Plain English Summary
Background and study aims
Age-related macular degeneration (AMD) is the most common cause of vision loss in people over 50. It involves the gradual damage to a part of the eye called the macula. The macula is a tiny area at the centre of the retina (the layer at the back of the eye which is sensitive to light), which is responsible for central vision (seeing what is directly ahead). Over time, the damage to the macula can lead to central vision becoming distorted or blurry, eventually causing a blank patch in the centre of your vision. In most cases, AMD is caused by fatty-protein deposits called drusen collecting under the retina (dry AMD) over a long period of time; currently there is no cure or effective treatment for this type however. About 10% of people suffering from AMD have what is known as wet AMD (or neovascular AMD). In wet AMD, the macula becomes damaged and new blood vessels start to grow behind the retina. These blood vessels are generally very weak and prone to leakage, causing the macula to swell and vision to deteriorate very quickly. Aflibercept is a drug treatment known as an anti-VEGF (anti-vascular endothelial growth factor). By injecting it directly into the eye, it works by preventing the weak, leaky blood vessels from growing (by blocking the action of the protein responsible). Currently, the recommended dose is 2mg once every eight weeks after the loading dose (initial large dose of a medicine used to ensure quick benefits), however more research is needed to find out if this is the most appropriate dose for everyone. The aim of this study is to compare the effects of standard treatment to a treat and extend regime, which uses the initial phases of a regimen to find the best dosing regimen for an individual patient.
Who can participate?
Adults over 50 suffering from bad eyesight due to wet AMD.
What does the study involve?
Participants are randomly allocated to one of two groups. Participants in both groups receive an initial three 2mg doses of aflibercept, given by intravitreal injection (an injection into the eye), spaced four weeks apart. Following this, for participants in the first group, the interval between treatments is extended to once every 8 weeks for the first year of treatment. In the second year of treatment, the treating physician can extend the intervals between treatments at their discretion. For participants in the second group, the treating physician is able to extend the treatment intervals at their discretion until the most appropriate dosing regimen for each individual participant is found. At the end of the study, the potential benefits of each dosing method are compared, in order to find the best way to conduct a larger study in the future.
What are the possible benefits and risks of participating?
Not provided at time of registration
Where is the study run from?
York Hospital (UK)
When is the study starting and how long is it expected to run for?
December 2015 to June 2015
Who is funding the study?
Bayer Health Centre (UK)
Who is the main contact?
Ms Tracey Dorey
Treating neovascular age-related Macular degeneration with Aflibercept: a pilot 24 month, multi-centre randomized controlled trial comparing standard care with an individualised Treat and Extend regimen
The aim of this study is to compare standard care with an individualised treat and extend regimen of aflibercept in the treatment of neovascular age-related macular degeneration.
Yorkshire & The Humber - Leeds West Research Ethics Committee, 20/08/2015, ref: 15/YH/0286
Randomised; Interventional; Design type: Treatment
Primary study design
Secondary study design
Randomised controlled trial
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Topic: Ophthalmology; Subtopic: Eye (all Subtopics); Disease: Ophthalmology
Participants are randomly allocated to one of two groups. Both groups will receive intravitreal injections of aflibercept 2mg.
Control group: Participants receive initial 3 doses of monthly aflibercept injections followed by 8 weekly treatments for the first year with an opportunity to extend the treatment intervals in the second year of treatment at the discretion of the treating physician.
Intervention group: Participants receive an initial 3 doses of monthly aflibercept followed by extension of treatment intervals at the discretion of the treatment physician until an interval appropriate for the individual is found. This has the potential to allow a minimum number of visits, on each of which a treatment is administered, whilst maintaining an acceptable efficacy.
Primary outcome measures
To evaluate the feasibility aspects of the study under these headings i.e. process, resources, management and scientific content.
Secondary outcome measures
Not provided at time of registration.
Overall trial start date
Overall trial end date
Participant inclusion criteria
1. Aged 50 years or above
2. Able to provide written, informed consent to the study
3. Able and willing to attend for hospital visits at the frequency required
4. Visual impairment predominantly due to neovascular age–related macular degeneration (AMD).
5. Active, treatment naive, angiographically active choroidal neovascular membrane in the study eye secondary to neovascular AMD with any part of the lesion or its sequelae (e.g. sub retinal fluid, intra retinal fluid, haemorrhage, pigment epithelial detachment, sub retinal pigment epithelium(RPE) fluid) in a sub foveal location
6. Visual acuity of 7824 ETDRS letters at screening and baseline in the study eye.
7. If both eyes are eligible at baseline, the worst seeing eye will be included in the study although the final decision will rest with the investigator. Any deviation from entering the worst seeing eye into the study will be explained and documented in the patient notes and the CRF. The choice of eye selected for inclusion into the study will be determined and documented before the patient is randomised. A patient who has both eyes that may be eligible may therefore undergo a different treatment regimen in each eye, however they will be treated with aflibercept in both eyes. Hospital visits will be co-ordinated to minimise the number of attendances required and therefore the inconvenience for the patient.
Target number of participants
Planned Sample Size: 40; UK Sample Size: 40; Description: Treatment naïve neovascular AMD patients will be recruited into the study from the Ophthalmology departments of the participating NHS hospitals of York, Hull, Leeds, Bradford and Harrogate. The sample size is 40 and the recruitment period is expected to last approximately 6 months.
Participant exclusion criteria
1. Inability to comply with the study or follow up procedures
2. Pregnant or lactating women
3. Women of child bearing potential unless they are using effective methods of contraception (total abstinence, female or male sterilization, barrier contraception, intrauterine device, oral or injectable hormonal methods of contraception)
4. Previous treatment for choroidal neovascularisation in the study eye
5. Fibrosis consisting of more than 50% of the lesion or involving the centre of the fovea
6. Coexisting pathology within 0.5 disc diameters of the fovea that could prevent an improvement in visual acuity in the opinion of the investigator (e.g. macular hole, dense epi - retinal membrane)
7. Cataract (causing significant visual impairment), aphakia, vitreous haemorrhage, retinal detachment, proliferative retinopathy or CNV due to any cause other than AMD at screening and baseline
8. Known allergy to aflibercept or fluorescein
9. History of cerebrovascular accident, transient ischemic attack or myocardial infarction within 3 months of the screening visit
10. Any type of systemic disease or treatment that may affect or expect to affect the clinical status of the patient to a significant degree
11. Blood pressure of >160mmHg systolic or >100mmHg diastolic at screening or baseline
12. Any active periocular infection or inflammation at screening or baseline
13. Uncontrolled glaucoma (30mmHg) at screening or baseline
14. Neovascularisation of the iris at screening or baseline
15. Treatment with any anti angiogenic drugs to either eye within 3 months of baseline
16. Nd-YAG laser capsulotomy within the last 2 months or expected within 6 months of baseline in the affected eye
17. Use of other investigational drugs within 30 days
18. Use of systemic anti –vascular endothelial growth factor agents within 3 months prior to baseline
19. Use of systemic corticosteroids for at least 30 consecutive days within the 3 months prior to baseline
20. Current or planned medications known to be toxic to the lens, retina or optic nerve e.g. hydroxychloroquine, desferoxamine, tamoxifen or ethambutol
Recruitment start date
Recruitment end date
Countries of recruitment
Trial participating centre
Bayer Health Centre
Funding Body Type
Funding Body Subtype
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Results - basic reporting