Adjunctive steroid therapy versus antibiotics alone for acute endophthalmitis after intraocular procedure
Abstract
Background
Endophthalmitis refers to severe infection within the eye that involves the aqueous humor or vitreous humor, or both, and threatens vision. Most cases of endophthalmitis are exogenous (i.e. due to inoculation of organisms from an outside source), and most exogenous endophthalmitis is acute and occurs after an intraocular procedure. The mainstay of treatment is emergent administration of broad‐spectrum intravitreous antibiotics. Due to their anti‐inflammatory effects, steroids in conjunction with antibiotics have been proposed to be beneficial in endophthalmitis management.
Objectives
To assess the effects of antibiotics combined with steroids versus antibiotics alone for the treatment of acute endophthalmitis following intraocular surgery or intravitreous injection.
Search methods
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2016, Issue 11), MEDLINE Ovid (1946 to 8 December 2016), Embase Ovid (1980 to 8 December 2016), LILACS (Latin American and Caribbean Health Sciences Literature Database) (1982 to 8 December 2016), the ISRCTN registry (www.isrctn.com/editAdvancedSearch); searched 8 December 2016, ClinicalTrials.gov (www.clinicaltrials.gov); searched 8 December 2016, and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en); searched 8 December 2016. We did not use any date or language restrictions in the electronic searches for trials.
Selection criteria
We included randomized controlled trials comparing the effectiveness of adjunctive steroids with antibiotics alone in the management of acute, clinically diagnosed endophthalmitis following intraocular surgery or intravitreous injection. We excluded trials with participants with endogenous endophthalmitis unless outcomes were reported by source of infection. We imposed no restrictions on the method or order of administration, dose, frequency, or duration of antibiotics and steroids.
Data collection and analysis
Two review authors independently screened the search results, assessed risk of bias, and extracted data using methods expected by Cochrane. We contacted study authors to try to obtain missing information or information to clarify risk of bias. We conducted a meta‐analysis for any outcomes that were reported by at least two studies. Outcomes reported from single studies were summarized in the text. We assessed the certainty of the evidence using GRADE.
Main results
We included three trials with a total of 95 randomized participants in this review and identified one ongoing trial. The studies were conducted in South Africa, India, and the Netherlands. Out of the 92 analyzed participants, 91 participants were diagnosed with endophthalmitis following cataract surgery. In the remaining participant, endophthalmitis was attributable to penetrating keratoplasty. All studies used intravitreous dexamethasone for adjunctive steroid therapy and a combination of two intravitreous antibiotics that provided gram‐positive and gram‐negative coverage for the antibiotic therapy. We judged one trial to be at overall low risk of bias and two studies to be at overall unclear risk of bias due to lack of reporting of study methods. None of the three trials had been registered in a clinical trial register.
While none of the included studies reported the primary outcome of complete resolution of endophthalmitis as defined in our protocol, one study reported combined anatomical and functional success (i.e. proportion of participants with intraocular pressure of at least 5 mmHg and visual acuity of at least 6/120). Very low‐certainty evidence suggested no difference in combined success when comparing adjunctive steroid antibiotics alone (risk ratio (RR) 1.08, 95% confidence interval (CI) 0.80 to 1.45; 32 participants). Low‐certainty evidence from two studies showed that a higher proportion of participants who received adjunctive dexamethasone had a good visual outcome (Snellen visual acuity 6/6 to 6/18) at three months compared with those in the antibiotics‐alone group (RR 1.95, 95% CI 1.05 to 3.60; 60 participants). Similarly, low‐certainty evidence from one study suggested that more participants in the dexamethasone group had a good visual outcome at 12 months compared to those who did not receive dexamethasone (RR 2.00, 95% CI 0.98 to 4.08; 28 participants). Investigators of one study reported improvement in visual acuity, but we could not estimate the effect of adjunctive steroid therapy because the study investigators did not provide standard deviations or standard errors. Two studies reported adverse events (retinal detachment, hypotony, proliferative vitreoretinopathy, and seclusion of pupil). The total numbers of adverse events were 8 out of 30 (26.7%) for those who received dexamethasone versus 6 out of 30 (20.0%) for those who did not. We could only perform a pooled analysis for the occurrence of retinal detachment; any difference between the two treatment groups was uncertain (RR 1.57, 95% CI 0.50 to 4.90; 60 participants) (very low‐certainty evidence). No study reported intraocular pressure or cost outcomes.
Authors' conclusions
Current evidence on the effectiveness of adjunctive steroid therapy versus antibiotics alone in the management of acute endophthalmitis after intraocular surgery is inadequate. We found no studies that had enrolled cases of acute endophthalmitis following intravitreous injection. A combined analysis of two studies suggests adjunctive steroids may provide a higher probability of having a good visual outcome at three months than not using adjunctive steroids. However, considering that most of the confidence intervals crossed the null and that this review was limited in scope and applicability to clinical practice, it is not possible to conclude whether the use adjunctive steroids is effective at this time. Any future trials should examine whether adjunctive steroids may be useful in certain clinical settings such as type of causative organism or etiology. These studies should include outcomes that take patient's symptoms and clinical examination into account, report outcomes in a uniform and consistent manner, and follow up at short‐ and long‐term intervals.
PICOs
Plain language summary
Steroids plus antibiotics versus antibiotics alone for treatment of acute endophthalmitis after eye surgery or injections into the eye
What is the aim of this review?
The aim of this Cochrane review was to find out whether using steroids in addition to antibiotics works better than using antibiotics alone for acute endophthalmitis (infection inside the eyeball that can cause vision loss) after eye surgery or injections into the eye. Cochrane researchers looked for all relevant studies to answer this question and found three studies.
Key messages
It is uncertain whether using steroids in addition to antibiotics is helpful or harmful compared with using antibiotics alone to treat acute endophthalmitis after eye surgery or injections into the eye.
What was studied in the review?
Although endophthalmitis is rare, it is important for people undergoing surgery or injections to the eye to be aware of the risk and for their doctors to know how best to treat it because it can result in vision loss. It is most commonly caused by entry of bacteria into the eye during, or a few days after, surgery or injection. As soon as endophthalmitis is suspected, a sample of the fluid inside the eye is usually obtained (and the fluid drained in severe cases) and antibiotics that cover most types of bacteria are injected into the eye. Although the use of antibiotics is widely accepted, the use of adjunctive steroids to treat endophthalmitis is debatable. Steroids may help to decrease the inflammation inside the eye in people with endophthalmitis. In this review, Cochrane researchers studied whether giving steroids in addition to antibiotics has any effect on patient outcome.
What are the main results of the review?
Cochrane researchers found three relevant studies from South Africa, India, and the Netherlands. Almost all the people that took part in these studies had endophthalmitis after cataract surgery. All three studies compared injecting dexamethasone (a steroid) plus two antibiotics into the eye versus injecting only the antibiotics into the eye. Low‐certainty evidence showed that more participants in the group receiving dexamethasone had a good visual outcome three and 12 months after treatment than in the group that did not receive dexamethasone. However, the effects of using steroids on resolution of endophthalmitis and harms were uncertain. Due to the uncertainty of evidence for most outcomes, it is not clear whether doctors should use steroids with antibiotics to treat endophthalmitis after a procedure in the eye.
How up‐to‐date is this review?
Cochrane researchers searched for studies that had been published up to 8 December 2016.
