Risk of post-injection endophthalmitis peaks within the first three injections of anti-vascular endothelial growth factor therapy: A nationwide registry-based study.
anti‐VEGF
diabetic macular edema
neovascular age‐related macular degeneration
post‐injection endophthalmitis
retinal vein occlusion
Journal
Acta ophthalmologica
ISSN: 1755-3768
Titre abrégé: Acta Ophthalmol
Pays: England
ID NLM: 101468102
Informations de publication
Date de publication:
03 Jun 2024
03 Jun 2024
Historique:
received:
14
03
2024
accepted:
21
05
2024
medline:
3
6
2024
pubmed:
3
6
2024
entrez:
3
6
2024
Statut:
aheadofprint
Résumé
To report the incidence of post-injection endophthalmitis (PIE) and the cumulative risk associated with repeated injections of intravitreal anti-vascular endothelial growth factor (anti-VEGF). We employed nationwide registries in Denmark to include all individuals aged ≥40 years who received at least one intravitreal anti-VEGF injection in 2007-2022. Our primary endpoint PIE was identified using specific diagnostic codes for endophthalmitis and procedure codes for vitreous biopsy within 10 days prior to and 120 days post-injection. Patients were stratified according to the underlying diagnoses for which they received the treatment. The relative risk (RR) for PIE was calculated between groups based on the number of injections received by the patients. We identified 60 825 patients who received intravitreal anti-VEGF treatment during study time, with a median age of 77.2 years and females constituting 58.1%. We identified 232 cases of PIE after 1 051 549 injections during follow-up, resulting in an incidence of 0.022% [95% CI 0.019%-0.025%]. Despite a linear growth in annual anti-VEGF use, the incidence remained stable at 0.020% [95% CI 0.017%-0.023%] from 2013 to 2022. Compared to patients receiving 1-3 injections, RR for patients receiving 4-20, 21-40, and >40 injections were 0.46 [95% CI 0.34-0.63], 0.32 [95% CI 0.21-0.50], and 0.54 [95% CI 0.36-0.81], respectively. Findings were similar across the different diagnoses. Based on 16 years of nationwide registry data, this study identified a low and stable incidence of PIE. Notably, the highest risk of endophthalmitis was within the first three anti-VEGF injections.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2024 The Author(s). Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.
Références
Altman, D.G. (1991) Practical statistics for medical research. London: Chapman and Hall.
Anderson, W.J., da Cruz, N.F.S., Lima, L.H., Emerson, G.G., Rodrigues, E.B. & Melo, G.B. (2021) Mechanisms of sterile inflammation after intravitreal injection of antiangiogenic drugs: a narrative review. International Journal of Retina and Vitreous, 7, 37.
Baudin, F., Benzenine, E., Mariet, A.S., Ben Ghezala, I., Bron, A.M., Daien, V. et al. (2022) Epidemiology of acute endophthalmitis after intraocular procedures: a National Database Study. Ophthalmology Retina, 6, 442–449.
Beal, S.L. (1987) Asymptotic confidence intervals for the difference between two binomial parameters for use with small samples. Biometrics, 43, 941–950.
Bloch, S.B., Larsen, M. & Munch, I.C. (2012) Incidence of legal blindness from age‐related macular degeneration in Denmark: year 2000 to 2010. American Journal of Ophthalmology, 153(2), 209–213.
Borkar, D.S., Obeid, A., Su, D.C., Storey, P.P., Gao, X., Regillo, C.D. et al. (2018) Endophthalmitis rates after bilateral same‐day intravitreal anti‐vascular endothelial growth factor injections. American Journal of Ophthalmology, 194, 1–6.
Cox, J.T., Eliott, D. & Sobrin, L. (2021) Inflammatory complications of intravitreal anti‐VEGF injections. Journal of Clinical Medicine, 10, 981.
Daien, V., Nguyen, V., Essex, R.W., Morlet, N., Barthelmes, D. & Gillies, M.C. (2018) Incidence and outcomes of infectious and noninfectious endophthalmitis after intravitreal injections for age‐related macular degeneration. Ophthalmology, 125, 66–74.
Dossarps, D., Bron, A.M., Koehrer, P., Aho‐Glélé, L.S. & Creuzot‐Garcher, C. (2015) Endophthalmitis after intravitreal injections: incidence, presentation, management, and visual outcome. American Journal of Ophthalmology, 160, 17–25.
Durand, M.L. (2013) Endophthalmitis. Clinical Microbiology and Infection, 19, 227–234.
ESCRS. (2013) ESCRS guidelines for prevention and treatment of endophthalmitis following cataract surgery. The European Society of Cataract and Refractive Surgeons. https://www.escrs.org/media/uljgvpn1/english_2018_updated.pdf
Fileta, J.B., Scott, I.U. & Flynn, H.W., Jr. (2014) Meta‐analysis of infectious endophthalmitis after intravitreal injection of anti‐vascular endothelial growth factor agents. Ophthalmic Surgery, Lasers & Imaging Retina, 45, 143–149.
Finger, R.P., Daien, V., Eldem, B.M., Talks, J.S., Korobelnik, J.F., Mitchell, P. et al. (2020) Anti‐vascular endothelial growth factor in neovascular age‐related macular degeneration ‐ a systematic review of the impact of anti‐VEGF on patient outcomes and healthcare systems. BMC Ophthalmology, 20, 294.
Frederiksen, K.H., Stokholm, L., Möller, S., Thinggaard, B.S., Kawasaki, R., Peto, T. et al. (2023) VEGF inhibition in retinal vein occlusion does not associate with cardiovascular morbidity or mortality. Ophthalmology Retina, 7(8), 652–660.
Freiberg, F.J., Brynskov, T., Munk, M.R., Sørensen, T.L., Wolf, S., Wirth, M.A. et al. (2017) Low endophthalmitis rates after intravitreal anti‐vascular endothelial growth factor injections in an operation room: a retrospective multicenter study. Retina, 37, 2341–2346.
Hvidberg, M.F., Johnsen, S.P., Glümer, C., Petersen, K.D., Olesen, A.V. & Ehlers, L. (2016) Catalog of 199 register‐based definitions of chronic conditions. Scandinavian Journal of Public Health, 44, 462–479.
Israilevich, R.N., Mansour, H., Patel, S.N., Garg, S.J., Klufas, M.A., Yonekawa, Y. et al. (2024) Risk of endophthalmitis based on cumulative number of anti‐vascular endothelial growth factor intravitreal injections. Ophthalmology, 131, 667–673.
Kuhn, F. & Gini, G. (2007) Complete and early vitrectomy for endophthalmitis (CEVE) as Today's alternative to the endophthalmitis vitrectomy study. In: Kirchhof, B. & Wong, D. (Eds.) Vitreo‐retinal surgery. Berlin, Heidelberg: Springer, pp. 53–68.
Merani, R. & Hunyor, A.P. (2015) Endophthalmitis following intravitreal anti‐vascular endothelial growth factor (VEGF) injection: a comprehensive review. Int J Retina Vitreous, 1, 9.
Morioka, M., Takamura, Y., Nagai, K., Yoshida, S., Mori, J., Takeuchi, M. et al. (2020) Incidence of endophthalmitis after intravitreal injection of an anti‐VEGF agent with or without topical antibiotics. Scientific Reports, 10, 22122.
Mun, Y., You, S.C., Lee, D.Y., Kim, S., Chung, Y.R., Lee, K. et al. (2021) Real‐world incidence of endopthalmitis after intravitreal anti‐VEGF injections in Korea: findings from the common data model in ophthalmology. Epidemiology and Health, 43, e2021097.
Nussenblatt, R.B., Lee, R.W., Chew, E., Wei, L., Liu, B., Sen, H.N. et al. (2014) Immune responses in age‐related macular degeneration and a possible long‐term therapeutic strategy for prevention. American Journal of Ophthalmology, 158, 5–11.
Ophthalmology AAo. (2021) Managing endophthalmitis after intravitreal injections. https://www.aao.org/eyenet/article/endophthalmitis‐after‐intravitreal‐injections
Patel, S.N., Hsu, J., Sivalingam, M.D., Chiang, A., Kaiser, R.S., Mehta, S. et al. (2021) The impact of physician face mask use on endophthalmitis after intravitreal anti‐vascular endothelial growth factor injections. American Journal of Ophthalmology, 222, 194–201.
Pottegård, A., Schmidt, S.A.J., Wallach‐Kildemoes, H., Sørensen, H.T., Hallas, J. & Schmidt, M. (2017) Data resource profile: the Danish National Prescription Registry. International Journal of Epidemiology, 46, 798.
Qiu, F., Ma, X., Shin, Y.H., Chen, J., Chen, Q., Zhou, K. et al. (2020) Pathogenic role of human C‐reactive protein in diabetic retinopathy. Clinical Science (London, England), 134, 1613–1629.
Quan, H., Li, B., Couris, C.M., Fushimi, K., Graham, P., Hider, P. et al. (2011) Updating and validating the Charlson comorbidity index and score for risk adjustment in hospital discharge abstracts using data from 6 countries. American Journal of Epidemiology, 173, 676–682.
Reibaldi, M., Pulvirenti, A., Avitabile, T., Bonfiglio, V., Russo, A., Mariotti, C. et al. (2018) Pooled estimates of incidence of endophthalmitis after intravitreal injection of anti‐vascular endothelial growth factor agents with and without topical antibiotic prophylaxis. Retina, 38, 1–11.
Schmidt, M., Pedersen, L. & Sørensen, H.T. (2014) The Danish civil registration system as a tool in epidemiology. European Journal of Epidemiology, 29, 541–549.
Schmidt, M., Schmidt, S.A., Sandegaard, J.L., Ehrenstein, V., Pedersen, L. & Sørensen, H.T. (2015) The Danish National Patient Registry: a review of content, data quality, and research potential. Clinical Epidemiology, 7, 449–490.
Schmidt, M., Schmidt, S.A.J., Adelborg, K., Sundbøll, J., Laugesen, K., Ehrenstein, V. et al. (2019) The Danish health care system and epidemiological research: from health care contacts to database records. Clinical Epidemiology, 11, 563–591.
Solborg Bjerrum, S., Kiilgaard, J.F., Mikkelsen, K.L. & la Cour, M. (2013) Outsourced cataract surgery and postoperative endophthalmitis. Acta Ophthalmologica, 91, 701–708.
Song, J., Chen, S., Liu, X., Duan, H., Kong, J. & Li, Z. (2015) Relationship between C‐reactive protein level and diabetic retinopathy: a systematic review and meta‐analysis. PLoS One, 10, e0144406.
Statistics NHaW. (2011) NCSP ‐ Classification of surgical procedures. https://norden.diva‐portal.org/smash/get/diva2:968721/FULLTEXT01.pdf
Storey, P.P., Tauqeer, Z., Yonekawa, Y., Todorich, B., Wolfe, J.D., Shah, S.P. et al. (2019) The impact of prefilled syringes on endophthalmitis following intravitreal injection of ranibizumab. American Journal of Ophthalmology, 199, 200–208.
Thinggaard, B.S., Frederiksen, K., Subhi, Y., Möller, S., Sørensen, T.L., Kawasaki, R., Grauslund, J. et al. (2024) VEGF Inhibition associates with decreased risk of mortality in patients with neovascular age‐related macular degeneration. Ophthalmology Science, 4(3), 100446. https://doi.org/10.1016/j.xops.2023.100446
Thinggaard, B.S., Pedersen, F., Grauslund, J. & Stokholm, L. (2023) Intravitreal vascular endothelial growth factor inhibitor therapy in Denmark and 5‐year projections. JAMA Network Open, 6, e2335148.
Thorand, B., Löwel, H., Schneider, A., Kolb, H., Meisinger, C., Fröhlich, M. et al. (2003) C‐reactive protein as a predictor for incident diabetes mellitus among middle‐aged men: results from the MONICA Augsburg cohort study, 1984‐1998. Archives of Internal Medicine, 163, 93–99.
Wang, Y., Zhong, Y., Zhang, L., Wu, Q., Tham, Y., Rim, T.H. et al. (2022) Global incidence, progression, and risk factors of age‐related macular degeneration and projection of disease statistics in 30 years: a modeling study. Gerontology, 68, 721–735.
WH Organization. (2003) The anatomical therapeutic chemical classification system with defined daily doses (ATC/DDD).