A stylised 3D illustration of an eye. It is rainbow coloured.

Bench to bedside’ is a staple phrase of translational research. It is a journey from scientific discovery at the laboratory bench through to directly benefiting patients at their bedside. We are proud to support this journey at Moorfields to improve eye healthcare.

Developments in eye research and treatments

A total of 99 therapeutic agents were approved in the US for eye diseases since the year 2000. The majority of these were currently approved drugs but repurposed for eye conditions, while 22% were new drugs and biologics.

What are biologics?

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Biologics, or biological products are isolated from living organisms (human, animal, microorganism), and can also be produced by cutting-edge biotechnologies. Examples include vaccines, gene therapy, stem cells, blood and tissues, and their components. Unlike conventional drugs, which are chemical compounds with known structures, most biologics are complex mixtures that are not fully characterized. Biologics are showing potential to effectively treat a range of conditions that presently have no other treatments available.

The eye is a robust target for testing new drugs and also developing new, personalised therapies such as gene therapy and bioengineered tissue solutions. 

The treatment delivery can be local and targeted using either drops applied to the surface of the eye or injections made directly into the eye. 

These direct applications can minimise systemic effects while potential benefits can be measured in a relatively easy way using standard eye imaging and tests.

Examples of eye treatments

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New drug

  • Pegcetacoplan, brand name Syfovre®, was approved earlier this year in the US for use in patients with advanced stages of age related macular degeneration (AMD) and geographic atrophy.
  • This drug blocks part of immune response called complement.
  • In clinical trials Syfovre slowed the progression and vision loss in dry AMD.

Repurposed drug

  • Bevacizumab, brand name Avastin®, helps slow down vision loss from eye diseases where blood vessels are affected, such as wet AMD and diabetic eye disease.
  • Avastin blocks vascular endothelial growth factor (VEGF), which promotes the growth of abnormal blood vessels in the back of the eye.
  • Avastin is an approved cancer drug but since its first use in eye disease in 2005, it has been shown to be also safe and effective in treating eye conditions.

Gene therapy

  • Luxturna® is a gene therapy that contains the active biologic voretigene neparvovec.
  • It has been approved and successfully used to treat adults and children with loss of vision due to rare inherited retinal dystrophies. Luxturna targets mutations in the gene RPE65, delivering healthy version of the gene to the retina to improve vision.
  • Luxturna was used to treat patients with retinitis pigmentosa due to mutation in RPE65 in July 2015 and Leber’s congenital amaurosis in April 2012.

The four main stages of bench to bedside process

1. Discovery science

Scientists perform experiments to understand how a disease affects us by first looking at the individual cells, the building blocks of our body and tissues. 

They run tests to investigate how these cells work and what happens if certain genes or signalling processes interrupt the function of these cells.

The scientists can then identify specific molecules or pathways that are disrupted, how this affects the function of the cell and whether it could explain how the disease progresses. This process is called target identification and validation.

Scientists and pharmaceutical companies work to develop drugs and biologics that have the potential to restore the normal function of the cell. 

High throughput screening tests many existing and/​or novel therapeutic agents to identify the best and most efficient candidates. 

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    250 out of 5,000+ screened therapeutic agents make it to the preclinical testing stage

2. Preclinical testing

Next, the best therapeutic candidates are refined, optimized, and extensively tested in laboratory cell, tissue and animal models. 

This is to ensure these agents are efficient, safe and do not elicit unwanted side effects in a living organism. 

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    5 out of 250 screened therapeutic agents make it to the clinical trial stage

3. Clinical trials

There are three main types of clinical trials:

Phase I:

The first phase tests the tolerance and safety of the therapeutic agent in a very small group of healthy subjects, usually 20 to 100. 

It aims to determine the therapeutic dose, which is an optimal dose with maximum effect and minimum side effects. It also looks at the most effective delivery method and how the body handles and clears therapeutic agents. 

Phase II:

This phase usually involves 100 to 500 patients, who have the disease in question. 

It aims to adjust and validate the therapeutic dose, check how well the treatment is working and investigate any side effects. 

Phase III:

This trial is conducted on a much larger population of patients with given disease. This is usually a collaborative effort between different hospitals so that hundreds of patients can participate. 

In order to obtain the most reliable and accurate results, the treatments are assigned randomly by a computer and the drug is tested against a sham treatment, called a placebo, or an existing treatment. 

This is called a randomisation process and together with blinding practice, is a foundation pillar of a well-designed clinical trial. 

Blinding means that neither the patients nor clinicians running the trial know which treatment option is given to each patient. This aims to eliminate any biases when assigning the treatments and analysing the results.

4. Regulatory approval

A UK regulatory body, Medicines and Healthcare products Regulatory Agency (MHRA), has an oversight of clinical trials, review the results and, if successful, approve the drug for clinical use. This completes the process of bench to bedside translational research. 

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    – Approximately 15 years from a scientific discovery to regulatory approval for clinical use

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    – Between $800 million to $5 billion

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    Success rate

    – Out of 5,000+ therapeutic agents, on average 1 is approved for clinical use

Bench to bedside at Moorfields

Operational since 2007, and in partnership with NIHR Moorfields Biomedical Research Centre, Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, the NIHR Moorfields Clinical Research Facility (CRF) has pioneered the bench to bedside pipeline for eye treatments to benefit patients. 

CRF has run a number of conventional drug trials, the first gene therapy for an inherited eye disease and the first stem cell therapy to treat AMD. These landmark medical studies are strengthening Moorfields reputation as a centre for translational medicine with aim to attract investment from biotech, device and pharmaceutical industry. 

CRF requires state-of-the-art testing and diagnostic equipment to continue on this path of excellence to develop and evaluate future treatments for eye conditions.

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    Our 2023 Summer Appeal

    This summer we are fundraising for a multi-modal eye scanner Spectralis for the NIHR Clinical Research Facility at Moorfields. This state-of-the-art equipment will help to expand their capacity for clinical research and testing new treatments to benefit patients. 

How is the charity supporting the bench to bedside process?

At Moorfields Eye Charity, it is part of our strategy to be the leading charity for research into eye health. 

Our funding enables innovative research and supports development of new clinical treatments arising from the excellent partnership between the UCL Institute of Ophthalmology and Moorfields Eye Hospital NHS Foundation Trust. 

Modelling disease and looking for new treatments

We are funding a wide range of pre-clinical projects and technologies, which aim to answer questions about the disease mechanisms, underlying genetic and environmental causes, and optimise and validate models of eye diseases. 

The overarching aim of these studies is to identify the next therapeutic targets. 

£12.7 million

our funding for 90 translational and preclinical research projects in the last 3 years

Examples of projects we fund

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Retinoblastoma research: We are supporting Professors Shin-ichi Ohnuma and Mandeep Sagoo to better understand a type of eye cancer, retinoblastoma, using cutting-edge gene sequencing technology. 

Improving gene therapy: In this back to bench project, we are supporting Professor Andrew Dick and Dr Colin Chu to study inflammation as a side effect of gene therapy. 

Fuchs endothelial corneal dystrophy (FECD) research: We are supporting Dr Alice Davidson to study FECD, which is a common, age-related, visually disabling disease, affecting the cornea, the clear outermost part of the eye. 

Modelling AMD: We are supporting Dr Amanda Carr to develop a new culture-based model system to characterise the cells from patients with AMD and directly examine interactions between key cell types involved in the disease. 

Retinas in a dish: We supported Professor Mariya Moosajee in her projects to use patient-derived 3D retinal organoids to model retinal development, cellular composition and maturation. The organoids recapitulate much better than traditional 2D cell cultures, what goes wrong in developing retinas with gene mutations leading to underdeveloped eye conditions such as microphthalmia (abnormally small eyes) and aniridia (lack of iris). 

Zebrafish facility to model eye diseases: We funded state-of-the-art zebrafish facility at the UCL Institute of Ophthalmology, which allows the researchers to house the zebrafish in optimal conditions and study them with the expressed interest to discover novel cell therapies and drug treatments for sight loss conditions. 

Artificial intelligence (AI) and and genetics in glaucoma: We supported Professor Anthony Khawaja to combine the genetic and innovative AI algorithms to create effective prediction and risk stratification tools for glaucoma. 

Stepping up to clinical trial funding

We are proud to support clinical trials testing innovative treatments and new clinical approaches delivered by the excellent Moorfields Eye Hospital. 

£1.3 million

our funding towards clinical trials at Moorfields

3D printed prosthetic eye

In the UK, 70,000 people and over 8 million people worldwide wear a prosthetic eye. 

We are supporting Professor Mandeep Sagoo who is conducting a phase I/II human clinical trial into 3D printed prosthetic eye. 

This pioneering approach aims to offer better fit and improved cosmetic result of the eye prosthesis following eye loss. 

The LiGHT trial extension

Professor Gus Gazzard led the revolutionary LiGHT trial in glaucoma, which showed that 75% patients having laser treatment did not need eye drops to control their eye pressure. 

This led to changes in the National Institute for Health and Care Excellence (NICE) guidelines, which now recommend selective laser trabeculoplasty (SLT) as the first line of treatment for newly diagnosed glaucoma patients. 

We funded monitoring of LiGHT trial participants for further three years, a blood biobank to collect and store blood samples from the LiGHT trial participants and a sister, three-year LiGHT trial in China.

Looking to the future

Clinical trials are the most expensive and time-consuming phase in the new treatment development process. The COVID-19 pandemic has demonstrated that it is feasible to speed up the traditional bench to bedside pathway, while still providing robust evidence to ensure treatments are safe and effective for clinical use. 

UK regulatory body MHRA is now developing a new clinical trials framework with the aim to improve clinical research, benefit patients and make the UK an attractive destination for testing new treatments.

Patient selection is key to the success of clinical trial and can inform the design and prospectively predict which patient groups are likely to benefit from a given treatment.

Moorfields is uniquely positioned as a world renowned specialist eye hospital to assemble thoroughly characterised cohorts of patients with detailed medical histories. This facilitates clinical trials, often testing treatments for rare conditions where patient recruitment can be challenging