Effectiveness of Multimodal Imaging for the Evaluation of Retinal Oedema And New vesseLs in Diabetic Retinopathy

• Research Hypothesis

The hypothesis is that the new form of surveillance for people with stable DMO and/or PDR will be as sensitive as the current standard of care but at a lower cost.

• Study Aim

EMERALD aims to determine the diagnostic performance and cost-effectiveness of a new form of surveillance for people with stable DMO and/or PDR, using the current standard of care as the reference standard.

• Study Objectives

The specific objectives of this study are to evaluate the new surveillance pathway to:

• Quantify and compare the diagnostic accuracy (in terms of sensitivity, specificity, overall agreement, positive and negative likelihood ratios) of the new pathway of surveillance (ophthalmic grader pathway) using the current standard of care pathway as the reference standard. This will be done separately for DMO and PDR.
• Assess acceptability of the new surveillance pathway.
• Determine the proportion of patients requiring subsequent full clinical assessment by an ophthalmologist under the new pathway.
• Determine the proportion of patients unable to undergo imaging tests, with images of inadequate quality and indeterminate findings under the new pathway.
• Establish relative cost-effectiveness of the new surveillance pathway.

• Outcome measures

4.1 Primary outcome

The primary outcome measure is:

• Sensitivity of the new pathway (ophthalmic grader pathway) in detecting active DMO/PDR, using the standard care pathway as the reference standard.

4.2 Secondary outcomes

There are a number of secondary outcomes which will be measured and include:

• Specificity, concordance (agreement) between new pathway (ophthalmic grader pathway) and the standard care pathway, positive and negative likelihood ratios
• Cost-effectiveness
• Acceptability
• Proportion of patients requiring subsequent full clinical assessment
• Proportions of patients unable to undergo imaging, with inadequate quality images or indeterminate findings.

• STUDY DESIGN

5.1 Study Design

EMERALD is a prospective, cross-sectional diagnostic study of patients with diabetic retinopathy and DMO or PDR (or both) who had been previously successfully treated and who, at the time of enrolment in the study, may have active or inactive disease (both are required to evaluate the diagnostic performance of the new pathway).

Specifically, EMERALD will have a case-referent cross-sectional diagnostic study design with both sampling (selection) of patients and data collection carried out prospectively (18). This approach provides both a cost-efficient study design while also having a low risk of bias in terms of diagnostic accuracy (19)

5.2 Study Setting

Specialist Hospital Eye Services (HES) in the UK. All centres involved have extensive experience with the management of patients with diabetic retinopathy, DMO and PDR.

• End of Study

For the purposes of submitting the end of trial notification to the Sponsor and the Research Ethics Committee (REC), the end of trial will be considered to be when the database lock occurs for the final analysis. The trial will be stopped prematurely if:

• Mandated by the REC
• Mandated by the Sponsor (e.g. following recommendations from the Trial Steering Committee (TSC)
• Funding for the trial ceases The REC that originally gave a favourable opinion of the trial will be notified in writing when the trial has been concluded or if it is terminated early.

Inclusion criteria

• Adults (18 years of age or older) with type 1 or 2 diabetes with previously successfully treated DMO and/or PDR in one or both eyes and in whom, at the time of enrolment in the study, DMO and/or PDR may be active or inactive.
• Active DMO will be defined as a central subfield retinal thickness (CRT) of > 300 microns and/or presence of intraretinal/subretinal fluid on spectral domain OCT.
• Inactive DMO will be defined as no intraretinal/subretinal fluid
• Active PDR will be defined by the presence of sub-hyaloid/vitreous haemorrhage and/or active new vessels (new vessels with lack of fibrosis on them)
• Inactive PDR will be defined by the lack of preretinal/vitreous haemorrhage and lack of active new vessels.

Exclusion criteria

• Unable to provide informed consent
• Patients do not read, speak or understand English