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23/166 L-dopa for neovascular (wet) age-related macular degeneration? Can it reduce the need for anti-VEGF injections?


Published: 30 November 2023

Version: 1.0 November 2023

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The aim of the Health Technology Assessment (HTA) Programme is to ensure that high quality research information on the clinical effectiveness, cost-effectiveness and broader impact of healthcare treatments and tests are produced in the most efficient way for those who plan, provide or receive care from NHS and social care services. The commissioned workstream invites applications in response to calls for research on specific questions which have been identified and prioritised for their importance to the NHS, patients and social care.

Research question

Are levodopa (L-dopa) tablets a clinical and cost-effective method for reducing the symptoms of neovascular (wet) age-related macular degeneration (AMD) and reduce the need for anti-VEGF injections?

  • Intervention: Carbidopa-Levodopa Oral Tablets (applicants to define and justify dosage, applicants should address safety issues if having ophthalmologists oversee trial involving a drug they have less experience with).
  • Patient group: Adults over 50 years old with a diagnosis of wet-AMD, exclusion criteria should include patients with a diagnosis of Parkinson’s disease. Applications are encouraged which include recruitment from geographic populations with high disease burden which have been historically underserved by research activity in this field.
  • Setting: Hospital-based care.
  • Control/Comparator: Placebo tablet alongside regular care. 
  • Study design: A randomised controlled trial with both an internal pilot phase to test key trial processes such as recruitment and adherence, and an interim analysis for efficacy. Clear stop/go criteria should be provided to inform progression from pilot to full trial.
    While the study should be designed to evaluate clinical and cost-effectiveness, applicants are expected to incorporate an early interim analysis for efficacy. Applications must also include a component which aims to elucidate any therapeutic mechanism of action of Levodopa. This must be hypothesis-testing (as opposed to hypothesis-generating) and must use patients and samples from the trial only, as described in mechanistic studies, explanation and examples for the MRC-NIHR Efficacy and Mechanism Evaluation (EME) Programme.
  • Important outcomes:
    • Visual acuity
    • frequency of anti-VGEF injections
    • adverse events
    • cost-effectiveness
    • quality of life
  • Other outcomes:
    • Patient acceptability
    • progression of AMD
    • NHS resource use
  • Existing Core Outcomes should be included amongst the list of outcomes unless a good rationale is provided to do otherwise. Applicants are encouraged to report recruitment and findings disaggregated by sex (and other demographic factors where relevant).
  • Minimum duration of follow-up: 6 months.
  • Longer-term follow-up: If appropriate, researchers should consider obtaining consent to allow potential future follow-up through efficient means (such as routine data) as part of a separately funded study.


Age-related macular degeneration (AMD) is a condition of the eye that typically first affects people in their 50s/60s and disrupts vision in the middle of the visual field making everyday activities difficult. In the absence of treatment, vision will progressively get worse and in the case of wet-AMD this worsening can occur rapidly over the course of months or even weeks. Wet-AMD, also known as neovascular AMD, is characterised by the development of new blood vessels in the choroid layer of the eye, leading to bleeding under the retina and retinal scaring. This process driven by vascular endothelial growth factor (VEGF), which is over produced in patients with wet-AMD.

In 2018 it was shown that around 39,800 people develop wet-AMD each year in the UK and while wet-AMD is less common than the alternative dry-AMD it accounts for up to 90% of severe vision loss for those with AMD. The prevalence of wet-AMD is between 1.2% and 6.3% of the UK population. As such wet-AMD is both prevalent in society and the cause of serious impairment to quality of life. Current treatment for wet-AMD involves the use of anti-VEGF medication that stops the growth of new blood vessels and thus mitigates the progression of wet-AMD. Anti-VEGF medication is given via injection into the eye in a process that takes between 5 and 7 minutes. The procedure is done under local anaesthetic to minimise pain and discomfort but the procedure remains disconcerting for many patients and has several risks. The risk of complications mostly arise from the process of injecting into the eye rather than the drug used and include detachment of the retina, increases in pressure within the eye, inflammation/infection of the eye and floaters in the visual field that may last for up to a few days after injection. These injections are required between monthly and once every 3 months.

An alternative treatment option for wet-AMD has been observed through analysis of Parkinson’s patients, where those who received the drug levodopa had a delayed average onset of wet-AMD compared to those patients who did not receive levodopa. This delay is approximately 8 years where the average onset of wet-AMD in those who did receive levodopa was 79.3 years while those that did not was 71.3 years. Levodopa is a widely available drug, typically in the form of carbidopa-levodopa, and taken as an ingestible tablet; the tablet is significantly cheaper than the anti-VEGF injections and the method of administering the treatment is more palatable for patients. Following on from this analysis several clinical trials have found that regular treatment with carbidopa-levodopa leads to improved visual acuity and a decreased need for anti-VEGF injections and that such a treatment was generally well-tolerated by patients.

A repurposing of this widely available medication for the treatment of wet-AMD could provide a more cost-effective and easier to administer treatment than the current standard of care.

To support the ambitions of NIHR’s Best Research for Best Health: the next chapter, we strongly encourage the inclusion of nurses, midwives and allied health professionals within well-developed research teams responding to this call, to increase the building of research activity, capacity and capability across these professions. Depending on the level of experience, this could be through the role of lead applicant, as joint co-applicant (supported by detailed mentoring plans submitted with the application), or as a co-applicant member of the research team. Through this activity, we aim to support nurses, midwives and allied health professionals to become future research leaders and release the potential to lead, use, deliver and participate in research as a part of their job.

Additional commissioning brief background information

A background document is available that provides further information to support applicants for this call. It is intended to summarise what prompted the call and the existing evidence base, including relevant work from the HTA and wider NIHR research portfolio. It was researched and written on the basis of information from a search of relevant sources and databases, and in consultation with a number of experts in the field. If you would like a copy please email

Making an application

If you would like to apply for this funding opportunity, you can begin your application via the funding opportunity page.

Your application must be submitted online no later than 1pm on 15 May 2024. Applications will be considered by the HTA Funding Committee at its meeting in July 2024.

Guidance notes and supporting information for HTA Programme applications are available.

Shortlisted Stage 1 applicants will be given 8 weeks to submit a Stage 2 application. The Stage 2 application will be considered at the Funding Committee in November 2024.

Applications received electronically after 1pm on the due date will not be considered.

For commissioned topics, the Programme strongly discourages the practice of the same co-applicant joining more than one competing team, other than in unusual circumstances (for example, a lead from a named charity or a unique national expert in a condition).

For such exceptions, each application needs to state the case as to why the same person is included. The shared co-applicant should not divulge application details between teams, and both teams should acknowledge in their application that they are aware of the situation, and that study details have not been shared.

Should you have any queries please contact