Association of Anterior Chamber Depth, Volume, and Intraocular Fluid Metabolome with Lens Hardness in Cataract Patients. Summary of the Doctoral Thesis

Cataracts are multifactorial diseases and remain one of the leading causes of blindness worldwide. Its pathogenesis is closely linked to oxidative stress-induced redox imbalance, protein aggregation, restructuring of metabolic pathways, and disruption in energy homeostasis. The aim of this study was to evaluate changes in the intraocular fluid metabolite profile in patients with varying degrees of cataract maturity and to analyse biometric data-namely, anterior chamber volume (ACV), anterior chamber depth (ACD), and their potential association with lens hardness. Metabolomic analysis revealed that patients with harder cataracts exhibited distinct alterations in mitochondrial β-oxidation products, including increased accumulation of acylcarnitines and reduced availability of glutathione (GSH). Taurine, a non-proteinogenic amino acid and a key intraocular osmolyte, facilitates GSH uptake into cells and stabilises cellular redox systems. With ageing, taurine concentrations decline, correlating with increased oxidative stress and cataract progression. Although biometric parameters such as ACV and ACD did not show a statistically significant correlation with lens hardness overall, patients with pseudoexfoliation syndrome (PEXS) demonstrated marked structural differences – including decreased ACD, ACV, and axial length. These changes indicate increased anterior segment instability and a higher risk of intraoperative complications. A novel formula for ACV estimation was also validated, based on WTW, CCT, and ACD measurements, enabling accurate volume assessment without the need for expensive imaging equipment. The study further identified significant alterations in tryptophan metabolism and activation of the kynurenine pathway, which were associated with GSH depletion, reduced NAD⁺ availability, and elevated markers of oxidative stress. These findings suggest mechanistic parallels with other protein aggregation disorders, such as Alzheimer's and Parkinson's diseases, where NAD⁺ depletion, mitochondrial dysfunction, and inflammatory activation are similarly observed. This work provides novel insights into the molecular mechanisms underlying cataract pathogenesis and highlights potential biomarkers for disease progression. The findings support the therapeutic potential of metabolically targeted interventions – such as supplementation with NAD⁺ precursors, taurine, and antioxidants – as viable prophylactic and treatment strategies. The validated ACV estimation method may also be of clinical utility in resource-limited settings, improving surgical risk stratification and treatment planning. The Doctoral Thesis was developed at Rīga Stradiņš University, Department of Ophthalmology, Latvia. Defence of the Doctoral Thesis will take place at the public session of the Promotion Council of Clinical Medicine on 8 January 2026 at 13.00 in the Senate Hall, 16 Dzirciema Street, Rīgas Stradiņš University. 3.2. Clinical Medicine; Sub-Sector – Ophthalmology. Keywords: Cataract; metabolomics; intraocular fluid; glutathione; taurine; kynurenine pathway; acylcarnitine; anterior chamber volume (ACV); anterior chamber depth (ACD); pseudoexfoliation syndrome; redox balance; protein aggregation.