Non-steroidal anti-inflammatory drugs versus corticosteroids for controlling inflammation after uncomplicated cataract surgery

Review aim
The aim of this review was to find out if topical non-steroidal anti-inflammatory drugs (NSAIDs) (alone or taken in combination with topical corticosteroids) or topical corticosteroids alone are better for controlling eye inflammation after cataract surgery. Cochrane review authors collected and analyzed all relevant studies to answer this question and found 48 studies.

Key messages
It is unclear whether NSAIDs or corticosteroids are better at treating eye inflammation after cataract surgery. There were many combinations of drugs and dosing regimens in the included studies. The majority of the studies did not provide data on inflammation.

What was studied in this review?
Cataract surgery is one of the most commonly performed eye surgeries. Eye inflammation is common after cataract surgery. If left untreated, this inflammation can cause many complications. NSAIDs or corticosteroids are typically used to control swelling after cataract surgery. These drugs work differently, so comparing their effects is necessary. Cochrane review authors compared the effectiveness of NSAIDs (alone or in combination with corticosteroids) versus corticosteroids alone for controlling swelling after cataract surgery.

Main results
We included 48 randomized controlled trials from 17 different countries. Fifteen studies compared an NSAID with a corticosteroid. Nineteen studies compared an NSAID plus corticosteroid versus a corticosteroid alone. Fourteen other studies had more than two study arms, with different combinations of NSAIDs and corticosteroids.

In comparing participants who received an NSAID with those who received a corticosteroid:

• it was unclear whether the number of cells, which were a sign of inflammation inside the eye, was higher or lower

• there was less flare (another sign of inflammation inside the eye, in which a beam of light becomes visible passing through the eye fluids, like the beam of a searchlight) in the back of the eye in the group that received only an NSAID

• it was unclear whether there was a higher instance of swelling of the cornea, the clear window at the front of the eye which becomes misty if swollen, one month after surgery

• there was a lower risk of developing cystoid macular edema (fluid and swelling in a part of the eye called the macula, the central part of the retina, a light-sensitive membrane at the back of the eye which is responsible for detailed vision and if so effected can make vision clouded and distorted) in the group that received only an NSAID

The included studies in this comparison did not provide enough information to look into sharpness of vision, how long participants needed treatment, side effects of the medications, or cost.

In comparing participants who received a combination of an NSAID plus a corticosteroid compared with those who received a corticosteroid alone:

• there was a higher instance of corneal edema in the group that received a combination of the two types of medications

• there was a lower risk of developing cystoid macular edema one week after surgery in the group that received a combination of the two types of medications

The included studies did not provide enough information to look into the amount of cells in the back of the eye, sharpness of vision, how long participants needed treatment, side effects of the medications or cost.

This review compared many different types of drugs, dosing, and treatments. We tried to look at all types of anti-inflammatory agents in this review. NSAIDs considered in this review were indomethacin, ketorolac, nepafenac, diclofenac, bromfenac, flurbiprofen, and pranoprofen. Corticosteroids included in this review were dexamethasone, prednisolone acetate, betamethasone, rimexolone, fluorometholone, and loteprednol. A future review with different outcomes may be more effective in determining whether NSAIDs or corticosteroids are better at treating swelling after cataract surgery.

How up to date is this review?
Cochrane review authors searched for studies that had been published up to 16 December 2016.

Authors' conclusions: 

We found insufficient evidence from this review to inform practice for treatment of postoperative inflammation after uncomplicated phacoemulsification. Based on the RCTs included in this review, we could not conclude the equivalence or superiority of NSAIDs with or without corticosteroids versus corticosteroids alone. There may be some risk reduction of CME in the NSAID-alone group and the combination of NSAID plus corticosteroid group. Future RCTs on these interventions should standardize the type of medication used, dosing, and treatment regimen; data should be collected and presented using the Standardization of Uveitis Nomenclature (SUN) outcome measures so that dichotomous outcomes can be analyzed.

Read the full abstract...
Background: 

Cataract is a leading cause of blindness worldwide. Cataract surgery is commonly performed but can result in postoperative inflammation of the eye. Inadequately controlled inflammation increases the risk of complications. Non-steroidal anti-inflammatory drugs (NSAIDs) and corticosteroids are used to prevent and reduce inflammation following cataract surgery, but these two drug classes work by different mechanisms. Corticosteroids are effective, but NSAIDs may provide an additional benefit to reduce inflammation when given in combination with corticosteroids. A comparison of NSAIDs to corticosteroids alone or combination therapy with these two anti-inflammatory agents will help to determine the role of NSAIDs in controlling inflammation after routine cataract surgery.

Objectives: 

To evaluate the comparative effectiveness of topical NSAIDs (alone or in combination with topical corticosteroids) versus topical corticosteroids alone in controlling intraocular inflammation after uncomplicated phacoemulsification. To assess postoperative best-corrected visual acuity (BCVA), patient-reported discomfort, symptoms, or complications (such as elevation of IOP), and cost-effectiveness with the use of postoperative NSAIDs or corticosteroids.

Search strategy: 

To identify studies relevant to this review, we searched the Cochrane Central Register of Controlled Trials (CENTRAL), which contains the Cochrane Eyes and Vision Trials Register (2016, Issue 12), MEDLINE Ovid (1946 to December 2016), Embase Ovid (1947 to 16 December 2016), PubMed (1948 to December 2016), LILACS (Latin American and Caribbean Health Sciences Literature Database) (1982 to 16 December 2016), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com; last searched 17 June 2013), ClinicalTrials.gov (www.clinicaltrials.gov; searched December 2016), and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en; searched December 2016).

Selection criteria: 

We included randomized controlled trials (RCTs) in which participants were undergoing phacoemulsification for uncomplicated cataract extraction. We included both trials in which topical NSAIDs were compared with topical corticosteroids and trials in which combination therapy (topical NSAIDs and corticosteroids) was compared with topical corticosteroids alone. The primary outcomes for this review were inflammation and best-corrected visual acuity (BCVA).

Data collection and analysis: 

Two review authors independently screened the full-text articles, extracted data from included trials, and assessed included trials for risk of bias according to Cochrane standards. The two review authors resolved any disagreements by discussion. We graded the certainty of the evidence using GRADE.

Main results: 

This review included 48 RCTs conducted in 17 different countries and two ongoing studies. Ten included studies had a trial registry record. Fifteen studies compared an NSAID with a corticosteroid alone, and 19 studies compared a combination of an NSAID plus a corticosteroid with a corticosteroid alone. Fourteen other studies had more than two study arms. Overall, we judged the studies to be at unclear risk of bias.

NSAIDs alone versus corticosteroids alone

None of the included studies reported postoperative intraocular inflammation in terms of cells and flare as a dichotomous variable. Inflammation was reported as a continuous variable in seven studies. There was moderate-certainty evidence of no difference in mean cell value in the participants receiving an NSAID compared with the participants receiving a corticosteroid (mean difference (MD) -0.60, 95% confidence interval (CI) -2.19 to 0.99), and there was low-certainty evidence that the mean flare value was lower in the group receiving NSAIDs (MD -13.74, 95% CI -21.45 to -6.04). Only one study reported on corneal edema at one week postoperatively and there was uncertainty as to whether the risk of edema was higher or lower in the group that received NSAIDs (risk ratio (RR) 0.77, 95% CI 0.26 to 2.29). No included studies reported BCVA as a dichotomous outcome and no study reported time to cessation of treatment. None of the included studies reported the proportion of eyes with cystoid macular edema (CME) at one week postoperatively. Based on four RCTs that reported CME at one month, we found low-certainty evidence that participants treated with an NSAID alone had a lower risk of developing CME compared with those treated with a corticosteroid alone (RR 0.26, 95% CI 0.17 to 0.41). No studies reported on other adverse events or economic outcomes.

NSAIDs plus corticosteroids versus corticosteroids alone

No study described intraocular inflammation in terms of cells and flare as a dichotomous variable and there was not enough continuous data for anterior chamber cell and flare to perform a meta-analysis. One study reported presence of corneal edema at various times. Postoperative treatment with neither a combination treatment with a NSAID plus corticosteroid or with corticosteroid alone was favored (RR 1.07, 95% CI 0.98 to 1.16). We judged this study to have high risk of reporting bias, and the certainty of the evidence was downgraded to moderate. No included study reported the proportion of participants with BCVA better than 20/40 at one week postoperatively or reported time to cessation of treatment. Only one included study reported on the presence of CME at one week after surgery and one study reported on CME at two weeks after surgery. After combining findings from these two studies, we estimated with low-certainty evidence that there was a lower risk of CME in the group that received NSAIDs plus corticosteroids (RR 0.17, 95% CI 0.03 to 0.97). Seven RCTs reported the proportion of participants with CME at one month postoperatively; however there was low-certainty evidence of a lower risk of CME in participants receiving an NSAID plus a corticosteroid compared with those receiving a corticosteroid alone (RR 0.50, 95% CI 0.23 to 1.06). The few adverse events reported were due to phacoemulsification rather than the eye drops.

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