Maculopathy is a term describing a group of diseases of the retina which together are the leading cause of blindness in developed countries. Treatment is at best only able to stabilize progression in some individuals and for many there is no effective therapy and irreversible sight loss cannot be avoided.

The most widespread form of macular disease is associated with ageing and is known as age-related maculopathy (ARM).The incidence of this rises with age (1). In the Beaver Dam study in USA (2), severe blinding macular changes were seen in 1%-2% of the overall population aged 50-80yr, with mild signs in 8-10% of people aged 43-54, rising to 14% in people aged 55-64y and 30% in people aged 75 or more. Subsequent population-based studies report similar findings.

A number of factors that we know are associated with ARM such as diet and smoking, are also associated with other diseases of ageing including cardiovascular disease and inflammatory conditions. These conditions are themselves more frequent in people with maculopathy and so the specific causal pathways that lead to ARM are still unclear and we are unsure how best to prevent the condition. By contrast myopic maculopathy (MM) is related mainly just to age and degree of myopia, although raised blood pressure is a risk factor. As myopia is increasing in prevalence across the world, so is the prevalence of MM and it is becoming a leading cause of blindness (3).

Treatment trials involving lifestyle changes such as dietary supplements have yet to show strong results in reducing ARM and there are no known lifestyles thought to protect against MM. It is likely that we have not yet identified either the correct pathways that lead to these diseases or the groups of people who are genetically more or less likely to be helped by lifestyle modifications.

We propose to make use of a unique opportunity - to “piggyback” onto a soon-to-start data collection sweep within the most detailed cohort study in the world- the Avon Longitudinal Study of Parents and Children, (ALSPAC, http://www.bristol.ac.uk/alspac). This sweep will involve 7000 very well-documented adults aged approximately 50-70 years4 who are the parents (the “G0 generation”) of a cohort of children (“G1 generation”) recruited in utero during the early 1990s. Detailed lifestyle and health data relating to these G0 parents are available stretching back 30 years, as well as detailed genetic data. We will collect high quality images of the retina and measurements of the eyes for these participants, to identify those with ARM or MM and we will use all the existing data to investigate the ways in which genetic, lifestyle and medical risk factors may have led to these diseases, over the last 30 years. A session for vision testing is already funded by a grant held by Prof Golding and Dr Northstone and we propose to take the retinal images in this session.

The costs of contacting the participants, bringing them to clinic and examining them, plus the collection of all the previous lifestyle and genetic data are already met and we have requested the costs of the retinal imaging, grading and analysis. There may be the chance to use old equipment to take some basic images showing existing ARM and MM assuming the clinic sweep starts before the grant we have submitted is decided upon. Thus, we will obtain results that will improve our understanding of the antecedents of ARM and MM and therefore potentially how to prevent them, by enhancing the vision data collection that is already planned.

References:
(1) Owen CG, et al; BJO 2012;96:752-756; (2)Emily Chew; Ophthalmology 2020. 127 S120-121 (3) .Baird PN al. Myopia. Nature Reviews Disease Primers. 2020; 6:99 (4) A Fraser et al; Int J Epidemiol 2012: 42 pp97-110: