The Effect of a Loading Dose Regimen in the Switch to Brolucizumab for Patients with Aflibercept-Resistant nAMD.

"Conflicts of Interest The authors declare that they have no conflicts of interest."

"We performed this study, which was conducted according to the Declaration of Helsinki principles and registered with the UMIN Clinical Trials Registry (UMIN000023676), with approval from the Kawasaki Medical School Ethics Committee (2543-03 and 5954-00). We obtained informed consent from patients via an opt-out method through the website of Kawasaki Medical School. We retrospectively studied 52 eyes of 49 consecutive nAMD patients who had retinal exudate, including intraretinal fluid (IRF) and subretinal fluid (SRF), under intravitreal aflibercept injection and were switched to brolucizumab from aflibercept at Kawasaki Medical School between July 2020 and April 2023. Upon the decision to switch to IVBr, one physician (H.K.) proposed the loading dose regimen (three initial monthly injections) to all patients. If consent was not secured, patients underwent brolucizumab administration without adherence to the loading dose regimen. Twenty-seven eyes of 27 nAMD patients consented to the loading dose regimen. We excluded 26 eyes of 23 patients who were followed up for less than one year after the medications were switched. All patients were treated with the treat-and-extend protocol of IVBr, which were adjusted for 2 to 4 weeks based on the retinal exudate findings (IRF and SRF) on OCT. The treatment interval was extended when no retinal exudate occurred for six months and reduced when the retinal exudate remained. As the primary outcome, the proportion of dry macula at the last visit was compared between the loading and nonloading groups. Data regarding cigarette smoking, hypertension, and diabetes were collected from patient recall or hospital records. We divided the patients into never-smokers and ever-smokers as described in a previous report []. All participants received a complete ophthalmologic examination, including measurement of best-corrected visual acuity (BCVA), indirect ophthalmoscopy, slit-lamp biomicroscopy with a noncontact lens, color fundus photography and fundus autofluorescence (Canon CX-1; Canon, Tokyo, Japan), swept-source optical coherence tomography (OCT) (DRI OCT-1 Atlantis; Topcon Corporation, Tokyo, Japan), and fluorescein and indocyanine green angiography (HRA-2; Heidelberg Engineering GmbH, Dossenheim, Germany). Visual acuity data were obtained in decimal BCVA and converted to the logarithm of the minimum angle of resolution (logMAR) units for the analysis. The retinal and choroidal thicknesses were measured by swept-source OCT as described in a previous report []. Conclusion: Switching to brolucizumab from aflibercept for eyes with nAMD with resistance to bimonthly injections of aflibercept is a valuable treatment option with and without the loading regimen. This trial is registered with UMIN000023676."