Preventing and treating cystoid macular oedema (CME) after cataract surgery

Topical nonsteroidal anti-inflammatory drugs (NSAIDs) may prevent postoperative CME in patients undergoing cataract surgery

Cheryl Guttman Krader

Posted: Thursday, July 20, 2017

Laura Wielders MD

Findings from systematic literature reviews provide some information about the efficacy of medications for preventing and treating cystoid macular oedema (CME) after cataract surgery, according to investigators from the University Eye Clinic Maastricht UMC+, Maastricht, The Netherlands.
Laura Wielders MD, PhD stated: “The results of our systematic reviews suggest that topical nonsteroidal anti-inflammatory drugs (NSAIDs) should be used to prevent postoperative CME in all patients undergoing cataract surgery, although it is unclear whether combination treatment with a corticosteroid has additional benefit. Topical NSAIDs also appear to be effective for treating CME after cataract surgery. However, more studies are needed investigating other treatment modalities and comparing them to NSAIDs.”
The prevalence of CME after uncomplicated surgery in healthy eyes has been reported to range between 1.2% and 20%. Most cases of pseudophakic CME, however, cause no to minimal visual symptoms.
“Clinically significant CME affects between 0.1% and 2.4% of healthy eyes, but up to 31% of patients with diabetes,” Dr Wielders said.
Knowledge of the costs and clinical consequences of CME underscores the need for effective prevention and treatment. Longstanding CME may cause retinal damage and sustained visual impairment. Previously, studies have shown that the cost of anti-inflammatory agents provided as prophylaxis is likely to be minimal compared with the cost savings from reducing the number of cases of CME. (Schmier JK, et al. retina 27:621–628, 2007)
In the absence of any formal guidelines on CME prophylaxis, surgeons’ practices vary. According to data from 2014 collected through the ESCRS PREvention of Macular EDema after cataract surgery (PREMED) study, under the supervision of Prof Rudy Nuijts and Dr Jan Schouten, 61% of centres used an NSAID with a corticosteroid, 17% used an NSAID alone, and 22% relied on corticosteroid monotherapy.

The systematic literature review of randomised controlled trials (RCTs) investigating pharmacologic prevention of CME after cataract surgery included 30 studies, after excluding trials enrolling patients who had CME preoperatively or risk factors other than diabetes mellitus. (Wielders LH, et al. Am J Ophthalmol. 2015;160(5):968-981)
A meta-analysis was performed for patients with diabetes, non-diabetics, and a mixed population. In all patient groups, topical NSAIDs or the combination of an NSAID and corticosteroid were more effective than corticosteroids for preventing CME. Results from three studies suggested that intravitreal corticosteroid or anti-vascular endothelial growth factor (anti-VEGF) treatment might reduce the risk of CME in patients with diabetes, as compared to topical steroids alone. Dr Wielders noted, however, that the latter studies were small, and the treatment effect was not statistically significant.
A difference in corrected distance visual acuity (CDVA) outcomes was found in a single study, was in diabetics, and favoured treatment with an NSAID versus a corticosteroid.

Clinically significant CME affects between 0.1% and 2.4% of healthy eyes, but up to 31% of patients with diabetes

Dr Wielders and colleagues also conducted a systematic review investigating the optimal pharmacological treatment of CME after cataract surgery. Again, the review excluded studies enrolling patients with any CME risk factors other than diabetes mellitus. Only 10 RCTs met the selection criteria, and many had small populations.
Three studies showed that topical NSAIDs were more effective than placebo for improving CDVA and retinal morphology. Studies comparing different NSAIDs (ketorolac, diclofenac, bromfenac, nepafenac) found no significant difference between the medications. In two studies, results were better using an NSAID with a corticosteroid compared with a corticosteroid alone, but the differences were not statistically significant, perhaps due to small sample size.
A few studies investigated alternate routes of administration. One study reported similar results in patients treated with a single sub-Tenon’s injection of triamcinolone versus a topical NSAID. Two placebo-controlled studies found no benefits of oral treatment with indomethacin or acetazolamide, although the results may reflect the very small sample sizes, Dr Wielders said.

Dr Wielders noted that the systematic reviews have limitations stemming from the poor to moderate quality of some of the RCTs and the absence of consistent methodology and CME definitions.
Thus, the PREMED study was undertaken by the ESCRS in order to develop evidence-based recommendations. It enrolled 914 patients without diabetes and 213 patients with diabetes at 12 European centres. Patients without diabetes were randomised to treatment with topical bromfenac, topical dexamethasone, or a combination of the two. Patients with diabetes were assigned to one of four groups to receive the topical combination regimen alone or with intravitreal bevacizumab (Avastin®, Genentech), subconjunctival triamcinolone, or both injections.
The results will be presented at the XXXV Congress of the ESCRS in October. Preliminary analyses of postoperative mean central subfield macular thickness and CDVA, however, indicate there may be some between-treatment outcomes differences, Dr Wielders reported.

Rudy Nuijts:
Jan Schouten:
Laura Wielders: