COMBAT: Clinical- and cost-effectiveness, safety and acceptability of COMBined phacovitrectomy, versus sequentiAl viTrectomy and cataract surgery, for the management of rhegmatogenous retinal detachment: A Randomised Equivalence Clinical Trial.

Research question: In people with non-highly myopic phakic rhegmatogenous retinal detachment (RRD) (Population) is phacovitrectomy (Intervention) equivalent (equivalence margin +/- 7 letters) or superior to vitrectomy and subsequent phacoemulsification (Comparator)?

Background: In RRD, the retina detaches from the eye wall. As a result, sight is lost. Most RRD are treated with vitrectomy surgery.

A common complication of vitrectomy is cataract, the opacification of the crystalline lens of the eye. Currently, patients presenting with phakic (no previous cataract surgery) non-highly myopic RRD are not routinely offered phacoemulsification (cataract surgery; phaco in short) at the same time as vitrectomy (phacovitrectomy). Following vitrectomy, most (if not all) will develop a cataract requiring phaco.

The COMBAT patient and public involvement (PPI) group voiced that surgery is stressful for patients; if phacovitrectomy were as safe and successful as vitrectomy and subsequent phaco, patients would likely prefer it. Phacovitrectomy may reduce visits/admissions to hospital and costs to patients and NHS.

Aims: To determine clinical and cost-effectiveness, safety and patient experience and acceptability of phacovitrectomy, compared with vitrectomy and subsequent cataract surgery (if/when needed), for non-highly myopic phakic RRD and to set basis for its implementation.

Methods: Design/Setting: Pragmatic, allocation-concealed, single-masked (outcome assessors), multicentre, randomised equivalence trial at 30 UK sites.

Population: Adults 50-years or older with non-highly myopic phakic RRD of any gender, ethnicity, religion, sexual orientation or socioeconomic status. Health technology assessed: Phacovitrectomy. Comparator: Vitrectomy and subsequent phaco (if/when needed) (current standard care). Primary outcome: Change in best-corrected visual acuity (BCVA) from baseline to month 12.

Secondary outcomes (at or by 12 months): Primary and final retinal reattachment (i.e. proportion of eyes with an attached retina after one, or two or more surgeries, respectively); complications; number of surgeries; refractive error; use of health and social care services and non-health care costs; health and visual related quality of life; participant’s preference and experience; proportion of participants with BCVA <69 letters and with <34 letters; time to achieve ‘best vision’; change in BCVA.

Sample size: COMBAT is powered to demonstrate treatment equivalence for the primary outcome. Based on two one-sided t-tests, 2.5% significance level, 15.2-letter standard deviation[13] and an equivalence margin of +/- 7 letters (a difference of 7 or fewer is not considered clinically meaningful)[14,15], 248 participants are required to be 90% sure the 95% confidence interval will exclude a difference in means of more than 7 letters. Allowing for 10% dropout, we will need a minimum of 276 participants.

Timelines: Set-up 6 months(m); recruitment 24m; follow-up 12m; analysis/write-up 6m.

Anticipated impact and dissemination: No patients in the COMBAT PPI group who had phakic RRD were offered phacovitrectomy. COMBAT will provide evidence base to guide care on this regard. Adding a phaco to the vitrectomy adds around 8 minutes surgical time[8] but could save 6000 cataract surgeries or more a year to the NHS. The research team/PPI group will ensure visibility of COMBAT and national/international dissemination of findings.