Elsevier

Ophthalmology

Volume 125, Issue 1, January 2018, Pages 66-74
Ophthalmology

Original article
Incidence and Outcomes of Infectious and Noninfectious Endophthalmitis after Intravitreal Injections for Age-Related Macular Degeneration

https://doi.org/10.1016/j.ophtha.2017.07.005Get rights and content

Purpose

To assess the incidence, cumulative rate, and long-term outcomes of infectious and noninfectious endophthalmitis after intravitreal injections (IVTs) of anti-vascular endothelial growth factor (VEGF) agents.

Design

Database study, prospectively designed.

Participants

Treatment-naïve eyes with neovascular age-related macular degeneration (nAMD) tracked by the Fight Retinal Blindness! (FRB!) registry that commenced anti-VEGF therapy between January 1, 2006, and November 30, 2016.

Methods

Cumulative rate of endophthalmitis and survival curves were measured using Cox-proportional hazards models. Locally weighted scatterplot smoothing curves were used to display visual acuity (VA).

Main Outcome Measures

Incidence and cumulative rate of endophthalmitis, and change in VA 12 months after endophthalmitis.

Results

Infectious endophthalmitis developed in 18 of 88 150 injections (1/4897 injections [0.020%]; 95% confidence interval [CI], 0.012–0.032) with no difference found between types of anti-VEGF medications (P = 0.896). The cumulative rate of infectious endophthalmitis per patient was 0.055%, 0.183%, 0.360%, 0.360%, 0.555%, and 0.843% after 10, 20, 30, 40, 50, and 60 IVTs, respectively. However, the “risk” of infectious endophthalmitis did not increase with each successive injection (P = 0.202). Noninfectious endophthalmitis developed in 11 of 88 150 injections (1/8013 injections [0.012%]; 95% CI, 0.006–0.022). The cumulative rate of noninfectious endophthalmitis per patient was 0.087% and 0.228% after 10 and 20 IVTs, respectively, and then remained stable up to 60 IVTs. The incidence of noninfectious endophthalmitis was higher for bevacizumab (8/9931, 0.081%) compared with ranibizumab (3/54 776, 0.005%; P = 0.005) and aflibercept (0/23 425; P = 0.016), and no differences were observed between ranibizumab and aflibercept (P = 1.0). The 12-month VA in infectious and noninfectious endophthalmitis was within ±2 lines of before endophthalmitis in 53% and 75% of eyes, respectively; a loss >2 lines was observed in 31% and 25% of eyes, respectively.

Conclusions

The incidences of infectious and noninfectious endophthalmitis after IVT were low, and the risk did not increase with each successive injection. We found higher rates of noninfectious endophthalmitis with bevacizumab compared with ranibizumab or aflibercept. Three quarters of cases with infectious and two thirds of cases with noninfectious endophthalmitis retained vision within 10 letters of the pre-endophthalmitis level.

Section snippets

Methods

This study followed the STROBE checklist items for reporting observational study data.27

Study Population

This study included 4564 patients collectively receiving 88 150 IVTs over 10 years between January 2006 and November 2016. Fifty-three percent of the 4564 patients completed at least 5 years of follow-up, and 8% went on to complete at least 10 years of follow-up. The average number of visits per patient was 22. During the study period, we recorded 18 infectious endophthalmitis and 11 noninfectious endophthalmitis. Two patients developed noninfectious endophthalmitis in both eyes and were

Incidence and Cumulative Rate of Noninfectious Endophthalmitis

Noninfectious endophthalmitis developed in 11 cases of 88 150 injections (1 per 8014 injections [0.012%]; 95% CI, 0.006–0.022). The cumulative rate of noninfectious endophthalmitis per patient increased to 0.087% and 0.228% after 10 and 20 injections, respectively (Table 1 and Fig 1C). Of note, no cases of noninfectious endophthalmitis were recorded in eyes after the 20th injection (Table 1 and Fig 1C). The risk of noninfectious endophthalmitis did not increase significantly with each

Discussion

The FRB! observational database allowed us to assess the incidence of infectious and noninfectious endophthalmitis and VA outcomes over a long period of time. Incidences of infectious endophthalmitis and noninfectious endophthalmitis “per injection” were in the range of previous studies. The prospective design of FRB! registry allowed us to report the median number of IVT before the occurrence of endophthalmitis and the cumulative rate of endophthalmitis “per patient,” which increased over time

Acknowledgments

The Fight Retinal Blindness! Investigators: Eye Associates, Sydney, NSW (Prof M. Gillies, Dr. Adrian Hunt); Canberra Hospital, Garran, ACT (Dr. R. Essex; Dr. C. Dayajeewa); Retina Associates, Chatswood, NSW (Prof A. Hunyor, A/Prof. S. Fraser-Bell, Dr. C. Younan, Dr. A. Fung); Centre for Eye Research Australia, East Melbourne, VIC (Prof R. Guymer, Dr. D. Louis); Marsden Eye Specialists, Parramatta, NSW (Dr. J. Arnold, Dr. D. Chan, Dr. H. Cass); Victoria Parade Eye Consultants, Fitzroy, VIC (Prof

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    Financial Disclosure(s): The author(s) made the following disclosures: V.D.: Research grant of the French Society of Ophthalmology.

    M.C.G.: Sydney Medical Foundation Fellow; Support − National Health and Medical Research Council practitioner fellowship.

    D.B.: Support − Walter and Gertrud Siegenthaler Foundation Zurich, Switzerland, and the Swiss National Foundation.

    Supported by grants from the Royal Australian NZ College of Ophthalmologists Eye Foundation (2007-2009), the National Health and Medical Research Council, Australia (2010-2012), and the Macular Disease Foundation, Australia. Funding was provided by Novartis and Bayer. These supporting organizations had no role in the design or conduct of the research.

    Author Contributions:

    Conception and design: Daien, Nguyen, Essex, Gillies

    Data collection: Daien, Morlet, Barthelmes, Gillies

    Analysis and interpretation: Daien, Nguyen, Essex

    Obtained funding: Not applicable

    Overall responsibility: Daien, Nguyen, Essex, Morlet, Barthelmes, Gillies

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