Tsai-Chu Yeh, MD, MTM

All Publications

• A Simplified Classification for Age-Related Macular Degeneration Based on Optical Coherence Tomography. Ophthalmic surgery, lasers & imaging retina Yeh, T. C., Lin, J. B., Mruthyunjaya, P., Leng, T., DeBoer, C., Sepah, Y. J., Almeida, D. R., Smith, S., Mahajan, V. B. 2026: 1-7

  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 OCT 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. Inter-grader agreement was assessed using weighted kappa coefficients.Among the 109 eyes from 108 patients (mean age 79.61 ± 7.57 years; 41.7% men, 58.3% women), AMD staging based on SOAC was distributed as follows: normal aging in nine 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 10.3928/23258160-20260409-02

  View details for PubMedID 42165512

• A novel IDS variant associated with an isolated ocular phenotype in Hunter syndrome. Documenta ophthalmologica. Advances in ophthalmology Yeh, T. C., Velez, G., Lee, S. H., Ngo, G. H., Kumar, A., Al-Moujahed, A., Yu, C., Leung, L. S., Mruthyunjaya, P., Mahajan, V. B. 2026

  Abstract

  Hunter syndrome (mucopolysaccharidosis type II, MPS II) is an X-linked lysosomal storage disorder caused by iduronate-2-sulfatase (IDS) mutations and is classically associated with multiple-organ-systems involvement. Ocular findings are usually reported in conjunction with systemic manifestations, and isolated ocular presentations have not been well characterized. Here, we report a novel hemizygous IDS variant in a patient who initially presented with isolated corneal and retinal pathology and was subsequently diagnosed with attenuated Hunter syndrome.Comprehensive ophthalmic and retinal evaluation was performed, including multimodal retinal imaging and full-field electroretinography, alongside genetic testing.A 44-year-old male with progressive nyctalopia demonstrated bilateral parafoveal and peripheral retinal depigmentation with central macular sparing on optical coherence tomography and a symmetric bull's-eye pattern on fundus autofluorescence. Visual field testing revealed bilateral ring scotomas, and full-field electroretinography showed subnormal rod-predominant responses. Pedigree analysis suggested X-linked inheritance. Genetic testing identified a novel hemizygous IDS variant (c.707A > G, p.Lys236Arg), and the diagnosis of Hunter syndrome was supported by markedly reduced IDS activity and elevated urinary glycosaminoglycans with increased heparan sulfate.A novel missense IDS mutation was identified in association with Hunter syndrome, highlighting the importance for ophthalmologists to consider MPS II in patients presenting with isolated retinopathy and the value of genetic diagnosis in revealing atypical systemic disease.

  View details for DOI 10.1007/s10633-026-10104-y

  View details for PubMedID 42033570

  View details for PubMedCentralID 6238255

• Mitochondrial Transplantation in the Eye: A Review and Evaluation of Surgical Approaches. bioRxiv : the preprint server for biology Cakir, B., Yeh, T. C., Lin, C. H., Wu, M. R., Boilard, É., Pelletier, M., Singh, A. M., Breton, Y., Patel, S., Benson, T., Almeida, D. R., Wang, S., Mahajan, V. B. 2026

  Abstract

  Mitochondrial dysfunction contributes to major blinding diseases, including age-related macular degeneration and glaucoma. Although mitochondrial transplantation has shown therapeutic potential in multiple organ systems, translation to the eye remains limited, partly due to uncertainty regarding optimal delivery. We summarize the biologic rationale and preclinical evidence supporting ocular mitochondrial transplantation and present feasibility data evaluating clinically relevant delivery routes.We conducted a focused narrative review of ocular mitochondrial transplantation. For feasibility experiments, mitochondria with an endogenous fluorescent dye were isolated from liver donor mice. Postnatal day 7 pups received subretinal injections, and adult CD1 mice received intravitreal injections, including optic nerve head directed delivery. Eyes were analyzed using fluorescence microscopy and immunohistochemistry. Mitochondrial uptake was assessed in cultured retinal pigmental epithelial (RPE) cells using co-incubation assays. Suprachoroidal delivery feasibility was evaluated in cadaveric human near-real surgical specimens using a novel dedicated suprachoroidal injector.The literature on ocular mitochondrial transplantation remains limited and consists primarily of small preclinical studies using intravitreal delivery and imaging-based detection. In our experiments, intravitreal delivery produced donor signals predominantly within inner retinal layers, with enrichment along retinal nerve fiber bundles when directed toward the optic nerve head. Cultured RPE cells demonstrated dose-dependent uptake of exogenous mitochondria. Subretinal delivery localized donors signal to the RPE and adjacent outer retina. Suprachoroidal injections demonstrated procedural feasibility with reliable access to the suprachoroidal space and visible injectate distribution.Ocular mitochondrial transplantation is in an early stage of investigation. Our feasibility data indicate that established posterior-segment delivery routes expose distinct retinal compartments and that route selection strongly influences anatomic distribution. Further studies are needed to verify intracellular uptake, define dosing and durability, and evaluate safety in disease-relevant models.

  View details for DOI 10.64898/2026.04.06.716722

  View details for PubMedID 41993457

  View details for PubMedCentralID PMC13081984

• 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

• Mitigating Visual Fatigue in Urine Cytology: AIxURO, an AI-Driven Review Platform, Improves Diagnostic Accuracy and Efficiency Yeh, T., Shao, G., Yang, W., Hsu, S., Yeh, C., Liu, Y., Lin, Y., Tung, M., Crothers, B., Liu, T. ELSEVIER SCIENCE INC. 2026

  View details for DOI 10.1016/j.labinv.2025.104816

  View details for Web of Science ID 001745164800021

• 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

• PREDICTING VISUAL OUTCOME AFTER SURGERY IN PATIENTS WITH IDIOPATHIC EPIRETINAL MEMBRANE USING A NOVEL CONVOLUTIONAL NEURAL NETWORK RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES Yeh, T., Chen, S., Chou, Y., Luo, A., Deng, Y., Lee, Y., Chang, P., Lin, C., Tai, M., Chen, Y., Ko, Y. 2023; 43 (5): 767-774

  Abstract

  To develop a deep convolutional neural network that enables the prediction of postoperative visual outcomes after epiretinal membrane surgery based on preoperative optical coherence tomography images and clinical parameters to refine surgical decision making.A total of 529 patients with idiopathic epiretinal membrane who underwent standard vitrectomy with epiretinal membrane peeling surgery by two surgeons between January 1, 2014, and June 1, 2020, were enrolled. The newly developed Heterogeneous Data Fusion Net was introduced to predict postoperative visual acuity outcomes (improvement ≥2 lines in Snellen chart) 12 months after surgery based on preoperative cross-sectional optical coherence tomography images and clinical factors, including age, sex, and preoperative visual acuity. The predictive accuracy, sensitivity, specificity, and area under the receiver operating characteristic curve of the convolutional neural network model were evaluated.The developed model demonstrated an overall accuracy for visual outcome prediction of 88.68% (95% CI, 79.0%-95.7%) with an area under the receiver operating characteristic curve of 97.8% (95% CI, 86.8%-98.0%), sensitivity of 87.0% (95% CI, 67.9%-95.5%), specificity of 92.9% (95% CI, 77.4%-98.0%), precision of 0.909, recall of 0.870, and F1 score of 0.889. The heatmaps identified the critical area for prediction as the ellipsoid zone of photoreceptors and the superficial retina, which was subjected to tangential traction of the proliferative membrane.The novel Heterogeneous Data Fusion Net demonstrated high accuracy in the automated prediction of visual outcomes after weighing and leveraging multiple clinical parameters, including optical coherence tomography images. This approach may be helpful in establishing personalized therapeutic strategies for epiretinal membrane management.

  View details for DOI 10.1097/IAE.0000000000003714

  View details for Web of Science ID 000978436500012

  View details for PubMedID 36727822

• Ophthalmic characteristics and retinal vasculature changes in Williams syndrome, and its association with systemic diseases EYE Yeh, T., Cheng, H., Li, H., Chi, S., Yang, H., Yu, J., Niu, D., Wang, A. 2023; 37 (11): 2265-2271

  Abstract

  We aim to characterise the ophthalmic findings and retinal vasculature changes in patients with WS, and to analyse the correlation between ophthalmic manifestations and the associated systemic diseases.This retrospective case-control study included 27 WS patients and 28 age-matched healthy participants. Stellate pattern of iris, central macular thickness (CMT), foveal width, retinal vessel diameter, superficial vascular density (SVD) of macula and foveal avascular zone (FAZ) were compared between WS patients and healthy participants.Twenty-five patients (93%) had the classic stellate iris presentation. Compared with healthy controls, WS patients had decreased CMT, increased foveal width and a lower SVD of macula (all P < 0.001). Significantly decreased mean retinal arterial (117.9 ± 9.9 µm vs. 133.0 ± 6.7 µm in WS and controls, respectively; p < 0.001) and venous (158.9 ± 11.2 µm vs. 174.0 ± 8.0 µm in WS and controls, respectively; p < 0.001) outer diameters, as well as mean arterial wall thickness (11.2 ± 1.3 µm vs. 12.2 ± 0.8 µm in WS and controls, respectively; p < 0.01) were found in WS. Stellate iris grading was significantly associated with CMT, foveal width, retinal vessel diameter (all p < 0.05), and a significant increase in the odds of having hypertension (Odds ratio (OR), 5.63; P < 0.05). The severity of stellate iris in WS seemed to have the trend of increasing risk of having pulmonary stenosis, tricuspid regurgitation and mitral regurgitation.This study provides the first in vivo evidence reflecting current knowledge on vessel morphology in WS patients that deficient circumferential growth is the predominant pathophysiologic changes resulting from elastin deficiency. The ophthalmic characteristics may serve as a complementary tool to diagnose and follow-up patients suffering from WS.

  View details for DOI 10.1038/s41433-022-02328-4

  View details for Web of Science ID 000889017800001

  View details for PubMedID 36437422

  View details for PubMedCentralID PMC10366147

• Plug-related canaliculitis: a rare or underdiagnosed disease? CLINICAL AND EXPERIMENTAL OPTOMETRY Yeh, T., Hou, T., Huang, Y., Yu, W., Tsai, C. 2022; 105 (4): 385-391

  Abstract

  Conjunctivitis, chalazion and blepharitis are routinely managed by optometrists. However, it is especially important to consider the diagnosis of canaliculitis in patients with chronic or recurrent conditions.This study aimed to report the clinical features, radiological findings and treatment outcomes in patients with plug-related canaliculitis.This retrospective study included patients with canaliculitis secondary to plug insertion between 2007 and 2020. All data regarding epidemiological characteristics, clinical presentation, isolated microorganisms, computed tomography imaging findings, treatment, and outcomes were analysed.A total of 20 plug-related canaliculitis from 19 patients (18.3%) among all 109 cases of canaliculitis were identified. All patients with plug-related canaliculitis were females with a past history of lacrimal plug insertion for dry eye (mean age: 58.2 years). Most patients were initially treated as conjunctivitis with the mean time lapse to a diagnosis of 5.2 months. The average time from plug insertion to onset of symptoms was 5.1 years. Eighteen patients underwent canaliculotomy, and one patient received lacrimal irrigation. Plugs were identified in 18 cases, with SmartPlug in 13 cases (72%), followed by EaglePlugTM (two cases), Herrick Lacrimal Plug (two cases), and migrated FCI Painless Plug (1 case). Cultures of discharge, concretions, and/or infected plugs mostly revealed Pseudomonas aeruginosa (42%). Orbital computed tomography in four cases with SmartPlug revealed central radiolucency with surrounding soft-tissue enhancement. No recurrent canaliculitis was observed throughout a mean follow-up period of 13.7 months. No patient needed re-plugging after canaliculotomy and plug removal, with only one required additional lubricants for recurrent dry eye.Plug-related canaliculitis is often underdiagnosed due to late onset and similar symptoms to common ocular diseases. Awareness of plug insertion history as well as meticulous removal of the plug, concretion and/or granulation tissue is important for early diagnosis and to ensure a good outcome.

  View details for DOI 10.1080/08164622.2021.1927675

  View details for Web of Science ID 000662918900001

  View details for PubMedID 34139956

• Retinal Artery Occlusion after Fat Injection Laryngoplasty OPHTHALMOLOGY Yeh, T. 2021; 128 (1): 47

  View details for Web of Science ID 000600748500020

  View details for PubMedID 33349344