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.

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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.

BackgroundThe application of artificial tears before performing perimetry can improve the reliability and results of perimetry in patients with glaucoma and dry eye (DE). However, the effects of ocular surface and tear film conditions on perimetry measurements and reliability have not been fully characterized.MethodsThis prospective, cross-sectional, multicenter study investigated tear metrics in perimetry and assessed the relationships that existed among ocular surface condition, tear condition, and perimetry reliability. Forty-three eyes (43 patients) with DE disease according to the 2016 Japanese diagnostic criteria of DE and 43 eyes (43 subjects) of age- and visual field mean deviation-matched normal control subjects were studied. Perimetry was performed using the Humphrey Field Analyzer (30–2 SITA-Standard). Schirmer’s test, strip meniscometry value, blink rate, tear film break-up time (TFBUT), fluorescein staining of ocular surface, and Dry Eye-related Quality of Life Score (DEQS) were measured. Blink rate was re-measured during perimetry. TFBUT and fluorescein staining were re-evaluated after perimetry. Perimetry reliability was evaluated with fixation loss, false-positive, and false-negative rates.ResultsBlink rate during perimetry was significantly lower for both patients with DE and normal controls (both P<0.001). TFBUT after perimetry was significantly higher than before perimetry in patients with DE (P<0.001). Fluorescein staining of ocular surface was significantly increased in patients with DE and normal control subjects (P = 0.002 and P<0.001, respectively). Spearman correlation analysis revealed that blink rate during perimetry was negatively correlated with fixation-loss rate (r = -0.393, P = 0.009) in patients with DE.ConclusionsPerforming perimetry was associated with a significant change in tear condition and ocular surface condition in both patients with DE and normal control subjects. The changes in tear condition and ocular surface condition may impact the reliability of perimetry in patients with DE.