Early Outcomes of Brolucizumab Switch in Wet Age- Related Macular Degeneration: A Tertiary Portuguese Hospital Experience

Abstract

INTRODUCTION: Age-related macular degeneration (AMD) is the leading cause of blindness in the developed world. The use of anti-vascular endothelial growth factor (VEGF) revolu- tionized the treatment of neovascular AMD (nAMD) despite being a known burden to both patients and healthcare systems. Brolucizumab is a newer anti-VEGF agent, whose noninferiority to aflibercept in visual outcomes in treatment-naïve eyes with nAMD was demonstrated in two clinical trials. A secondary favorable outcome was the extended dosing intervals in more than half of eyes treated with this agent. Although it exhibited a safety profile comparable to aflibercept, the rate of intraocular inflammatory events was superior. Few studies report the outcomes of non-naïve patients after switching to brolucizumab. Our aim is to evaluate the functional and anatomic outcomes, and safety of brolucizumab in nAMD patients previously treated with other anti-VEGF agents with poor response in our center.
METHODS: Retrospective and observational study in patients with nAMD receiving intra- vitreal treatment with anti-VEGF that showed no response or persistent presence of significant intra- and/or subretinal fluid despite injections intervals of 6 weeks or less. Those patients switched to therapy with brolucizumab between January to August of 2022. Functional (best corrected visual acuity [BCVA], intraocular pressure [IOP]) and anatomical (central subfield thickness [CST], presence of intra- and/or subretinal fluid and presence of pigment epithelial detachment) outcomes were measured and analyzed both at baseline and at a posterior visit 8-to-12 weeks after the first injection. Any sign of adverse effect was reported. For statistical analysis SPSS v.28 was used. Results were deemed significant if p < 0.05, in the parametric, non-parametric and categori- cal tests used.
RESULTS: Thirteen eyes of 12 patients, with a mean age of 77.4 ± 11.6 years and 41.7% of females, switched to brolucizumab during the mentioned period, receiving a mean of 1.77 ± 0.8 injections. Patients were previously followed for a mean of 43.1 ± 25.6 months and received a median of 23 ± 31 other anti-VEGF injections. After the switch, it was observed a significant change in the treatment interval (p = 0.008). A significant mean change in BCVA of -0.17 ± 0.19 logMAR (95% CI: -0.278; -0.053, p = 0.007), as well as in CST of -43.38 ± 57.70 μm (95% CI: -78.25; -8.52; p = 0.019) was found. A significant reduction was observed regarding subretinal fluid (p= 0.031), but no change was observed in the presence of intraretinal fluid or pigment epithelial detachment. There were no reported adverse effects.
CONCLUSION: Our results align with previous clinical trials and reports of real-world settings of naïve and non-naïve treatment patients treated with brolucizumab. The improvement in functional and anatomical outcomes in addition to extending treatment interval demonstrates that this agent is a promising treatment against nAMD and reduces the burden of repeated in- travitreal injections. Despite no reports of IOI in this cohort, careful patient selection, a vigilant follow-up and suitable patient education for warning signs is vital.