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Subspecialties Neuro-ophthalmology, Imaging & Diagnostics, Retina, Basic & Translational Research

From the Eye to the Brain

Estimates suggest that 50 million people were living with dementia in 2017. With the progressive aging of the population, the number is predicted to reach 75 million by 2030. Yet it has been noted that 50 to 80 percent of cases remain undiagnosed in high income-countries. Why? Part of the issue lies with the logistics of making a diagnosis. The gold standard for the most common form of dementia, Alzheimer’s disease, has classically been neuropathological confirmation, post-mortem. Research into newer techniques, such as amyloid positron emission tomography (PET) scanning and cerebrospinal fluid analysis, has supported their utility as potential biomarkers; however, these tests are invasive, expensive, and not pragmatic on a large scale. Could assessment of the neurosensory retina – derived embryologically from the same tissue – be the answer?

“Not only will AlzEye allow the development and validation of traditional statistical models, it will also provide an opportunity to employ cutting-edge AI techniques for the potential for prediction.”

The impact of Alzheimer’s disease on ocular anatomy was first convincingly demonstrated in 1986 when widespread axonal degeneration was found in the optic nerve of eight recently deceased patients with the disease. Though subsequent work showed some evidence of an association between retinal venous diameter and Alzheimer’s disease, true relationships only began to emerge when cross sectional measurement of the retinal nerve fiber layer became possible. In particular, the introduction of OCT and the establishment of large prospective cohort studies that incorporate ocular imaging have demonstrated that people with dementia show thinning of the retinal nerve fiber (RNFL) and ganglion cell-inner plexiform layers. However, thinning of the inner retina is not just a feature of prevalent dementia; rather, it may be predictive of its development. Last September, two large prospective studies – UK Biobank and the Rotterdam Study – revealed that participants with thinner RNFL were significantly more likely to develop cognitive decline and dementia.

However, as noted by the Rotterdam Study team, prediction modeling to identify those individuals at risk of developing dementia has not yet been feasible because of the small number of cases in prospective cohorts, which generally recruit healthy middle-aged volunteers. Moreover, it remains unclear whether these relationships are generalizable to the non-Caucasian population. To address these observations and more, we designed AlzEye: a large-scale record linkage dataset combining all forms of retinal imaging captured over the last ten years at Moorfields Eye Hospital – the largest ophthalmic center in Europe and North America – with the national Hospital Episode Statistics (HES) database. HES is a centralized data warehouse, overseen by the UK’s National Health Service (NHS) Digital arm, which contains details of all hospital admissions, emergency attendances and outpatient appointments in England. In the AlzEye Study, we have linked approximately 2.3 million images of more than 250,000 patients across a diverse population of varying ethnicity and socioeconomic status with diagnostic codes – including dementia. The approach will provide an estimated 5,000 cases of incident dementia. Not only will AlzEye allow the development and validation of traditional statistical models, it will also provide an opportunity to employ cutting-edge artificial intelligence techniques for the potential for prediction. Leveraging the expertise at the Centre for Medical Image Computing of University College London, AlzEye aims to provide a much-needed risk stratification tool to identify people at risk of dementia.

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Moorfields experts share their vision

Subspecialties Retina

Thoroughly Modern Medicine

| Michel Michaelides

Retinal imaging in the era of personalized medicine

Subspecialties Health Economics and Policy

In This Day and Age

| Paul Foster

The challenges of delivering high-quality eye care to an aging population

Subspecialties Glaucoma

Genomics and Glaucoma

| Anthony Khawaja

Advances in genotyping offer great potential in the prediction of ocular disease and treatment outcomes – but also present ethical challenges

Subspecialties Glaucoma

Banking on Data

| Paul Foster

Research groups around the UK are investigating over 100,000 clinical eye images and other data gathered by the UK Biobank

Subspecialties Glaucoma

Pressure to Change

| Michelle Chan

How a cross-sectional study raised the glaucoma referral threshold by 3 mmHg – and reduced referrals by 67 percent

Subspecialties Health Economics and Policy

Glimpses of the Future

| Dawn Sim

In the UK, just 1,500 ophthalmologists manage nine million outpatient appointments each year. This imbalance needs to change

Subspecialties Business and Innovation

Getting Eye Care Down to a Science

| Konstantinos Balaskas

Using digital technologies to streamline care for patients with common retinal conditions

Subspecialties Practice Management

Broad Vision, High Impact

| Aleksandra Jones

Eight Moorfields experts share their vision of big data, AI and personalized medicine in current and future ophthalmic practice

About the Authors
Pearse Keane

A specialist in in applied clinical imaging research, Pearse has a particular interest in optical coherence tomography. Now a consultant at Moorfields Eye Hospital, he previously carried out OCT research with some of the original inventors of the technology at the Doheny Eye Institute. As the first UK ophthalmologist to receive a Clinician Scientist Award from the National Institute of Health Research, his current work focuses on exploring the potential of new technologies and innovations in the treatment of visual impairment and blindness.

Siegfried Wagner

NIHR Academic Clinical Fellow at Moorfields Eye Hospital

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