The UK clinical eye research strategy: refreshing research priorities for clinical eye research in the UK

,


INTRODUCTION
Ophthalmology is a rapidly growing research area in the UK recruiting on average more than 15,000 patients into clinical research trials annually with most National Health Service (NHS) trusts participating in eye research [1].Ophthalmology is one of the leading areas of novel treatments [1] and in the past few decades we have seen the introduction of novel diagnostic and treatment modalities that have markedly improved outcomes in people with eye diseases.Despite active research within ophthalmology, there are still unanswered questions about prevention, diagnosis, and treatment of eye conditions and sight loss, half of which is presumed avoidable (although the UK lacks nationally-representative population-based prevalence data) [2].Funding for eye research is limited [3], so it is important to identify the unanswered questions of highest clinical importance so that research targeting greatest needs can be well invested for the benefits of patients and public in the future [4]. 1   Vision and Eye Research Institute, School of Medicine, Anglia Ruskin University, Cambridge, UK. 2 Department of Ophthalmology, Cambridge University Hospitals, Cambridge, UK. 3 Imperial College NHS Foundation Trust, London, UK. 4 Centre for Public Health, Queen's University Belfast, Belfast, UK. 5 Research, Cataract and Adnexal Dept, Moorfields Eye Hospital, London, UK. 6 University of Southampton, Southampton, UK. 7 NIHR Moorfields Clinical Research Facility, Moorfields Eye Hospital, London, UK. 8 Dept of Ophthalmology, Oxford Eye Hospital, Oxford University Hospitals NHS Trust, Oxford, UK. 9 Aswan University Hospital, Aswan, Egypt. 10 NIHR Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London, UK. 11 Centre for Optometry & Vision Sciences, School of Biomedical Sciences, Ulster University, Coleraine, Northern Ireland, UK. 12 Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia, Brescia, Italy. 13Macular Society, Andover, UK. 14 Fight for Sight, London, UK. 15 Moorfields Eye Charity, Moorfields Eye Hospital, London, UK. 16 Eye care and living well services, Royal National Institute of Blind people, London, UK. 17 Bradford Teaching Hospitals, Royal Infirmary, Bradford, West Yorkshire, UK. 18 York Hospital, University of York, York, UK. 19 Department of Ophthalmology, London North West University Healthcare NHS Trust, London, UK. 20 Brain Sciences, Imperial College London, London, UK. 21NIHR Clinical Research Network, University of Liverpool, Liverpool, UK. *Lists of authors and their affiliations appear at the end of the paper.Group Information: A list of the members of the NIHR CRN Ophthalmology Specialty Group can be found by accessing this link: https://www.nihr.ac.uk/explore-nihr/specialties/ophthalmology.htm.Group Information: A list of the members of the Executive Group of the UK Clinical Eye Research Strategy can be found by accessing this webpage: https://ukeyeresearchstrategy.ac.uk.✉ email: rb@rupertbourne.co.uk The UK Vision Strategy was developed in 2008 to set the framework to address the issues on visual impairment in society and research was identified as one of the important strategies [4].The Vision 2020 UK Eye Research Group was formed subsequently as part of the Vision 2020 initiative to minimise avoidable visual impairment as well as to reduce the impact of unavoidable sight loss [5].It aimed to set priorities for the research agendas using well-constructed methods by collaboration with the James Lind Alliance (JLA) [4].JLA is a non-profit organisation that has been working in partnership with stakeholders including patients, their representatives, and clinicians to set research priorities in a wide range of conditions since 2004.The JLA Priority Setting Partnerships (PSPs) reflect the views of current NHS service users and clinicians to prioritise funding for research that is of high clinical relevance.
The Sight Loss and Vision PSP was formed in 2012 to launch a project for eye research priority setting in collaboration with the JLA [4].This was overseen by a steering committee made up of diverse backgrounds of patients, clinicians, and the representatives from sight loss organisations and the project was funded by the College of Optometrists, Fight for Sight, National Institute for Health and Care Research (NIHR) Moorfields Biomedical Research Centre, Royal National Institute of Blind People, Royal College of Ophthalmologists, and UK Vision Strategy.In 2013, their Sight Loss and Vision Loss Report published top 10 lists of research priorities across 12 ophthalmology subspecialities following surveys and consultations with more than 2000 ophthalmology stakeholders, supported by the JLA [4].This was the first time in the world that research priorities were set in ophthalmology based on the systematic approach of reaching consensus from service users and providers [5].
However, there is still room for more patient-centred research, especially in those subspecialties that carry high clinical burden in the NHS [1].There is also a growing role of commercial studies in the UK which may affect the paradigm of future eye research in the UK [1].In addition, there have been emerging new eye treatments available in the NHS over the last decades and new models of care designed to make the services more efficient.The Covid-19 pandemic has further introduced some changes to our clinical practice and treatment goals.As such, it is time to revisit the original research priorities to ensure they still reflect current health needs.
The NIHR Clinical Research Network (CRN; which will become the NIHR Research Delivery Network in late 2024) has supported a transformation in the strength of England's research delivery system, promoted the successful delivery of studies and underpinned the dramatic expansion of health research participation.The CRN's Ophthalmology Specialty Group represents Ophthalmology within this network and oversees clinical research into medical and surgical treatments of eye diseases, optometry, visual rehabilitation and other key areas within the broader discipline of vision sciences [6].The CRN's Ophthalmology Specialty Group initiated a UK Clinical Eye Research Strategy in 2020 [7].This strategy started with a major initiative to update the previous James Lind Alliance (JLA) Sight and Vision Loss Priority Setting Partnership (PSP) [4].The results are the subject of this report.

METHODS
In January 2021, a meeting was convened with the original JLA facilitator involved in 2013 to look at exploring a suitable methodology to validate and update the research priorities already identified from this report.We sought a pragmatic and novel approach as an updated PSP methodology did not exist at that time.A two-phase process was agreed.
Phase 1: Twelve ophthalmology research themes/sub-specialties identified from the 2013 Sight and Vison Loss JLA report [4] were allocated to five Clinical Study Groups (CSGs), which cover 9 different subspecialties.The formation of CSGs is an initial output of the UK Clinical Eye Research Strategy, and each is chaired by an ophthalmologist with a strong clinical research record (GS, AAB, JS, SS, SS).Each Chair was tasked with convening a committee of diverse stakeholders to collectively review the top 10 research priorities of each of these themes.The consensus from the five CSG areas was that the majority of JLA research priority questions remained valid as they were generally very broad in scope.When considered appropriate, CSG committees refined some original questions and added others.
Phase 2: An online survey was designed using SurveyMonkey software (SurveyMonkey Inc., San Mateo, California, USA; the online survey's landing page is shown in Appendix 1).The survey went live on 19 April 2021 and closed in February 2023.A formal communication and dissemination strategy (Appendix 2) was agreed with the NIHR which included distribution of the survey link to a wide range of organisations across the UK including the Ophthalmology Specialty Group leads for each region of England and devolved nations.A direct contact person for each organization was established (usually the communications lead) to promote and disseminate the survey.In advance of this, the NIHR worked with the project team to produce a press release with a direct link to the survey.An NIHR press release had a Quick Response (QR) code added as another method to direct respondents to the online survey.Each organization sent the survey to all of its members as well as adding the links on to e-newsletters, direct emails to their members with the survey links above and promoting via their own organization websites and via Twitter (a social media website, now known as X).
National and local charities and professional organisations were involved in its dissemination strategy which aimed to maximise diversity, for example among minority ethnic groups and across all four devolved nations.
Respondents were able to enter anonymized data, in response to questions regarding demographics of the respondents, which included questions regarding age, sex, ethnicity, nation within the UK, and whether respondents were health care professionals, vision researchers, charity support workers or patients and carers.One or more of the nine surveys could be selected for completion by respondents from the following subspecialties: cataract, cornea, childhood-onset disorders, glaucoma, neuro-ophthalmology, optometry, refractive disorders, retinal disease, and uveitis.
Within each of these subspecialties, there were two tasks.The first task presented at least 10 research questions and requested the respondent to indicate which they felt was important.Each research question was also accompanied by a lay explanation.The second task listed only the research questions which the respondent had indicated were important and requested the respondent to rank these questions in a scale 1-10.A freetext option was optional for respondents to add comments.Descriptive statistics were used for the analysis involving frequency distribution, central tendency, and variability of the data set.
The research question most commonly ranked as of highest priority is given in Fig. 2 for each of the nine subspecialties.These and all top 10 research priorities for each of the 9 subspecialty surveys are presented in Tables 1-3.
Highest ranked questions by subspecialty can be summarized as follows: cataract (prevention), cornea (improving microbial keratitis treatment), optometric (impact of integration of ophthalmic primary and secondary care via community optometric care pathways), refractive (factors influencing development and/or progression of refractive error), childhood onset (improving early detection of visual disorders), glaucoma (effective and improved treatments), neuro-ophthalmology (improvements in prevention, diagnosis and treatment of neurodegeneration affecting vision), retina (improving prevention, diagnosis and treatment of dry age-related macular degeneration), uveitis (effective treatments for ocular and orbital inflammatory diseases).Understanding the cause and most effective medical management for thyroid eye disease was also highlighted as an important research priority.

DISCUSSION
Priority Setting Partnerships enable clinicians, patients and carers to work together to identify and prioritise evidence-based uncertainties in particular areas of health and care that could be answered by research.This informs researchers and research funders about priorities so that they can tailor their research making it as meaningful as possible and targeted to those people who most need it while making a wider impact.We have described an iterative process that first established wide stakeholder engagement within each of the subspecialties of Ophthalmology, then reviewed and refined the original 2013 JLA outputs of the PSP [4], and finally disseminated these research questions to a large group of 2240 respondents.The results provide a 'refresh' of the most important research questions for each of these subspecialties of Ophthalmology a decade after the initial PSP.
Comparing this latest work with that of the original PSP, the residence of respondents was very similar, differing by less than 1 percentage point for each of the nations (original PSP respondents: England 89%, Scotland 6%, Wales 4%, Northern Ireland 1%).Average age of the original PSP was 65.7 years which was slightly higher than the average age of 59.3 years in this recent survey.The sex of respondents was relatively similar to the original PSP (males 38%, females 62%) and the proportion of healthcare professional respondents (16% in the original PSP).The total number of respondents was also similar (2220 participated in the original PSP).Ethnicity of respondents was not reported in the original PSP.
Within the refractive error, cataract and glaucoma subspecialties, the top priority research question remained the same in both the original PSP and this recent survey, yet there was variance among other subspecialties in terms of highest ranked questions.The design of the original PSP and this most recent survey is of course different involving different respondents, and the purpose of the recent survey was not to repeat the original PSP but rather to provide an up-to-date perspective on what a wide group of stakeholders judge as most important.Strengths of this study include the large and diverse stakeholder group involved in each of the topic areas in Phase 1 and the large sample that answered the online survey in Phase 2. Additionally, ranking of the research questions in order of importance offers some insight into their relative importance from the perspective of the respondents.Although significant efforts were made to disseminate the survey to as diverse a group as possible, the representativeness of the sample among the patient population is unknown.For example, socioeconomically deprived populations may not be well represented on account of online access and other factors.An additional limitation was the low proportion of non-white respondents.It should also be noted that thyroid eye disease was included among the uveitis section for convenience, yet it is not a uveitic condition.
The next step to be taken by the UK Clinical Eye Research Strategy will be to take the highest priority research questions, and within subspecialties, work up research proposals around these using a Patient/Population/Problem, Intervention/exposure, Comparison/Control, and Outcome measure (PICO) methodology [8, 9].This is a pressing issue as more commissioned calls for clinical Ophthalmology research will increase the amount of research funding directed towards Ophthalmology which currently receives significantly less NIHR research grant funding than other medical specialties.This imbalance is a particular concern given the substantial burden of disability caused by eye disease, which in terms of disability-adjusted life-years, is not commensurate with the funding received.

SUMMARY
What was known before

•
The Sight Loss and Vision Priority Setting Partnership was formed in 2012 to launch a project for eye research priority setting in collaboration with the James Lind Alliance (JLA).

•
In 2013, the Sight Loss and Vision Loss Report published top 10 lists of research priorities across 12 ophthalmology subspecialities following surveys and consultations with more than 2000 ophthalmology stakeholders, supported by the JLA.

•
This was the first time in the world that the research priority was set in ophthalmology based on the systematic approach on reaching consensus from the service users and providers.

Fig. 2
Fig. 2 Most popular high priority question selected by respondents in each survey.

Fig. 1
Fig. 1 Proportion of healthcare practitioners (black bars) and non-healthcare practitioner respondents (grey bars) by gender, age and ethnicity.

Table 3 .
Top 10 research priorities for retina and uveitis topics.

Table 3
EyeEditorial member of Cochrane Library Eyes and Vision Group.PS reports grants from Bayer Ltd 2022-2024.Department has a contract for data analysis of Real-World study of 21 UK centres using Aflibercept for Wet AMD and Zeiss Ltd Aug 22. Financial support for an investigator-initiated trial on "Scanning Confocal Ophthalmoscopy for Diabetic Eye Screening (CONCORDIA)".Jan 23.Paymentof speaker fees and expenses to attend Bayer conference from Bayer Ltd Oct 22. Payment of speaker fee for the Topcon Global Leadership Programme Topcon Ltd Oct 23.Payment of expenses to attend Euretina from Boehringer Ingelheim Nov 22. Payment of expenses to attend Euretina Boehringer Ingelheim.JS reports Support for attending meetings and/or travel from the NIHR for UK CRN Meetings and also is a Uveitis Study Advisory Board Member and receives Support for Educational meetings and Advisory Boards as Medical Consultant for Roche, Bayer and Alimera.VS reports Cosecretary of UK Paediatric Glaucoma Society Unpaid-voluntary.AJT reports grants from AbbVie and Nova Eye Medical; consulting fees from Thea, AbbVie and Alcon, payment or honoraria from Thea, AbbVie and Viatris, Participation on a Data Safety Monitoring Board or Advisory Board on Thea, AbbVie and Alcon, Member of European Glaucoma Society Executive Committee, Editorial Board membership of the journal Eye.DV reports Grants for trials Boerhringer Ingelheim, Alimera, Roche, Gyroscope paid to Institution (Sunderland Eye Infirmary, South Tyneside and Sunderland NHS Foundation Trust), Speaker fees AbbVie, Roche, Bayer, Travel sponsorships AbbVie, Roche, Bayer, Honorary Treasurer North of England Ophthalmological society and Executive on Clinical Research Network-North East and North Cumbria.AAB reports Member of NICE Interventional Procedures Committee and Member of NIHR HTA CET committee.RRAB reports research grants from World Health Organization, Royal National Institute of Blind People, Royal National Institute for Deaf People, Thomas Pocklington Trust, Guide Dogs, Deafblind UK, Macular Society, Fight for Sight, Glaucoma UK, Blind Veterans; paid leadership roles as follows: NIHR Clinical Research Network National Specialty Lead for Ophthalmology, NHS England Ophthalmology Improvement Lead East of England; Support for attending meetings received from World Health Organization and the SEVA Foundation; advisory board participation with Santen; payments and honoraria for lectures/education events from Santen, Thea Pharma, AbbVie; Editorial Board member for the journal Eye; Faculty member European Glaucoma Society & World Glaucoma Association.MB reports being full time employee of The College of Optometrists, and contributions to the work relating to this paper were done during my working hours.The costs for attending meetings were covered by the College.Lead applicant on grant: NIHR eLearning for Professionals Grant Co-applicant on this grant NIHR funding for DIPP Study.Payment from the Association of Optometrists (AOP) Payment for lecture at the Hospital Optometrists Annual Conference in November 2024.Expenses to cover travel to UK meetings from, NIHR UK CRN Meetings, Trustee of Vision North Somerset (VNS Vision North Somerset is a UK Registered Charity).Role as a Trustee is unpaid.CB reports Editorial Board membership of the journal Eye.RC reports Glaucoma UK Board member as Voluntary role.RPG reports a grant from Bayer, Roche and consulting fees from Alimera, Abbvie, Amgen, Apellis, Bayer, Biogen Boehringer Ingelheim, Novartis, Roche.Payment or Honoraria received from Novartis, Apellis, Bayer, Roche, Alimera.Louise Gow reports Employed by RNIB a charity that represents people living with sight loss, Employed by SeeAbility a charity that represents people living with sight loss and learning disabilities, Member of the registration committee for GOC.AM reports Moorfields Eye Charity awarded UK Clinical Eye Research Strategy Group total of £117,194.02for this work.Payment made from institution.PJP reports consulting fees from Bayer UK and Roche UK, Payment or honoraria from Bayer UK and Roche UK, Support for attending meetings and/or travel from Bayer UK and Roche UK, Participation on a Data Safety Monitoring Board or Advisory Board with Bayer UK.JS reports Editorial Board membership of the journal Eye.SS reports grants paid to institution from Bayer, Boehringer Ingleheim and consulting fees from AbbVie, Amgen, Apellis, Bayer, Biogen, Boehringer Ingelheim, Novartis, Eyebiotech, Eyepoint Phamaceuticals, Janssen Pharmaceuticals, Nova Nordisk, Optos, Ocular Therapeutix, Kriya Therapeutics, OcuTerra, Roche, Stealth Biotherapeutics and Sanofi.Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Boehringer Ingleheim, Bayer, Support for attending meetings and/or travel from Roche and Bayer, Participation on a Data Safety Monitoring Board or Advisory Board Bayer, Nova Nordisk, Trustee Macular