Associations between migraine and retinal vascular occlusion have been reported, but there is no large-scale and comprehensive study. Therefore, we aimed to determine risks of retinal vascular occlusion in patients with migraine. Using the Taiwan National Health Insurance Research Database from 2009 to 2020, we enrolled 628,760 patients with migraine and 628,760 matched individuals without migraine. Study outcomes were diagnoses of retinal vascular occlusion, including retinal artery occlusion (RAO) and retinal vein occlusion (RVO). Adjusted hazard ratio (aHR) of retinal vascular occlusion related to migraine was estimated. The cumulative incidences of subsequent retinal vascular occlusion, RAO, and RVO were significantly higher in migraine patients compared with controls (0.31% vs. 0.21%; 0.09% vs. 0.05%; 0.22% vs. 0.17%; all p < 0.001). The hazards of retinal vascular occlusion, RAO, and RVO were significantly greater in the migraine group (aHR, 1.69 [95% CI, 1.57, 1.83], 2.13 [95% CI, 1.84, 2.48] and 1.53 [95% CI, 1.40, 1.68], respectively). Risks of retinal vascular occlusion were significantly higher in migraine both with aura (MA) and without aura (MO) (aHR, 1.77 [95% CI, 1.58, 1.98], and 1.92 [95% CI, 1.64, 2.25]). Among patients with migraine, nonsteroidal anti-inflammatory drugs, propranolol, and flunarizine significantly reduce their risks of retinal vascular occlusion (aHR, 0.19 [95% CI, 0.16, 0.22], 0.73 [95% CI, 0.62, 0.86], 0.84 [95% CI, 0.76, 0.93]). Migraine, MA and MO are independently associated with higher risks of retinal vascular occlusion, RAO, and RVO.

BACKGROUND: Retinal vascular occlusions, including retinal vein occlusion and retinal artery occlusion, are common causes of visual impairment. In order to evaluate the national medical burden and help improve ophthalmic health care policy planning, we investigated the incidence of retinal vascular occlusive diseases from 2011 to 2020 in Korea.
METHODS: This study is a nationwide population-based retrospective study using data from the Korea national health claim database of the Health Insurance Review and Assessment (HIRA) service. We identified retinal vascular occlusive diseases registered from January 1, 2009, to December 31, 2020, according to the retinal vascular occlusion code (H34) and its sub-codes from international classification of disease, tenth revision diagnosis code. We used data from the entire Korean population based on the 2015 census of the population in Korea to calculate standardized incidence rates.
RESULTS: We identified 348,775 individuals (male, 161,673 [46.4%]; female, 187,102 [53.6%]) with incident retinal vascular occlusion (H34), 10,451 individuals (males, 6,329 [60.6%]; females, 4,122 [39.4%]) with incident central retinal artery occlusion (H34.1), and 252,810 individuals (males, 114,717 [45.4%]; females, 138,093 [54.6%]) with incident retinal vein occlusion (H34.8) during the 10-year study period. The weighted mean incidence rate of retinal vascular occlusion was 70.41 (95% CI, 70.18-70.65) cases/100,000 person-years. The weighted mean incidence rate of central retinal artery occlusion was 2.10 (95% CI, 2.06-2.14) cases/100,000 person-years. The weighted mean incidence rate of retinal vein occlusion was 50.99 (95% CI, 50.79-51.19) cases/100,000 person-years.
CONCLUSIONS: The total retinal vascular occlusion and retinal vein occlusion showed a decreasing trend until 2020. However, the central retinal artery occlusion decreased until 2014 and remained stable without a significant further decline until 2020. The incidence of total retinal vascular occlusion and retinal vein occlusion was higher in females than in males, while the incidence of central retinal artery occlusion was higher in males. All retinal vascular occlusive diseases showed an increasing incidence with older age; the peak age incidence was 75-79 years for total retinal vascular occlusion and retinal vein occlusion, and 80-85 years for central retinal artery occlusion.

Purpose: To determine the time-based incidence of total blindness after central retinal artery occlusion (CRAO) with secondary ocular neovascularization (ONV). Methods: In this retrospective cohort study, electronic records were queried using ICD-9 and ICD-10 codes to identify patients with secondary ONV post-CRAO. Patients with possible alternative ONV etiologies, previous panretinal photocoagulation (PRP), and/or previous antivascular endothelial growth factor (anti-VEGF) therapy were excluded. Clinical data included demographics, medical comorbidities, ONV manifestations, medical/surgical management, and best-corrected visual acuity (BCVA). Kaplan-Meier analysis was performed with total blindness (defined as a BCVA of no light perception) as the outcome of interest. Results: Of 345 eyes with CRAO, 34 met the inclusion criteria with a mean (±SD) follow-up of 22.0 ± 26.2 months. ONV management included PRP (70.6%), glaucoma drainage implant surgery or transscleral cyclophotocoagulation (32.4%), and intravitreal anti-VEGF therapy (mean 2.8 ± 5.6 injections per patient). The cumulative incidence of total blindness was 49.4% (95% confidence interval, 27.2%-71.6%) at 24 months, with 53.3% of cases occurring within 4 months of ONV onset. Conclusions: Post-CRAO ONV is associated with a high risk for progression from severe vision loss to total blindness. Neovascular glaucoma can present up to 4 months after CRAO, challenging the paradigm of \"30-day-glaucoma.\" Routine gonioscopy should extend through this period, while glaucoma surgery can delay further vision loss. These findings can be used to counsel patients on the importance of follow-up adherence.

UNASSIGNED: The aim of this analysis was to characterize the spectrum of inflammatory changes arising from brolucizumab use in routine clinical practice.
UNASSIGNED: Retrospective analysis of fluorescein angiography (FA), fundus photography (FP) and OCT images taken at the time of adverse event.
UNASSIGNED: Brolucizumab-treated patients with neovascular age-related macular degeneration with retinal vasculitis (RV) and/or retinal vascular occlusion (RO) reported to Novartis Patient Safety between February 2020 and January 2021.
UNASSIGNED: Ocular images were reviewed by an external reading center using predefined grading lists for FA, FP, and OCT.
UNASSIGNED: Classification of images, the most common imaging features of RV and/or RO by each imaging modality, and the anatomical location of the adverse event in relation to the macula.
UNASSIGNED: Gradable images (N = 475; 222 eyes; 198 patients) were classified as RV only (n = 72); RO only (n = 9), RV + RO (n = 63); posterior segment intraocular inflammation (n = 31); or none by imaging (n = 47). Of the 144 eyes with RV and/or RO, the most common imaging features were vascular leakage on FA, perivascular sheathing on FP, and hyperreflective dots in the vitreous humor on OCT. Retinal vascular occlusion was mainly branched and arterial, affecting multiple vessels.
UNASSIGNED: Although no distinct inflammatory phenotype pathognomonic to brolucizumab-related inflammation was identified, this study increases our understanding of the spectrum of posterior segment inflammatory changes that may occur in brolucizumab-treated neovascular age-related macular degeneration patients, highlighting the potential value of widefield retinal imaging and angiography to detect these inflammatory adverse events.
UNASSIGNED: Proprietary or commercial disclosure may be found after the references.

Early poor outcomes of intraocular inflammation (IOI) after intravitreal brolucizumab (IVB) have negatively affected the use of brolucizumab in clinical routine. We wished to identify factors related to the treatment details of IOI involving the posterior segment resulting from IVB for neovascular AMD (nAMD), if these were reported in detail. Articles were retrieved from PubMed, Scopus, ClinicalTrials, and CENTRAL using the following search terms: AND AND . The risk of bias was rated using the JBI Critical Appraisal Tool. We included 31 reports (41 patients and 46 eyes). Patients were 75.9 ± 8.5 years, and 58.5% were female. IOI occurred 41.7 ± 37.5 (median 37.0) days after treatment initiation with 2.0 ± 1.3 (1-6) IVB injections. A mean change in visual acuity of -14.6 ± 21.0 (median -6.5) letters was reported. The mean time from first IOI signs to the initiation of any anti-inflammatory treatment was 3.3 ± 6.2 days, with 63% of the patients receiving systemic corticosteroids as standard treatment. Finally, a period effect was observed, with a change in visual acuity of -25.3 ± 27.1 and -2.6 ± 7.3 letters in the chronologically first and last third, respectively, of treated eyes (effect size: r = 0.71; p = 0.006). Functional outcomes markedly improved with increasing experience in managing IOI.

BACKGROUND: Intraocular inflammation (IOI)-related adverse events (AEs) that may result in severe vision loss have been associated with the anti-vascular endothelial growth factor brolucizumab. In this study, we investigate the timing, management and resolution of IOI-related AEs in a large cohort of patients treated with at least one injection of brolucizumab in routine clinical practice.
METHODS: Retrospective review of medical records from patients with neovascular age-related macular degeneration treated with ≥ 1 brolucizumab injection between October 2019 and November 2021 at the Retina Associates of Cleveland, Inc. clinics.
RESULTS: Of the 482 eyes included in the study, IOI-related AEs occurred in 22 (4.6%) eyes. Four (0.8%) eyes developed retinal vasculitis (RV) and of these, 2 (0.4%) had concomitant retinal vascular occlusion (RO). Most eyes [14/22 (64%)] developed the AE within 3 months and 4/22 (18%) within 3-6 months of the first brolucizumab injection. The median [interquartile range (IQR)] time from the last brolucizumab injection to development of the IOI-related AE was 13 (4-34) days. At the time of event, 3 (0.6%) eyes with IOI (no RV/RO) developed severe vision loss of ≥ 30 ETDRS letters, and a further 5 (1.0%) eyes (1 with IOI + RV, 1 with IOI + RV + RO) developed moderate vision loss of ≥ 15 letters compared with their last visual acuity (VA) prior to the AE. The median (IQR) vision loss was -6.8 (-19.9, -0.0) letters. Taking the best VA at either 3 or 6 months after AE resolution (or stability for occlusive events), VA decreased by ≥ 5 letters compared with prior to the AE in 3 (14%) of the 22 affected eyes, and was preserved (< 5-letter loss) in 18 (82%) eyes.
CONCLUSIONS: In this real-world study, most IOI-related AEs occurred early after brolucizumab treatment initiation. With appropriate monitoring and management of IOI-related AEs, vision loss associated with brolucizumab may be limited.

Anti-vascular endothelial growth factor (anti-VEGF) therapies have become the standard of care in the treatment of neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME), resulting in a remarkable decrease in disease-related vision loss. However, the need for regular injections places a significant burden on patients, caregivers, and the healthcare system and improvements in vision may not be maintained long term. As a result of its drying potency and duration of action, brolucizumab, an intravitreal anti-VEGF therapy approved for the treatment of nAMD and DME, could decrease injection frequency for patients and provide an efficacious treatment; however, balancing its benefits and risks can be challenging. There have been reports of intraocular inflammation (IOI) in patients treated with brolucizumab, which, if left untreated, may result in severe vision loss. Recent evidence, however, indicates that early recognition of IOI and prompt and aggressive systemic corticosteroid treatment in response to posterior segment involvement can lead to favorable outcomes in these relatively rare but severe cases. A series of consensus meetings were conducted in 2022 between Swiss medical retina experts and diabetologists, discussing the current data for brolucizumab and exploring various challenges to its use, including the associated risk of IOI. The outcome is a collation of practical insights and guidance for ophthalmologists on the use of brolucizumab in patients with nAMD and DME, including patient selection and assessment, treatment regimen and monitoring, and the recognition and management of adverse events.

BACKGROUND: Brolucizumab, a low-molecular weight anti-vascular endothelial growth factor, was approved in the USA in October 2019 for the treatment of neovascular age-related macular degeneration. Following post-marketing reports of vasculitis, including retinal occlusive vasculitis, a safety signal of retinal vasculitis (RV) and/or retinal vascular occlusion (RO) that may result in severe vision loss was confirmed. This brief communication reviews the trends in the cumulative reporting rates of RV and/or RO and associated vision loss from May 2020 to September 2022.
METHODS: This is a descriptive analysis of the cumulative post-marketing reporting rates of RV and/or RO cases, and associated vision loss included in the Novartis safety database between May 2020 and September 2022, utilizing an enhanced pharmacovigilance program.
RESULTS: The RV-alone rates demonstrated an upward trend, rising to 5.1 events per 10,000 injections by October 2020 and subsequently remained stable until July 2021. Thereafter, the rate for RV-alone events increased modestly until October 2021 and then remained stable until September 2022. The RO-alone rates increased to 3.4 events per 10,000 injections by January 2021 and subsequently remained stable until September 2022. The combined reports of RV and RO showed an upward trend until December 2020 (7.5 events per 10,000 injections), followed by a plateau until September 2021 and then a downward trend until September 2022. Vision loss associated with RV and/or RO progressively increased until December 2020 (5.9 events per 10,000 injections) followed by a declining trend until September 2022 to the most recent reporting rate of 4.1 events per 10,000 injections.
CONCLUSIONS: The cumulative post-marketing reporting rates of vision loss associated with RV and/or RO, following brolucizumab treatment, have shown a declining trend after an initial rise in the reporting rates immediately after identification of the safety signal.

The causal effects of plasma lipid levels and the risk of retinal vascular occlusion (RVO) have not been clearly identified, especially for high-density lipoprotein-cholesterol (HDL-C) and low-density lipoprotein-cholesterol (LDL-C). Here, we try to identify these causal risk factors using a two-sample Mendelian randomization (MR) analysis. Single nucleotide polymorphisms (SNPs) were chosen as instrumental variables (IVs). We obtained genetic variants associated with lipid exposure at the genome-wide significance (P<5×10-8) level from a meta-analysis of GWAS from the Global Lipids Genetics Consortium (GLGC) based on 188,577 individuals of mostly European ancestry for MR analyses. Meanwhile, we used lipid GWAS from UK Biobank (UKB) with a sample size of 115,078 individuals as a supplement. We obtained genetic predictors of RVO from a FinnGen biobank study. We conducted both univariable and multivariable MR (MVMR) analyses to identify the causal effects of RVO. Although inverse variance weighted (IVW) was the primary method used for MR analyses, MR-Egger and weighted-median methods were used as supplements to IVW. We determined the heterogeneity of IVs using Cochrane\'s Q test and I2 , and used the MR-Egger intercept and MR-PRESSO Global test to detect horizontal pleiotropy. A leave-one-out sensitivity analysis was conducted by removing a single variant from the analysis. Genetically predicted increased HDL-C level was associated with decreased risk of RVO from GLGC [OR=0.806; 95% CI=(0.659, 0.986); P=0.036], which was consistent with UKB results [OR=0.766; 95% CI=(0.635, 0.925); P=0.005]. MVMR analysis for plasma lipids [adjusted OR=0.639; 95% CI=(0.411, 0.992); P=0.046] or diabetes [adjusted OR=0.81; 95% CI=(0.67, 0.979); P=0.029] suggested that low HDL-C may be an independent risk factor for RVO. However, there was no evidence to support a causal association between LDL-C {GLGC [adjusted OR=1.015; 95% CI=(0.408, 2.523); P=0.975], UKB [OR=1.115; 95% CI=(0.884, 1.407); P=0.359]}, total cholesterol {GLGC [adjusted OR=0.904; 95% CI=(0.307, 2.659); P=0.854], UKB [OR=1.047; 95% CI=(0.816, 1.344); P=0.716]} or triglycerides {GLGC [OR=1.103; 95% CI=(0.883, 1.378); P=0.385], UKB [OR=1.003; 95% CI=(0.827, 1.217); P=0.098]} and RVO. Using two-sample MR analysis, our study suggested that dyslipidemia was a risk factor for RVO. Furthermore, our results indicated that a low HDL-C level may be an independent risk factor for RVO, suggesting that controlling HDL-C level may be effective in RVO development.

UNASSIGNED: To assess early real-world outcomes with brolucizumab in Canadian patients with neovascular age-related macular degeneration (nAMD) for which they previously received ≥1 anti-vascular endothelial growth factor (anti-VEGF) agent(s).
UNASSIGNED: This multisite, real-world, retrospective chart review included data from a consecutive sample of 73 patients who received brolucizumab for nAMD after treatment with ≥1 other anti-VEGF agents. The principal reasons for switching to brolucizumab were to extend the treatment interval (51.6% of patients) and to treat persistent macular fluid (34.2%). The primary outcomes were best-corrected visual acuity (BCVA) and the incidence rates of intraocular inflammation (IOI), retinal vasculitis (RV), and retinal vascular occlusion (RVO). Secondary outcomes included central retinal thickness (CRT), injection interval, and presence of intraretinal and subretinal fluid (IRF and SRF). All parameters were measured at baseline until the last treatment visit between April 27, 2020, and August 31, 2021.
UNASSIGNED: Over a mean follow-up of 28 weeks, a nonsignificant mean improvement in BCVA was identified (4.3 [standard deviation (SD) 8.3] letters; P=0.057), with 47.9% experiencing a gain of ≥5 letters. IOI was detected in 3 patients (4.1%), one of whom also developed RV and RVO (1.4%), which is consistent with existing brolucizumab data. Significant reductions were observed in mean CRT (-36.6 μm [SD 56.1 μm]; P=0.0002) and presence of any macular fluid (56.1% [SD 5.6%]; P<0.001), IRF (66.6% [SD 6.3%]; P<0.001), and SRF (62.7% [SD 6.3%]; P<0.001). The mean injection interval increased significantly by 2.1 weeks (SD 2.7; P<0.001).
UNASSIGNED: In the first real-world Canadian analysis, brolucizumab was associated with improvements in functional outcomes in treatment-experienced patients, consistent with other real-world studies. The incidence of IOI, RV, and RVO were in line with the post hoc safety analysis of HAWK and HARRIER data.