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      Incidence of Acute Endophthalmitis after Intravitreal Antivascular Endothelial Growth Factor Injection in Age-related Macular Degeneration

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          Abstract

          Purpose

          Antivascular endothelial growth factor (anti-VEGF) agents are routinely intravitreously injected to treat neovascular age-related macular degeneration (AMD). Postoperative endophthalmitis, a side effect after intravitreal anti-VEGF injection, has been reported to have a low incidence but may threaten vision. In this study, we aimed to analyze the incidence of acute endophthalmitis after intravitreal anti-VEGF injection and associated risk factors in patients with neovascular AMD in South Korea.

          Methods

          Using the health claims data recorded in the Korean National Health Insurance System database, we identified newly developed neovascular AMD cases from 2010 through 2019. Acute endophthalmitis was defined as a case of invasive treatment for accompanying symptoms. All statistical analyses were performed with a significance level p < 0.05. To find risk factors, we used univariate and multivariable Poisson regression.

          Results

          The overall incidence of acute endophthalmitis was 0.019% ( p = 0.21) during the 10-year period: 0.025% for aflibercept injection and 0.014% for ranibizumab injection. The incidence was higher in metropolitan city residents than in Seoul (incidence rate ratio [IRR], 1.96; 95% confidence interval [CI], 1.02–3.79; p = 0.04) and was higher for aflibercept injections than for ranibizumab injections (IRR, 1.82; 95% CI, 1.17–2.82; p = 0.01). However, in multivariate analysis, only aflibercept injections showed a significant effect on the incidence of acute endophthalmitis (IRR, 1.80; 95% CI, 1.16–2.79; p = 0.01).

          Conclusions

          The incidence of acute endophthalmitis after intravitreal anti-VEGF injections was generally low, and aflibercept was revealed as a significant risk factor.

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          Most cited references28

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          Ranibizumab for neovascular age-related macular degeneration.

          Ranibizumab--a recombinant, humanized, monoclonal antibody Fab that neutralizes all active forms of vascular endothelial growth factor A--has been evaluated for the treatment of neovascular age-related macular degeneration. In this multicenter, 2-year, double-blind, sham-controlled study, we randomly assigned patients with age-related macular degeneration with either minimally classic or occult (with no classic lesions) choroidal neovascularization to receive 24 monthly intravitreal injections of ranibizumab (either 0.3 mg or 0.5 mg) or sham injections. The primary end point was the proportion of patients losing fewer than 15 letters from baseline visual acuity at 12 months. We enrolled 716 patients in the study. At 12 months, 94.5% of the group given 0.3 mg of ranibizumab and 94.6% of those given 0.5 mg lost fewer than 15 letters, as compared with 62.2% of patients receiving sham injections (P<0.001 for both comparisons). Visual acuity improved by 15 or more letters in 24.8% of the 0.3-mg group and 33.8% of the 0.5-mg group, as compared with 5.0% of the sham-injection group (P<0.001 for both doses). Mean increases in visual acuity were 6.5 letters in the 0.3-mg group and 7.2 letters in the 0.5-mg group, as compared with a decrease of 10.4 letters in the sham-injection group (P<0.001 for both comparisons). The benefit in visual acuity was maintained at 24 months. During 24 months, presumed endophthalmitis was identified in five patients (1.0%) and serious uveitis in six patients (1.3%) given ranibizumab. Intravitreal administration of ranibizumab for 2 years prevented vision loss and improved mean visual acuity, with low rates of serious adverse events, in patients with minimally classic or occult (with no classic lesions) choroidal neovascularization secondary to age-related macular degeneration. (ClinicalTrials.gov number, NCT00056836 [ClinicalTrials.gov].). Copyright 2006 Massachusetts Medical Society.
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            Immune dysfunction in patients with diabetes mellitus (DM)

            Patients with diabetes mellitus (DM) have infections more often than those without DM. The course of the infections is also more complicated in this patient group. One of the possible causes of this increased prevalence of infections is defects in immunity. Besides some decreased cellular responses in vitro, no disturbances in adaptive immunity in diabetic patients have been described. Different disturbances (low complement factor 4, decreased cytokine response after stimulation) in humoral innate immunity have been described in diabetic patients. However, the clinical relevance of these findings is not clear. Concerning cellular innate immunity most studies show decreased functions (chemotaxis, phagocytosis, killing) of diabetic polymorphonuclear cells and diabetic monocytes/macrophages compared to cells of controls. In general, a better regulation of the DM leads to an improvement of these cellular functions. Furthermore, some microorganisms become more virulent in a high glucose environment. Another mechanism which can lead to the increased prevalence of infections in diabetic patients is an increased adherence of microorganisms to diabetic compared to nondiabetic cells. This has been described for Candida albicans. Possibly the carbohydrate composition of the receptor plays a role in this phenomenon.
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              Ranibizumab versus verteporfin photodynamic therapy for neovascular age-related macular degeneration: Two-year results of the ANCHOR study.

              The 2-year, phase III trial designated Anti-vascular endothelial growth factor (VEGF) Antibody for the Treatment of Predominantly Classic Choroidal Neovascularization (CNV) in Age-related Macular Degeneration (ANCHOR) compared ranibizumab with verteporfin photodynamic therapy (PDT) in treating predominantly classic CNV. Multicenter, international, randomized, double-masked, active-treatment-controlled clinical trial. Patients with predominantly classic, subfoveal CNV not previously treated with PDT or antiangiogenic drugs. Patients were randomized 1:1:1 to verteporfin PDT plus monthly sham intraocular injection or to sham verteporfin PDT plus monthly intravitreal ranibizumab (0.3 mg or 0.5 mg) injection. The need for PDT (active or sham) retreatment was evaluated every 3 months using fluorescein angiography (FA). The primary, intent-to-treat efficacy analysis was at 12 months, with continued measurements to month 24. Key measures included the percentage losing or=15 letters from baseline, and mean change over time in VA score and FA-assessed lesion characteristics. Adverse events were monitored. Of 423 patients (143 PDT, 140 each in the 2 ranibizumab groups), the majority (>or=77% in each group) completed the 2-year study. Consistent with results at month 12, at month 24 the VA benefit from ranibizumab was statistically significant (P or=15 letters (vs. 6.3% of PDT group); and, on average, VA was improved from baseline by 8.1 to 10.7 letters (vs. a mean decline of 9.8 letters in PDT group). Changes in lesion anatomic characteristics on FA also favored ranibizumab (all comparisons P<0.0001 vs. PDT). Overall, there was no imbalance among groups in rates of serious ocular and nonocular adverse events. In the pooled ranibizumab groups, 3 of 277 (1.1%) patients developed presumed endophthalmitis in the study eye (rate per injection = 3/5921 [0.05%]). In this 2-year study, ranibizumab provided greater clinical benefit than verteporfin PDT in patients with age-related macular degeneration with new-onset, predominantly classic CNV. Rates of serious adverse events were low. Proprietary or commercial disclosure may be found after the references.
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                Author and article information

                Journal
                Korean J Ophthalmol
                Korean J Ophthalmol
                Korean Journal of Ophthalmology : KJO
                Korean Ophthalmological Society
                1011-8942
                2092-9382
                October 2022
                19 August 2022
                : 36
                : 5
                : 435-442
                Affiliations
                [1 ]Department of Ophthalmology, National Health Insurance Service Ilsan Hospital, Goyang, Korea
                [2 ]Department of Ophthalmology, Yonsei University College of Medicine, Seoul, Korea
                [3 ]Department of Research and Analysis, National Health Insurance Service Ilsan Hospital, Goyang, Korea
                Author notes
                Corresponding Author: Eun Jee Chung, MD, PhD. Department of Ophthalmology, National Health Insurance Service Ilsan Hospital, 100 Ilsan-ro, Ilsandong-gu, Goyang 10444, Korea. Tel: 82-31-900-0964, Fax: 82-31-900-0049, E-mail: eunjee95@ 123456nhimc.or.kr
                Article
                kjo-2022-0088
                10.3341/kjo.2022.0088
                9582495
                35989065
                048daf28-8075-46bd-a549-4872589efbbd
                © 2022 The Korean Ophthalmological Society

                This is an Open Access journal distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 6 July 2022
                : 11 August 2022
                : 14 August 2022
                Categories
                Original Article

                Ophthalmology & Optometry
                aflibercept,endophthalmitis,intravitreal injections,macular degeneration,ranibizumab

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