Short-term real-world outcomes of diabetic macular edema treated with intravitreal faricimab

Short-term real-world outcomes of diabetic macular edema treated with intravitreal faricimab | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Short-term real-world outcomes of diabetic macular edema treated with intravitreal faricimab Toshiaki Hirakata, Fumihiro Hara, Yuta Nochi, Daisuke Shinohara, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4364919/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 Faricimab, a new drug for diabetic macular edema (DME), was made available in Japan in 2022. However, few reports have been published about its treatment outcomes in clinical practice. To assess the short-term outcomes of intravitreal faricimab (IVF) in patients with DME, the records of patients with DME receiving IVF therapy between July 2022 and July 2023 at Juntendo University Hospital were retrospectively reviewed. Their best-corrected visual acuities in the logarithm of the minimum angle of resolution units and central macular thicknesses were compared at baseline and one month after the final IVF. Eighteen patients and 22 eyes were included and allocated to the naïve and switched groups: 12 cases (15 eyes) and 6 cases (7 eyes), respectively. The best-corrected visual acuity improved for the naïve group, but no difference was observed for the switched group. In contrast, the central macular thickness improved for both the naïve and switched groups. IVF demonstrated good short-term outcomes for DME, suggesting that it is effective for DME in clinical practice. Health sciences/Diseases/Eye diseases Health sciences/Diseases/Eye diseases/Retinal diseases faricimab diabetic macular edema diabetic retinopathy diabetes mellites Figures Figure 1 Figure 2 Figure 3 Introduction Diabetic retinopathy (DR) is the most common microvascular complication in patients with diabetes. 1 Diabetic macular edema (DME), which is a component of DR, causes vision loss. Intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF) agents are currently the most effective treatment for DME. 2 However, they have several limitations, including the need for repetitive injections and insufficient response in a subset of patients. Faricimab (Roche/Genentech, Basel, Switzerland) was developed as a bispecific antibody to bind VEGF-A and Ang2. 3 It was approved in Japan in March 2022 and its use began in May 2022. It has anti-Ang2 effects and is expected to be more effective for DME than previous treatments. 4 It is also expected to be effective for cases of ineffectiveness or resistance to existing drugs such as ranibizumab and aflibercept. This study aimed to determine the short-term efficacy of faricimab for the treatment of DME. Results The clinical characteristics of the patients are summarized in Table 1. This study included naïve (15 eyes of 12 patients) and switched (seven eyes of six patients) cases. The mean follow-up duration was 6.3 ± 3.6 months. The number of intravitreal faricimab (IVFs) was 3.3 ± 1.9, 2.7 ± 1.3, and 4.2 ± 2.4 for the all cases and the naïve and switched groups, respectively. For the switched group, the number of previous anti-VEGF injections was 7.6 ± 9.2. Five aflibercept and two ranibizumab drugs were previously administered as anti-VEGF drugs before switching to faricimab. Two eyes in the naive group had a history of vitrectomy. Table 1. Demographic all patients All case Naïve Switch Case (eye) 18 (23) 12 (15) 6 (8) male (female) 12 (6) 9 (2) 3 (4) The number of IVF 3.3 ± 1.9 2.7 ± 1.3 4.2 ± 2.4 Past history of anti-VEGF 7.6 ± 9.2 Avitreous case (eye) 2 (2) 2 (2) 0 PRN (TAE)* 15 (7) 11 (4) 4 (3) Mean follow-up period (months) 6.3 ± 3.6 5.1 ± 3.7 8.4 ± 1.7 PRN, pro re nata; TAE, treat and extend *The teatment regimen of IVF. The change in the logarithm of the minimum angle of resolution best-corrected visual acuity (logMAR BCVA) is shown in Fig. 1 . For all cases and the naïve group, the logMAR BCVA improved after IVF (Fig. 1 B). In contrast, the logMAR BCVA at baseline and after IVF were not different for the switched group (Fig. 1 C). Changes in the central macular thickness (CMTs) are shown in Fig. 2 . The CMT significantly improved after IVF from the baseline for both groups (Figs. 2 A–C). Additionally, both groups succussed the macula thickness under 300 µm (Figs. 3 A–C). Discussion In the present study, DME treatment with IVF was assessed retrospectively. IVF improved CMT for both the naïve and switched groups, suggesting a reduction in the retinal fluid. Visual acuity improved for the naïve but not for the switched group. These suggest that IVF is more effective at improving retinal morphological changes in DME. This was a retrospective study, and the methods of drug administration varied (PRN or TAE, with or without the administration period of IVF). Cases in which no induction phase was provided were included, and the reasons for this were recognized, including the financial burden of the patient and fear of injecting the drug into the eye. Cases for which the exact number of injections required was not administered were also included, suggesting that this study reflects the actual clinical real-world aspects of the study. This drug, anti-Ang2, has a new effect and is expected to be more effective for DME than previous treatments. 3 It is also expected to be effective for cases of ineffectiveness or resistance to existing drugs such as ranibizumab and aflibercept. In this study, naïve patients showed improvements in visual acuity and retinal thickness, suggesting good fluid control. In contrast, the switched case group showed improvement in retinal thickness but not in visual acuity. The risk factors for poor visual improvement after DME treatment for the naïve group were older age and poor vision before treatment. 5 Murakami et al. showed that visual acuity was significantly worse for patients with cystoid macular edema than for those with the serous retinal detachment or diffuse type. 6 Moreover, a disrupted ELM or parafoveal thickening was significantly correlated with poor visual acuity of patients with diffuse DME. However, the switched group in this study showed no obvious abnormalities in the outer retinal layers on OCT. Some previous reports have shown the efficacy of IVF for the switched cases. 7–9 These differences in results may be attributed to the small sample in this study, given the trend toward improvement in this study. The pathomorphology and photoreceptor statuses at the fovea and retinal edema in the parafovea should be continually considered as prognostic factors for DME. This study has several limitations. First, the sample was small. Second, the IVF treatment methods varied from case to case. Third, the follow-up was relatively short. We intend to continue this longitudinal study using additional cases. In this real-world study, IVF showed good short-term outcomes for DME. IVF may be effective for treating DME in clinical practice. Methods This study included 18 patients with 23 consecutive eyes treated with intravitreal faricimab (IVF) for DME between July 2022 and July 2023. They were divided into the naïve (15 eyes of 12 patients) and switched (seven eyes of six patients) groups, and their medical records were retrospectively reviewed. For the switched cases, one eye from each patient was excluded because of concomitant age-related macular degeneration. Finally, 22 eyes from the 18 patients with DME treated with IVF were included in this study. The follow-up lasted from July 2022 to August 2023. This study was conducted in accordance with the Declaration of Helsinki and approved by the Institutional Review Board of Juntendo University (16–292). All patients signed informed consent forms before IVF, and it was administered when retinal exudative changes (intraretinal and subretinal fluids) were detected by OCT. All patients underwent comprehensive ophthalmic examinations, including logMAR BCVA, fundus ophthalmoscopy, and spectral-domain OCT (SD-OCT; Carl Zeiss and Hidelberg). OCT analyzed the CMT. The baseline data obtained immediately before IVF administration and data from the last visit during the follow-up were compared. The statistical analyses were performed using Prism 10 software. Declarations Data Availability The data that support the findings of this study are available from the corresponding author upon reasonable request. Acknowledgments This work was supported by grants from MEXT/JSPS KAKENHI (19K23851, 20K18395 and 23K15918 to T.H.). Author contribution T. Hirakata, and S.N. designed all experiments. T. Hirakata, F.H., Y.N., D.S., S.Y., Y.H., and S.N recruited and followed all of the patients. T. Hirakata and S.N. analyzed the data. T. Hirakata wrote the manuscript. Conflict of interest No conflicting relations. References Kusuhara, S., Fukushima, Y., Ogura, S., Inoue, N. & Uemura, A. Pathophysiology of Diabetic Retinopathy: The Old and the New. Diabetes Metab J 42, 364–376 (2018). https://doi.org:10.4093/dmj.2018.0182 Tatsumi, T. Current Treatments for Diabetic Macular Edema. Int J Mol Sci 24 (2023). https://doi.org:10.3390/ijms24119591 Sahni, J. et al. Simultaneous Inhibition of Angiopoietin-2 and Vascular Endothelial Growth Factor-A with Faricimab in Diabetic Macular Edema: BOULEVARD Phase 2 Randomized Trial. Ophthalmology 126, 1155–1170 (2019). https://doi.org:10.1016/j.ophtha.2019.03.023 Wykoff, C. C. et al. Efficacy, durability, and safety of intravitreal faricimab with extended dosing up to every 16 weeks in patients with diabetic macular oedema (YOSEMITE and RHINE): two randomised, double-masked, phase 3 trials. Lancet 399, 741–755 (2022). https://doi.org:10.1016/S0140-6736(22)00018-6 Shah, J. et al. Characterization of Poor Visual Outcomes of Diabetic Macular Edema: The Fight Retinal Blindness! Project. Ophthalmol Retina 6, 540–547 (2022). https://doi.org:10.1016/j.oret.2022.03.007 Murakami, T. et al. Association of pathomorphology, photoreceptor status, and retinal thickness with visual acuity in diabetic retinopathy. Am J Ophthalmol 151, 310–317 (2011). https://doi.org:10.1016/j.ajo.2010.08.022 Ohara, H. et al. Faricimab for Diabetic Macular Edema in Patients Refractory to Ranibizumab or Aflibercept. Medicina (Kaunas) 59 (2023). https://doi.org:10.3390/medicina59061125 Rush, R. B. & Rush, S. W. Faricimab for Treatment-Resistant Diabetic Macular Edema. Clin Ophthalmol 16, 2797–2801 (2022). https://doi.org:10.2147/OPTH.S381503 Rush, R. B. One Year Results of Faricimab for Aflibercept-Resistant Diabetic Macular Edema. Clin Ophthalmol 17, 2397–2403 (2023). https://doi.org:10.2147/OPTH.S424314 Additional Declarations No competing interests reported. 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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-4364919","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":307256771,"identity":"1c77a587-5615-41cf-89b4-1edb34bbd215","order_by":0,"name":"Toshiaki Hirakata","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABDUlEQVRIie3Qv0rEMBzA8V8JtEt6rh3k+gq/0uE4UPsqOQI31cmlQ8G49JagT+A7dHRMOahLH+DGc+lUQRdxUDHxPLwl542C+Q4lKfmQPwAu15+MggJgekAUbv6wry+xg29CwWea4GEENoSa5T/EWgZhsyzKeZwF3dNFePc2ngRcwWsJwcS6y4g1XZsnkp7XadhhOpU982QLZCosJB6wEX7hSTCkwlm9yhFCAQSV9S6afBSZPBrWhlwa4r3/Rq6qfCajHAxhqAnZu4sy5HrO5arH5LZKk7rr2fK4jax3CQRNn8ULP13c8B4fq3GM97x5GMoTbnux3XzcjvSRIo57lm4j693Z2SHE5XK5/kWfZ9RWolODF14AAAAASUVORK5CYII=","orcid":"","institution":"Juntendo University Faculty of Medicine","correspondingAuthor":true,"prefix":"","firstName":"Toshiaki","middleName":"","lastName":"Hirakata","suffix":""},{"id":307256772,"identity":"86cec51c-bc69-4ebf-b26e-e479025d8221","order_by":1,"name":"Fumihiro Hara","email":"","orcid":"","institution":"Juntendo University Faculty of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Fumihiro","middleName":"","lastName":"Hara","suffix":""},{"id":307256773,"identity":"d808f0a8-1c32-47ed-bae4-7e678995a7bf","order_by":2,"name":"Yuta Nochi","email":"","orcid":"","institution":"Juntendo University Faculty of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Yuta","middleName":"","lastName":"Nochi","suffix":""},{"id":307256774,"identity":"6e52cba5-c728-44f7-abae-1a21ca5d23ba","order_by":3,"name":"Daisuke Shinohara","email":"","orcid":"","institution":"Juntendo University Faculty of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Daisuke","middleName":"","lastName":"Shinohara","suffix":""},{"id":307256775,"identity":"1db6d5b8-def4-49bf-9e76-8041a3878c71","order_by":4,"name":"Shutaro Yamamoto","email":"","orcid":"","institution":"Juntendo University Faculty of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Shutaro","middleName":"","lastName":"Yamamoto","suffix":""},{"id":307256776,"identity":"a438dc92-b91b-4c21-b198-adeb8ddadcc5","order_by":5,"name":"Yoshimune Hiratsuka","email":"","orcid":"","institution":"Juntendo University Faculty of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Yoshimune","middleName":"","lastName":"Hiratsuka","suffix":""},{"id":307256779,"identity":"a8d8f698-0519-4dff-8511-fcec32741f36","order_by":6,"name":"Shintaro Nakao","email":"","orcid":"","institution":"Juntendo University Faculty of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Shintaro","middleName":"","lastName":"Nakao","suffix":""}],"badges":[],"createdAt":"2024-05-03 15:17:31","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4364919/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4364919/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":57722482,"identity":"0cb86d15-cbe7-4bc4-801a-111d19b0cc5d","added_by":"auto","created_at":"2024-06-04 19:08:50","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":254708,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eVisual acuity improved in the naïve group treated with IVF. \u003c/strong\u003e(A) For all cases, the logarithm of the minimum angle of resolution best-corrected visual acuity (LogMAR BCVA) improved after intravitreal faricimab (IVF) administration. (B) For the naïve cases, the LogMAR BCVA also improved after IVF. (C) For the switched cases, no change in the LogMAR BCVA was observed. Data were analyzed using the paired t-test. Data are expressed as mean ± SD. *P\u0026lt;0.05, naïve vs. after IVF.\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-4364919/v1/26b1b3edac80b8d16259168e.jpeg"},{"id":57722484,"identity":"78852abf-0d0e-4d1f-a78b-8e13253a07a7","added_by":"auto","created_at":"2024-06-04 19:08:51","extension":"jpeg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":248265,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eCMT improved for both the naïve and switched groups after IVF. \u003c/strong\u003e(A) For all cases, central macular thickness (CMT) improved after intravitreal faricimab (IVF) administration. (B) CMT improved after IVF for the naïve cases. (C) CMT also improved after IVF for the switched cases. Data were analyzed using the paired t-test. Data are expressed as means ± SD. *P\u0026lt;0.05, **P\u0026lt;0.01, ***P\u0026lt;0.001, naïve vs. after IVF.\u003c/p\u003e","description":"","filename":"floatimage2.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-4364919/v1/9012e1eac2fd580697df3112.jpeg"},{"id":57722483,"identity":"84006183-73d5-4102-b337-e0fb78e76fcd","added_by":"auto","created_at":"2024-06-04 19:08:50","extension":"jpeg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":208812,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eIVF treatment increased the proportion of CMTs below 300 µm.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e(A) For all cases, central macular thicknesses (CMT) of ≤ 300 µm improved after intravitreal faricimab (IVF). (B) For the naïve cases, CMT improved after IVF. (C) For the switched cases, CMT also improved after IVF. Data were analyzed using Fisher’s exact test. Data are expressed as means ± SD. ***P\u0026lt;0.001, ****P\u0026lt;0.0001, naïve vs. after IVF.\u003c/p\u003e","description":"","filename":"floatimage3.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-4364919/v1/4dc933370c66ca7c04e36ccf.jpeg"},{"id":58259111,"identity":"158506c5-ab38-428d-be76-8113107ef996","added_by":"auto","created_at":"2024-06-13 05:52:46","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1026016,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4364919/v1/266a7a03-78c4-4078-b6e4-ae0184361e77.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Short-term real-world outcomes of diabetic macular edema treated with intravitreal faricimab","fulltext":[{"header":"Introduction","content":"\u003cp\u003eDiabetic retinopathy (DR) is the most common microvascular complication in patients with diabetes.\u003csup\u003e1\u003c/sup\u003e Diabetic macular edema (DME), which is a component of DR, causes vision loss. Intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF) agents are currently the most effective treatment for DME.\u003csup\u003e2\u003c/sup\u003e However, they have several limitations, including the need for repetitive injections and insufficient response in a subset of patients.\u003c/p\u003e \u003cp\u003eFaricimab (Roche/Genentech, Basel, Switzerland) was developed as a bispecific antibody to bind VEGF-A and Ang2.\u003csup\u003e3\u003c/sup\u003e It was approved in Japan in March 2022 and its use began in May 2022. It has anti-Ang2 effects and is expected to be more effective for DME than previous treatments.\u003csup\u003e4\u003c/sup\u003e It is also expected to be effective for cases of ineffectiveness or resistance to existing drugs such as ranibizumab and aflibercept.\u003c/p\u003e \u003cp\u003eThis study aimed to determine the short-term efficacy of faricimab for the treatment of DME.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eThe clinical characteristics of the patients are summarized in Table 1. This study included na\u0026iuml;ve (15 eyes of 12 patients) and switched (seven eyes of six patients) cases. The mean follow-up duration was 6.3\u0026thinsp;\u0026plusmn;\u0026thinsp;3.6 months. The number of intravitreal faricimab (IVFs) was 3.3\u0026thinsp;\u0026plusmn;\u0026thinsp;1.9, 2.7\u0026thinsp;\u0026plusmn;\u0026thinsp;1.3, and 4.2\u0026thinsp;\u0026plusmn;\u0026thinsp;2.4 for the all cases and the na\u0026iuml;ve and switched groups, respectively. For the switched group, the number of previous anti-VEGF injections was 7.6\u0026thinsp;\u0026plusmn;\u0026thinsp;9.2. Five aflibercept and two ranibizumab drugs were previously administered as anti-VEGF drugs before switching to faricimab. Two eyes in the naive group had a history of vitrectomy.\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"565\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" colspan=\"3\" rowspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eTable 1. Demographic all patients\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"0%\" height=\"32\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"NaN%\" height=\"34\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"58.56353591160221%\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"41.43646408839779%\" colspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eAll case\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"0%\" height=\"32\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"58.67158671586716%\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.66420664206642%\"\u003e\n \u003cp\u003e\u003cstrong\u003eNa\u0026iuml;ve\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.66420664206642%\"\u003e\n \u003cp\u003e\u003cstrong\u003eSwitch\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"0%\" height=\"32\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"58.56353591160221%\" rowspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eCase (eye)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"41.43646408839779%\" colspan=\"2\"\u003e\n \u003cp\u003e18 (23)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"0%\" height=\"32\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"50%\"\u003e\n \u003cp\u003e12 (15)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"50%\"\u003e\n \u003cp\u003e6 (8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"0%\" height=\"32\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"58.56353591160221%\" rowspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003emale (female)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"41.43646408839779%\" colspan=\"2\"\u003e\n \u003cp\u003e12 (6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"0%\" height=\"32\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"50%\"\u003e\n \u003cp\u003e9 (2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"50%\"\u003e\n \u003cp\u003e3 (4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"0%\" height=\"32\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"58.56353591160221%\" rowspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eThe number of IVF\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"41.43646408839779%\" colspan=\"2\"\u003e\n \u003cp\u003e3.3 \u0026plusmn; 1.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"0%\" height=\"32\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"50%\"\u003e\n \u003cp\u003e2.7 \u0026plusmn; 1.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"50%\"\u003e\n \u003cp\u003e4.2 \u0026plusmn; 2.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"0%\" height=\"32\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"58.56353591160221%\" rowspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003ePast history of anti-VEGF\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"41.43646408839779%\" colspan=\"2\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"0%\" height=\"32\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"50%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"50%\"\u003e\n \u003cp\u003e7.6 \u0026plusmn; 9.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"0%\" height=\"32\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"58.56353591160221%\" rowspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eAvitreous case (eye)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"41.43646408839779%\" colspan=\"2\"\u003e\n \u003cp\u003e2 (2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"0%\" height=\"32\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"50%\"\u003e\n \u003cp\u003e2 (2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"50%\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"0%\" height=\"32\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"58.56353591160221%\" rowspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003ePRN (TAE)*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"41.43646408839779%\" colspan=\"2\"\u003e\n \u003cp\u003e15 (7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"0%\" height=\"32\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"50%\"\u003e\n \u003cp\u003e11 (4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"50%\"\u003e\n \u003cp\u003e4 (3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"0%\" height=\"32\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"58.56353591160221%\" rowspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eMean follow-up period\u0026nbsp;\u003cbr\u003e\u0026nbsp;(months)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"41.43646408839779%\" colspan=\"2\"\u003e\n \u003cp\u003e6.3 \u0026plusmn; 3.6\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"0%\" height=\"32\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"50%\"\u003e\n \u003cp\u003e5.1 \u0026plusmn; 3.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"50%\"\u003e\n \u003cp\u003e8.4 \u0026plusmn; 1.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"0%\" height=\"34\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" colspan=\"3\" rowspan=\"2\"\u003e\n \u003cp\u003ePRN, pro re nata; TAE, treat and extend\u003cbr\u003e\u0026nbsp;*The teatment regimen of IVF.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"0%\" height=\"32\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"NaN%\" height=\"32\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eThe change in the logarithm of the minimum angle of resolution best-corrected visual acuity (logMAR BCVA) is shown in Fig. \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e. For all cases and the na\u0026iuml;ve group, the logMAR BCVA improved after IVF (Fig. \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003eB). In contrast, the logMAR BCVA at baseline and after IVF were not different for the switched group (Fig. \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003eC).\u003c/p\u003e\n\u003cp\u003eChanges in the central macular thickness (CMTs) are shown in Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e. The CMT significantly improved after IVF from the baseline for both groups (Figs.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003eA\u0026ndash;C). Additionally, both groups succussed the macula thickness under 300 \u0026micro;m (Figs.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003eA\u0026ndash;C).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn the present study, DME treatment with IVF was assessed retrospectively. IVF improved CMT for both the na\u0026iuml;ve and switched groups, suggesting a reduction in the retinal fluid. Visual acuity improved for the na\u0026iuml;ve but not for the switched group. These suggest that IVF is more effective at improving retinal morphological changes in DME.\u003c/p\u003e \u003cp\u003eThis was a retrospective study, and the methods of drug administration varied (PRN or TAE, with or without the administration period of IVF). Cases in which no induction phase was provided were included, and the reasons for this were recognized, including the financial burden of the patient and fear of injecting the drug into the eye. Cases for which the exact number of injections required was not administered were also included, suggesting that this study reflects the actual clinical real-world aspects of the study.\u003c/p\u003e \u003cp\u003eThis drug, anti-Ang2, has a new effect and is expected to be more effective for DME than previous treatments.\u003csup\u003e3\u003c/sup\u003e It is also expected to be effective for cases of ineffectiveness or resistance to existing drugs such as ranibizumab and aflibercept. In this study, na\u0026iuml;ve patients showed improvements in visual acuity and retinal thickness, suggesting good fluid control. In contrast, the switched case group showed improvement in retinal thickness but not in visual acuity.\u003c/p\u003e \u003cp\u003eThe risk factors for poor visual improvement after DME treatment for the na\u0026iuml;ve group were older age and poor vision before treatment.\u003csup\u003e5\u003c/sup\u003e Murakami et al. showed that visual acuity was significantly worse for patients with cystoid macular edema than for those with the serous retinal detachment or diffuse type.\u003csup\u003e6\u003c/sup\u003e Moreover, a disrupted ELM or parafoveal thickening was significantly correlated with poor visual acuity of patients with diffuse DME. However, the switched group in this study showed no obvious abnormalities in the outer retinal layers on OCT. Some previous reports have shown the efficacy of IVF for the switched cases.\u003csup\u003e7\u0026ndash;9\u003c/sup\u003e These differences in results may be attributed to the small sample in this study, given the trend toward improvement in this study. The pathomorphology and photoreceptor statuses at the fovea and retinal edema in the parafovea should be continually considered as prognostic factors for DME.\u003c/p\u003e \u003cp\u003eThis study has several limitations. First, the sample was small. Second, the IVF treatment methods varied from case to case. Third, the follow-up was relatively short. We intend to continue this longitudinal study using additional cases.\u003c/p\u003e \u003cp\u003eIn this real-world study, IVF showed good short-term outcomes for DME. IVF may be effective for treating DME in clinical practice.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eThis study included 18 patients with 23 consecutive eyes treated with intravitreal faricimab (IVF) for DME between July 2022 and July 2023. They were divided into the na\u0026iuml;ve (15 eyes of 12 patients) and switched (seven eyes of six patients) groups, and their medical records were retrospectively reviewed. For the switched cases, one eye from each patient was excluded because of concomitant age-related macular degeneration. Finally, 22 eyes from the 18 patients with DME treated with IVF were included in this study. The follow-up lasted from July 2022 to August 2023. This study was conducted in accordance with the Declaration of Helsinki and approved by the Institutional Review Board of Juntendo University (16\u0026ndash;292). All patients signed informed consent forms before IVF, and it was administered when retinal exudative changes (intraretinal and subretinal fluids) were detected by OCT.\u003c/p\u003e \u003cp\u003eAll patients underwent comprehensive ophthalmic examinations, including logMAR BCVA, fundus ophthalmoscopy, and spectral-domain OCT (SD-OCT; Carl Zeiss and Hidelberg). OCT analyzed the CMT. The baseline data obtained immediately before IVF administration and data from the last visit during the follow-up were compared. The statistical analyses were performed using Prism 10 software.\u003c/p\u003e "},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eData Availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data that support the findings of this study are available from the corresponding author upon reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was supported by grants from MEXT/JSPS KAKENHI (19K23851, 20K18395 and 23K15918 to T.H.).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contribution\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eT. Hirakata, and S.N. designed all experiments. T. Hirakata, F.H., Y.N., D.S., S.Y., Y.H., and S.N recruited and followed all of the patients. T. Hirakata and S.N. analyzed the data. T. Hirakata wrote the manuscript.\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo conflicting relations.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eKusuhara, S., Fukushima, Y., Ogura, S., Inoue, N. \u0026amp; Uemura, A. Pathophysiology of Diabetic Retinopathy: The Old and the New. Diabetes Metab J 42, 364\u0026ndash;376 (2018). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org:10.4093/dmj.2018.0182\u003c/span\u003e\u003cspan address=\"https://doi.org:10.4093/dmj.2018.0182\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTatsumi, T. Current Treatments for Diabetic Macular Edema. Int J Mol Sci 24 (2023). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org:10.3390/ijms24119591\u003c/span\u003e\u003cspan address=\"https://doi.org:10.3390/ijms24119591\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSahni, J. \u003cem\u003eet al.\u003c/em\u003e Simultaneous Inhibition of Angiopoietin-2 and Vascular Endothelial Growth Factor-A with Faricimab in Diabetic Macular Edema: BOULEVARD Phase 2 Randomized Trial. Ophthalmology 126, 1155\u0026ndash;1170 (2019). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org:10.1016/j.ophtha.2019.03.023\u003c/span\u003e\u003cspan address=\"https://doi.org:10.1016/j.ophtha.2019.03.023\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWykoff, C. C. \u003cem\u003eet al.\u003c/em\u003e Efficacy, durability, and safety of intravitreal faricimab with extended dosing up to every 16 weeks in patients with diabetic macular oedema (YOSEMITE and RHINE): two randomised, double-masked, phase 3 trials. Lancet 399, 741\u0026ndash;755 (2022). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org:10.1016/S0140-6736(22)00018-6\u003c/span\u003e\u003cspan address=\"https://doi.org:10.1016/S0140-6736(22)00018-6\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eShah, J. \u003cem\u003eet al.\u003c/em\u003e Characterization of Poor Visual Outcomes of Diabetic Macular Edema: The Fight Retinal Blindness! Project. Ophthalmol Retina 6, 540\u0026ndash;547 (2022). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org:10.1016/j.oret.2022.03.007\u003c/span\u003e\u003cspan address=\"https://doi.org:10.1016/j.oret.2022.03.007\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMurakami, T. \u003cem\u003eet al.\u003c/em\u003e Association of pathomorphology, photoreceptor status, and retinal thickness with visual acuity in diabetic retinopathy. Am J Ophthalmol 151, 310\u0026ndash;317 (2011). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org:10.1016/j.ajo.2010.08.022\u003c/span\u003e\u003cspan address=\"https://doi.org:10.1016/j.ajo.2010.08.022\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOhara, H. \u003cem\u003eet al.\u003c/em\u003e Faricimab for Diabetic Macular Edema in Patients Refractory to Ranibizumab or Aflibercept. Medicina (Kaunas) 59 (2023). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org:10.3390/medicina59061125\u003c/span\u003e\u003cspan address=\"https://doi.org:10.3390/medicina59061125\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRush, R. B. \u0026amp; Rush, S. W. Faricimab for Treatment-Resistant Diabetic Macular Edema. Clin Ophthalmol 16, 2797\u0026ndash;2801 (2022). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org:10.2147/OPTH.S381503\u003c/span\u003e\u003cspan address=\"https://doi.org:10.2147/OPTH.S381503\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRush, R. B. One Year Results of Faricimab for Aflibercept-Resistant Diabetic Macular Edema. Clin Ophthalmol 17, 2397\u0026ndash;2403 (2023). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org:10.2147/OPTH.S424314\u003c/span\u003e\u003cspan address=\"https://doi.org:10.2147/OPTH.S424314\" 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":"faricimab, diabetic macular edema, diabetic retinopathy, diabetes mellites ","lastPublishedDoi":"10.21203/rs.3.rs-4364919/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4364919/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eFaricimab, a new drug for diabetic macular edema (DME), was made available in Japan in 2022. However, few reports have been published about its treatment outcomes in clinical practice. To assess the short-term outcomes of intravitreal faricimab (IVF) in patients with DME, the records of patients with DME receiving IVF therapy between July 2022 and July 2023 at Juntendo University Hospital were retrospectively reviewed. Their best-corrected visual acuities in the logarithm of the minimum angle of resolution units and central macular thicknesses were compared at baseline and one month after the final IVF. Eighteen patients and 22 eyes were included and allocated to the naïve and switched groups: 12 cases (15 eyes) and 6 cases (7 eyes), respectively. The best-corrected visual acuity improved for the naïve group, but no difference was observed for the switched group. In contrast, the central macular thickness improved for both the naïve and switched groups. IVF demonstrated good short-term outcomes for DME, suggesting that it is effective for DME in clinical practice.\u003c/p\u003e","manuscriptTitle":"Short-term real-world outcomes of diabetic macular edema treated with intravitreal faricimab","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-06-04 19:08:45","doi":"10.21203/rs.3.rs-4364919/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":"c04af3b8-63f4-4e13-a437-487101fd22e6","owner":[],"postedDate":"June 4th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":32453515,"name":"Health sciences/Diseases/Eye diseases"},{"id":32453516,"name":"Health sciences/Diseases/Eye diseases/Retinal diseases"}],"tags":[],"updatedAt":"2024-06-13T05:44:40+00:00","versionOfRecord":[],"versionCreatedAt":"2024-06-04 19:08:45","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4364919","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4364919","identity":"rs-4364919","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}