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oai:figshare.com:article/31451707 2025-12-01T00:00:00Z portal_693 item_type_8 month_year_12_2025

Development of Multielectrode Electroretinography (meERG) for Human Clinical Use Giri Balasubramanian (23292034) Neural Engineering Vision Sciences Electrophysiology Development of Multielectrode Electroretinography (meERG) for Human Clinical use. Introduction Progressive retinal diseases such as macular degeneration, glaucoma, and retinitis pigmentosa begin with localized dysfunction that spreads, often remaining undetected until advanced stages. Existing clinical electroretinography (ERG) techniques either lack spatial sensitivity (full-field ERG) or are restricted to central vision (multi-focal ERG). Prior animal studies have demonstrated that multielectrode electroretinography (meERG), which records simultaneous ERG waveforms from multiple corneal locations, can reveal localized deficits in retinal function. Translating this technique to humans could provide a clinically feasible, objective method for functional retinal imaging. Purpose This work aimed to develop and evaluate a human-compatible meERG system using a Contact Lens Electrode Array (CLEAr) lens, with the overarching goal of advancing the technique toward clinical translation. Methods Three Specific Aims were pursued. Aim 1 focused on improving CLEAr lens design, incorporating wireless amplification, improved fit and optimized stimulus delivery; this Aim was the main focus of the overall study. Aim 2 involved pilot human recording to establish proof of concept for the improved designs. Aim 3 developed a computational bioelectric model to relate corneal potential maps to underlying retinal activity through forward and inverse modeling. Results The first human meERG system with potential for translation to a clinical setting was designed, fabricated and tested. Key developments included an improved CLEAr lens design to minimize channel crosstalk while accommodating inter-subject variability in corneal and scleral topography. Light transmission (for the ERG stimulus) was enhanced by optimizing electrode cable design, improving nasal–temporal trace symmetry for more uniform retinal illumination, and implementing transparent electrode cables (BioCLEAR), resulting in a 13% improvement in overall light transmittance. A full-field light stimulus source with excellent spatial uniformity (luminance CV <5%) was developed to minimize systemic bias in meERG measurement. Additional advances improved lens stability, biocompatibility, shelf life, packaging, and machining yield were achieved. Initial proof-of-concept human recordings demonstrated, for the first time, spatially distinct meERG signals with excellent signal to noise ratio. An analysis strategy for measuring small spatial differences in corneal potentials was established and demonstrated. Finally, a computational forward model based on a human atlas dataset was developed, capable of predicting field potentials across the anterior surface of the eye. Conclusion This work establishes the feasibility of human meERG as a clinically relevant functional imaging technique. By providing rapid, objective, and spatially resolved measures of retinal function, meERG has the potential to significantly improve early detection of retinal diseases and monitoring of localized therapies such as gene or protein delivery. Continued development will focus on optimizing clinical usability and validating diagnostic sensitivity in patient populations. 2025-12-01T00:00:00Z Text Thesis 10.25417/uic.31451707.v1 https://figshare.com/articles/thesis/Development_of_Multielectrode_Electroretinography_meERG_for_Human_Clinical_Use/31451707 In Copyright Open Access after 2028-01-01