Review
Endophthalmitis following intravitreal injection of anti-vascular endothelial growth factor agents

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Abstract

Although intravitreal injections of anti-vascular endothelial growth factor medications are generally safe and effective, endophthalmitis remains a rare but potentially devastating complication. This review evaluates recent evidence for prophylactic strategies to prevent postinjection endophthalmitis. Povidone-iodine applied to the ocular surface before injection remains the most effective technique to prevent infection although aqueous chlorhexidine may be an acceptable alternative. Minimizing oral flora exposure, particularly with a no-talking policy, has been shown to reduce endophthalmitis rates. Recent studies of prefilled syringes suggest that the technology significantly lowers the risk of injection, likely by eliminating the transfer of medication from a storage vial to a syringe. Avoiding lid or lash touch during the injection process is an important tool to decrease patient risk, although this may be accomplished with manual lid retraction rather than a lid speculum. Same-day bilateral intravitreal injections have been shown to be safe. Several other strategies have not shown efficacy. The use of drapes or gloves, the clinical setting of injection administration, and ocular location of injection do not appear to affect infection rates. Topical prophylactic antibiotics do not reduce the risk of endophthalmitis and should not be routinely used.

Résumé

Si les injections intravitréennes d'anti-VEGF (facteur de croissance endothélial vasculaire) sont généralement sûres et efficaces, elles posent toujours un risque d'endophtalmie. Bien que rare, cette complication peut avoir des conséquences désastreuses. La présente revue de synthèse examine les données récentes sur les stratégies de prévention de l'endophtalmie post-injection. L'application de povidone-iode sur la surface oculaire avant l'injection représente la technique de prévention des infections la plus efficace; cela dit, la chlorhexidine aqueuse peut aussi constituer une solution de rechange acceptable. La réduction de l'exposition de la surface oculaire à la flore orale – notamment en s'abstenant de parler – a permis de réduire le taux d'endophtalmie. Selon des études récentes, les seringues préremplies réduisent significativement le risque d'infection, vraisemblablement en éliminant l’étape du transfert du médicament de la fiole à la seringue. De même, il est important d’éviter de toucher à la paupière ou aux cils pendant l'injection afin de réduire le risque d'infection; pour ce faire, la rétraction manuelle des paupières peut être préférable au spéculum palpébral. Les injections intravitréennes bilatérales réalisées le même jour se sont révélées sûres. Plusieurs autres stratégies se sont avérées inefficaces. Le recours à des champs opératoires ou à des gants, le milieu clinique où l'injection est donnée et l'emplacement de l'injection dans l’œil ne semblent pas influer sur les taux d'infection. Enfin, l'administration topique d'antibiotiques à titre préventif ne réduit pas le risque d'endophtalmie et ne devrait donc pas faire partie de l'arsenal habituel de l'ophtalmologiste.

Section snippets

Incidence

The reported incidence of postinjection endophthalmitis following anti-VEGF agents has varied widely. Published studies have reported incidence rates per injection ranging from 0.095% (1 in ∼1050 injections) to as low as 0.0053% (1 in ∼19 000 injections).2, 3, 4, 5 The wide range of incidence rates across different studies may be owing to the inclusion of false-negative cultures as well as postinjection inflammatory reactions.6, 7, 8 The majority of large series has reported incidence rates in

Presentation

Patients with endophthalmitis following intravitreal injection of anti-VEGF agents generally present with redness, pain, decreased vision, and vitritis, although not all signs or symptoms are required for diagnosis.9,12 Eyes that develop endophthalmitis after intravitreal injection may have more early posterior inflammation than eyes with infection following cataract surgery owing to an increased prevalence of more virulent bacteria. Endophthalmitis cases typically present within 3 days of

Treatment

Even though a vitreous or aqueous tap is generally performed for postinjection endophthalmitis, some evidence suggests that vitreous culture results may have a limited impact on clinical management. In a recent study of over 200 000 intravitreal injections, 60 cases of suspected endophthalmitis were identified.14 Six of 60 eyes (10%) had a change in clinical management of endophthalmitis. However, in all cases, management changes were based on declining visual acuity or worsening clinical

Outcomes

Visual outcomes of patients with endophthalmitis following anti-VEGF injection vary considerably. In several large retrospective studies of endophthalmitis secondary to anti-VEGF injection, roughly half of patients returned to baseline visual acuity within 3 months of infection.5,9 However, approximately 40% of patients may have vision of count fingers or worse.9 In one study, less than one-fifth of eyes with culture-positive endophthalmitis returned to baseline vision at 6 months compared with

Povidone Iodine

Povidone iodine (PI) application before intravitreal injection is the most commonly used method to reduce the risk of endophthalmitis. Povidone is typically applied in either a 5% or a 10% formula to the ocular surface for at least 30 seconds before injection. Povidone is broadly effective against gram-positive and gram-negative bacteria, viruses, and fungi. Although no trial has directly compared rates of infection with and without PI, reported rates of endophthalmitis with the use of PI are

Minimizing Risk Factors

Although there are no absolute contraindications to intravitreal injection of anti-VEGF medications, some studies have noted factors that may be associated with an increased risk of infection. In a study of 47 cases of endophthalmitis in patients with age-related macular degeneration, active blepharitis was associated with nearly 20 times higher odds of infection. Additionally, eyelid squeezing or moving during the injection also was significantly associated with increased risk of

Minimizing Oral Flora Exposure

Multiple studies have reported an increased prevalence of endophthalmitis secondary to oral flora, particularly Streptococcus and Enterococcus species, after intravitreal injection. A study including over 100 000 intravitreal injections reported that Streptococcus species represented 31% of culture-positive endophthalmitis. In contrast, studies of postcataract and postvitrectomy endophthalmitis have reported Streptococcus species in only 0%–9.0% of culture-positive cases.57 One study evaluated

Conclusions

Intravitreal injections of anti-VEGF agents are typically safe and generally effective for retinal vascular diseases. Although postinjection endophthalmitis is rare, visual outcomes may be poor, particularly when endophthalmitis is caused by oral pathogens. A range of prophylactic techniques have been developed to attempt to reduce the risk of endophthalmitis. The application of topical PI has the strongest clinical evidence and remains the most widely used approach to mitigate infectious risk.

Footnotes and Disclosure

The authors have no proprietary or commercial interest in any materials discussed in this article.

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