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FROM THE ARCHIVE – PREMED study recruitment

This story on the PREMED study was first published in EuroTimes in September 2016

Gearoid Tuohy

Posted: Wednesday, June 28, 2017

On 1 June 2016, the ESCRS PREvention of Macular EDema after cataract surgery (PREMED) study completed recruitment of all 1,135 patients, comprising 926 non-diabetic and 209 diabetic participants. The study, funded solely by the society, is focused on building an evidence-based approach to prevention of cystoid macular oedema (CME) following cataract surgery.
Results are expected to be presented at the XXXV Congress of the ESCRS, scheduled for October 2017 in Lisbon, Portugal.

The completion of recruitment represents a further milestone in ESCRS support of independent clinical research aimed at improving patient care and clinical management.
Most recently, the society’s support for clinical research has included the ESCRS Endophthalmitis Study led by the late Dr Peter Barry (Ireland), the series of EUREQUO studies led by Dr Mats Lundström (Sweden), and the ESCRS-EUREQUO FLACS Study, which reported its results at the XXXIII Congress of the ESCRS in Barcelona, Spain. Three new and exciting independent research studies will shortly be added to the ESCRS portfolio, all of which will be highlighted in future issues of EuroTimes.

SIGNIFICANT CHALLENGE

The PREMED study, led by Dr Rudy MMA Nuijts, Professor of Ophthalmology at the University Eye Clinic Maastricht UMC+, The Netherlands, was set up in September 2012 and has involved the recruitment of cataract patients at over 13 surgical clinics across the EU, including centres in Austria, Belgium, Germany, Hungary, Portugal, Spain and The Netherlands.

The complication under investigation by the international PREMED team represents a significant clinical challenge across surgical practice. The trial aims to establish an evidence-based treatment strategy for what is believed to be a common cause of vision loss after cataract surgery. In the last few years, several new treatments have been applied to address the problem of CME after cataract surgery in diabetic and non-diabetic patients.

However, no randomised controlled clinical trial has compared all the currently existing interventions. The PREMED study therefore represents a large randomised clinical trial with the objective of providing more definite evidence-based recommendations for clinical guidelines, to prevent the occurrence of CME after cataract surgery in patients with and without diabetes.

Highlighting the rationale for the study, Dr Nuijts explained to EuroTimes: “Although the incidence of complications after cataract surgery has significantly decreased, CME remains one of the most prevalent postoperative complications in cataract surgery. Right now, treatment is largely dependent on the preferences of individual ophthalmologists, since evidence-based guidelines are lacking. The aim of the ESCRS PREMED study is to investigate the optimal pre- and postoperative treatment to prevent the occurrence of CME after cataract surgery. The results of the study will be used to provide evidence-based clinical guidelines for optimal treatment after regular phacoemulsification cataract surgery.”

PREVENTIVE STRATEGIES

According to Dr Nuijts, the outcomes of the PREMED randomised controlled trial should benefit all ESCRS members and cataract surgeons. He explained to EuroTimes that: “Studies have reported incidence rates of up to 20 per cent in healthy subjects depending on the diagnostics used, however the majority of patients with CME have minimal to no reduction in visual acuity. The rate of clinically significant macular oedema (CSME) is estimated to be between 0 per cent and 5.8 per cent in healthy subjects. By contrast, other studies have reported incidence rates of CSME up to 56 per cent in diabetic patients with diabetic retinopathy.”

CAREFULLY DESIGNED

The clinical study, led by a team from the University Eye Clinic Maastricht UMC+, was carefully designed to evaluate the effect of different preventive strategies on the occurrence of macular oedema in both non-diabetic and diabetic patients. All patients in the study received a 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 patients received either a topical nonsteroidal anti-inflammatory drug (NSAID) or a topical corticosteroid, or a combination of both, and these participants will be compared on preventing central retinal thickening and on the effect of the treatments on corrected distance visual acuity (CDVA).

In the diabetic population, a 2×2 factorial design was employed whereby patients received one of these:
• A topical NSAID and a topical corticosteroid
• A topical NSAID and a topical corticosteroid, and a sub-conjunctival injection of 40mg triamcinolone
• A topical NSAID and a topical corticosteroid, and an intravitreal injection of 1.25mg bevacizumab
• A topical NSAID and a topical corticosteroid, and a sub-conjunctival injection of 40mg triamcinolone and an intravitreal injection of 1.25mg bevacizumab

ENDPOINTS

The primary endpoint for the study is the change in central subfield mean thickness (CSMT) in the 1.0mm area as compared to baseline within the first six weeks. The secondary endpoint is the occurrence of postoperative CSME within three months postoperatively. Additional endpoints include the mean BCVA in logMAR at six weeks and three months postoperatively; optical coherence tomography (OCT), average retinal thickness measured in the central macular subfield (1mm), the inner circle (3mm), the outer circle (6mm), and the macular volume at six weeks and three months postoperatively; and intraocular pressure at six weeks and three months postoperatively.

The study will also investigate health-related and vision-related quality of life at three months postoperatively as compared to baseline, using the Health Utilities Index Mark 3 (HUI3) and National Eye Institute Visual Functioning Questionnaire-25 (NEI VFQ-25) questionnaires. These will be used to determine the cost-effectiveness of the treatments in non-diabetic and diabetic patients.

HIGH INCIDENCE

It is well established that the incidence of postoperative CSME in diabetic patients is higher compared to healthy people, and this high incidence among diabetics can occur despite preventive measures being taken in accordance with standard of care. As 16 per cent of cataract surgery patients also have diabetes, this represents a significant part of the total postoperative CME cases and may be estimated to be approximately 50 per cent of all postoperative CME patients. The occurrence and impact of postoperative CME in non-diabetics and diabetics strongly affect the outcome of cataract surgery and is a common problem to all cataract surgeons.

While the society looks forward to learning the full results of the PREMED trial, new clinical research studies, supported by the ESCRS, were launched in June and July of this year. The most recent recipients of the ESCRS Clinical Research Awards initiated three clinical research projects in Coimbra, Leiden and Vienna.

At the University of Coimbra, Portugal, Dr Joaquim Murta is investigating neuroplasticity and neuroadaptation in patients following cataract and refractive surgery, while at the Leiden University Medical Centre in The Netherlands, Dr Jan-Willem Beenakker is currently assessing the potential for virtual refractive surgery modelling in the prevention of negative dysphotopsia. Finally, at Austria’s Vienna Institute for Research in Ocular Surgery, Hanusch Hospital, Dr Oliver Findl has begun clinical studies investigating the influence of posterior vitreous detachment on retinal detachment after lens surgery in myopic eyes.

SIGNIFICANT FUNDING

The ESCRS has now successfully led and managed significant funding and resources in the execution of independent clinical research across several EU centres. The society will aim to announce the winner of its next funding round at the annual ESCRS Winter Meeting in February 2017.

Commenting on the significance of the awards for clinician-led research, Dr Nuijts told EuroTimes: “We owe many thanks to the ESCRS, including many members of the ESCRS Board and Research Committee, for the continuing support of our research. The financial and organisational support of the society has enabled us to conduct the PREMED multicentre pharmacological trial, which would not have been possible across 13 European study centres without the backing of the ESCRS. I would encourage any clinician to consider applying to the annual ESCRS Clinical Research Awards for funding, especially given the broad range of topics and clinically relevant problems that have not yet been adequately solved.”

Rudy Nuijts: rudy.nuijts@mumc.nl