Over the past decade, intravitreal (IVT) injection of therapeutic agents has become one of the most commonly performed surgical procedures in ophthalmology. Intravitreal antivascular endothelial growth factor (anti-VEGF) therapy with bevacizumab, ranibizumab, or aflibercept is now the standard first-line treatment for many retinal diseases, including neovascular age-related macular degeneration, diabetic macular edema, macular edema due to retinal vein occlusion, and myopic choroidal neovascularization. Intravitreal steroid injection is also being incorporated in clinical practice, often either by itself or combined with anti-VEGF injections. In 2013 alone, more than 4 million injections were performed in the United States (US), and it has been estimated that almost 6 million injections will be carried out in 2016.1 Among the complications associated with IVT injection, endophthalmitis is one of the most serious. Based on published epidemiological studies, the incidence of endophthalmitis after IVT anti-VEGF injection is estimated to range from 0.020% to 0.085%.2–5 To prevent the occurrence of endophthalmitis, a number of guidelines have been developed for the best practice of IVT injection.6,7 This article provides perspective on the application of such guidelines, the various povidone-iodine (PVI) regimens used in cataract surgery and IVT injection (Table 1), and how we can further increase the safety of IVT injection. The standard operating procedure for IVT injection at the Dennis Lam and Partners Eye Center and the C-MER (Shenzhen) Dennis Lam Eye Center is described in Figure 1. A comparison between the protocol used at these facilities and the most recent international guidelines is presented in Table 2.
The first step for improving the safety of IVT injection is selecting the appropriate environment for the injection. Some clinicians prefer to use a clinic room for convenience, whereas others advocate the use of a sterile operating room. Tabandeh et al showed the rate of endophthalmitis after IVT injections performed in a sterile operating room setting to be as low as 0.0075% per injection.8 A retrospective comparative study in 2 different settings found that the rates of endophthalmitis were low and appeared similar, 0.035% in the office-based examination room and 0.065% per injection in the operating room.8 With limited data available in the literature and inconsistent results, further randomized controlled trials are warranted.
LOCAL ANESTHESIA AND PUPIL DILATATION
When preparing patients for IVT injection, topical local anesthetic eye drops should be applied at least 2 to 3 times at 5-minute intervals to provide adequate pain-free anesthesia. Some clinicians advocate the use of anesthetic eye gel or even subconjunctival injection of local anesthetic agents. If anesthetic eye gel is used, special attention must be paid to the potential risk of decreasing the disinfection effect. Dilating eye drops may also be used before the injection to allow easy assessment of the retina and optic disc immediately after the injection, should vitreoretinal complications occur.
SURGICAL MASKS AND GLOVES
Personnel in the injection procedure room, including support staff and the injecting surgeon, should wear surgical masks during the procedure. A meta-analysis showed that streptococcal species were found to be 3 times more common after intravitreal anti-VEGF injections compared with that after intraocular surgery, and oropharyngeal droplets have been postulated to be the main cause of transmission.9 Thus, injection personnel and patients should wear surgical masks and minimize talking and coughing during the procedure. For personal protection, gloves should also be worn during the procedure. However, glove use varies, as surveys conducted in the United States, Canada, and Brazil have reported rates of 58%, 39%, and 95%, respectively.10–12
Among the steps for IVT injection, disinfection is probably the most important for preventing endophthalmitis. The correct application of 5% to 10% PVI to the ocular surface and eyelids is essential for the prevention of endophthalmitis. Contact of 10% PVI to the eyelids and periorbital area should be maintained for at least 5 minutes, and 5% PVI applied to the ocular surface for 5 minutes can prevent the growth of most postcataract surgery endophthalmitis bacterial isolates.1,14 Although the report by Lad et al15 showed little effect of lignocaine gel on asepsis, when anesthetic eye gel is used, additional PVI should be applied before and after the IVT injection as the gel might act as a barrier to asepsis.16 This is in line with the general agreement among an expert panel in the updated guidelines for IVT injection.1 Immediately after IVT injection, the additional application of 5% PVI solution with a cotton applicator at the injection site can also be performed (Fig. 1). A sterile eye drape should be placed correctly so as to prevent the eyelashes from entering the injection area and close the air pathway from the mouth and nostrils to the surgical field.
USE OF PERIOPERATIVE TOPICAL ANTIBIOTICS
One of the most controversial areas of perioperative care for IVT injection is the use of topical antibiotics before and after the injection. In the past, many doctors routinely prescribed topical antibiotics before and after IVT injection in an attempt to reduce the risk of postinjection endophthalmitis. In fact, the use of topical antibiotics was mandatory in many early industry-sponsored randomized controlled trials for anti-VEGF agents. However, more recently, several studies have reported that the incidence of postinjection endophthalmitis appeared to be similar with or without the use of topical antibiotics.4,17 In addition, the use of topical antibiotics after injection has been postulated to increase the risk of microbial drug resistance.18 Nonetheless, topical antibiotics are still commonly used before and after injection, and a recent survey in the United Kingdom reported that 74% of hospitals provide take-home antibiotics after IVT injection.18 A recently published guideline on IVT injection also recommended the use of postinjection antibiotic prophylaxis in patients with 1 eye and patients with uncertain hygiene.7 Therefore, the decision to use perioperative topical antibiotics remains unclear. Due to the large variation in IVT injection practice patterns—such as the setting of the injection; the various types and duration of topical antibiotics; the concentration and duration of PVI application; and whether a lid speculum, surgical masks, gloves, and postinjection eye pads are used—it is difficult to ascertain whether the use of perioperative topical antibiotics reduces the risk of endophthalmitis after injection. Large-scale, multicenter randomized controlled trials with standardized pre- and postinjection methodology to evaluate the role of perioperative antibiotics in the prevention of postinjection endophthalmitis seem warranted. Based on existing evidence, half-hearted use of topical antibiotics for only 1 to 3 days after IVT injection should be avoided as this may induce more microbial drug resistance. Furthermore, there is a new trend of not using fourth-generation fluoroquinolones to reduce the chances of developing resistance to these drugs and thus making them inefficient in controlling endophthalmitis when needed.19
Lastly, early and accurate diagnosis of postinjection endophthalmitis is important as timely intervention will make a difference in the outcome.20–23Table 3 shows some of the differentiating features among true, sterile, and pseudo endophthalmitis.30–38
Many clinics and hospitals are now being overwhelmed by a large volume of patients requiring IVT injection. However, despite the heavy workload, meticulous care should still be taken before and after the injection to prevent infective endophthalmitis. Although there is a new trend of not using perioperative antibiotics as prophylaxis in the prevention of post-injection endophthalmitis, further studies are needed before concrete conclusions can be made. However, insufficient doses of PVI and half-hearted use of antibiotics should be avoided. We propose that 5% PVI should be applied to the ocular surface for at least 5 minutes to reduce the risk of endophthalmitis after injection. If a topical antibiotic is used after injection, it should be used for a course of 1 week, instead of just 1 to 3 days.
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Who looks outside, dreams; who looks inside, awakes.
— Carl Jung