to report the functional and anatomical outcomes of brolucizumab as a third-line therapy in eyes with recalcitrant nAMD and PCV.\u003c/p\u003e"},{"header":"Patients and Methods","content":"\u003cp\u003eIn this retrospective, consecutive case series, we included patients with recalcitrant nAMD, with or without imaging criteria favoring PCV, who received brolucizumab as a third-line treatment to control disease activity. All patients gave their general consent to use their coded data for quality control and clinical research purposes after this study was approved by the Bern Institutional Cantonal Ethics Committee (registration number 2020\u0026thinsp;\u0026minus;\u0026thinsp;01847). The study complied with Swiss federal laws, the International Council for Harmonization E6 Good Clinical Practice Guideline, and the Declaration of Helsinki, latest version.\u003c/p\u003e\u003cp\u003e\"Recalcitrant nAMD\" was defined as persistent intraretinal and/or subretinal fluid on spectral-domain optical coherence tomography (SD-OCT) after at least six months of monthly anti-VEGF treatment or a maximum treatment interval of less than ten weeks following a treat-and-extend protocol.\u003csup\u003e\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u003c/sup\u003e PCV was defined in a non-ICGA-based manner, as described by Cheung et al., based on color fundus photography and OCT features.\u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eThe following \u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003einclusion criteria\u003c/span\u003e were applied:\u003c/p\u003e\u003cp\u003eactive nAMD or PCV, as defined by the presence of retinal fluid requiring intravitreal therapy with brolucizumab as a third-line treatment; Snellen best-corrected visual acuity at or above 0.1 at diagnosis; prior treatment with ranibizumab, aflibercept, or faricimab (switching between agents was permitted); and written consent to further use of coded data.\u003c/p\u003e\u003cp\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eExclusion criteria\u003c/span\u003e included:\u003c/p\u003e\u003cp\u003eRefusal to grant consent for the use of the patient\u0026rsquo;s coded data; subretinal bleeding greater than one optic nerve head (ONH) diameter at diagnosis; pretreatment with photodynamic therapy; and preexisting structural damage to the macula for any reason other than nAMD without functional potential. Any systemic comorbidities that interfere with treatment outcomes were also excluded, namely any local or systemic rheumatoid diseases and/or vasculitis requiring topical, intravitreal, or systemic treatment. Any opacifications in the optic axis that prohibit ocular imaging and fundoscopy were excluded, as were any intraocular surgeries and/or laser treatments (except YAG laser capsulotomy) within three months prior to inclusion. Eyes switched to bro did not receive formal loading but were initially maintained at the same interval as before the switch.\u003c/p\u003e\u003cp\u003eData were collected retrospectively from electronic medical records at the following prespecified time points: at diagnosis, prior to the first anti-VEGF treatment (baseline), after the loading phase, six months before switching to bro, before the last anti-VEGF treatment prior to switching, at the time of switching, after the first bro injection, after three bro injections, and after six and twelve months of bro treatment. At each time point, Snellen best-corrected visual acuity (BCVA) was recorded. For statistical use, Snellen VA was converted to ETDRS letter scores (BCVA of 1.0 is defined as 85 ETDRS letters).\u003c/p\u003e\u003cp\u003eIntraocular pressure, optical coherence tomography (OCT) imaging data (using a Heidelberg Spectralis device and HRA-2 software, Heidelberg, Germany), including center point retinal thickness (CRT), central subfield thickness (CST), maximal PED height in the central 3 mm around the foveola (ETDRS grid), and the presence of subretinal fluid (SRF) and/or intraretinal fluid (IRF) were recorded, as well as adverse events. CRT and CST measurements were assessed according to a standard operating procedure after manually correcting the segmentation, if necessary.\u003c/p\u003e\u003cp\u003eThe primary outcome measures were the changes in BCVA, morphological parameters (CST, CRT, and PED height), and treatment intervals (i.e., comparing the injection intervals before and after switching). Secondary outcomes included the total number of injections per eye before switching and the number of injections in the first year after switching. The proportion of eyes that switched to another drug and clinically relevant side effects of interest, e.g., signs of intraocular inflammation (IOI), with or without retinal vasculitis (RV) or retinovascular occlusion (RO), were recorded. Data from patients who switched to another anti-VEGF drug were censored after the switch and were no longer included in the evaluation.\u003c/p\u003e\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eStatistical Analysis\u003c/h2\u003e\u003cp\u003eDescriptive statistics and subgroup comparison analyses were performed. According to the Shapiro-Wilk test, most of the data were not normally distributed. Therefore, the data are presented as the mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation (SD), as well as the median and interquartile range (IQR: 25%-75%). A t-test was applied to group comparisons when the data were normally distributed, and a nonparametric Mann-Whitney U test was used when the data were not normally distributed. The Wilcoxon signed-rank test was used to analyze longitudinal changes in functional and morphological parameters, and the Friedman test for dependent samples was used to compare multiple time points in longitudinal analyses. A p-value of \u0026le;\u0026thinsp;0.05 was considered statistically significant. All statistical analyses were performed using the SPSS software package, version 27 (SPSS, Inc., Chicago, Illinois, USA), and R, version 4.4.2 (R: A language and environment for statistical computing; R Foundation for Statistical Computing, Vienna, Austria, 2024).\u003c/p\u003e\u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e\u003ch2\u003ePatients\u003c/h2\u003e\u003cp\u003eTwenty-seven eyes from 27 patients were included, with a mean age of 78.7\u0026thinsp;\u0026plusmn;\u0026thinsp;7.2 years (12 females [44.4%] and 15 males [55.6%]). Sixteen eyes were diagnosed with \"typical\" nAMD (59.3%), and according to imaging findings, eleven were categorized as PCV (40.7%). Subgroup analysis revealed that patients with nAMD were older than those with PCV (81.4\u0026thinsp;\u0026plusmn;\u0026thinsp;5.7 years vs. 74.7\u0026thinsp;\u0026plusmn;\u0026thinsp;7.7 years, respectively; \u003cem\u003ep\u0026thinsp;=\u0026thinsp;0.016\u003c/em\u003e), though no differences were observed for other baseline parameters, including gender, BCVA, and CST, besides age and CRT (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Both groups showed similar improvements in BCVA, CRT, and CST after switching to bro (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eBaseline demographic findings\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"8\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBaseline characteristics\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u003cp\u003enAMD\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e\u003cp\u003ePCV\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e\u003cp\u003epooled\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c8\"\u003e\u003cp\u003ep-value \u003c/p\u003e\u003cp\u003e(nAMD vs. PCV)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eParticipants (=\u0026thinsp;number of eyes), n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e(59.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e(40.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e27\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e(100)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFemales, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e(31.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e(63.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e(44.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e0.13\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge at baseline, (years (SD))\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e81.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e(5.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e74.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e(7.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e78.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e(7.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e\u003cb\u003e0.016\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBest-corrected visual acuity (ETDRS letters (SD))\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e65.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e(13.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e64.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e(18.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e65.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e(15.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e1.0\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCentral retinal thickness (\u0026micro;m (SD))\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e349.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e(95.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e597.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e(348.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e435.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e(242.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e\u003cb\u003e0.005\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCentral subfield thickness, (\u0026micro;m (SD))\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e384.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e(78.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e569.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e(326.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e448.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e(214.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e0.12\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eEvolution of functional and anatomical outcomes\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"5\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003enAMD\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003ePCV\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003epooled\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003ep-value\u003c/p\u003e\u003cp\u003e(nAMD vs. PCV)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBest-corrected visual acuity (ETDRS letters (SD); \u003c/p\u003e\u003cp\u003emedian; IQR\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAt baseline (diagnosis)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e65.7 (13.8)\u003c/p\u003e\u003cp\u003e69.9; 56.5\u0026ndash;75.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e64.8 (18.0)\u003c/p\u003e\u003cp\u003e69.9; 62.0\u0026ndash;75.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e65.3 (15.2)\u003c/p\u003e\u003cp\u003e69.9; 60.3\u0026ndash;75.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e1.0\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eEnd of loading\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e67.2 (15.3)\u003c/p\u003e\u003cp\u003e73.9; 57.6\u0026ndash;75.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e72.6 (15.6) \u003c/p\u003e\u003cp\u003e80.2; 69.9\u0026ndash;80.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e69.1 (15.2)\u003c/p\u003e\u003cp\u003e74.4; 69.9\u0026ndash;80.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.31\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAt switch to bro\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e59.9 (15.8)\u003c/p\u003e\u003cp\u003e60.3; 51.3\u0026ndash;69.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e66.8 (11.5)\u003c/p\u003e\u003cp\u003e69.9; 60.3\u0026ndash;75.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e62.7 (14.4)\u003c/p\u003e\u003cp\u003e65.1; 58.9\u0026ndash;73.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.23\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e12 months after switch\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e67.4 (16.8)\u003c/p\u003e\u003cp\u003e72.5; 55.9\u0026ndash;80.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e75.7 (4.7)\u003c/p\u003e\u003cp\u003e73.9; 73.9\u0026ndash;78.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e71.5 (12.7)\u003c/p\u003e\u003cp\u003e73.9; 69.9\u0026ndash;80.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.57\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003ep-value (longitudinal)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBaseline \u0026ndash; end of loading\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e0.046\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0.012\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.08\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBaseline \u0026ndash; switch to bro\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.80\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.17\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.14\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAt switch \u0026ndash; 12 months\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.89\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.07\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.23\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.15\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eCentral retinal thickness \u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003e\u0026micro;m (SD)\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003emedian; IQR\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBaseline (diagnosis)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e349.3 (95.3)\u003c/p\u003e\u003cp\u003e315; 279\u0026ndash;381\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e597.1 (348.4)\u003c/p\u003e\u003cp\u003e487; 354\u0026ndash;691\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e435.5 (242.8)\u003c/p\u003e\u003cp\u003e365; 305\u0026ndash;480\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003e0.005\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eEnd of loading\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e314.8 (89.1)\u003c/p\u003e\u003cp\u003e 295; 230\u0026ndash;414\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e520.3 (393.9)\u003c/p\u003e\u003cp\u003e450; 281\u0026ndash;527\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e383.3 (248.1)\u003c/p\u003e\u003cp\u003e336; 244\u0026ndash;438\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.13\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAt switch to bro\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e479.5 (306.6)\u003c/p\u003e\u003cp\u003e366; 329\u0026ndash;523\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e512.6 (209.7)\u003c/p\u003e\u003cp\u003e465; 366\u0026ndash;580\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e493.0 (267.2)\u003c/p\u003e\u003cp\u003e414; 331\u0026ndash;555\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.27\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e12 Months after switch\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e336.9 (105.6)\u003c/p\u003e\u003cp\u003e297; 256\u0026ndash;443\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e433.9 (140.1)\u003c/p\u003e\u003cp\u003e435; 306\u0026ndash;556\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e388.2 (131.1)\u003c/p\u003e\u003cp\u003e345; 275\u0026ndash;523\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.11\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003ep-value (longitudinal)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBaseline \u0026ndash; end of loading\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.30\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.60\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.052\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.27\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBaseline \u0026ndash; switch to bro\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003e0.033\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.42\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.12\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSwitch \u0026ndash; 12 months\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003e0.025\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0.006\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.60\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eCentral subfield thickness, \u0026micro;m (SD)\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003emedian; IQR\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAt baseline (diagnosis)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e384.5 (78.9)\u003c/p\u003e\u003cp\u003e374; 312\u0026ndash;405\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e569.6 (326.8)\u003c/p\u003e\u003cp\u003e423; 367\u0026ndash;679\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e448.9 (214.7)\u003c/p\u003e\u003cp\u003e395; 348\u0026ndash;445\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.12\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eEnd of loading\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e343.7 (71.3)\u003c/p\u003e\u003cp\u003e341; 275\u0026ndash;424\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e506.4 (367.6)\u003c/p\u003e\u003cp\u003e396; 266\u0026ndash;524\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e398.0 (223.7)\u003c/p\u003e\u003cp\u003e342; 275\u0026ndash;442\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.44\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAt switch to bro\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e443.1 (105.5)\u003c/p\u003e\u003cp\u003e390; 364\u0026ndash;495\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e539.0 (181.2)\u003c/p\u003e\u003cp\u003e530; 372\u0026ndash;564\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e483.7 (147.3)\u003c/p\u003e\u003cp\u003e457; 368\u0026ndash;563\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.15\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e12 Months after switch\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e369.4 (90.3)\u003c/p\u003e\u003cp\u003e370; 284\u0026ndash;427)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e442.2 (94.2)\u003c/p\u003e\u003cp\u003e450; 345\u0026ndash;530\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e407.9 (97.0)\u003c/p\u003e\u003cp\u003e401; 327\u0026ndash;505\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.17\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003ep-value (longitudinal)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBaseline \u0026ndash; end of loading\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e0.034\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0.013\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.29\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBaseline \u0026ndash; switch to bro\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003e0.035\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.58\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.37\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.13\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSwitch \u0026ndash; 12 months\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.069\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e0.008\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.54\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eIn the pooled cohort, BCVA increased from diagnosis to the end of the loading phase, then decreased until the switch to BRO. After switching, mean BCVA recovered over 12 months (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eThe mean baseline CRT was higher in the PCV group (nAMD: 349.3\u0026thinsp;\u0026plusmn;\u0026thinsp;95.3 \u0026micro;m; PCV: 597.1\u0026thinsp;\u0026plusmn;\u0026thinsp;348.4 \u0026micro;m; \u003cem\u003ep\u0026thinsp;=\u0026thinsp;0.005\u003c/em\u003e), while the CST was comparable in both groups (nAMD: 384.5\u0026thinsp;\u0026plusmn;\u0026thinsp;78.9 \u0026micro;m; PCV: 569.6\u0026thinsp;\u0026plusmn;\u0026thinsp;326.8 \u0026micro;m; \u003cem\u003ep\u0026thinsp;=\u0026thinsp;0.12\u003c/em\u003e; see Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eDuring the loading phase, CRT improved in the pooled cohort to 383.3\u0026thinsp;\u0026plusmn;\u0026thinsp;248.1 \u0026micro;m (-52.2). Thereafter, it increased to 493.0\u0026thinsp;\u0026plusmn;\u0026thinsp;267.2 \u0026micro;m (+\u0026thinsp;57.5 \u0026micro;m). Twelve months after the switch, the CRT improved to 388.2\u0026thinsp;\u0026plusmn;\u0026thinsp;131.1 (\u0026ndash;104.8) \u0026micro;m (\u003cem\u003ep\u0026thinsp;=\u0026thinsp;0.006\u003c/em\u003e; Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Similarly, CST decreased after the loading phase but increased again in both groups until the switch to BRO (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). After that, CST decreased again until 12 months after the switch (-75.8 \u0026micro;m; \u003cem\u003ep\u0026thinsp;=\u0026thinsp;0.001\u003c/em\u003e).\u003c/p\u003e\u003cp\u003ePooled data indicate an increase in the prevalence of PED from 23 patients (85.2%) to 25 patients (92.6%) after switching to BRO. Twelve months after the switch, two nAMD eyes (12.5%) were completely dry. Persistent PED was observed in six eyes (37.5%), while none of the PCV eyes were completely dry and ten (81.8%) showed persistent PED.\u003c/p\u003e\u003cp\u003eThe number of injections and treatment intervals before and after the switch are displayed in Tables\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e and \u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e. Pooled data showed an increase in treatment intervals after switching to Bro after the third injection, accompanied by a decrease in the annual number of injections in the year after switching to Bro compared to the year before switching to Bro (Tables\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e and \u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). Bro treatment had to be discontinued due to IOI in three cases (11.1%). No systemic adverse events (AEs) were reported (Table\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eTreatment intervals\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"8\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTreatment intervals (weeks (SD))\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u003cp\u003enAMD\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e\u003cp\u003ePCV\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e\u003cp\u003epooled\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c8\"\u003e\u003cp\u003e\u003cem\u003ep\u003c/em\u003e-value\u003c/p\u003e\u003cp\u003e(nAMD vs. PCV)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLast prior to switch\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e(1.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e5.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e(1.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e5.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e(1.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.81\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eafter third bro injection\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e8.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e(3.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e7.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e(1.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e8.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e(3.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.75\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eafter fifth bro injection\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e10.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e(3.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e7.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e(1.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e8.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e(2.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e\u003cb\u003e0.038\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e12 months after switch to brolucizumab\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e12.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e(5.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e8.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e(1.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e10.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e(4.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e\u003cb\u003e0.040\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003ep-value (longitudinal)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLast prior to switch - after third bro injection\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u003cp\u003e\u003cb\u003e0.004\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0.035\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.75\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLast prior to switch - after fifth bro injection\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u003cp\u003e\u003cb\u003e0.012\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e\u003cp\u003e0.11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e\u003cp\u003e\u003cb\u003e0.003\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.07\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLast prior to switch \u0026minus;\u0026thinsp;12 months after switch to bro\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u003cp\u003e\u003cb\u003e0.012\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0.018\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e\u003cp\u003e\u003cb\u003e0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.054\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003e\u003cb\u003eTreatment demand\u003c/b\u003e (number of injections)\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"5\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNumber of injections\u003c/p\u003e\u003cp\u003en (SD)\u003c/p\u003e\u003cp\u003emedian; IQR\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003enAMD\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003ePCV\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003epooled\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eIntergroup p-value\u003c/p\u003e\u003cp\u003e(nAMD vs. PCV)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eprior to switch) baseline to switch to bro)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e32.6(25.6)\u003c/p\u003e\u003cp\u003e28; 12\u0026ndash;46\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e39.5 (32.4)\u003c/p\u003e\u003cp\u003e30; 14\u0026ndash;78\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e35.4 (27.7)\u003c/p\u003e\u003cp\u003e30; 12\u0026ndash;47\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.65\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e12 months prior to switch to bro\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e8.9 (1.9)\u003c/p\u003e\u003cp\u003e9.0; (7\u0026ndash;10)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e10.5 (2.0)\u003c/p\u003e\u003cp\u003e11.0; (9\u0026ndash;12)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e9.6 (2.0)\u003c/p\u003e\u003cp\u003e10.0; 8\u0026ndash;11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003e0.039\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e12 months after switch to bro\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e7.3 (2.1)\u003c/p\u003e\u003cp\u003e7; 6\u0026ndash;9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e8.0 (1.2)\u003c/p\u003e\u003cp\u003e8; 7\u0026ndash;9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e7.6 (1.7)\u003c/p\u003e\u003cp\u003e7; 7\u0026ndash;9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.41\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003ep-value (longitudinal)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003e12 months prior to switch \u0026ndash; 12 months after switch\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eN/A\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e0.027\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0.032\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab5\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eTreatment discontinuation due to intraocular inflammation (IOI)\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"7\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePatients who discontinued treatment due to IOI\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003ePathology/Complication\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eNumber of bro before IOI\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eBCVA prior to IOI\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eBCVA after completion of anti-inflammatory therapy\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003eintraocular pressure\u003c/p\u003e\u003cp\u003e\u0026gt;\u0026thinsp;21 mmHg\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u003cp\u003eTreatment\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAnterior uveitis with papillitis and vasculitis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.25\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.25\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eno\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eSolumedrol intravenously followed by prednisone orally.\u003c/p\u003e\u003cp\u003eTopical therapy: Prednisolone acetate\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003esevere uveitis/occlusive retinal vasculitis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eno\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eSolumedrol intravenously followed by prednisone orally. \u003c/p\u003e\u003cp\u003eTopical therapy: none\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003earteriovenous occlusion\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.32\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eno\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eAcetylsalicylate\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe prevalence of PCV in our series was fivefold higher than expected in European cohorts of treatment-na\u0026iuml;ve patients with nAMD.\u003csup\u003e\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e,\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u003c/sup\u003e PCV generally responds well to anti-VEGF treatment in Caucasians,\u003csup\u003e\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u003c/sup\u003e but complete drying of the macula is less common compared to Asian cohorts.\u003csup\u003e\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u003c/sup\u003e Consequently, treatment in these eyes may be challenging. Nevertheless, eyes with PCV appear to respond similarly to bro as eyes with recalcitrant nAMD (Figs.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e1\u003c/span\u003e and \u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eAlthough polyp regression is likely in both Asian and Caucasian populations,\u003csup\u003e\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e,\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e\u003c/sup\u003e recurrence within one year is expected with as-needed (PRN) treatment.\u003csup\u003e\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e\u003c/sup\u003e None of the difficult-to-treat eyes with PCV and nAMD in our series qualified for PRN treatment or treatment interruption before switching. A reduced probability of complete polyp regression has been reported previously in Caucasians.\u003csup\u003e\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e\u003c/sup\u003e This deserves to be confirmed independently while explaining the overrepresentation of PCV in our series.\u003c/p\u003e\u003cp\u003eDespite the limited sample size, the decrease in central retinal thickness (CRT) and central subfield thickness (CST) after switching to bro (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e) indicates that bro may be more effective than previous anti-VEGF agents in treating recalcitrant nAMD and PCV. Published evidence strongly supports this, as bro has been shown to be highly effective in reducing retinal fluid and CRT.\u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e,\u003cspan additionalcitationids=\"CR35\" citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e\u003c/sup\u003e However, a strong anatomic response after switching does not necessarily lead to significant visual improvement in pretreated nAMD.\u003csup\u003e\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e\u003c/sup\u003e In contrast, our PCV patients experienced a remarkable functional response in addition to a twofold increase in treatment intervals and a significant reduction in the number of injections after switching (Tables\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e) which adds to published evidence.\u003csup\u003e\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e,\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eThe fact that three of our patients (11%) experienced intraocular inflammation (IOI) after switching to bro (requiring systemic corticosteroid treatment in two instances to maintain the visual function achieved prior to IOI) is understandable given the inadequate pre-switch control of disease activity and the absence of other therapeutic options. Nevertheless, this must be discussed critically with treatment-experienced patients, who may accept this additional risk and report any post-injection irregularity immediately.\u003c/p\u003e\u003cp\u003eAn obvious limitation of our study is its small sample size. This is due to the strict selection of patients who demanded treatment of six weeks or less during the 12 months prior to switching to bro and who had a minimum follow-up period of 12 weeks. On the other hand, the robustness of our findings is consistent with a majority of recent reports.\u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e,\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e,\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e,\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e,\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e,\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e,\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e,\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eIn conclusion, PCV is overrepresented in the group of eyes with recalcitrant nAMD. After other anti-VEGF agents failed to control disease activity, switching to bro extended the treatment interval from 5.6 to 10.5 weeks for PCV as for other types of macular neovascularization. Despite the inherent risk of IOI in response to brolucizumab, these results justify considering switching to brolucizumab in eyes requiring anti-VEGF treatment intervals of six weeks or less.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAuthor contributions:\u0026nbsp;\u003c/strong\u003eJS: data collection, writing of manuscript, preparation of tables and figures; IP: data collection and analysis, preparation of tables and figures; AW: data collection; JGG: data collection, writing and revising the manuscript\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFinancial disclosures:\u0026nbsp;\u003c/strong\u003eJS: none; IP: none;AW: AW acts for several pharmaceutical companies (Roche, Bayer, Apellis, AbbVie, Novartis,) as an advisor. \u0026nbsp;JGG acts as an advisor for several pharmaceutical companies (AbbVie, Bayer, Novartis, Roche) and has received research funding from Bayer and Roche. None of the authors received financial support for the undertaking of the present study or have conflicts of interest with the data that are presented in this report.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e: This study did not receive any external funding\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability statement:\u0026nbsp;\u003c/strong\u003eThe datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eFenner, B. J. et al. 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(Philadelphia Pa)\u003c/em\u003e. \u003cb\u003e14\u003c/b\u003e, 100176. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.apjo.2025.100176\u003c/span\u003e\u003cspan address=\"10.1016/j.apjo.2025.100176\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e (2025).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKimura, M. \u0026amp; Sakurada, Y. Association of Polyp Regression after Loading Phase with 12-Month Outcomes of Eyes with Polypoidal Choroidal Vasculopathy. \u003cb\u003e17\u003c/b\u003e, (2024). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3390/ph17060687\u003c/span\u003e\u003cspan address=\"10.3390/ph17060687\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eNguyen, Q. D. et al. 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Med.\u003c/em\u003e \u003cb\u003e11\u003c/b\u003e, 1467160. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3389/fmed.2024.1467160\u003c/span\u003e\u003cspan address=\"10.3389/fmed.2024.1467160\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e (2024).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eDugel, P. U. et al. Brolucizumab Versus Aflibercept in Participants with Neovascular Age-Related Macular Degeneration: A Randomized Trial. \u003cem\u003eOphthalmology\u003c/em\u003e \u003cb\u003e124\u003c/b\u003e, 1296\u0026ndash;1304. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.ophtha.2017.03.057\u003c/span\u003e\u003cspan address=\"10.1016/j.ophtha.2017.03.057\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e (2017).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBilgic, A. et al. 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Switching to brolucizumab from aflibercept in age-related macular degeneration with type 1 macular neovascularization and polypoidal choroidal vasculopathy: an 18-month follow-up study. \u003cb\u003e261\u003c/b\u003e, 345\u0026ndash;352, (2023). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s00417-022-05793-5\u003c/span\u003e\u003cspan address=\"10.1007/s00417-022-05793-5\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKamao, H. et al. Punctate Hyperfluorescence as a Favorable Predictive Factor for Treatment Response Following a Switch to Brolucizumab for Patients with Aflibercept-Refractory Neovascular Age-Related Macular Degeneration. \u003cb\u003e14\u003c/b\u003e, (2025). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3390/jcm14145141\u003c/span\u003e\u003cspan address=\"10.3390/jcm14145141\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Recalcitrant neovascular age-related macular degeneration (nAMD), polypoidal choroidal vasculopathy (PCV), anti-VEGF, brolucizumab, intraocular inflammation, disease control","lastPublishedDoi":"10.21203/rs.3.rs-7357019/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7357019/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose\u003c/h2\u003e\u003cp\u003eTo report the anatomical and functional outcomes after switching to brolucizumab in patients with recalcitrant neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV).\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eThis retrospective case series assessed the impact of switching to brolucizumab on disease activity over 12 months in patients with recalcitrant nAMD and PCV. The data are presented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eOf the 27 eyes, 16 (59.3%) presented with recalcitrant nAMD and 11 (40.7%) presented with PCV. Patients with nAMD were older (81.4\u0026thinsp;\u0026plusmn;\u0026thinsp;5.7 vs. 74.7\u0026thinsp;\u0026plusmn;\u0026thinsp;7.7 years; \u003cem\u003ep\u0026thinsp;=\u0026thinsp;0.016\u003c/em\u003e) and had less fluid (central retinal thickness: nAMD: 349.3\u0026thinsp;\u0026plusmn;\u0026thinsp;95.3 \u0026micro;m, PCV: 597.1\u0026thinsp;\u0026plusmn;\u0026thinsp;348.4 \u0026micro;m; \u003cem\u003ep\u0026thinsp;=\u0026thinsp;0.005\u003c/em\u003e), which was explained by different pigment epithelial detachment heights (nAMD: 176.5\u0026thinsp;\u0026plusmn;\u0026thinsp;102.6 \u0026micro;m, PCV: 384.6\u0026thinsp;\u0026plusmn;\u0026thinsp;284.6 \u0026micro;m; \u003cem\u003ep\u0026thinsp;=\u0026thinsp;0.023\u003c/em\u003e). Twelve months after switching to bro (159 injections), the treatment interval increased from 5.6\u0026thinsp;\u0026plusmn;\u0026thinsp;1.8 to 10.5\u0026thinsp;\u0026plusmn;\u0026thinsp;4.5 weeks (\u003cem\u003ep\u0026thinsp;=\u0026thinsp;0.01\u003c/em\u003e). Visual gains after switch were maintained in two out of three patients with intraocular inflammation (IOI).\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e\u003cp\u003ePCV is remarkably overrepresented in the group of eyes with recalcitrant nAMD. Despite the risk of IOI, the strong drying potential of brolucizumab justifies its use in eyes requiring anti-VEGF treatment intervals of six weeks or less.\u003c/p\u003e","manuscriptTitle":"Brolucizumab for Treating Recalcitrant Neovascular Age-Related Macular Degeneration and Polypoidal Choroidal Vasculopathy","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-09-01 09:31:12","doi":"10.21203/rs.3.rs-7357019/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"933619b4-44c3-439e-8759-c3b90d97fe16","owner":[],"postedDate":"September 1st, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":53691520,"name":"Health sciences/Diseases"},{"id":53691521,"name":"Health sciences/Medical research"}],"tags":[],"updatedAt":"2025-09-10T20:53:11+00:00","versionOfRecord":[],"versionCreatedAt":"2025-09-01 09:31:12","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7357019","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7357019","identity":"rs-7357019","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}