Title: A Randomised, single masked, non inferiority trial of Femtosecond Laser Assisted vs Manual Phacoemulsification Cataract Surgery for Adults with Visually Significant Cataract: The FACT trial
Funder: Department of Health and Social Care

Abstract: Cataract is one of the leading causes of low vision in the UK. Cataract surgery is the most commonly performed operation by the NHS with over 310,000 procedures in 2011-12 at an approximate cost of £250 million. The current surgical method introduced over 20 years ago uses ultrasound (phacoemulsification) to help remove the cataract. Following surgery, 91% achieve a Snellen visual acuity of 6/12 (the minimum required for driving, 0.30 logMAR) and 46% achieve Snellen 6/6 (0.00 logMAR, 20/20 equivalent in the United States, perceived as normal vision. The overall complication rate for cataract surgery is 7.4%. Complications can affect recovery and some are serious and associated with long term poor outcomes; eg. posterior capsule rupture/ vitreous loss (PCR/VL) that occurs in ~1.9% cases. Of these one third of patients have complaints about their eye & vision 3.5 years after surgery. One in 5 cases need further surgery and there is a 15 times higher risk of retinal detachment within 3 years. The surgical learning curve is associated with complications, with a 3.7 and 1.6 times higher risk of PCR/VL for SHOs and SpRs respectively. Other complications, the majority of which are less serious, may mean a longer operation and delayed healing with additional appointments and eye drops. Patients can be devastated when suffering a complication and due to the importance of vision for daily activities, can find even minor complications very distressing. Laser systems are now available that can make the incisions, open the lens capsule and fragment the cataract in 1 minute, leaving only removal lens fragments and insertion of the lens implant to be done by the surgeon. The potential advantages are broad and include better visual outcomes through greater precision and reproducibility and improved safety. These systems are expensive, however costs may be mitigated by fewer complications, less repeat surgery and better outcomes. DESIGN: Multi-centre randomised controlled trial of laser versus manual phacoemulsification cataract surgery with an internal pilot. SETTING: Secondary care. NHS cataract day surgery units in England including St Ann's Hospital, Tottenham, London TARGET POPULATION: Adults with age related cataract. HEALTH TECHNOLOGY BEING ASSESSED: Intervention: Laser assisted cataract surgery Control: Phacoemulsification cataract surgery (standard care) INCLUSION/ EXCLUSION CRITERIA: Inclusion criteria: Symptomatic age related cataract, one or both eyes. Patients must be sufficiently fluent in English for informed consent and completion of the health state questionnaires. Willing to attend follow-up appointments at 4 and 12 months after cataract surgery. Exclusion criteria: Secondary causes of cataract, previous cataract or glaucoma surgery, unable to give consent or unable to attend follow-up assessment, unable to be positioned for surgery, scheduled to undergo combined surgery eg. cataract and trabeculectomy. These inclusion and exclusion criteria have been kept to a minimum to ensure the trial is representative of clinical practice. MEASUREMENT OF OUTCOMES AND COSTS: All outcomes will be assessed at 4 & 12 months after surgery by a masked hospital Optometrist. The study eye is defined as the 1st eye to undergo cataract surgery. Primary: - Uncorrected distance visual acuity (UDVA) at 4 months after surgery in the study eye (logMAR chart at 4 meters). Secondary - UDVA at 12 months in the study eye. - Corrected distance visual acuity (CDVA) at 4 & 12 months in the study eye. - UDVA, CDVA and complications in the second eye within 4 & 12 months of surgery for patients with bilateral cataracts. - Ocular complications within 4 & 12 months of cataract surgery in the study eye. A complication will be defined as any event that causes unintentional injury to an ocular structure, or requires additional treatment, or has a negative effect on a patient's health or eyesight. - Residual refractive error at 4 and 12 months. - Patient reported outcome measures: Catquest-9SF and Priquest questionnaires at six weeks, 4, 9 and 12 months. - Patient reported outcome measures: EQ-5D-3L+vision bolt-on question (EQ-5DV) at six weeks, 4, 9 and 12 months. - Complications in the study eye (and second eye) at 4 and 12 months. -Within-trial cost-effectiveness analyses at 4 and 12 months and expected cost-effectiveness over patient lifetime. Cost-utility analysis will conform to accepted economic evaluation methods. - Corneal endothelial cell count change (additional safety measure) at 4 & 12 months. SAMPLE SIZE AND ANALYSIS: Non-inferiority design, with non-inferiority margin based on a difference in means of 0.1 logMAR UDVA (5 letters or 1 line of the vision chart) assuming a common standard deviation of 0.32 logMAR (based on RCOphth National Ophthalmic Database outcome data). After accounting for an anticipated 15% loss to follow up, and clustering by surgeon (16 surgeons), 808 patients (404 per arm) are required. TEAM EXPERTISE: The trial will be run by a strong multidisciplinary team comprising Consultant Ophthalmologists with previous cataract clinical trial experience and also a previous trial steering committee chair, a senior statistician with extensive experience of ophthalmology research, a senior statistician with extensive experience of multi-centre trials, trial manager and administrator, health economist, optometrists and a patient and public involvement (PPI) research associate. PPI is integral to our study design, including choice of primary outcomes measure and study management. The trial has been designed and will be run in conjunction with UCL CCTU.

Lay abstract: This is a study comparing 2 different methods of cataract surgery. The current standard method is done by hand using ultrasound to break up the cataract. We want to compare this to a new technique using a laser, which makes automates over half of the surgery, so potentially making it safer, faster and with better outcomes. Background: Cataract surgery is the most commonly performed operation by the NHS with more than 310,000 operations performed in 2011-12. Cataracts are usually related to older age and as our population is ageing, we can expect the number of cataract operations to increase. After cataract surgery in people who have no eye problems other than cataract, 91% cases achieve visual acuity scores of "6/12" and 46% "6/6" Snellen respectively using glasses or equivalent. The Snellen equivalent required for driving is approximately "6/12," and normal vision is perceived as "6/6" ("20/20" equivalent in the United States). Surgery complication rates are 7.4% overall per eye, and about 2% of these are serious with long term implications. While complication rates appear low, patients can be devastated when suffering a complication from surgery and due to the importance of vision for daily activities, can find even relatively minor complications distressing. Description of the intervention: Computer controlled laser systems are now available that can automate over half of the steps in cataract surgery. The potential advantages of laser assisted cataract surgery are that the steps completed by this method can be performed more precisely, more reliably and faster than they can be done by hand. This should translate to better visual outcomes and better patient safety as a result of fewer complications. The use of lasers in eye surgery is not new, and they have been used for surgery on the cornea (the structure at the front of the eye) for over a decade. Why is it important to do this study? Worldwide the conversion to laser cataract surgery is rapid and appears to be accelerating despite no high quality evidence demonstrating its effectiveness, safety or cost effectiveness compared to the current surgical technique that uses ultrasound. There are already NHS trusts tendering for laser cataract surgery units. Proposed study: A 42 month study where 808 patients will be randomly selected so that half have their cataract surgery done using the standard (ultrasound) method, and half have the new laser assisted method (404 patients per study arm). The two types of surgery will be compared by looking at visual acuity, visual satisfaction through questionnaires, complications and health economic measures at 4 & 12 months following first eye cataract surgery. The study will be carried out at 2 sites, the main site is a Community Hospital in North London (St. Ann's Hospital), and a second District General Hospital. We have kept the criteria necessary for patients to take part to a minimum so that those in the study are representative of typical NHS cataract patients. Our research team comprises eye surgeons, experts in the design, running and analysis of clinical trials and patients who have experience of cataract surgery. The study findings will provide high quality evidence to NHS service providers, patients and eye specialists about these two methods of cataract surgery and so help guide any possible introduction of laser cataract surgery in the NHS.

Research activity codes: 6.4 SURGERY
Health categories: EYE