Real world experience of brolucizumab in recalcitrant macular edema in retinal vein occlusions (RVO’s): 12 months follow up – A pilot study
Year: 2024
Type: article
Abstract: Dear Editor, This pilot study enrolled 17 eyes of 17 patients with recalcitrant macular edema secondary to retinal vein occlusion (RVO), who received intravitreal brolucizumab (IVBr) and were followed for a minimum 1 year. These eyes were subdivided into two groups: Group 1, consisting of seven eyes with branch retinal vein occlusion (BRVO) and recalcitrant macular edema and Group 2, consisting of ten eyes with central retinal vein occlusion (CRVO) and recalcitrant macular edema. Recalcitrant macular edema was defined as a change of ≤15% in central macular thickness (CMT) of >350 µm over the past 6 months despite receiving at least three intravitreal anti-vascular endothelial growth factor (VEGF) injections. Exclusion criteria included eyes with significant media opacities that precluded the observation of the ocular fundus, coexisting diabetic retinopathy or diabetic macular edema (DME), high myopia (>4 diopters), glaucoma, choroidal neovascular membrane, trauma, coexisting vitreoretinal pathology or other maculopathies, past history of any retinal surgery, any history of anterior or posterior segment inflammation, any history of systemic vasculitis or autoimmune disease, and patients who could not complete one year of follow-up. All patients underwent a detailed ophthalmic evaluation, including best corrected visual acuity (BCVA) using the Snellen’s visual acuity chart, intraocular pressure (IOP) measurement with a Goldmann applanation tonometer, slit lamp examination, 78-dioptre (D) slit lamp biomicroscopy, and a dilated fundus examination using an indirect ophthalmoscope with a 20-D lens. Additionally, color fundus photography [Figs. 1a and 2a], fundus fluorescein angiography (FFA) [Figs. 1b and 2b], and ultra-wide field (16.5 * 12 mm) spectral domain optical coherence tomography (SD-OCT) [Figs. 1c and 2c] were performed before initiating IVBr. Diagnosis was based on clinical evaluation, FFA, and SD-OCT findings. All patients were placed on a pro re nata (PRN) dosing regimen from the start of the study.Figure 1: (a-f) Color fundus photographs, FFA, and OCT at various intervals in a case of BRVOFigure 2: (a-f) Color fundus photograph, FFA, and OCT at various intervals in a case of CRVOPost injection, all patients underwent SD-OCT at 3, 6, and 12 months [Figs. 1d-1f and 2d-2f]. If a patient required additional injections, an OCT was performed just before the repeat injection. Measurements on SD-OCT were conducted manually using the calliper incorporated in the software, marking the distance from the maximum height of fluid to the retinal pigment epithelium. All analyses were performed by two vitreoretinal specialists who were blinded to the treatment administered to the patient. The study was conducted in accordance with the tenets of the Declaration of Helsinki and approved by the Institutional Review Board Committee. Written informed consent for off-label use, treatment on a PRN basis from the start, and data collection was obtained from each patient. After obtaining the necessary consent, the IVBr injection was performed in the operation theatre under all aseptic precautions. Patients were reviewed on day 1, every four weeks for 12 weeks, and subsequently every 8 weeks. All patients were advised to report any ocular or systemic adverse events and to follow up immediately in the event of further diminution of vision. In the BRVO group, the BCVA at presentation was 0.79 (SD: 0.60), which improved to 0.63 (SD: 0.64) at 3 months, further to 0.40 (SD: 0.28) at 6 months, and 0.39 (SD: 0.29) at 12 months [Fig. 3a]. The improvement from presentation to 12 months was statistically significant, with a P value of 0.047. The mean CMT at presentation was 577.29 (SD: 154.77) µm, which reduced to 346.57 (SD: 75.43) µm at 3 months, 310 (SD: 69.76) µm at 6 months, and 287.14 (SD: 94.64) µm at 12 months [Fig. 3b]. The change in the mean CMT from presentation to 12 months was statistically significant, with a P value < 0.0001. The median number of IVBr injections required was 2, and the mean time between consecutive injections was 5 (SD: 2.83) months.Figure 3: (a) Line plot showing the mean BCVA at different time points for two diagnostic categories. (b) Line plot showing the mean CMT at different time points for two diagnostic categoriesIn the CRVO group, the mean BCVA at presentation was 0.89 (SD: 0.61), which improved to 0.83 (SD: 0.65) at 3 months, further to 0.43 (SD: 0.29) at 6 months, and 0.37 (SD: 0.31) at 12 months. The improvement from presentation to 12 months was statistically significant, with a P value of 0.002 [Fig. 3a]. The mean CMT at presentation was 615.50 (SD: 207.04) µm, which reduced to 510.20 (SD: 237.50) µm at 3 months, 318.90 (SD: 136.83) µm at 6 months, and 255.50 (SD: 58.14) µm at 12 months. The change in mean CMT from presentation to 12 months was statistically significant, with a P value of 0.002 [Fig. 3b]. The median number of injections required were 3, and the mean time between consecutive injections was 3.79 (SD: 1.78) months. Discussion Vision loss in RVO is primarily due to macular edema[1], which results from the release of VEGF. This leads to increased permeability and vasodilation[2-4], making VEGF inhibitors the mainstay of treatment.[5] Vein occlusion occurs due to obstruction of the retinal venous system and is classified based on the location of the obstruction into central RVO (CRVO) or branch RVO (BRVO).[6] According to the National Eye Institute visual function questionnaire,[7,8] vision-related quality of life is decreased, necessitating the treatment of macular edema. Early and aggressive treatment is crucial to reduce macular edema, as prolonged edema can lead to secondary changes in the retinal pigment epithelial, resulting in poor visual acuity despite resolution of the edema.[1,9,10] Various intravitreal anti-VEGF agents, such as bevacizumab, ranibizumab, and aflibercept, have been found to be superior compared to the natural history of the disease.[11-13] Steroid implants have shown more benefit in recalcitrant cases, but their use is limited by the risk of cataract progression and increased IOP.[14] According to various randomized clinical trials,[15-17] significant improvement in visual acuity was observed with frequent anti-VEGF injections. However, in real-world scenarios, patients who were monitored less frequently and received fewer injections demonstrated less visual gain over first year.[11,12] This has highlighted the need for a longer-acting molecule that can reduce hospital visits and the number of injections required in real-world scenario. Brolucizumab (Br) has demonstrated noninferiority to aflibercept in clinical trials related to neovascular age-related macular degeneration (nAMD)[18] and DME[19] with a 12-week injection regimen. Two short-term case reports[20,21] involving three eyes with recalcitrant macular edema in RVO cases demonstrated visual acuity gains and reduction of fluid that lasted up to 8–12 weeks. As the underlying mechanism of nAMD, DME, and RVO involves a surge in VEGF, brolucizumab can also be used in RVO cases with similar efficacy and a reduced number of injections. Novartis conducted the RAPTOR trial for BRVO and the RAVEN trial for CRVO with a 4-week dosing regimen; however, these trials were terminated due to a high incidence of IOI.[22] In the present study, brolucizumab was injected on a PRN basis from the start in both groups, and the BCVA gain along with CMT reduction was studied over 1 year. There was a continuous gain in vision over the year, with a mean gain of 0.16, 0.39, and 0.40 logmar units in BRVO and 0.06, 0.46, and 0.52 logmar units in CRVO at 3, 6, and 12 months, respectively. The greater visual gain in CRVO may be attributed to the more significant initial drop in vision in these cases. Previous case reports also showed visual gains that were maintained for 2–3 months.[20,21] The mean CMT at presentation was 577.29 microns in BRVO and 615.5 microns in CRVO, with mean reductions of 290.15 microns and 360 microns, respectively. While a previous case report[20] indicated recurrence of edema at 16 weeks, in our case series, only 1 patient (in the CRVO group) experienced recurrence of edema at 12 weeks. Additionally, 9 patients (7 in CRVO and 2 in BRVO) had suboptimal reduction in edema, warranting a repeat dose of brolucizumab. In this study, which involved 28 procedures, there was not a single case of intraocular inflammation (IOI), vasculitits, or vascular occlusion. The Falcon study, a randomized, open-label, multicenter study investigating the efficacy and safety of 12-week dosing of brolucizumab (as opposed to monthly dosing) in patients with suboptimal anatomically controlled neovascular age-related macular degeneration, is currently underway.[23] This study is expected to provide insights into reducing IOI associated with frequent dosing of the drug. Limitations of the current study include a small sample size and the absence of subclassification of CRVO cases into ischemic and nonischemic variants. Table 1: Types of drugs used prior to brolucizumab, along with the diagnosis and number of cases.Table 1: Type of previous injections in number of cases according to diagnosisFinancial support and sponsorship: Nil. Conflicts of interest: There are no conflicts of interest.
Source: Indian Journal of Ophthalmology
Language: English
Subfield: Ophthalmology
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W4404839362