Brolucizumab results and adverse visual outcomes study: A single-center real-world Indian experience
Year: 2025
Type: article
Study design: Observational Study
Abstract: Brolucizumab (BZB), [Pagenax® in India], is a low molecular weight humanized monoclonal single-chain variable fragment that inhibits all isoforms of vascular endothelial growth factor – A (VEGF-A).[1–3] It acts by reducing vascular leakage and retinal or choroidal neovascularization and demonstrates efficacy in a variety of retinal and choroidal vascular pathologies.[4] The U.S Food and Drug Administration approved BZB for the treatment of neovascular age-related macular degeneration (nAMD) in 2019 and diabetic macular edema in 2022.[5,6] Safety concerns have been raised due to the high incidence of intraocular inflammation (IOI), retinal vasculitis (RV), and/or vision-threatening retinal vascular occlusion reported with BZB-treated eyes.[7–10] However, a latest paper published by the Vitreo Retina Society of India (VRSI) reported 21 instances of IOI, accounting for 0.79% of 2,655 eyes treated for various on-label and off-label indications.[11] We retrospectively analyzed the efficacy and safety of 926 intravitreal BZB injections in 450 eyes of 390 patients treated for retinal and choroidal diseases at a single facility of a tertiary eye care center in Bangalore, India, from 2020–24. The mean patient age was 65.5 years, with 59% treated for choroidal and 41% for retinal pathologies. The main indication for treatment was nAMD, accounting for 48% (215 cases) [Fig. 1]. Of the cohort, 30% (135 eyes) were treatment-naïve, while 70% (315 eyes) had switched treatments. The average number of injections per eye was 2.4 ± 2.16 (range: 1–18), with 93% following a pro-re-nata regimen. Overall, the mean change in visual acuity (VA) was + 0.693 ± 27.02 ETDRS letters (P = 0.472), and central subfield thickness (CSFT) reduced by −101.6 ± 163.3 µm (P < 0.001). Choroidal cases showed a mean VA worsening of −2.33 ETDRS letters (P < 0.05) and a significant CSFT reduction of −84.27 ± 141.6 µm (P < 0.05). Retinal cases saw a VA improvement of + 5.6 ETDRS letters and a CSFT decrease of −130.4 ± 190.9 µm. There was a significant improvement in VA and CSFT in retinal cases after treatment [Table 1]. Table 2 compared the number of injections per eye, the change in the VA and CSFT before and after treatment with intravitreal BZB injection, and the number of eyes who received some alternative form of treatment after getting initially treated with intravitreal BZB injection. We observed three cases of IOI post-injection, with incidences of 0.32% per injection, 0.67% per eye, and 0.77% per patient. Two cases were successfully re-treated with no recurrence, while the third required no further treatment due to disease resolution [Table 3].Figure 1: Bar diagram demonstrating the various indications of eyes treated with intravitreal BZBTable 1: Efficacy outcomes across all retinal and choroidal indicationsTable 2: Comparisons in efficacy outcomes for eyes treated with intravitreal BZB injections between retinal and choroidal pathologiesTable 3: Ocular findings of patients diagnosed with intraocular inflammation after intravitreal brolucizumab injectionIn summary, this study demonstrated favorable anatomical and safety outcomes for intravitreal BZB injection in treating various retinal and choroidal pathologies. Comparative analysis revealed statistically significant differences between the two sets of indications. Eyes with retinal vascular pathologies exhibited superior structural and functional outcomes, including greater reductions in macular thickness and significant VA improvement following each BZB injection. Conversely, eyes treated for choroidal pathologies showed significant anatomical improvements on OCT but less pronounced functional outcome improvements. In addition, BZB exhibited a well-tolerated safety profile in this study. A type III hypersensitivity reaction has been linked to RV caused by the deposition of the antigen-antibody immune complex.[12] The increased molar concentration produces a high antigenic load, which is accompanied by a high rate of anti-drug antibodies in the population. These antibodies are specific to BZB and thus have a higher propensity to form immune complexes that, when present in the correct balanced ratio, cause tissue deposits, inflammation, and damage, all of which are characteristic of RV.[12] An interesting finding was that all cases of IOI occurred in eyes with nAMD or polypoidal choroidal vasculopathy (choroidal pathologies), with none in eyes treated for retinal pathologies. This may be due to RPE damage in choroidal diseases, as RPE cells play a key role in retinal immunity, regulating both innate and adaptive responses.[13] A post hoc analysis of the HAWK and HARRIER clinical trials regarding nAMD reported an incidence of IOI of 4.5%, with 2.1% of eyes experiencing concomitant vascular occlusions.[14] In parallel, the KITE and KRESTEL studies for DME demonstrated comparable rates of IOI between the BZB and aflibercept treatment arms.[15] A comprehensive real-world analysis encompassing 10,654 eyes from the Intelligent Research in Sight (IRIS) Registry and 11,161 eyes from the Komodo Health database revealed an overall incidence of IOI and/or retinal occlusion at 2.4%.[16] To date, the literature does not appear to have adequately compared the rates of IOI following BZB injections for nAMD or polypoidal choroidal vasculopathy versus other indications. However, a recent study from the VRSI identified 21 instances of IOI following BZB injection. Among these, 18 (86%) cases were linked to treatment for choroidal pathologies, while only 3 (14%) cases were associated with indications related to retinal diseases.[11] In summary, this real-world BZB study showed improved anatomical outcomes for both retinal and choroidal pathologies, but visual improvement occurred only in retinal cases. The study also reported a lower incidence of IOI and RV compared to key clinical trials and other real-world data.
Source: Indian Journal of Ophthalmology
Institution: Narayana Nethralaya
Language: English
Subfield: Ophthalmology
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W4410818512