Steroids plus antibiotics versus antibiotics alone for the 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 is more effective than using antibiotics alone for acute endophthalmitis (infection inside the eyeball that can cause vision loss) after eye surgery or injections into the eye. We looked for all studies that answered this question and found four 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?

Endophthalmitis is rare, but 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 additional steroids to treat endophthalmitis is the subject of debate. Steroids may help to decrease the inflammation inside the eye in people with endophthalmitis. We looked at whether giving steroids in addition to antibiotics affects patient outcomes.

What are the main results of the review?

We found four studies from South Africa, India, and the Netherlands. Almost all study participants had endophthalmitis after cataract surgery. All four studies compared injecting dexamethasone (a steroid) plus two antibiotics into the eye versus injecting only antibiotics into the eye. Low certainty evidence showed that more participants in the group receiving dexamethasone had a good visual outcome 3 months after treatment than in the antibiotics-only group, but the evidence was uncertain at 12 months. The effects of using steroids on resolution of endophthalmitis and harms were also uncertain. Given 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?

We searched for studies published up to 17 August 2021.

Authors' conclusions: 

The currently available 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 that use of adjunctive steroids may provide a higher chance 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 of 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 patients' symptoms and clinical examination into account; report outcomes in a uniform and consistent manner; and follow up at short- and long-term intervals.

Read the full abstract...
Background: 

Endophthalmitis refers to severe infection within the eye that involves the aqueous humor or vitreous humor, or both, and that 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 as being 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 strategy: 

We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2021, Issue 8), MEDLINE Ovid (1946 to August 2021), Embase Ovid (1980 to August 2021), LILACS (Latin American and Caribbean Health Sciences Literature database) (1982 to August 2021), the ISRCTN registry; searched August 2021, ClinicalTrials.gov; searched August 2021, and the WHO International Clinical Trials Registry Platform; searched August 2021. We did not use any date or language restrictions in the electronic searches for trials.

Selection criteria: 

We included randomized controlled trials (RCTs) 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: 

We used standard Cochrane methodology, and graded the certainty of the body of evidence for six outcomes using the GRADE classification.

Main results: 

We included four RCTs with a total of 264 eyes of 264 participants in this review update. The studies were conducted in South Africa, India, and the Netherlands. 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 two trials to be at overall low risk of bias, and the other two studies to be at overall unclear risk of bias due to lack of reporting of study methods. Only one study was 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 to antibiotics alone (risk ratio (RR) 1.08, 95% confidence interval (CI) 0.80 to 1.45; 32 participants). Low certainty evidence from two studies suggested that adjunctive dexamethasone may result in having a good visual outcome (Snellen visual acuity 6/6 to 6/18) at 3 months compared with antibiotics alone (RR 1.95, 95% CI 1.05 to 3.60; 60 participants); however, the evidence was less conclusive at 12 months (RR 1.12, 95% CI 0.92 to 1.37; 2 studies; 195 participants; low certainty evidence). 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 any estimates of precision. Only one study examined intraocular pressure (IOP). The evidence suggests that adjunctive dexamethasone may reduce IOP slightly after 12 months of interventions (mean difference −1.90, 95% CI −3.78 to 0.07; 1 study; 167 participants; low certainty evidence). Three studies reported adverse events (retinal detachment, hypotony, proliferative vitreoretinopathy, seclusion of pupil, floaters, and pucker). The total numbers of adverse events were 14 out of 111 (12.6%) for those who received dexamethasone versus 12 out of 116 (10.3%) 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 1.41, 95% CI 0.53 to 3.74; 227 participants; low certainty evidence). No study reported cost-related outcomes.