Early Vitrectomy and Intravitreal Antibiotics for post-operative exogenous eNdophthalmitis (EVIAN) study: A feasibility multicentre randomised controlled trial

Research question To explore the feasibility and acceptability of carrying out a randomised clinical trial of early surgical treatment compared to standard treatment for endophthalmitis.

Background Primary Objectives: To assess the recruitment and retention rates of participants,willingness of surgeons to refer patients into the study,and willingness of participants to be randomised.

Secondary objectives: To report mean (SD) visual acuity gain from randomisation to 6 months after randomisation as measured using an ETDRS chart at a starting distance of 4 metres in patients treated with early vitrectomy and with standard treatment, and to report the mean difference with 95 % confidence intervals.

To assess the safety of early vitrectomy plus intravitreal antibiotics versus standard of care. Methods This is a multicentre,national clinical trial with 1:1 randomisation and control group. Follow-up period:6 months.

Ophthalmic Entry Criteria: Symptomatic visual loss attributable to newly-diagnosed postoperative,exogenous endophthalmitis.

Best corrected vision worse than 35 ETDRS letters in the study eye We will recruit 70 patients: 35 patients allocated to each study arm.

We estimate our expected 70% recruitment rate (95%CI:60-80) will be achieved if 105 eligible patients with acute endophthalmitis are approached.

Twenty UK sites have confirmed participation,committing total of 250 endophthalmitis participants over 21-month recruitment period.

Timelines for delivery (start adjusted/delayed due to Covid-19 pandemic) Start:March 1st 2021 End:March 1st 2024 Months 1-6: Staff recruitment/support,document development,obtaining regulatory approvals (ethics,R&D approvals),setting up trial management,randomisation systems,trial databases,and constituting trial management group (TMG).

Months 7-27: Site initiation and training planned for months 4-12.

Recruitment of trial participants will run between months 7-27 lasting 21 months,with trial intervention and follow-up assessments completed within timelines. Data entry/data cleaning will be a continuous process. Months 27-30: Final follow-up assessments;final data entry;data cleaning, and database lock.

Final trial steering committee/TMG meetings.

Months 31-36: Data analysis and report writing;Dissemination of trial report Anticipated Impact and Dissemination Impact The role of early vitrectomy for any type of exogenous endophthalmitis remains unproven.The absence of evidence for patient treatment has led to lack of consensus among clinicians with unacceptably wide variations in clinical practice regarding thresholds of visual acuity to surgically intervene,and timings of vitrectomy operation after initial non-response to antibiotic eye injections.

Study outcomes will enable development of a full clinical trial that will aim to improve evidence-based guidelines,and reduce the socioeconomic burden and NHS management costs provided that feasibility is shown and a promising signal of efficacy.

Dissemination We aim to publish study results in peer-reviewed journals and present results at national/ international clinical meetings (in particular,Royal College of Ophthalmologists,European Society of Retina Specialists,BEAVRS).One patient co-applicant will co-present study findings alongside principal investigators at a UK meeting.

The patient advisory group (PAG) will create a lay Results summary for research participants,and assist with results disseminating to non-professional audiences (Moorfields/BRC websites) and Moorfields Patient Involvement Days.The Royal National Institute of Blind People (RNIB) have agreed to webpost recruitment calls, and disseminate trial results on RNIB website/networks to promote uptake by NHS users.Results disseminated to trial centres for discussion at local and regional clinical governance meetings.