Tsai-Chu Yeh, MD, MTM

All Publications

• A Simplified Classification for Age-Related Macular Degeneration Based on Optical Coherence Tomography. medRxiv : the preprint server for health sciences Yeh, T. C., Lin, J. B., Mruthyunjaya, P., Leng, T., DeBoer, C., Sepah, Y. J., Almeida, D. R., Smith, S., Mahajan, V. B. 2026

  Abstract

  As optical coherence tomography (OCT) has enabled the identification of an expanding set of age-related macular degeneration (AMD) risk biomarkers and become central to routine clinical practice, there remains a need for a simplified grading scheme that allows physicians to communicate and synchronize AMD grading directly from standard OCT imaging rather than relying on traditional color fundus imaging. This study aims to establish a standardized OCT-based AMD classification that balances diagnostic accuracy with practicality for use across clinical and research settings.Spectral-domain optical coherence tomography scans were independently graded by two retinal specialists following the newly proposed Stanford OCT-Based AMD Classification (SOAC). Discrepancies were adjudicated by a third independent retinal specialist. Intergrader agreement was assessed using weighted kappa coefficients.Among the 109 eyes from 108 patients (mean age 79.61 ± 7.57 years; 41.7% male, 58.3% female), AMD staging based on SOAC was distributed as follows: normal aging in 9 patients (8.3%), early AMD in 16 (14.7%), intermediate AMD in 32 (29.4%), neovascular AMD (nAMD) in 18 (16.5%), geographic atrophy (GA) in 20 (18.3%), and combined nAMD and GA in 14 (12.8%). The overall intergrader agreement demonstrated robust consistency, with a weighted kappa value of 0.95 (95% CI: 0.92-0.98), signifying excellent intergrader reliability and reinforcing the validity of SOAC.SOAC provides a standardized, OCT-based framework for AMD grading that demonstrates high intergrader agreement. By enabling consistent classification from commonly acquired OCT scans, SOAC supports reliable disease staging and facilitates integration across clinical studies and translational research. As imaging and molecular data continue to expand, SOAC can serve as a common OCT-based reference for phenotype refinement and longitudinal AMD studies.

  View details for DOI 10.64898/2026.03.29.26349635

  View details for PubMedID 41959804

  View details for PubMedCentralID PMC13060428

• Multi-omics liquid biopsy identifies mitochondrial dysfunction in geographic atrophy and supports the longevity-associated metabolite α-ketoglutarate as a therapeutic strategy. medRxiv : the preprint server for health sciences Yeh, T. C., Velez, G., Prasad, A., Lee, S. H., Rasmussen, D. K., Kumar, A., Chadha, M., Dabaja, M. Z., Singh, A. M., Sanislo, S., Smith, S., Mryuthyunjaya, P., Montague, A., Bassuk, A. G., Almeida, D., Dufour, A., Mahajan, V. B. 2026

  Abstract

  Mitochondrial dysfunction is an emerging metabolic hallmark of age-related diseases, yet tools to directly profile mitochondrial pathways and test metabolic interventions in the living human eye remain limited. Multi-omics ocular liquid biopsy enables real-time proteomic and metabolomic profiling of the intraocular microenvironment, complementing systemic biomarkers and imaging surrogates. Here, we used this approach to define mitochondrial and tricarboxylic acid (TCA) cycle dysregulation in geographic atrophy (GA) and to assess whether oral α-ketoglutarate (α-KG) supplementation can modulate mitochondrial metabolites within the eye.Mitochondrial and TCA cycle-related proteins were profiled in aqueous humor (AH) samples from patients with GA using DNA-aptamer-based proteomics. In a phase 0 study, a second cohort undergoing sequential cataract surgery provided paired AH samples collected at first-eye surgery and at second-eye surgery after interim α-KG supplementation. These samples underwent targeted metabolomic profiling using hydrophilic interaction liquid chromatography coupled with mass spectrometry.In GA, 64 mitochondrial proteins were differentially expressed, including coordinated TCA-cycle deficiencies marked by reduced expression of enzymes regulating TCA entry and flux, including PDHB and DLST. In the phase 0 cohort, oral α-KG supplementation significantly increased intraocular α-KG levels and the α-KG-to-succinate ratio (P < 0.05), with coordinated shifts across TCA intermediates consistent with enhanced TCA cycle flux.AH proteomics demonstrated mitochondrial pathway depletion in GA, consistent with reduced oxidative bioenergetic capacity. AH metabolomics provided first-in-human in vivo evidence that systemic α-KG supplementation can modify intraocular metabolites and may enhance intraocular energy metabolism. These findings support ocular liquid biopsy as a precision-health framework for per-patient biomarker-guided metabolic trials in GA.

  View details for DOI 10.64898/2026.03.12.26347263

  View details for PubMedID 41891014

  View details for PubMedCentralID PMC13015626

• Protocol to extract tear fluid for proteomics using Schirmer strips. STAR protocols Ngo, G. H., Chadha, M., Sun, Y. J., Yu, G., Lee, S. H., Yeh, T. C., Almeida, D. R., Bassuk, A. G., Mruthyunjaya, P., Dufour, A., Mahajan, V. B. 2025; 6 (4): 104146

  Abstract

  Schirmer strips are widely regarded as the gold standard for tear fluid collection. However, their use presents several challenges for proteomic analysis. Here, we present a protocol for extracting tear proteins from Schirmer strips. We describe steps for acquisition and handling of strips, extraction buffer preparation, strip preparation, and protein extraction. This protocol is designed to improve protein yield and facilitate proteomic workflows and is adaptable for various protein-based studies, particularly in the context of ocular disease research and diagnostics.

  View details for DOI 10.1016/j.xpro.2025.104146

  View details for PubMedID 41108683