Anti-VEGF therapy

Reducing endophthalmitis risk with intravitreal injections

Dermot McGrath

Posted: Wednesday, May 1, 2019

Source: Parikh, et al. “Trends of anti-vascular endothelial growth factor use in ophthalmology among privately insured and medicare advantage patients.” Ophthalmology 2017

Recent years have seen an enormous increase in the number of intravitreal injections as anti-VEGF agents such as ranibizumab, bevacizumab, and aflibercept have become standard-of-care treatment for AMD and other retinal diseases.

The reported cumulative endophthalmitis incidence related to intravitreal injections (IVI) is around 0.048% based on different studies carried out between 2011 and 2018, although there is disparity between different studies, noted Dr Grzybowski, Professor of Ophthalmology, Chair of Ophthalmology, University of Warmia and Mazury, Olsztyn, Poland, and Head of the Institute for Research in Ophthalmology, Poznan, Poland.

“One study from Denmark shows a zero endophthalmitis rate, although that was based on a case series with quite low numbers of intravitreal injections of around 20,000. Two other studies, by Casparis et al. in 2014 and Freiberg et al. in 2017, both reported rates of endophthalmitis of 0.0075% and 0.0074% that were six or seven times lower than the other studies,” he said.

There seems to be no increased risk based on the choice of agent, said Dr Grzybowski. This was shown in a study by Rayess et al. in 2016, which concluded that endophthalmitis following intravitreal bevacizumab, ranibizumab and aflibercept injection appears to occur at similar rates and have comparable visual outcomes.

Dr Grzybowski and colleagues recently published expert consensus recommendations to guide members in their use of IVIs. In terms of the ideal clinical setting, operating theatre, adequate room or in-office settings are all recommended.

“There has been a bit of controversy about the ideal setting for administering injections. However, recent literature confirms that office-based and in particular OR-based injections have very low endophthalmitis incidence,” he said.

It is also advised to administer 5% povidone-iodine antisepsis for a minimum of 30 seconds.

“In fact, this is the only intervention that has been demonstrated by a randomised controlled trial to reduce the risk of postoperative endophthalmitis,” noted Dr Grzybowski. Chlorhexidine may also be used for patients that are sensitive to PVI, although it is known that chlorhexidine is a much weaker antiseptic agent, and it should be remembered that true PVI allergy is unique and commonly overestimated.

By contrast, perioperative antibiotics are not recommended as part of the guidelines, with pooled estimates of the risk of endophthalmitis after IVI found to be three times higher when they were used.

“There is no evidence that topical antibiotics lower endophthalmitis rates after intravitreal injection. And as we are all aware, frequent use of topical antibiotics promotes increasing antibiotic resistance and growth of pan-drug-resistant bacteria, which might lead to more severe cases,” said Dr Grzybowski.
Use of an eye speculum is also recommended during the procedure.

“Any effective way to avoid lid closure during the procedure is justified, and ideally we should use a sterile speculum. It has also been reported that the instillation of additional povidone-iodine antisepsis after placement of the lid speculum decreases the incidence of endophthalmitis compared with other tested protocols,” he added.

With most patients preferring same-day bilateral injections and an estimated 46% of ophthalmologists in a recent US study performing bilateral IVI, appropriate measures should be taken to minimise the risk of endophthalmitis, said Dr Grzybowski.

“It is important to remember to treat each injection as a separate procedure and not to reuse any equipment,” he said.

A recent study published in the American Journal of Ophthalmology found a 0.027% rate of endophthalmitis in 102,932 injections with no increased risk of infection from bilateral injections, added Dr Grzybowski.

While there is no significant evidence that the use of sterile gloves or drapes reduces endophthalmitis rates or adverse events, the use of gloves, either sterile or non-sterile, is consistent with modern practice combined with hand washing before and after patient contact, he said. The use of face masks is highly recommended, however, with a zero-talking, sneezing and coughing policy also advisable, said Dr Grzybowski.

It was recently shown that the use of lidocaine jelly or Tetravisc might increase the endophthalmitis rate in IVI.

There is increasing accumulation of evidence that low concentrations of PVI, between 0.25-1.25%, are as effective as 5%. PVI, however, must be used more often. Lower concentrations are much better tolerated, and rarely irritate the ocular surface. However, the precise procedure of low-concentration PVI use, including contact time, number of repetitions, etc, still needs to be established.

Andrzej Grzybowski: