Subconjunctival lidocaine may reduce endophthalmitis rate after intravitreal injection

Study author views lidocaine as an adjunct to povidone-iodine.

Issue: August 10, 2014

The bactericidal properties of lidocaine may account for a reduced rate of endophthalmitis after intravitreal injection, according to a study.

Perspective from Andrew P. Schachat, MD

In a retrospective chart review, there were no reports of endophthalmitis after intravitreal injection when 2% lidocaine/0.1% methylparaben was first administered subconjunctivally.

“The method of anesthesia used for intravitreal injections may influence rates of endophthalmitis, and further investigation into this to improve the safety of this technique is therefore needed,” study co-author Stephen J. Kim, MD, told Ocular Surgery News.

Kim and colleagues further examined in vitro the antibacterial effects of lidocaine on organisms that are considered common causes of endophthalmitis.

The study was published in Retina.

Chart review

The retrospective chart review included 15,042 intravitreal injections over a 7-year period.

Of the 15,042 injections, 6,853 received subconjunctival 2% lidocaine/0.1% methylparaben and 8,189 received other forms of anesthesia. Eight patients who received other forms of anesthesia developed endophthalmitis, but no patients who received subconjunctival lidocaine developed endophthalmitis. The difference was statistically significant (P = .03).

Patients received intravitreal injections of Avastin (bevacizumab, Genentech), Lucentis (ranibizumab, Genentech) or Kenalog-40 (triamcinolone acetonide, Bristol-Myers Squibb). Endophthalmitis cases that occurred within 7 days of injection were analyzed. One case occurred with triamcinolone, three cases occurred with bevacizumab, and four cases occurred with ranibizumab.

In patients who received lidocaine, topical 1% proparacaine was given first. Next, 0.5 mL of 2% lidocaine/0.1% methylparaben was injected in the inferotemporal subconjunctival space at the fornix to create a bleb, and then povidone-iodine was applied to the ocular surface. Povidone-iodine was reapplied after at least a 5-minute wait before the intravitreal injection.

“Povidone-iodine should continue to be the standard of care or, at minimum, common practice in the setting of intravitreal injections. I would think of lidocaine and its application as additive,” Kim said.

In vitro results

In a separate but related in vitro study, the researchers extracted isolates of Staphylococcus epidermidis, Staphylococcus aureus and Streptococcus viridans from patients who showed signs of endophthalmitis after intravitreal injection.

Isolates were incubated in soy broth before lidocaine solution was added. Lidocaine showed bactericidal effects against all three organisms. After 10 minutes of exposure, S. epidermidis demonstrated a 95% reduction in colony-forming units (P < .001), S. aureus demonstrated a 90% reduction (P = .01), and S. viridans demonstrated a 92% reduction (P < .001).

“Our study was observational and retrospective and thus limited. I do not believe the standard of care should be in any way influenced by these data at this time, but I would encourage further investigation into this topic and better-designed studies for the future. We have an obligation to always be improving the safety of intravitreal injections for our patients,” Kim said.

With further larger studies, the application of 2% lidocaine/0.1% methylparaben may show clinical importance in preventing post-injection endophthalmitis, the study said.

“I would emphasize the lack of evidence that antibiotics affect the safety of this technique and the potential for harm if they promote resistance. Similar to povidone-iodine, lidocaine is presumed to have a generalized bactericidal mechanism of action and is therefore not subject to bacterial resistance. This is a key advantage and would allow for its repeated safe application. This is particularly important to individuals who will likely have serial injections for years,” Kim said. – by Nhu Te

Reference:

Tustin A, et al. Retina. 2014;doi:10.1097/IAE.0000000000000014.

For more information:

Stephen J. Kim, MD, can be reached at Vanderbilt Eye Institute, 2311 Pierce Ave., Nashville, TN 37232; email: skim30@gmail.com.
Disclosure: Kim has no relevant financial disclosures.

Perspective

Andrew P. Schachat, MD

Endophthalmitis is a rare but important complication of intravitreal injections. The incidence is around one per 1,000 injections (0.02% to 0.2%, according to Kim and colleagues). The authors report that subconjunctival 2% lidocaine/0.1% methylparaben appears to reduce the rate of endophthalmitis after intravitreal injection. They report in vitro experiments that support their findings and then summarize endophthalmitis rates after more than 15,000 injections using different techniques from different time periods and institutions. For the clinical study, there were no cases identified after the subconjunctival lidocaine technique, but there were after other methods of anesthesia (0/6,853 vs. 8/8,189, 0% vs. 0.1%).

Retrospective study designs are prone to unintended sources of bias. Could other things have changed over time, or were there other differences in the techniques used that were not identified or considered? Were infections ascertained with equal completeness? Were criteria for endophthalmitis diagnosis comparable? We cannot be sure, but I agree with the authors who say the subconjunctival approach may reduce the risk. To prove this prospectively would take a huge sample size for a definitive study.

There may be unintended consequences when a different approach, eg, subconjunctival anesthesia, is introduced. For example, there is now another syringe with a clear fluid on the injection tray with a presumably greater chance of injecting a wrong drug. Although I support labeling all drugs on the field, of course, it is amusing that when a survey of causes of staff needlestick injuries was reported by Shah et al, having the sticky edge of a label on the syringe stick to the glove was found to play a role in the injury. The label may reduce drug errors (from near zero to an even lower number) but could be associated with increased needlestick injuries.

Congratulations to Tustin, Kim, Chomsky, Hubbard and Sheng for a nice report with good potential practical value.

References:

Kim SJ, et al. Ophthalmology. 2010;doi:10.1016/j.ophtha.2010.03.034.
Shah SU, et al. Retina. 2014;doi:10.1097/IAE.0b013e3182a2f523.

Andrew P. Schachat, MD

Vice Chairman for Clinical Affairs

Disclosures: Schachat is a consultant at Allergan and Bausch + Lomb.