NIHR Signal Antibiotics by injection into the eye can prevent severe infection following cataract surgery

Published on 11 April 2017

Injecting the antibiotics vancomycin or moxifloxacin into the eyeball after eye surgery can reduce the risk of developing severe infection inside the eye (endophthalmitis) compared to other routes. Cefuroxime is currently the antibiotic of choice for this in the UK, but researchers wanted to see if drugs with lower rates of resistance might also be effective.

A review of 34 studies, mostly observational studies with nine randomised controlled trials (RCTs), explored the effects of different types of antibiotic regimens on the risk of endophthalmitis in people who had received eye surgery. There were no randomised trials of vancomycin or moxifloxacin injections but there were nine observational studies that linked to fewer infections with use of the injection.

Another, more recent, review also includes an RCT of cefuroxime injections into the eye. This shows that this drug is also effective when compared to surface antibiotics or injections just under the surface.

Therefore, the main question remains the choice of antibiotic. There is always a trade-off between using antibiotics to prevent infection and keeping them effective for treating other infections. Vancomycin is the drug of choice for MRSA infections, with few other options, but resistance is increasing. Widespread use to prevent eye infection following surgery has been discouraged for this reason. There are similar concerns for the use of moxifloxacin.  

So although the resistance to cefuroxime might also be rising, careful consideration of all the “pros and cons” including drug resistance will be required before prescribing guidance and antibiotic stewardship guidance can be offered.

Without firm guidelines, there is likely to be continued variation in practice.

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Why was this study needed?

People undergoing invasive eye procedures, such as cataract surgery, are at risk of endophthalmitis. This is severe inflammation inside the eyeball thought to be due to infection. Although a rare complication, it can quickly lead to blindness.

In the UK in 2004, 14 people in 10,000 developed endophthalmitis after cataract surgery. Between two and six people in 10,000 developed endophthalmitis after injections into the back of the eye for conditions such as macular degeneration.

A large trial conducted in 2007 found that injecting cefuroxime into the eyeball at the end of cataract surgery could reduce the rate of endophthalmitis. This prompted more ophthalmologists to use this prevention technique. However, there remains inconsistency around what types of antibiotics are used, as different antibiotics target different bacteria. There are also variations in using antibiotics on other parts of the eye.

So, this review aimed to assess how well various antibiotic regimens and routes, except intra-ocular cefuroxime, work to prevent endophthalmitis after eye surgery.

What did this study do?

This was a systematic review of nine randomised controlled trials and 15 observational study reports, which included 1,264,797 eyes.

Researchers excluded studies that looked at the effectiveness of cefuroxime injections and combined the results in a meta-analysis. They focussed on the effectiveness of the antibiotics in preventing endophthalmitis after eye surgery. Drugs evaluated included vancomycin and moxifloxacin injected inside the eyeball, or under the conjunctiva, or as antibiotic drops applied to the surface of the eye.

The results were assessed as moderate to high quality with a low risk of bias. However they were mostly observational studies and these were assessed using a non-standard scale. The authors analysed the data in separate ways to test the variability in results across the studies. All the trials of injections into the eyeball were observational. Topical antibiotics were tested in all the randomised trials. There were no trials allowing a direct comparison of antibiotics injected into the eye against each other.

What did it find?

  • Nine observational studies found that endophthalmitis was less common after vancomycin or moxifloxacin antibiotic injections into the eye (17 out of 105,003) compared to no injection (156 out of 236,742), (odds ratio [OR] 0.20, 95% confidence interval [CI] 0.10 to 0.42).
  • Results from seven observational studies suggest that injecting antibiotics under the conjunctiva has no effect on the risk of endophthalmitis (109 out of 274586 versus 118 out of 414701), (OR 1.67, 95% CI 0.55 to 5.05). The wide confidence interval and differences between the studies such as type of antibiotic reduces the precision of this result.
  • An analysis of five studies, including two randomised controlled trials, found that endophthalmitis was less likely to occur when antibiotic drops had been applied to the eye surface (35 out of 104,243) compared to no antibiotic drops (201 out of 667,359), (OR 0.65, 95% CI 0.43 to 0.99).

What does current guidance say on this issue?

The Royal College of Ophthalmologists 2010 advises using a preoperative sterilising solution containing iodine to help prevent endophthalmitis. Updated guidance from 2016 recommends a series of surgical measures to reduce the risk of infection occurring during the surgical procedure.

In terms of antibiotics, it advises to continue with whatever preventive/prophylactic measures are in place, if local rates of endophthalmitis are fairly low. If local rates are higher then cefuroxime injection into the eyeball is advised as part of a package of measures to lower endophthalmitis rates. The exact dose and best antibiotic prophylaxis (for example combining two different antibiotics) has not yet been determined.

What are the implications?

The results support current guidance that injecting antibiotics inside the eyeball can reduce the risk of post-operative endophthalmitis. Taking into account the excluded study of cefuroxime and a recent systematic review that included it, the combination of research suggest all injections inside the eyeball are effective.

Clinicians choosing between antibiotics and would need to weigh up the prevalence of endopthalmitis in their practice or country, the risk of antibiotic resistance, the likelihood of drug reactions and drug costs. Local rates of MRSA would also need consideration.

Randomised trials remain the better sources of evidence but are hard to undertake and fund when cases of endopthalmitis are rare. Large sample sizes would be needed if this remains an important enough question for future experimental studies.

Citation and Funding

Huang J, Wang X, Chen X, et al. Perioperative antibiotics to prevent acute endophthalmitis after ophthalmic surgery: a systematic review and meta-analysis. PLoS One. 2016;(11)11: e0166141.

No funding information was provided for this study.

Gower EW, Lindsley K, Tulenko SE, et al. Perioperative antibiotics for prevention of acute endophthalmitis after cataract surgery. Cochrane Database Syst Rev. 2017;2:CD006364.

No funding information was provided for this study.

Bibliography

ESCRS. Guidelines for Prevention and Treatment of Endophthalmitis Following Cataract Surgery: Data, Dilemmas and Conclusions. Ireland: European Society of Cataract and Refractive Surgeons; 2013. 

Nago J. Anti-VEGF intravitreal injection treatment. London: Moorfields Eye Hospital NHS Foundation Trust; 2012.

Patient. Endophthalmitis. Leeds: Patient; 2014.

Royal College of Ophthalmologists. Cataract Surgery Guidelines. London: Royal College of Ophthalmologists; 2010.

Royal College of Ophthalmologists. Ophthalmic services guidance. Managing an outbreak of endophthalmitis. London: Royal College of Ophthalmologists; 2016.

Wakely L, Sheard R. Focus: Recent advances in Endophthalmitis Management. Sheffield: Royal College of Ophthalmologists; 2014.

Why was this study needed?

People undergoing invasive eye procedures, such as cataract surgery, are at risk of endophthalmitis. This is severe inflammation inside the eyeball thought to be due to infection. Although a rare complication, it can quickly lead to blindness.

In the UK in 2004, 14 people in 10,000 developed endophthalmitis after cataract surgery. Between two and six people in 10,000 developed endophthalmitis after injections into the back of the eye for conditions such as macular degeneration.

A large trial conducted in 2007 found that injecting cefuroxime into the eyeball at the end of cataract surgery could reduce the rate of endophthalmitis. This prompted more ophthalmologists to use this prevention technique. However, there remains inconsistency around what types of antibiotics are used, as different antibiotics target different bacteria. There are also variations in using antibiotics on other parts of the eye.

So, this review aimed to assess how well various antibiotic regimens and routes, except intra-ocular cefuroxime, work to prevent endophthalmitis after eye surgery.

What did this study do?

This was a systematic review of nine randomised controlled trials and 15 observational study reports, which included 1,264,797 eyes.

Researchers excluded studies that looked at the effectiveness of cefuroxime injections and combined the results in a meta-analysis. They focussed on the effectiveness of the antibiotics in preventing endophthalmitis after eye surgery. Drugs evaluated included vancomycin and moxifloxacin injected inside the eyeball, or under the conjunctiva, or as antibiotic drops applied to the surface of the eye.

The results were assessed as moderate to high quality with a low risk of bias. However they were mostly observational studies and these were assessed using a non-standard scale. The authors analysed the data in separate ways to test the variability in results across the studies. All the trials of injections into the eyeball were observational. Topical antibiotics were tested in all the randomised trials. There were no trials allowing a direct comparison of antibiotics injected into the eye against each other.

What did it find?

  • Nine observational studies found that endophthalmitis was less common after vancomycin or moxifloxacin antibiotic injections into the eye (17 out of 105,003) compared to no injection (156 out of 236,742), (odds ratio [OR] 0.20, 95% confidence interval [CI] 0.10 to 0.42).
  • Results from seven observational studies suggest that injecting antibiotics under the conjunctiva has no effect on the risk of endophthalmitis (109 out of 274586 versus 118 out of 414701), (OR 1.67, 95% CI 0.55 to 5.05). The wide confidence interval and differences between the studies such as type of antibiotic reduces the precision of this result.
  • An analysis of five studies, including two randomised controlled trials, found that endophthalmitis was less likely to occur when antibiotic drops had been applied to the eye surface (35 out of 104,243) compared to no antibiotic drops (201 out of 667,359), (OR 0.65, 95% CI 0.43 to 0.99).

What does current guidance say on this issue?

The Royal College of Ophthalmologists 2010 advises using a preoperative sterilising solution containing iodine to help prevent endophthalmitis. Updated guidance from 2016 recommends a series of surgical measures to reduce the risk of infection occurring during the surgical procedure.

In terms of antibiotics, it advises to continue with whatever preventive/prophylactic measures are in place, if local rates of endophthalmitis are fairly low. If local rates are higher then cefuroxime injection into the eyeball is advised as part of a package of measures to lower endophthalmitis rates. The exact dose and best antibiotic prophylaxis (for example combining two different antibiotics) has not yet been determined.

What are the implications?

The results support current guidance that injecting antibiotics inside the eyeball can reduce the risk of post-operative endophthalmitis. Taking into account the excluded study of cefuroxime and a recent systematic review that included it, the combination of research suggest all injections inside the eyeball are effective.

Clinicians choosing between antibiotics and would need to weigh up the prevalence of endopthalmitis in their practice or country, the risk of antibiotic resistance, the likelihood of drug reactions and drug costs. Local rates of MRSA would also need consideration.

Randomised trials remain the better sources of evidence but are hard to undertake and fund when cases of endopthalmitis are rare. Large sample sizes would be needed if this remains an important enough question for future experimental studies.

Citation and Funding

Huang J, Wang X, Chen X, et al. Perioperative antibiotics to prevent acute endophthalmitis after ophthalmic surgery: a systematic review and meta-analysis. PLoS One. 2016;(11)11: e0166141.

No funding information was provided for this study.

Gower EW, Lindsley K, Tulenko SE, et al. Perioperative antibiotics for prevention of acute endophthalmitis after cataract surgery. Cochrane Database Syst Rev. 2017;2:CD006364.

No funding information was provided for this study.

Bibliography

ESCRS. Guidelines for Prevention and Treatment of Endophthalmitis Following Cataract Surgery: Data, Dilemmas and Conclusions. Ireland: European Society of Cataract and Refractive Surgeons; 2013. 

Nago J. Anti-VEGF intravitreal injection treatment. London: Moorfields Eye Hospital NHS Foundation Trust; 2012.

Patient. Endophthalmitis. Leeds: Patient; 2014.

Royal College of Ophthalmologists. Cataract Surgery Guidelines. London: Royal College of Ophthalmologists; 2010.

Royal College of Ophthalmologists. Ophthalmic services guidance. Managing an outbreak of endophthalmitis. London: Royal College of Ophthalmologists; 2016.

Wakely L, Sheard R. Focus: Recent advances in Endophthalmitis Management. Sheffield: Royal College of Ophthalmologists; 2014.

Perioperative Antibiotics to Prevent Acute Endophthalmitis after Ophthalmic Surgery: A Systematic Review and Meta-Analysis

Published on 9 November 2016

Huang, J.,Wang, X.,Chen, X.,Song, Q.,Liu, W.,Lu, L.

PLoS One Volume 11 Issue 11 , 2016

BACKGROUND: Post-operative endophthalmitis is a rare and dreaded complication in ophthalmic operations because it often induces irreparable vision loss. Although many ophthalmological studies aimed at reducing the rate of endophthalmitis have been performed around the world, controversy continues to surround some issues, including the choice of antimicrobials and their route of administration, duration and timing. The aim of this study is to investigate some of these unresolved issues. METHODS: A systematic review and meta-analysis of randomized controlled trials and observational studies was performed. The PubMed, EMBASE, Cochrane Library and Clinical Trials databases were searched to identify studies published until Feb. 2016. The relative risk (RR) for each clinical outcome data is presented with 95% confidence intervals (CIs). Pooled estimates of effects were calculated using random-effect models. RESULTS: Thirty-four studies from twenty-four reports involving 1264797 eyes were included in this analysis. Endophthalmitis occurred, on average, in one out of 6177 eyes when intracameral vancomycin/moxifloxacin were used and in one out of 1517 eyes when intracameral vancomycin/moxifloxacin were not used. The relative risk (95% CI) of endophthalmitis was reduced to 0.20 (0.10, 0.42) when intracameral antibiotics were used (p<0.0001). The subconjunctival injection of antibiotics was not superior to other administration routes included in this study (RR = 1.67, 95% CI (0.55, 5.05), p = 0.36). A statistically significant difference was found in the rate of endophthalmitis between the use and lack of use of topical antibiotics (RR = 0.65, 95% CI (0.43, 0.99), p = 0.04). However, no statistically significant difference was found in microbial isolation rates between these groups (RR = 0.77, 95% CI (0.34, 1.75), p = 0.53). When long-term and short-term use of topical antibiotics before surgery were compared, a statistically significant difference was found in microbial isolation rates (RR = 0.57, 95% CI (0.44, 0.74), p<0.0001). CONCLUSIONS: This meta-analysis concluded intracameral antibiotics are effective at preventing endophthalmitis in ocular surgery. A randomized controlled trial confirms the efficacy of cefuroxime but recent large cohort studies support the efficacy of vancomycin/moxifloxacin intracamerally. Intracameral antibitoics are superior to subconjunctival injections but that irrigation antibitoic data are not of enough quality to make a comparison. Different results were found in two clinical outcomes between the use or lack of use of topical antibiotic therapy, we did not find sufficient evidence to conclude that its use prevents endophthalmitis.

The European Society of Cataract and Refractive Surgeons performed a randomised controlled trial in 2007 on the prophylaxis of postoperative endophthalmitis after cataract surgery. It included over 16,000 people in 23 medical centres in nine European countries. It found that injecting 1mg of cefuroxime, an antibiotic, into the eyeball at the end of eye surgery reduced the risk of endophthalmitis five-fold compared to levofloxacin eye drops.

Expert commentary

Cataract is the commonest cause of treatable sight impairment worldwide. Outcomes of cataract surgery are typically excellent but intraocular infection occasionally causes devastating loss of sight. The risk of postoperative endophthalmitis is managed by various regimens of prophylactic antibiotics. The results of this meta-analysis demonstrate that the antibiotics vancomycin and moxifloxacin administered intra-ocularly at the end of the surgical procedure provide strong protection, with a five-fold reduction in risk. In contrast, the value of antibiotics administered sub-conjunctivally or topically is less clear.

James Bainbridge, Professor of Retinal Studies, UCL Institute of Ophthalmology; NIHR Research Professor, NIHR Biomedical Research Centre for Ophthalmology; Consultant Ophthalmologist, Moorfields Eye Hospital NHS Foundation Trust