Early vitrectomy and intravitreal antibiotics for post-operative exogenous endophthalmitis (EVIAN): a randomised control trial of feasibility.

Abstract

Background: Endophthalmitis is a blinding complication following any invasive ocular procedure, and historical treatment guidelines do exist but only for cataract surgery cases. To the best of our knowledge, no randomised controlled trial evidence exists to answer the question of early vitrectomy surgery for the treatment of endophthalmitis following any eye surgery.

Methods: We conducted a multicentre, national prospective randomized controlled clinical (RCT) trial aimed to assess the feasibility of randomizing patients to an early vitrectomy (Arm-A) intervention within 48-96 hours compared to current standard patient care of repeated, immediate intravitreal antibiotic injection (Arm-B) and delayed vitrectomy. There was no blinding or masking conducted in the trial. The key inclusion criteria were: over 18 years of age; confirmed diagnosis of POE at any time-point following an ocular surgery, procedure, or injection; symptomatic visual loss attributable to POE; best corrected visual acuity (VA) worse than 35 ETDRS letters, including counting fingers, hand motions and perception of light vision. The key exclusion criteria were: known adverse reaction to intravitreal antibiotics (amikacin/vancomyin/cephalosporins); optic atrophy in study eye; corneal oedema or haze that would prevent visualisation of fundus to perform vitrectomy surgery. The primary outcome measure was, the feasibility and acceptability of carrying out a RCT of early surgical treatment compared to standard treatment for POE.

Clinicaltrials: gov NCT04522661 (13/08/2020).

Results: Here we show that the study is feasible and meets the primary endpoint whereby 63 participants are randomized at 79% recruitment rate. Median change in VA (IQR) as per-protocol from baseline-to-week 24 was 40 (28-70) letters in Arm-A (n = 24) versus 13 (0-66) letters in Arm-B (n = 25); corresponding to a between-group difference of 24 letters, adjusted for baseline, in favour of early vitrectomy (p = 0.139). Higher rate of non-serious adverse events observed in Arm-B (68%) compared to Arm-A (47%), with higher incidence of retinal detachment 8 cases (24%) in Arm-B versus 2 cases in Arm-A (6.7%).

Conclusions: The EVIAN trial meets the primary endpoint demonstrating feasibility in conducting a trial to randomize the target population at multiple eye centres. Although not statistically significant, the effect on VA change indicates a potential meaningful benefit of vitrectomy compared to standard of care treatment, which can now be tested in a definitive phase 3 clinical trial.