Gizachew T. Belete ^1* Lei Zhou ^1,2,3,4* King Kit Li ¹ Pui Kin So ⁵ Chi Wai Do ^1,2,3,6 Chuen Lam ^1,2,3,6*

• ¹ Centre for Myopia Research, School of Optometry, the Hong Kong Polytechnic University, Kowloon, Hong Kong, SAR China
• ² Research Centre for SHARP Vision (RCSV), The Hong Kong Polytechnic University, Kowloon, Hong Kong, SAR China
• ³ Centre for Eye and Vision Research (CEVR), The Hong Kong Polytechnic University, 17W, Hong Kong Science Park, Hong Kong, SAR China
• ⁴ Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Kowloon, Hong Kong, SAR China
• ⁵ University Research Facility in Life Sciences, The Hong Kong Polytechnic University, Kowloon, Hong Kong, SAR China
• ⁶ Research Centre for Chinese Medicine Innovation (RCMI), The Hong Kong Polytechnic University, Kowloon, Hong Kong, SAR China

Introduction: Multifactorial Eye disorders are a significant public health concern and have a huge impact on quality of life. The pathophysiological mechanisms underlying these eye disorders were not completely understood since functional and low-throughput biological tests were used. By identifying biomarkers linked to eye disorders, metabolomics enables early identification, tracking of the course of the disease, and personalized treatment.The electronic databases of PubMed, Scopus, PsycINFO, and Web of Science were searched for research related to Age-Related macular degeneration (AMD), glaucoma, myopia, and diabetic retinopathy (DR). The search was conducted in August 2023. The number of cases and controls, the study's design, the analytical methods used, and the results of the metabolomics analysis were all extracted. Using the QUADOMICS tool, the quality of the studies included was evaluated, and metabolic pathways were examined for distinct metabolic profiles. We used MetaboAnalyst 5.0 to undertake pathway analysis of differential metabolites.Results: Metabolomics studies included in this review consisted of 36 human studies (5 Age-related macular degeneration, 10 Glaucoma, 13 Diabetic retinopathy, and 8 Myopia). The most networked metabolites in AMD include glycine and adenosine monophosphate, while methionine, lysine, alanine, glyoxylic acid, and cysteine were identified in glaucoma. Furthermore, in myopia, glycerol, glutamic acid, pyruvic acid, glycine, cysteine, and oxoglutaric acid constituted significant metabolites, while glycerol, glutamic acid, lysine, citric acid, alanine, and serotonin are highly networked metabolites in cases of diabetic retinopathy. The common top metabolic pathways significantly enriched and associated with AMD, glaucoma, DR, and myopia were arginine and proline metabolism, methionine metabolism, glycine and serine metabolism, urea cycle metabolism, and purine metabolism.This review recapitulates potential metabolic biomarkers, networks and pathways in AMD, glaucoma, DR, and myopia, providing new clues to elucidate disease mechanisms and therapeutic targets. The emergence of advanced metabolomics techniques has significantly enhanced the capability of metabolic profiling and provides novel perspectives on the metabolism and underlying pathogenesis of these multifactorial eye conditions. The advancement of metabolomics is anticipated to foster a deeper comprehension of disease etiology, facilitate the identification of novel therapeutic targets, and usher in an era of personalized medicine in eye research.