Markedly Lower Rates of Age-Related Macular Degeneration in Malta Compared to European Countries: Results from The Malta Eye Study, Indicating Possible Divergent Genetic Ancestry?

David Agius,1,2 Julian J Mamo,3 Neville Calleja,3 Daniel Cassar,2 Xeniya Marku,2 Maria Christina Nappa,4 Michaela Zammit,4 Maria Elena Pace,5 Francis Carbonaro1,2,6 1Department of Surgery, University of Malta, Msida, Malta; 2Department of Ophthalmology, Mater Dei Hospital, Msida, Malta; 3Department of Public Health, University of Malta, Msida, Malta; 4Department of Medicine, Mater Dei Hospital, Msida, Malta; 5Medical School, University of Malta, Msida, Malta; 6Department of Twin Research, King’s College, London, UKCorrespondence: David Agius, Ophthalmology Outpatients, Mater Dei Hospital, Triq id-Donaturi tad-Demm, Msida, MSD 2090, Malta, Email [email protected]: To estimate the prevalence of age-related macular degeneration (ARMD) in a nationally representative sample of older adults from Malta, evaluate associations with established risk factors, and compare rates with those reported in other European populations, where substantial variation has been observed.Patients and Methods: A population-based cross-sectional study was conducted involving 1794 participants aged 50– 80 years from Malta (1% of the represented population), recruited as part of The Malta Eye Study. Standardized ophthalmic examinations were performed, including retinal imaging graded for ARMD according to Age-Related Eye Disease Study criteria and optical coherence tomography scans. Data on demographics, medical history, behavioural risk factors, and ocular characteristics were collected via structured questionnaires. Associations were assessed using multivariable logistic regression. DNA samples were also collected for future genetic analyses.Results: The overall prevalence of ARMD was 6.5% (95% CI 5.4– 7.8%), with early ARMD accounting for 5.6% (95% CI 4.6– 6.7%) and late ARMD for 0.4% (95% CI 0.2– 0.8%). Multivariate analysis showed that ARMD prevalence increased significantly with age (OR per year 1.08; 95% CI 1.05– 1.11, p< 0.001) and in the male sex (OR 1.57; 95% CI 1.01– 2.44, p=0.043). The other traditional ARMD risk factors did not show significant associations in this cohort. Compared to other European populations, ARMD prevalence was notably lower.Conclusion: This study reports a relatively low prevalence of ARMD compared to other European settings, with age and male sex emerging as the only significant risk factors. The absence of association with other traditional risk factors may reflect underlying genetic differences or distinct gene–environment interactions. As DNA samples were collected, further investigation incorporating genetic data is warranted to better understand ARMD susceptibility in this population.Plain Language Summary: This study looked at how common age-related macular degeneration (ARMD) is in Malta and what factors might increase the chances of developing it.Why was this study done?ARMD is a leading cause of vision loss in older adults across Europe, where many studies report high rates of disease. Malta has some of the highest European rates of risk factors linked to ARMD, such as obesity and ultraviolet (UV) exposure. Smoking rates in Malta are similar to other European countries. Despite this, little is known about prevalence of ARMD in Malta.What did the researchers do and find?We examined a large, representative group of adults aged 50 and older living in Malta. We checked for signs of ARMD and collected information about their age, gender, medical history, and lifestyle.We found that 6.5% of people had ARMD, which is lower than reported in other European countries.Only older age and being male were clearly linked to ARMD.Other factors often thought to increase ARMD risk, like smoking, diabetes, high blood pressure, or obesity, were not strongly linked in our study.What do these results mean?Lower ARMD rates in Malta may be due to unique genetic or environmental factors. We collected DNA samples to support future research. Our findings suggest ARMD risk varies more between populations than previously thought, highlighting the need for further study in Mediterranean countries.Keywords: macular degeneration, prevalence, risk factors, ageing, population-based study, gene–environment interaction