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.

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Background: Immune checkpoint inhibitors have recently been widely used for advanced cancers and are known to cause ocular complications. We herein report a case developing bilateral serous retinal detachments, without ocular inflammation, after starting nivolumab treatment. Case presentation: A 73-year-old man was referred to our hospital, having become aware of metamorphopsia 2 months after starting nivolumab (anti-programmed cell death protein 1 monoclonal antibody) for malignant melanoma of the nasal cavity. The initial corrected visual acuity of the right eye was 20/20, and that of the left eye was 20/16. There were no inflammatory findings in the anterior segment or the vitreous. Vitelliform lesions were found in the macular area of both ocular fundi, consistent with serous retinal detachment and subretinal deposits. Swept source optical coherence tomography showed diffuse thickening of the outer photoreceptor segment and thickening of the choroid. Two months after the initial diagnosis, multiple vitelliform lesions were noted, and the fundus findings had worsened. Indocyanine green fluorescein angiography showed delayed inflow in the peripapillary and posterior pole regions in the early phase of imaging. Fundus autofluorescence showed hyperautofluorescence consistent with most of the vitelliform lesions on color fundus photography. Conclusions: Nivolumab may have impaired the pumping and phagocytosis functions of retinal pigment epithelial cells, resulting in bilateral serous retinal detachments and thickening of the photoreceptor outer segment. This is the first case report, to our knowledge, describing multiple bilateral serous retinal detachments and outer segment thickening without inflammation in a patient treated with nivolumab.

During the COVID-19 pandemic, intravitreal injections are performed with patients wearing masks. The risk of endophthalmitis after intravitreal injection is reported to increase due to an influx of exhaled air containing oral bacteria from the upper part of the mask onto the ocular surface. We retrospectively investigated the incidence of endophthalmitis when intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections were performed using the same infection control measures before and during the pandemic. Vitreoretinal specialists performed intravitreal injections of anti-VEGF agents in the outpatient room of a university hospital. Infection control measures before and during the pandemic included covering the patient’s eye with adhesive face drape and irrigating the ocular surface with 0.25% povidone-iodine before draping, and immediately before and after injection. Before the COVID-19 pandemic (February 2016 to December 2019), one case of endophthalmitis occurred among 31,173 injections performed (0.0032%; 95% confidence interval (CI), 0.000008–0.017872%). During the COVID-19 pandemic (January 2020 to August 2021), one case of endophthalmitis occurred among 14,725 injections performed (0.0068%; 95% CI, 0.000017–0.037832%). There was no significant difference between the two periods (Fisher’s exact test: p = 0.5387). Even during the COVID-19 pandemic, very low incidence of endophthalmitis after intravitreal injection can be maintained by implementing basic infection prophylactic measures, including face draping and 0.25% povidone-iodine irrigation, established before COVID-19 pandemic.

Pachychoroid neovasculopathy (PNV) is treated with antivascular endothelial growth factor (VEGF) injection and photodynamic therapy (PDT), but no curative treatment has yet been established. We aimed to clarify the treatment results of a reduced dose of PDT for PNV. The subjects were 27 eyes of 27 patients (male:female = 20:7, mean age 58.9 years). PDT, at 2/3 of the conventional dose (2/3PDT), was administered once. The patients were then observed for one year. Eyes with polypoidal choroidal vasculopathy (PCV) were excluded. We investigated the associations among the central retinal thickness, choroidal thickness, and visual acuity changes before treatment and one, three, six and 12 months after PDT. When serous retinal detachment was increased or unchanged or new hemorrhages were observed, as compared with pretreatment findings, intravitreal injection of an anti-VEGF agent was performed. Visual acuity was significantly improved, as compared to before treatment, at three, six, and 12 months after 2/3PDT. Foveal retinal thickness was significantly decreased after versus before treatment in the 2/3PDT group (p < 0.001). Foveal choroidal thickness was also significantly reduced in the 2/3PDT group (p = 0.001). Additional intravitreal anti-VEGF agent injections were administered to three patients (11%), while 24 (89%) required no additional treatment during the one-year follow-up period. For PNV without polyps, 2/3PDT appears to be effective.

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The purpose of this study was to quantitatively analyze heart rate variability (HRV) in patients with central serous chorioretinopathy (CSC) by using a smartphone-based application (ANBAI: DUMSCO Inc.) for measurement, and to clarify its relationships with CSC. The subjects were 64 CSC patients (mean age 48.7 ± 7.6 years, 57 males and 7 females). After providing consent, the patients downloaded ANBAI apps to their smartphones. HRV was measured by photoelectric volume pulse wave measurement with a smartphone camera each morning for a minimum of 1 week. The primary outcome was to analyze HRV by calculating log LF/HF (Low Frequency/High Frequency components), an index of autonomic tone, which was then compared with a control group of 35,226 individuals from the application. Secondary outcome measures included disease duration, body mass index, exercise habits, smoking history, steroid use, occupation, lifestyle regularity, psychological fatigue, physical fatigue, and average sleep time. The log LF/HF was significantly higher in the patient group than in the control group (P < 0.001). Log LF/HF was significantly lower in patients with exercise habits as a factor contributing to log LF/HF in the patient group (P = 0.019). Analysis of HRV in CSC patients showed an impairment of the autonomic nervous system. Exercise habits may also be associated with CSC.