Background Age-related macular degeneration (AMD) is a leading cause of blindness in aging populations, and intravitreal injections of anti-vascular endothelial growth factor (VEGF) agents are the mainstay of its treatment. Recently, environmental air pollution has been proposed as a potential risk factor for ocular diseases. However, few nationwide studies have examined the association between demand for anti-VEGF therapy and environmental factors. Objective This study aimed to investigate the relationship between intravitreal anti-VEGF treatment volume and air pollution indicators across all prefectures in Japan using a nationwide database. Methods Using the National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB), we extracted data for the fiscal year 2020 on the number of intravitreal brolucizumab injections administered to AMD patients, as well as the total number of anti-VEGF intravitreal injections (including brolucizumab, ranibizumab, and aflibercept) for macular diseases across 48 prefectures. Brolucizumab was approved only for AMD during this year, allowing us to use its usage as a proxy for AMD cases. Environmental data, including average annual concentrations of PM2.5 (μg/m3), sulfur oxides (SOX), nitrogen oxides (NOX), and particulate matter dust (PMD; m3N/h), were obtained from the Ministry of the Environment. We then analyzed the correlation between anti-VEGF injection volumes per 10,000 persons aged 60 and older and air pollution indicators for each prefecture. Results A strong positive correlation was observed between the number of brolucizumab injections (AMD-specific indicator) and total anti-VEGF injections (non-specific indicator) (r = 0.82, p < 0.001). Both were significantly correlated with PM2.5 concentrations (brolucizumab: r = 0.25, p = 0.045; total anti-VEGF: r = 0.37, p = 0.005). In contrast, no significant correlations were found with SOX (brolucizumab: r = -0.28, p = 0.969; total anti-VEGF: r = -0.13, p = 0.802), NOX (r = -0.06, p = 0.656; r = 0.11, p = 0.224), or PMD (r = 0.03, p = 0.430; r = 0.14, p = 0.180). Moreover, PM2.5 showed no meaningful correlations with SOX, NOX, or PMD. Conclusion This nationwide analysis revealed a significant association between regional PM2.5 levels and the use of anti-VEGF intravitreal injections for macular diseases. No such relationship was observed for SOX, NOX, or PMD. These findings suggest that PM2.5 may contribute to the regional demand for AMD treatment, highlighting the need for further investigation into the impact of air pollution on ocular health.

Regional association between PM2.5 exposure and anti-VEGF treatment demand for age-related macular degeneration: a nationwide ecological study in Japan

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发表日期：

2026年1月22日

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Tatsuya Mimura,
Hidetaka Noma

摘要

Background

Age-related macular degeneration (AMD) is a leading cause of blindness in aging populations, and intravitreal injections of anti-vascular endothelial growth factor (VEGF) agents are the mainstay of its treatment. Recently, environmental air pollution has been proposed as a potential risk factor for ocular diseases. However, few nationwide studies have examined the association between demand for anti-VEGF therapy and environmental factors.

Objective

This study aimed to investigate the relationship between intravitreal anti-VEGF treatment volume and air pollution indicators across all prefectures in Japan using a nationwide database.

Methods

Using the National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB), we extracted data for the fiscal year 2020 on the number of intravitreal brolucizumab injections administered to AMD patients, as well as the total number of anti-VEGF intravitreal injections (including brolucizumab, ranibizumab, and aflibercept) for macular diseases across 48 prefectures. Brolucizumab was approved only for AMD during this year, allowing us to use its usage as a proxy for AMD cases. Environmental data, including average annual concentrations of PM_2.5 (μg/m³), sulfur oxides (SO_X), nitrogen oxides (NO_X), and particulate matter dust (PMD; m³N/h), were obtained from the Ministry of the Environment. We then analyzed the correlation between anti-VEGF injection volumes per 10,000 persons aged 60 and older and air pollution indicators for each prefecture.

Results

A strong positive correlation was observed between the number of brolucizumab injections (AMD-specific indicator) and total anti-VEGF injections (non-specific indicator) (r = 0.82, p < 0.001). Both were significantly correlated with PM_2.5 concentrations (brolucizumab: r = 0.25, p = 0.045; total anti-VEGF: r = 0.37, p = 0.005). In contrast, no significant correlations were found with SO_X (brolucizumab: r = -0.28, p = 0.969; total anti-VEGF: r = -0.13, p = 0.802), NO_X (r = -0.06, p = 0.656; r = 0.11, p = 0.224), or PMD (r = 0.03, p = 0.430; r = 0.14, p = 0.180). Moreover, PM_2.5 showed no meaningful correlations with SO_X, NO_X, or PMD.

Conclusion

This nationwide analysis revealed a significant association between regional PM_2.5 levels and the use of anti-VEGF intravitreal injections for macular diseases. No such relationship was observed for SO_X, NO_X, or PMD. These findings suggest that PM_2.5 may contribute to the regional demand for AMD treatment, highlighting the need for further investigation into the impact of air pollution on ocular health.