Treatment of retinal detachment in people who have not had cataract surgery and are not very short-sighted with either vitrectomy surgery alone or with vitrectomy and removal of the cataract at the same time

ISRCTN	ISRCTN13728688
DOI	https://doi.org/10.1186/ISRCTN13728688
IRAS number	338079
Secondary identifying numbers	CPMS 60043

Submission date: 11/04/2025
Registration date: 17/04/2025
Last edited: 17/04/2025

Recruitment status: Recruiting
Overall study status: Ongoing
Condition category: Eye Diseases

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English Summary

Background and study aims
The retina is the layer at the back of the eye that allows us to see. Sometimes, it can detach from the wall of the eye, causing a condition called rhegmatogenous retinal detachment (RRD), which leads to vision loss and requires surgery. The most common surgery for RRD is vitrectomy, but this can lead to complications like cataracts, which worsen over time and need to be removed with another surgery. Cataract surgery involves replacing the cloudy lens with a clear artificial one. Currently, it's unclear whether it's better to perform both surgeries at the same time or separately. The COMBAT study aims to find out which approach is best by comparing the outcomes of patients who have vitrectomy alone versus those who have both surgeries together.

Who can participate?
Adults aged 50 and older who have RRD but are not highly myopic (less than -6 diopters or an axial length of 26.5 mm or less) and have not had previous vitreoretinal surgery. Participants must be scheduled for a pars plana vitrectomy to repair their RRD.

What does the study involve?
Participants will be randomly assigned to one of two groups: one group will have vitrectomy first and, if needed, cataract surgery later; the other group will have both surgeries at the same time. The study will compare their vision, the number of successful retina reattachments, patient satisfaction, complications, and costs.

What are the possible benefits and risks of participating?
The possible benefits include improved vision and a better understanding of the best surgical approach for RRD. However, there are risks associated with any surgery, including complications from vitrectomy and cataract surgery.

Where is the study run from?
Queen's University Belfast (UK)

When is the study starting and how long is it expected to run for?
November 2024 to October 2028.

Who is funding the study?
Queen's University Belfast (UK)

Who is the main contact?
Colette Jackson, Trial Manager, colette.jackson@nictu.hscni.net
Professor Noemi Lois, Chief Investigator, at n.lois@qub.ac.uk

Contact information

Ms Colette Jackson
Public

Northern Ireland Clinical Trials Unit
7 Lennoxvale
Belfast
BT9 5BY
United Kingdom

ORCID ID	0000-0001-7814-0749
Email	colette.jackson@nictu.hscni.net

Prof Noemi Lois
Scientific, Principal Investigator

The Wellcome-Wolfson Institute for Experimental Medicine, Queen’s University Belfast, 97 Lisburn Road
Belfast
BT9 7BL
United Kingdom

ORCID ID	0000-0003-2666-2937
Email	n.lois@qub.ac.uk

Study information

Study design	Interventional randomized controlled trial
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Hospital
Study type	Treatment
Participant information sheet	To follow
Scientific title	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
Study acronym	COMBAT
Study hypothesis	Aim To determine whether, in people with non-highly myopic phakic rhegmatogenous retinal detachment (RRD) (Population), phacovitrectomy (Intervention) is equivalent (equivalence margin +/- 7 Early Treatment Diabetic Retinopathy Study ETDRS letters) to vitrectomy and subsequent cataract surgery (phacoemulsification) if/when needed (Comparator) for improving vision following surgery (primary Outcome) but superior for other (secondary) outcomes (as listed in this protocol) in the 52 weeks (+/- 6 weeks) after surgery. Objectives To determine if, in people presenting with non-highly myopic phakic RRD, phacovitrectomy (i.e. removing the cataract and doing vitrectomy to repair the RRD) is as good or better as doing only the retinal detachment repair with vitrectomy and then, if and when the cataract develops, doing a phaco (i.e. cataract surgery) and to assess post-trial implementation strategies and scalability.
Ethics approval(s)	Approved 25/03/2025, Yorkshire & The Humber - Leeds West Research Ethics Committee (NHSBT Newcastle Blood Donor Centre, Holland Drive, Newcastle-upon-Tyne, NE2 4NQ, United Kingdom; +44 2071048100; leedswest.rec@hra.nhs.uk), ref: 25/YH/0056
Condition	Rhegmatogenous retinal detachment
Intervention	Following consent, participants will be reviewed by the research team, including their surgeon. Previous medical and eye history will be reviewed, and measurements of the eye and baseline data (including 5 questionnaires) will then be collected. Patients will then be seen again at 1, 6, 12, and 52 weeks (+/- 6 weeks) post-surgery for the measurements and baseline data collection. Participation in the study will end following the 52-week visit. Participants will also have the option at their initial study discussion to give consent to be contacted in the future to take part in individual interviews to talk about their opinions and experiences of treatment. The study PPI group gave favorable feedback about the proposed options for the consenting process (written/verbal) for interviews. Participants can receive an audio recording of their consent if they request this. A total of 3 (maximum) individual interviews will be undertaken by the participant. Health care professionals will also be invited to give online consent to take part in an individual/small group discussion to share their views on the barriers and facilitators involved in the implementation of the COMBAT study. Studies within a Trial (SWAT) There will be 2 SWATs embedded in the trial: SWAT A - Will record the proportion in each of the demographic groups who are recruited and retained at each site. We will also collect information over the course of the trial on how often the translated PIL are used and whether people for whom these are used are recruited and retained. SWAT B - Sites who are willing to take part will evaluate whether an EDI-informed PIL increases the recruitment of underserved groups compared to the standard PIL. The exact content of the modified PIL is dependent on qualitative, diverse PPI work to be done during (around) the first year of the COMBAT study. Timeline The total study duration will be 48 months: Months 1-6: Set up activities. Months 7-15: Pilot Phase - Opening site, recruitment, data collection & follow-up, qualitative small discussions/interviews tasks. Months 16-30: Main Study - Opening site, recruitment, data collection & follow-up, qualitative small discussions/interviews tasks. Months 31-42: Follow-up, data cleaning, qualitative small discussions/interviews tasks. Months 43-48: Write-up, reporting, and dissemination.
Intervention type	Procedure/Surgery
Primary outcome measure	Change in Best-Corrected Visual Acuity (BCVA) in the study eye from baseline to 52 weeks (+/- 6 weeks) after surgery (equivalence margin +/- 7 ETDRS letters).
Secondary outcome measures	1. Primary anatomical success is measured using retinal attachment status at 52 weeks (+/- 6 weeks) after one vitrectomy 2. Final anatomical success is measured using retinal attachment status at 52 weeks (+/- 6 weeks) after two or more vitrectomies 3. Intraoperative complications are measured using severity score during surgery 4. Postoperative complications are measured using severity score at 52 weeks (+/- 6 weeks) after surgery 5. Number and type of surgeries performed are measured using surgical records at 52 weeks (+/- 6 weeks) after surgery 6. Refractive error is measured using the difference between aimed and obtained post-operative refraction at 12 weeks after surgery in the phaco-vitrectomy arm and 6-8 weeks post-cataract surgery in the vitrectomy only arm 7. Proportion of participants with BCVA <69 letters is measured using BCVA test at 52 weeks (+/- 6 weeks) after surgery 8. Proportion of participants with BCVA <34 letters is measured using BCVA test at 52 weeks (+/- 6 weeks) after surgery 9. Time to achieve ‘best vision’ is measured using BCVA test at baseline and 52 weeks (+/- 6 weeks) after surgery 10. Change in BCVA from baseline over time is measured using BCVA test at baseline and 52 weeks (+/- 6 weeks) after surgery 11. Health-related quality of life is measured using EuroQol-5 level (EQ-5D-5L) at baseline and 52 weeks (+/- 6 weeks) after surgery 12. Vision-specific quality of life is measured using the National Eye Institute Visual Function Questionnaire-25 (NEI VFQ-25) at baseline and 52 weeks (+/- 6 weeks) after surgery 13. Participant’s experience and acceptability of treatments are measured using questionnaires at 52 weeks (+/- 6 weeks) after surgery 14. Use of health and social care services and non-health care is measured using questionnaires at 52 weeks (+/- 6 weeks) after surgery 15. Safety is measured using AE/SAE reporting at 52 weeks (+/- 6 weeks) after surgery
Overall study start date	01/11/2024
Overall study end date	31/10/2028

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	50 Years
Sex	Both
Target number of participants	Planned Sample Size: 276; UK Sample Size: 276
Participant inclusion criteria	1. Adults ≥50 years of age 2. Non-highly myopic (< -6 diopters; ≤26.5 mm axial length) phakic RRD 3. Naïve to previous vitreoretinal surgery 4. Pars plana vitrectomy is planned to repair their RRD
Participant exclusion criteria	1. Presence of a “formed/established cataract.” A “formed/established cataract” is defined as a cataract that, based on the Age-Related Eye Disease Study (AREDS) Research Group, is graded as nuclear sclerosis of >3 and/or if there is an anterior cortical cataract and/or a subcapsular posterior cataract involving the visual axis. 2. Pseudophakia or aphakia. 3. High myopia (≥ -6 diopters; >26.5 mm axial length). 4. Giant retinal tear (i.e. presence of one or more retinal tears of >3 clock hours in size) 5. Retinal dialysis 6. Inclusion in an investigational drug study 7. Declined consent for participation
Recruitment start date	01/05/2025
Recruitment end date	30/04/2027

Locations

Countries of recruitment

England
Northern Ireland
Scotland
United Kingdom

Study participating centres

Belfast Health and Social Care Trust

Trust Headquarters
A Floor - Belfast City Hospital
Lisburn Road
Belfast
BT9 7AB
United Kingdom

Barts Health NHS Trust

The Royal London Hospital
80 Newark Street
London
E1 2ES
United Kingdom

Bradford Teaching Hospitals NHS Foundation Trust

Bradford Royal Infirmary
Duckworth Lane
Bradford
BD9 6RJ
United Kingdom

Guys and St Thomas' NHS Foundation Trust

249 Westminster Bridge Road
London
SE1 7EH
United Kingdom

Kings College Hospital

Mapother House
De Crespigny Park
Denmark Hill
London
SE5 8AB
United Kingdom

Liverpool University Hospitals NHS Foundation Trust

Royal Liverpool University Hospital
Prescot Street
Liverpool
L7 8XP
United Kingdom

Buckinghamshire Healthcare NHS Trust

Amersham Hospital
Whielden Street
Amersham
HP7 0JD
United Kingdom

County Durham and Darlington NHS Foundation Trust

Darlington Memorial Hospital
Hollyhurst Road
Darlington
DL3 6HX
United Kingdom

Hull University Teaching Hospitals NHS Trust

Hull Royal Infirmary
Anlaby Road
Hull
HU3 2JZ
United Kingdom

Manchester University NHS Foundation Trust

Cobbett House
Oxford Road
Manchester
M13 9WL
United Kingdom

Moorfields Eye Hospital NHS Foundation Trust

162 City Road
London
EC1V 2PD
United Kingdom

Oxford University Hospitals NHS Foundation Trust

John Radcliffe Hospital
Headley Way
Headington
Oxford
OX3 9DU
United Kingdom

Sandwell and West Birmingham Hospitals NHS Trust

City Hospital
Dudley Road
Birmingham
B18 7QH
United Kingdom

Sheffield Teaching Hospitals NHS Foundation Trust

Northern General Hospital
Herries Road
Sheffield
S5 7AU
United Kingdom

South Tees Hospitals NHS Foundation Trust

James Cook University Hospital
Marton Road
Middlesbrough
TS4 3BW
United Kingdom

South Tyneside and Sunderland NHS Foundation Trust

Sunderland Royal Hospital
Kayll Road
Sunderland
SR4 7TP
United Kingdom

Leeds Teaching Hospitals NHS Trust

St. James's University Hospital
Beckett Street
Leeds
LS9 7TF
United Kingdom

The Newcastle upon Tyne Hospitals NHS Foundation Trust

Freeman Hospital
Freeman Road
High Heaton
Newcastle upon Tyne
NE7 7DN
United Kingdom

The Royal Wolverhampton NHS Trust

New Cross Hospital
Wolverhampton Road
Heath Town
Wolverhampton
WV10 0QP
United Kingdom

University Hospital Southampton NHS Foundation Trust

Southampton General Hospital
Tremona Road
Southampton
SO16 6YD
United Kingdom

University Hospitals Bristol and Weston NHS Foundation Trust

Trust Headquarters
Marlborough Street
Bristol
BS1 3NU
United Kingdom

University Hospitals Dorset NHS Foundation Trust

Management Offices
Poole Hospital
Longfleet Road
Poole
BH15 2JB
United Kingdom

University Hospitals of Leicester NHS Trust

Leicester Royal Infirmary
Infirmary Square
Leicester
LE1 5WW
United Kingdom

University Hospitals Sussex NHS Foundation Trust

Worthing Hospital
Lyndhurst Road
Worthing
BN11 2DH
United Kingdom

York and Scarborough Teaching Hospitals NHS Foundation Trust

York Hospital
Wigginton Road
York
YO31 8HE
United Kingdom

University Hospitals Plymouth NHS Trust

Derriford Hospital
Derriford Road
Derriford
Plymouth
PL6 8DH
United Kingdom

Mid and South Essex NHS Foundation Trust

Prittlewell Chase
Westcliff-on-sea
SS0 0RY
United Kingdom

NHS Greater Glasgow and Clyde

J B Russell House
Gartnavel Royal Hospital
1055 Great Western Road Glasgow
Glasgow
G12 0XH
United Kingdom

Queen's University Belfast

Centre for Public Health
Belfast
BT7 1NN
United Kingdom

Royal Berkshire NHS Foundation Trust

Royal Berkshire Hospital
London Road
Reading
RG1 5AN
United Kingdom

Sponsor information

Queen's University Belfast
University/education

University Road
Belfast
BT7 1NN
Northern Ireland
United Kingdom

Phone	+44 2890976462
Email	K.Taylor@qub.ac.uk
Website	https://www.qub.ac.uk
"ROR"	https://ror.org/00hswnk62

Funders

Funder type

University/education

Queen's University Belfast
Private sector organisation / Universities (academic only)

Alternative name(s): QUB
Location: United Kingdom

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	Yes
IPD sharing plan summary	Available on request
Publication and dissemination plan	The study will be used to inform participants and public, clinicians and policy makers of the best options available to treat people who present with phakic, non-highly myopic RRD. The results of COMBAT will be disseminated widely through presentations at national and international ophthalmology meetings and in invited lectures. The results will be presented at participant group meetings. The COMBAT PPI Group will contribute to the dissemination efforts to ensure the results are available to participants, their families, and the public. The research team includes lead clinicians and researchers with contacts across the world. They will use these international contacts to ensure trial results are disseminated widely and incorporated into future guidelines on the management of RRD. COMBAT will be reported in accordance with the CONSORT guideline (43). If necessary, the CONSORT and SPIRIT Extension for RCTs Revised in Extenuating Circumstances (CONSERVE) statement will be applied if extenuating circumstances require major modifications to the trial. The protocol, SAP and HEAP will be made publicly available to ensure transparency in the methods used in the study. In accordance with the open access policies proposed by the NIHR, we plan to publish the clinical findings of the trial as well as a separate paper describing the health economic findings in high quality, high impact, peer reviewed open access journals. Other papers are planned (e.g. to present data on patient experience and acceptability of the treatments, and the results of the SWAT, among others). We will actively promote the findings of the study to journal editors and opinion leaders in ophthalmology to ensure findings are widely disseminated (e.g. through editorials and conference presentations) and are included in future guidelines. The most significant results will be communicated to the wider public through media releases. An ongoing update of the study will be provided on the NICTU website.
IPD sharing plan	Following publication of the primary and secondary outcomes and after data has been fully exploited by the COMBAT research team, there may be scope to conduct additional analyses on the data collected. In such instances, formal requests for data will need to be made in writing to the CI via the NICTU. If there are requests for data sharing, these will be reviewed on a case-by-case basis by the CI and NICTU (Northern Ireland Clinical Trials Unit, 7 Lennoxvale, Belfast) with approval by the Sponsor required before data are shared.

Editorial Notes

11/04/2025: Trial's existence confirmed by the National Institute for Health and Care Research (NIHR) (UK).