Dear Editor, We report short-term data on the development of intraocular inflammation (IOI) after intravitreal brolucizumab injection for exudative age-related macular degeneration (AMD) in Japanese patients in this letter. Brolucizumab (Novartis Pharma AG, Basel, Switzerland), a new anti-vascular endothelial growth factor (VEGF) agent for the treatment of exudative AMD, differs from previous anti-VEGF agents by its smaller molecular weight allowing administration at high concentrations and presumably improved tissue penetration. In the HAWK and HARRIER studies, brolucizumab was reportedly non-inferior to aflibercept in terms of visual outcomes and more effective in reducing intraretinal and subretinal fluid [1]. Early US reports regarding the adverse effect of IOI [2] prompted a Novartis-appointed Safety Review Committee (SRC) to re-evaluate data from the clinical trials [3]. At the 2020 Annual Meeting of the American Academy of Ophthalmology, Heier et al. [4] described SRC findings suggesting that female gender and Japanese ethnicity were risk factors.

To investigate the characteristics of complement activation products and angiogenic cytokines in the aqueous humor in eyes with pachychoroid neovasculopathy (PNV) and neovascular age-related macular degeneration (nAMD). METHODS. This was a prospective, comparative, observational study. All patients with choroidal neovascularization were classified as PNV without polyps, PNV with polyps (polypoidal choroidal vasculopathy [PCV]), or drusen-associated nAMD according to the presence or absence of pachychoroid features and soft drusen. This study included a total of 105 eyes. Aqueous humor samples were collected from 25 eyes with PNV without polyps, 23 eyes with PCV, and 24 eyes with drusen-associated nAMD before intravitreal anti-vascular endothelial growth factor (VEGF) injection and cataract surgery in 33 control eyes. Clinical samples were measured for complement component 3a (C3a), C4a, C5a, VEGF, and macrophage chemoattractant protein 1 (MCP-1) using a bead-based immunoassay. RESULTS. C3a and MCP-1 levels were significantly higher in PCV (P = 0.032 and P = 0.039, respectively) and drusen-associated nAMD (P = 0.01 for both comparisons) than in controls, and no difference was seen in C3a and MCP-1 levels between PNV and controls (P = 0.747 and P = 0.294, respectively). VEGF levels were significantly higher in PNV (P = 0.016), PCV (P = 0.009), and drusen-associated nAMD (P = 0.043) than in controls. In PNV, the VEGF levels elevated without elevated C3a and MCP-1. CONCLUSIONS. PNV, PCV, and drusen-associated nAMD had significantly distinct profiles of complement activation products and cytokines in the aqueous humor.

the choroid is a complex vascular tissue that is covered with the retinal pigment epithelium. Ultra high speed swept source optical coherence tomography (SS-oct) provides us with high-resolution cube scan images of the choroid. Robust segmentation techniques are required to reconstruct choroidal volume using SS-oct images. for automated segmentation, the delineation of the choroidal-scleral (c-S) boundary is key to accurate segmentation. Low contrast of the boundary, scleral canals formed by the vessel and the nerve, and the posterior stromal layer, may cause segmentation errors. Semantic segmentation is one of the applications of deep learning used to classify the parts of images related to the meanings of the subjects. We applied semantic segmentation to choroidal segmentation and measured the volume of the choroid. the measurement results were validated through comparison with those of other segmentation methods. As a result, semantic segmentation was able to segment the c-S boundary and choroidal volume adequately.

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We evaluated changes in the complement system resulting from anti-vascular endothelial growth factor (VEGF) in eyes with age-related choroidal neovascularization (CNV) including neovascular age-related macular degeneration, pachychoroid neovasculopathy, and polypoidal choroidal neovasculopathy. We measured the concentrations of the complement activation products (C3a, C4a), VEGF, and monocyte chemotactic protein-1 in the aqueous humor during intravitreal anti-VEGF injections for CNV. The VEGF level decreased significantly (P < 0.001), while the C3a and C4a levels increased significantly (P < 0.001 for both comparisons) 1 month after two monthly anti-VEGF injections. The VEGF level was correlated with the C3a (R = 0.328, P = 0.007) and C4a (R = − 0.237, P = 0.055) levels at baseline, but the correlation between the VEGF and C3a levels (R = − 0.148, P = 0.242) changed significantly (P = 0.028 by analysis of covariance) after anti-VEGF treatment. The C3a increase after anti-VEGF therapy did not change the visual outcomes in eyes with CNV for 1 year. Dysregulation of the complement system can be induced after anti-VEGF therapy.