Can deep phenotyping using retinal images predict response to intravitreal aflibercept therapy in patients with neovascular age-related macular degeneration?
| ISRCTN | ISRCTN28276860 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN28276860 |
| Secondary identifying numbers | SIVS1045 |
- Submission date
- 27/06/2019
- Registration date
- 27/08/2019
- Last edited
- 17/09/2024
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Eye Diseases
Plain English Summary
Background and study aims
Regular injections of the drug aflibercept into the eye are the most common treatment option for neovascular (wet) age related macular degeneration (AMD) in the UK. Aflibercept treatment typically begins with three injections given at monthly intervals (loading dose), followed by regular review for up to and often beyond 2 years. It is clear that some patients respond to very well after the first three injections, with the retina being completely “dry” (that is without any retinal fluid in the subfoveal area). If the retina is completely dry, it is unlikely additional treatment can improve the visual outcome. In previous studies, it was suggested that these good responders account for about 35-40% of all patients in clinical trials. Recent data suggests that it might be as high as 50% as patients are now presenting earlier to retinal clinics. However, at present, it is impossible to predict the good responders to aflibercept treatment in order to provide patients with better information at the start of treatment. The aim of this study is to use artificial intelligence to evaluate markers of response. The accuracy of artificial intelligence to identify markers of response on optical coherence tomography (OCT) and OCT angiography (OCTA) will be compared to human graders.
Who can participate?
Patients aged 50 to 100 with new onset wet AMD being treated with the loading doses of aflibercept
What does the study involve?
The OCT and OCTA scans done to assess response to aflibercept treatment are collected and analysed by retinal specialists as well as by artificial intelligence.
What are the possible benefits and risks of participating?
The study may not be of benefit to the participant but it will provide better information to retinal specialists for the future management of patients. There is no risk to the participants as these tests are routinely done in the management of patients with AMD having treatment with aflibercept.
Where is the study run from?
Moorfields Eye Hospital (UK)
When is the study starting and how long is it expected to run for?
July 2019 to June 2022 (updated 14/04/2021, previously: December 2021)
Who is funding the study?
Boehringer Ingelheim
Who is the main contact?
Prof. Sobha Sivaprasad
sobha.sivaprasad@nhs.net
Contact information
Scientific
NIHR Moorfields Biomedical Research Centre
Moorfields Eye Hospital & UCL Institute of Ophthalmology
162 City Road
London
EC1V 2PD
United Kingdom
 ORCID ID |
0000-0001-8952-0659 |
|---|---|
| Phone | +44 (0)7817886759 |
| sobha.sivaprasad@nhs.net |
Study information
| Study design | Diagnostic accuracy study |
|---|---|
| Primary study design | Observational |
| Secondary study design | Longitudinal study |
| Study setting(s) | Hospital |
| Study type | Diagnostic |
| Participant information sheet | Not available in web format, please use contact details to request a patient information sheet |
| Scientific title | Can deep phenotyping using retinal images predict response to intravitreal aflibercept therapy in patients with neovascular age-related macular degeneration? |
| Study acronym | PRECISE |
| Study hypothesis | Can artificial intelligence predict treatment response with aflibercept for neovascular age-related macular degeneration better than human graders? |
| Ethics approval(s) | Approved 13/09/2019, London – Stanmore REC (Health Research Authority, Ground Floor, NRES/HRA, Skipton House, SE1 6LH, UK; Email: nrescommittee.london-stanmore@nhs.net), REC Ref: 19/LO/1385 |
| Condition | Wet age-related macular degeneration |
| Intervention | The OCT and OCTA images taken at baseline and various time points until after the third aflibercept injection for wet AMD will be evaluated by retinal specialists and artificial intelligence to develop a prognostic model to define response to treatment. The total duration of observation is up to 20 weeks post first aflibercept injection. Duration of follow-up is also up to a maximum of 20 weeks. |
| Intervention type | Other |
| Primary outcome measure | Diagnostic accuracy of artificial intelligence over human graders in assessing the response of loading phase of intravitreal aflibercept injections for wet age-related macular degeneration |
| Secondary outcome measures | 1. The analyses will be repeated excluding patients who appeared in the training set and the primary validation set 2. Performance of the AI will be evaluated using higher-quality images with no media opacity (eg, cataracts) as noted by professional graders 3. AUC subgroups will be computed stratified by age and sex, smoking or medical history 4. The analysis will be repeated by calculating the AUC, sensitivity, and specificity of the AI and the proportion of concordant and discordant eyes on the external validation datasets, compared with the reference standards |
| Overall study start date | 01/07/2019 |
| Overall study end date | 30/06/2022 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Sex | Both |
| Target number of participants | 3,000 |
| Total final enrolment | 2128 |
| Participant inclusion criteria | Inclusion criteria for both retrospective and prospective parts: 1. Adults who are ≥ 50 years and ≤ 100 years 2. Treatment naïve neovascular AMD at baseline 3. Media clarity, pupillary dilation and patient cooperation for adequate imaging 4. Ability to give informed consent Inclusion criteria for retrospective part only in addition to the above: 1. Have received 3 loading injections of intravitreal aflibercept therapy at monthly intervals as per standard care 2. Review up to 10 weeks after the 3rd loading dose with or without injection at this visit 3. Had Heidelberg OCT at least at baseline and after the loading phase but ideally 4 Heidelberg OCTs for the 4 visits 4. Heidelberg OCTA images if available for baseline and any visit thereafter (2nd, 3rd or 4th visit) provided there is a baseline OCTA (optional criteria) |
| Participant exclusion criteria | 1. Co-existent ocular disease: any other ocular condition that, in the opinion of the investigator, might affect or alter visual acuity during the course of the study 2. Any patient who has opted out of their information being used for research nationally or locally at any site |
| Recruitment start date | 01/12/2019 |
| Recruitment end date | 01/12/2021 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centre
London
EC1V 2PD
United Kingdom
Sponsor information
Hospital/treatment centre
162 City Road
London
EC1V 2PD
England
United Kingdom
| Phone | +44 (0)20 7253 3411 ext 2036 |
|---|---|
| lauren.leitch-devlin@nhs.net | |
"ROR" |
https://ror.org/03tb37539 |
Funders
Funder type
Industry
Private sector organisation / For-profit companies (industry)
- Alternative name(s)
- Boehringer Ingelheim Pharmaceuticals, Inc., Boehringer Ingelheim International GmbH, BI, BIPI
- Location
- United States of America
Results and Publications
| Intention to publish date | 01/12/2022 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Data sharing statement to be made available at a later date |
| Publication and dissemination plan | The protocol will be published after ethics approval. Planned publication of the results in a high-impact peer-reviewed journal. |
| IPD sharing plan | The data sharing plans for the current study are unknown and will be made available at a later date. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol file | version 2.1 | 24/02/2021 | 16/08/2022 | No | No |
| HRA research summary | 28/06/2023 | No | No | ||
| Results article | PRECISE Study Report 1 | 20/04/2023 | 17/07/2023 | Yes | No |
| Results article | PRECISE study report 3: baseline characteristics in patients with and without early residual fluid | 15/12/2023 | 17/09/2024 | Yes | No |
Additional files
Editorial Notes
17/09/2024: Publication reference and total final enrolment added.
17/07/2023: Publication reference added.
16/08/2022: Uploaded protocol (not peer-reviewed) as an additional file.
14/04/2021: The following changes were made to the trial record:
1. The recruitment end date was changed from 01/03/2021 to 01/12/2021.
2. The overall end date was changed from 31/12/2021 to 30/06/2022.
3. The intention to publish date was changed from 01/12/2021 to 01/12/2022.
4. The plain English summary was updated to reflect these changes.
19/11/2019: The following changes were made to the trial record:
1. Ethics approval details added.
2. The recruitment start date was changed from 01/09/2019 to 01/12/2019.
08/07/2019: Trial's existence confirmed by funder.
