Anti-vascular Endothelial Growth Factor (Anti-VEGF) Monotherapy vs Anti-VEGF Followed by Subthreshold Micropulse Laser for Treating Severe Diabetic Macular Oedema When the Central Retina Goes <400 Microns

NCT06985706 | Recruiting Phase 3 DMC

• 2 other identifiers: 24014NL-UCISRCTN12693443
• Study Type: interventional
• Target: 264
• Locations: 1 country
• Sites: 22

Brief Summary

The macula is the centre of the retina; it gives central sight, colour and fine detail. People with diabetes may develop diabetic macular oedema (DMO). In DMO, fluid leaks from blood vessels and builds up at the macula, causing sight loss. DMO can be mild or severe; this is determined by measuring, in microns (µm), how thick the macula is. One µm is one-thousandth of a millimetre. People presenting with mild DMO (macula less than 400 µm thick; normally it is around 250 µm but varies with sex and ethnicity) are offered macular laser treatment. Laser works well for these patients. Subthreshold micropulse laser (SML), which does not damage the macula, works as well as standard laser, which produces a burn, and is cost-effective. However, many people present with severe DMO (macula 400 µm or thicker) where the laser does not work well. The standard treatment is eye injections of anti-VEGFs. VEGF stands for vascular endothelial growth factor. VEGF is high in eyes with DMO and causes blood vessel leakage. Anti-VEGFs block VEGF. They are given monthly to begin with, then every 2-3 months for months or years until DMO clears. In many patients DMO comes back after clearing and anti-VEGFs need to be re-started most often monthly initially again. To improve the care of people with severe DMO this study will compare the current standard care (anti-VEGFs alone) with a strategy in which patients begin with an anti-VEGF but switch to SML once the macula is less than 400 µm thick. Patients aged over 18 years with type 1 or type 2 diabetes and severe DMO can participate. They are randomly allocated either anti-VEGFs alone or anti-VEGFs then SML when the macula is less than 400 µm thick.

Conditions

Severe Diabetic Macular Oedema

Keywords

Diabetic macular oedema; anti-VEGF; Subthreshold micropulse laser

Outcome Measures

Primary Outcomes (1)

• Best-Corrected Visual Acuity (BCVA)

  Change in best corrected visual acuity (BCVA) in the study eye from randomisation (baseline) to 104 weeks (24 months) (equivalence margin +/- 5 ETDRS letters)

  104 weeks after randomisation

Secondary Outcomes (14)

• Central Retinal Thickness (CRT) in the study eye

  104 weeks after randomisation

• Health-related and vision-related quality of life

  104 weeks after randomisation

• Safety of procedures

  By 104 weeks after randomisation

• Treatments used in the study eye

  By 104 weeks after randomisation

• "Rescue" treatment in the study eye

  By 104 weeks after randomisation

Study Arms (2)

Subthreshold Micropulse Laser (SML)

ACTIVE COMPARATOR

Procedure: Subthreshold Micropulse Laser (SML)

Anti-VEGF Monotherapy (standard care)

ACTIVE COMPARATOR

Drug: Anti-VEGF Monotherapy (standard care)

Interventions

Subthreshold Micropulse Laser (SML) PROCEDURE

SML will be applied in line with the DAME Guideline and follow the DAME participant pathway.

Subthreshold Micropulse Laser (SML)

Anti-VEGF Monotherapy (standard care) DRUG

Anti-VEGFs including ranibizumab and biosimilars, aflibercept, faricimab, and brolucizumab will be used, as per the standard of care at participating sites. The anti-VEGF should be administered in line with the summary of product characteristics (SmPC).

Anti-VEGF Monotherapy (standard care)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults (\>18 years)
• Diabetes type 1 or type 2
• Presented with severe centre-involving (CI)-DMO (CRT ≥400 μm)
• Within the first year of initiating anti-VEGF therapy but who still have DMO and their CRT is below 400 μm (and it remains, at the time of randomisation) following anti-VEGF therapy in either one eye or both eyes

You may not qualify if:

• Causes of macular oedema other than DMO
• DMO with CRT ≥400 μm
• Receipt of anti-VEGFs before their presentation with severe DMO (previous macular laser treatment for DMO is allowed)
• Use of unlicensed anti-VEGFs (e.g. bevacizumab)
• Inability, for any reason, to attend study visits
• Active proliferative diabetic retinopathy (PDR) (treated and inactive PDR is allowed)
• Use of pioglitazone which cannot be stopped for the duration of the trial
• Cataract surgery or laser pan-retinal photocoagulation (PRP) within the previous 6 weeks
• Currently enrolled in a Clinical Trial of an Investigational Medical Product
• Declined consent for participation

Sponsors & Collaborators

• Belfast Health and Social Care Trust: lead
• Queen's University, Belfast: collaborator

Study Sites (22)

The Royal Hospitals Belfast

Belfast, United Kingdom

RECRUITING

Birmingham and Midland Eye Centre

Birmingham, United Kingdom

NOT YET RECRUITING

Sussex Eye Hospital

Brighton, United Kingdom

NOT YET RECRUITING

Bristol Eye Hospital

Bristol, United Kingdom

NOT YET RECRUITING

Frimley Park Hospital

Camberley, United Kingdom

RECRUITING

Gloucestershire Royal Hospital

Gloucester, United Kingdom

RECRUITING

Hull Royal Infirmary

Hull, United Kingdom

NOT YET RECRUITING

Hinchingbrooke Hospital

Huntingdon, United Kingdom

NOT YET RECRUITING

Royal Liverpool University Hospital

Liverpool, United Kingdom

RECRUITING

Central Middlesex Hospital

London, United Kingdom

RECRUITING

Chelsea and Westminster Hospital

London, United Kingdom

NOT YET RECRUITING

Kings College Hospital

London, United Kingdom

RECRUITING

Moorfields Eye Hospital

London, United Kingdom

RECRUITING

James Cook Hospital

Middlesbrough, United Kingdom

RECRUITING

Royal Gwent Hospital

Newport, United Kingdom

NOT YET RECRUITING

Queen's Medical Centre

Nottingham, United Kingdom

NOT YET RECRUITING

East Surrey Hospital

Redhill, United Kingdom

NOT YET RECRUITING

University Hospital Southampton

Southampton, United Kingdom

NOT YET RECRUITING

Sunderland Eye Hospital

Sunderland, United Kingdom

RECRUITING

Singleton Hospital

Swansea, United Kingdom

NOT YET RECRUITING

Torbay Hospital

Torquay, United Kingdom

NOT YET RECRUITING

Hillingdon Hospital

Uxbridge, United Kingdom

RECRUITING

Related Links

• DAME trial

MeSH Terms

Interventions

Standard of Care

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Officials

• Noemi Lois

  Wellcome-Wolfson Institute for Experimental Medicine, Queen's University Belfast, Belfast, United Kingdom, BT9 7BL

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Mary Guiney

CONTACT

+44 28 96151447; mary.guiney@nictu.hscni.net

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Professor of Ophthalmology and Honorary Consultant Ophthalmologist and Vitreoretinal Surgeon

Model Details: Pragmatic randomised equivalence trial

Study Record Dates

• First Submitted: May 10, 2025
• First Posted: May 22, 2025
• Study Start: May 19, 2025
• Primary Completion (Estimated): November 30, 2028
• Study Completion (Estimated): November 30, 2028
• Last Updated: September 19, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share
• Access Criteria: Following publication of the primary and secondary outcomes and once data has been fully exploited by the DAME research team, there may be scope to conduct additional analyses on the data collected. In such instances formal requests for data will need to be made in writing to the Chief Investigator via the NICTU. If there are requests for data sharing, these will be reviewed on a case-by-case basis by the CI/NICTU with approval by the Sponsor.

Locations

GB (22)