Predicting Progression to Advanced Age-Related Macular Degeneration from Clinical, Genetic, and Lifestyle Factors Using Machine Learning

Ajana, Soufiane; Cougnard‐Grégoire, Audrey; Colijn, Johanna M.; Merle, Bénédicte M. J.; Verzijden, Timo; Jong, Paulus T. V. M. de; Hofman, Albert; Vingerling, Johannes R.; Hejblum, Boris P.; Korobelnik, J.-F.; Meester-Smoor, Magda A.; Ueffing, Marius; Jacqmin‐Gadda, Hélène; Klaver, Caroline C W; Delcourt, Cécile

doi:10.1016/j.ophtha.2020.08.031

Cited by 45 publications

(31 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…60 More broadly, a recent machine learning-derived model inclusive of PRS, age, diet, smoking, education, and ocular measurements was found to be highly predictive of incident advanced AMD at 5, 10, and 15 years follow-up (AUC, 0.92; 95% CI, 0.90-0.95 at 10 years). 64 As observed in POAG and many other conditions, the inclusion of additional AMD risk variants in a PRS improves its predictive performance. Ding et al 57 used a PRS comprising 34 AMD-associated SNPs to stratify the risk of progression to late AMD over up to 10.3 (SD 1.7) years.…”

Section: Age-related Macular Degenerationmentioning

confidence: 98%

See 1 more Smart Citation

Risk Stratification and Clinical Utility of Polygenic Risk Scores in Ophthalmology

Qassim

Souzeau

Hollitt

et al. 2021

Trans. Vis. Sci. Tech.

View full text Add to dashboard Cite

Combining genetic and clinical data into an informative risk prediction profile has been an important ambition of personalized medicine. Single-nucleotide polymorphisms are commonly found throughout the genome and account for the majority of interindividual genetic variation. To date, genome-wide association studies have led to the discovery of thousands of disease-associated loci, including across dozens of ophthalmic diseases and traits. However, compared with the clinical utility of identifying rare Mendelian variants, the translation of these results to clinical practice has so far been limited because such variants are found commonly in the population, and individually account for a very small risk. Recently, combining large numbers of these genetic variants into polygenic risk scores (PRS) has shown clinically meaningful risk prediction across several common diseases. PRS have the potential to translate the discovery of common risk variants into individualized disease risk prediction, prognostication, and may enable targeted treatments. In this context, we review the clinical utility of PRS in three common, genetically complex ophthalmic conditions: primary open angle glaucoma, age-related macular degeneration, and myopia.Translational Relevance: Common genetic variants can be used to effectively stratify the risk of disease development and progression and may be used to guide screening, triaging, monitoring, or treatment thresholds.

show abstract

Section: Age-related Macular Degenerationmentioning

confidence: 98%

“… 60 More broadly, a recent machine learning–derived model inclusive of PRS, age, diet, smoking, education, and ocular measurements was found to be highly predictive of incident advanced AMD at 5, 10, and 15 years follow-up (AUC, 0.92; 95% CI, 0.90–0.95 at 10 years). 64 …”

Section: Clinical Utility Of the Prs In Ophthalmologymentioning

confidence: 99%

Risk Stratification and Clinical Utility of Polygenic Risk Scores in Ophthalmology

Qassim

Souzeau

Hollitt

et al. 2021

Trans. Vis. Sci. Tech.

View full text Add to dashboard Cite

show abstract

“…This is, at least in part, due to the fact that AMD is not entirely a genetic disease and indeed, epidemiology studies pinpoint other environmental and lifestyle factors that define the individual risk for disease. In the recent years, a plethora of additional, but just as important, risk factors have been identified, including physiological changes that occur with age and lifestyle, such as smoking and nutrition, which can alter retinal health [3,4]. At the genetic level, beside inflammation associated with gene variants mapping into the complement pathway, turnover of extracellular matrix (ECM) components and lipid handling are all likely to be important in AMD pathogenesis.…”

mentioning

confidence: 99%

The complement system in age-related macular degeneration

Armento

Ueffing

Clark

2021

Cell. Mol. Life Sci.

Self Cite

165

128

View full text Add to dashboard Cite

Age-related macular degeneration (AMD) is a chronic and progressive degenerative disease of the retina, which culminates in blindness and affects mainly the elderly population. AMD pathogenesis and pathophysiology are incredibly complex due to the structural and cellular complexity of the retina, and the variety of risk factors and molecular mechanisms that contribute to disease onset and progression. AMD is driven by a combination of genetic predisposition, natural ageing changes and lifestyle factors, such as smoking or nutritional intake. The mechanism by which these risk factors interact and converge towards AMD are not fully understood and therefore drug discovery is challenging, where no therapeutic attempt has been fully effective thus far. Genetic and molecular studies have identified the complement system as an important player in AMD. Indeed, many of the genetic risk variants cluster in genes of the alternative pathway of the complement system and complement activation products are elevated in AMD patients. Nevertheless, attempts in treating AMD via complement regulators have not yet been successful, suggesting a level of complexity that could not be predicted only from a genetic point of view. In this review, we will explore the role of complement system in AMD development and in the main molecular and cellular features of AMD, including complement activation itself, inflammation, ECM stability, energy metabolism and oxidative stress.

show abstract

“… 3 5 6 Factors including diet and lifestyle have also been investigated. 20 Iron is important for metabolism and phototransduction of the retina. 21 RPE-65, an iron-containing protein expressed in the retinal pigment epithelium, is an enzyme required to catalyse the conversion of all-trans-retinyl ester to 11-cis-retinol, which is an essential step in the visual cycle.…”

Section: Discussionmentioning

confidence: 99%

COVID-19 lockdown measures induced severe iron-deficiency anaemia resulting in central retinal vein occlusion and amenorrhea

et al. 2021

View full text Add to dashboard Cite

During the COVID-19 pandemic, precautionary measures taken by various countries include individual movement restrictions causing significant lifestyle changes and affecting dietary patterns. A 23-year-old woman presented with reduced left eye vision over 1 week and amenorrhea for 4 months. She was diagnosed with severe iron-deficiency anaemia causing central retinal vein occlusion and amenorrhea. During the lockdown, there was a change in her diet with greatly reduced iron intake. Iron is an essential mineral for retina metabolism and function. Iron supplementation was done with improvement in her vision. This case demonstrates the potential impact of lockdown measures on nutrition and health. Education of the general population on maintaining appropriate nutrition during periods of movement restriction is important and that nutritional evaluation and supplementation should be considered in patients with drastic changes in dietary pattern.

show abstract

Predicting Progression to Advanced Age-Related Macular Degeneration from Clinical, Genetic, and Lifestyle Factors Using Machine Learning

Cited by 45 publications

References 50 publications

Risk Stratification and Clinical Utility of Polygenic Risk Scores in Ophthalmology

Risk Stratification and Clinical Utility of Polygenic Risk Scores in Ophthalmology

The complement system in age-related macular degeneration

COVID-19 lockdown measures induced severe iron-deficiency anaemia resulting in central retinal vein occlusion and amenorrhea

Contact Info

Product

Resources

About