Clinical trial NCT03490318: Effectiveness of Multimodal Imaging for the Evaluation of Retinal Oedema And New vesseLs in Diabetic Retinopathy
Official title: Effectiveness of Multimodal Imaging for the Evaluation of Retinal Oedema And New vesseLs in Diabetic Retinopathy
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Proliferative Diabetic Retinopathy
Diabetic Macular Edema
Lead sponsor: Belfast Health and Social Care Trust
Sponsor class: OTHER
Collaborators: name: National Institute for Health Research, United Kingdom
First posted: 2018-04-06
Enrollment: 401
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Adults with type 1 or type 2 diabetes with previously successfully treated DMO and/or PDR and in whom, at the time of enrolment in the study, DMO and/or PDR may be active or inactive.

Brief summary: Given the high number of people with DMO and PDR, the need for patients to be seen at short follow-up intervals, the need for frequent treatments and the requirement for long-term follow-up, there is a very large workload in Hospital Eye Services related to DMO/PDR which is making it difficult for the NHS to cope with the demand, in particular, due to shortage of ophthalmologists. This is only expected to get worse given the increasing prevalence of DM. Identifying new ways of increasing the NHS capacity and efficiency without compromising the quality of care would greatly benefit the NHS.

The purpose of this study is to determine whether successfully treated patients with DMO and PDR could be followed up without a face-to-face examination by an ophthalmologist. EMERALD will evaluate a new care pathway which will include multimodal retinal imaging and separate image assessment by trained ophthalmic graders. This new pathway will be compared to the current standard care pathway: for DMO: ophthalmologist evaluating patients in clinic by slit-lamp biomicroscopy and with access to OCT images; for PDR ophthalmologists evaluating patients in clinic by slit-lamp biomicroscopy. EMERALD will compare how accurate the new pathway is at determining which patients have active or inactive disease. The costs and acceptability of current and new models of care will also be compared.

Detailed description: 1. 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.
2. 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.
3. Study Objectives

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

1. 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.
2. Assess acceptability of the new surveillance pathway.
3. Determine the proportion of patients requiring subsequent full clinical assessment by an ophthalmologist under the new pathway.
4. Determine the proportion of patients unable to undergo imaging tests, with images of inadequate quality and indeterminate findings under the new pathway.
5. Establish relative cost-effectiveness of the new surveillance pathway.

4. 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.

  5. 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.

6. 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.

Eligibility criteria: 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

Primary outcomes:
measure: Sensitivity of the new pathway (ophthalmic grader pathway) in detecting active DMO/PDR, using the standard care pathway as the reference standard.
timeFrame: 30 months
Secondary outcomes:
measure: Specificity, concordance (agreement) between new pathway (ophthalmic grader pathway) and the standard care pathway, positive and negative likelihood ratios
timeFrame: 30 months
measure: Cost-effectiveness
timeFrame: 30 months
measure: Acceptability
timeFrame: 30 months
measure: Proportion of patients requiring subsequent full clinical assessment
timeFrame: 30 months
measure: Proportions of patients unable to undergo imaging, with inadequate quality images or indeterminate findings.
timeFrame: 30 months
Other outcomes:
Locations:
city: Middlesbrough
country: United Kingdom
facility: James Cook University Hopsital
state: North Yorkshire
city: Dunfermline
country: United Kingdom
facility: Queen Margaret Hospital
state: Scotland
city: Belfast
country: United Kingdom
facility: Royal Victoria Hospital
city: Bradford
country: United Kingdom
facility: Bradford Royal Infirmary
city: Bristol
country: United Kingdom
facility: Bristol Eye Hospital
city: Frimley
country: United Kingdom
facility: Frimley Park Hospital
city: Gloucester
country: United Kingdom
facility: Gloucestershire Royal Hospital
city: London
country: United Kingdom
facility: Moorfields eye Hospital
city: London
country: United Kingdom
facility: King's College Hospital
city: Manchester
country: United Kingdom
facility: Manchester Eye Hospital
city: Oxford
country: United Kingdom
facility: Oxford John Radcliffe Hospital
city: Sheffield
country: United Kingdom
facility: Sheffield Eye Hospital
city: Sunderland
country: United Kingdom
facility: City Hopsitals Sunderland
Study officials:
affiliation: Queen's University, Belfast
name: Noemi Lois, PhD, FRCS(Ed). FRCOphth.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Maredza M, Mistry H, Lois N, Aldington S, Waugh N; EMERALD Study Group. Surveillance of people with previously successfully treated diabetic macular oedema and proliferative diabetic retinopathy by trained ophthalmic graders: cost analysis from the EMERALD study. Br J Ophthalmol. 2022 Nov;106(11):1549-1554. doi: 10.1136/bjophthalmol-2021-318816. Epub 2021 Jun 3.
citation: Lois N, Cook J, Wang A, Aldington S, Mistry H, Maredza M, McAuley D, Aslam T, Bailey C, Chong V, Ghanchi F, Scanlon P, Sivaprasad S, Steel D, Styles C, Azuara-Blanco A, Prior L, Waugh N. Multimodal imaging interpreted by graders to detect re-activation of diabetic eye disease in previously treated patients: the EMERALD diagnostic accuracy study. Health Technol Assess. 2021 May;25(32):1-104. doi: 10.3310/hta25320.
citation: Lois N, Cook J, Aldington S, Waugh N, Mistry H, Sones W, McAuley D, Aslam T, Bailey C, Chong V, Ghanchi F, Scanlon P, Sivaprasad S, Steel D, Styles C, McNally C, Rice R, Prior L, Azuara-Blanco A; EMERALD Study Group. Effectiveness of Multimodal imaging for the Evaluation of Retinal oedema And new vesseLs in Diabetic retinopathy (EMERALD). BMJ Open. 2019 Jun 28;9(6):e027795. doi: 10.1136/bmjopen-2018-027795.