Safety and efficacy of an artificial intelligence-enabled decision tool for treatment decisions in neovascular age-related macular degeneration and an exploration of clinical pathway integration and implementation: protocol for a multi-methods validation study.

INTRODUCTION: Neovascular age-related macular degeneration (nAMD) management is one of the largest single-disease contributors to hospital outpatient appointments. Partial automation of nAMD treatment decisions could reduce demands on clinician time. Established artificial intelligence (AI)-enabled retinal imaging analysis tools, could be applied to this use-case, but are not yet validated for it. A primary qualitative investigation of stakeholder perceptions of such an AI-enabled decision tool is also absent. This multi-methods study aims to establish the safety and efficacy of an AI-enabled decision tool for nAMD treatment decisions and understand where on the clinical pathway it could sit and what factors are likely to influence its implementation. METHODS AND ANALYSIS: Single-centre retrospective imaging and clinical data will be collected from nAMD clinic visits at a National Health Service (NHS) teaching hospital ophthalmology service, including judgements of nAMD disease stability or activity made in real-world consultant-led-care. Dataset size will be set by a power calculation using the first 127 randomly sampled eligible clinic visits. An AI-enabled retinal segmentation tool and a rule-based decision tree will independently analyse imaging data to report nAMD stability or activity for each of these clinic visits. Independently, an external reading centre will receive both clinical and imaging data to generate an enhanced reference standard for each clinic visit. The non-inferiority of the relative negative predictive value of AI-enabled reports on disease activity relative to consultant-led-care judgements will then be tested. In parallel, approximately 40 semi-structured interviews will be conducted with key nAMD service stakeholders, including patients. Transcripts will be coded using a theoretical framework and thematic analysis will follow. ETHICS AND DISSEMINATION: NHS Research Ethics Committee and UK Health Research Authority approvals are in place (21/NW/0138). Informed consent is planned for interview participants only. Written and oral dissemination is planned to public, clinical, academic and commercial stakeholders.

Two week, OCT-based follow-up as guidance for retreatment with ranibizumab for CNV apparently refractory to therapy.

PURPOSE: To assess the value of 2-week optical coherence tomography (OCT) follow-up for re-treatment decision-making in patients receiving monthly ranibizumab injections for choroidal neovascular membrane (CNV), which was apparently refractory to treatment. METHODS: A total of 25 eyes of 25 consecutive patients with refractory CNV were included. Patients were classified as having refractory disease if no visual acuity (VA) change and no change in the pattern of macular fluid was noticed on OCT after at least 3 consecutive monthly injections, excluding the loading doses. Repeat injection was given and reassessment with VA and OCT was undertaken at 2, 4, 8, and 12 weeks. RESULTS: Complete resolution or marked reduction of macular fluid was noted in 19 patients at 2 weeks (responders). In 18 responders, the fluid increased on 4- and persisted on 8- and 12-week follow-ups, so that further injections were given at these time points. In 6 patients, no significant change was noted at 2 weeks (nonresponders). In all of them, VA and OCT were stable on 4-, 8-, and 12-week follow-ups, without further injections. CONCLUSIONS: As some patients are responding for at least part of the month, injections may be worth continuing or possibly more frequent injections, tailored to the individual's response, may need to be considered. Alternative therapies such as aflibercept may also need to be considered. In nonresponding eyes, other cytokines except for vascular endothelial growth factor are probably involved in the pathogenesis or such cases may have structural damage that will not respond to therapy.