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PREMED Results

PREMED study highlights benefit of combination treatment to prevent CME

Dermot McGrath

Posted: Friday, December 1, 2017

ESCRS PREMED study investigators pictured at the XXXIV Congress of the ESCRS in Copenhagen

A combination of a topical corticosteroid and a nonsteroidal anti-inflammatory drug (NSAID) is more effective than either agent alone in reducing the risk of developing cystoid macular edema (CME) after cataract surgery in non-diabetic patients, according to the results of the ESCRS PREMED European study presented at the XXXV Congress of the ESCRS in Lisbon.

The ESCRS PREvention of Macular EDema after cataract surgery (PREMED) study is the first international, multi-centre, randomised, controlled clinical trial specifically designed to answer questions relating to the prevention of CME after cataract surgery in diabetic and non-diabetic patients.

The study outcomes pave the way for the first evidence-based clinical guidelines to prevent CME after cataract surgery in diabetic and non-diabetic patients.

“CME remains one of the most prevalent postoperative complications in cataract surgery and especially in the diabetic population, where the incidence can be as high as 31%,” said Rudy MMA Nuijts MD, PhD, Professor of Ophthalmology at the University Eye Clinic Maastricht UMC+, the Netherlands, and lead investigator of the PREMED Study.

“This landmark study in over 1,000 patients will give us the foundation to draw up concrete evidence-based recommendations for clinical guidelines to prevent the occurrence of CME after cataract surgery in patients with and without diabetes,” he said.

RATIONALE
Dr Nuijts said that the rationale for the study stemmed from the lack of any real consensus regarding the optimal means of preventing the occurrence of CME after cataract surgery.

“There is a wide disparity in opinion about the most effective anti-inflammatory drops to use. For instance, the American Academy of Ophthalmology (AAO) has stated that there is a lack of level one evidence supporting the long-term visual benefit of NSAID therapy when applied solely or in combination with corticosteroid therapy. By contrast, the American Society of Cataract and Refractive Surgery (ASCRS) says that there is compelling evidence of the efficacy of NSAIDs as an anti-inflammatory drug whether used alone, synergistically with steroids or for specific high-risk eyes. Our study sought to answer the question once and for all backed by clinical evidence,” he said.

Dr Nuijts presented the results of the non-diabetic arm of the study while his colleague Laura Wielders MD focused on the implications for diabetic patients.

Carried out at 12 surgical centres across the European Union, the PREMED Study was carefully designed to evaluate the effect of different preventive strategies on the occurrence of macular edema in 914 non-diabetic and 213 diabetic patients. All patients in the study received standard phacoemulsification for cataract and placement of an intraocular lens. Intraoperative and postoperative antibiotics were administered according to local protocols.

In the non-diabetic population, the 914 patients received either a topical NSAID (bromfenac 0.09%) or a topical corticosteroid (dexamethasone 0.1%), or a combination of both. The primary outcome was the difference in central subfield mean macular thickness (CSMT) at six weeks postoperatively. Important secondary outcome measures included postoperative corrected distance visual acuity (CDVA), as well as the incidence of CME and clinically significant macular edema (CSME) within six and 12 weeks postoperatively.

At the six-week point, the CSMT was 9.6 microns higher in the dexamethasone group compared to the combination treatment group. Furthermore, the incidence of CSME within 12 weeks postoperatively was found to be lower in the combination treatment group, at 1.5%, compared to 3.6% for bromfenac alone and 5.1% for dexamethasone alone.

“The conclusion is clear – patients treated with a combination of topical bromfenac 0.09% and dexamethasone 0.1% have a lower risk of developing clinically significant macular edema after cataract study compared to patients treated with either bromfenac or dexamethasone alone,” said Dr Nuijts.

DIABETIC OUTCOMES
The 213 diabetic patients in the study were randomly allocated to receive no additional treatment, a subconjunctival injection with 40mg triamcinolone acetonide (TA), an intravitreal injection with 1.25mg bevacizumab or a combination of both after cataract surgery. The main outcomes were the difference in CSMT, CDVA, and the incidence of CME and CSME within six and 12 weeks postoperatively.

The macular thickness and volume was found to be significantly lower in patients who received a subconjunctival injection with TA compared to patients who did not. No patient who received subconjunctival TA developed CME, while intravitreal bevacizumab had no significant effect on macular thickness.

The study also found a significantly higher IOP in patients who received a TA injection, with six patients in the TA group recording an IOP higher than 25mmHg compared to none in the non-TA-treated group. Fifteen patients (7.1%) had an IOP increase of more than 5mmHg in the TA group, compared to one patient in the other treatment arms.

“A single subconjunctival TA injection effectively prevents the development of CME after cataract surgery in diabetic patients. However, the risk of developing CME should be carefully weighed against the risk of developing an increased IOP,” concluded Dr Wielders.

Rudy MMA Nuijts: rudy.nuijts@mumc.nl
Laura Wielders: laura.wielders@mumc.nl

Watch Oliver Findl talk to Rudy MMA Nuijts MD, PhD, Professor of Ophthalmology at the University Eye Clinic Maastricht UMC+, The Netherlands, and lead investigator of the PREMED Study, about the implications of this groundbreaking study here. You can also view the whole main symposia here.