Endophthalmitis Post Intravitreal Injections Comparison EPIIC Trial: Pars Plana Vitrectomy Versus Tap and Inject

Background The use of intravitreal injections (IVIs) has been steadily increasing for several years, because this method of drug delivery minimizes systemic exposure and allows for intraocular drug levels not achievable through systemic or topical drug administration. Intravitreal injection (IVI) of agents such as anti-vascular endothelial growth factor (anti-VEGF) or corticosteroids are efficacious for several retinal diseases, including age-related macular degeneration, macular edema due to retinal vein occlusion or diabetic macular edema, and uveitis, among others. But IVIs are not without their risk of complications and the most feared of which is infectious endophthalmitis. Although endophthalmitis´s incidence ranges from 0-0.2% per infection, the cumulative risk for patients under sequential treatment may equate to more than 1% after 2 years of treatment. Endophthalmitis management following IVIs generally consists of a vitreous tap and inject (TAI) and/or a pars plana vitrectomy (PPV) with intravitreal injection of antibiotics. However, there is no consensus on the optimal treatment of IVI-related endophthalmitis. Thus, an established treatment protocol for IVI-related endophthalmitis is warranted to optimize patient outcomes.

Objectives and Innovation The aim of this study is to determine whether PPV or TAI is superior for the treatment of IVI-related endophthalmitis. The primary objective is to compare final visual acuity (VA) between treatment regimens at 12-months post-treatment. Secondary objectives include subgroup analysis between patients of varying VAs and demographic variables, aqueous humor analysis, comparison of complications and/or need for retreatment, and comparison of anatomic outcomes by autofluorescence, optical coherence tomography (OCT), and OCT angiography (OCTA) imaging.

Methods Consenting patients 18 years and older with presumed infectious endophthalmitis after non-steroid intravitreal injections will undergo stratified block randomized into the PPV or TAI intervention group based on their baseline VA in the study eye. Patient demographics will be collected and a standard ocular examination at baseline will be performed.

Randomization Stratified block randomization (block size = 4) will be used to randomize patients into one of the two interventions according to baseline visual acuity in the study eye (worse than or equal to hand motions and counting fingers or worse) A computer-generated block randomization design will be used to create the randomization list, which will be uploaded to the randomization system (RedCap). Once a patient has consented and been enrolled in the study, the local study coordinator will access the randomization system to enter the patient's assigned study ID and visual acuity status. The treatment group assignment will then be displayed by randomization system to the study coordinator who will inform the recruiting physician.

Masking Study personnel involved in visual acuity assessments and imaging will be masked to group assignment.