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Prospective validation of serial aqueous humor sampling for longitudinal ocular proteomics: safety results from the OPTICA trial in geographic atrophy
Presenter:
Tsai-Chu Yeh, MD MTM
Authors:
Tsai-Chu Yeh, MD MTM (Presenting Author); Vinit B. Mahajan, MD, PhD; David RP Almeida, MD, MBA, PhD
1. Stanford University
2. ClinOmicsAI
Affiliation:
Purpose
Aqueous humor (AH) proteomics can identify biomarkers predictive of therapeutic response and disease progression, yet no prospective trial has validated the safety of serial anterior chamber paracentesis (ACP) for longitudinal molecular profiling. While retrospective data from over 1,400 single ACP procedures demonstrate an excellent safety profile (0.07% complication rate), the cumulative risk of repeated sampling in elderly patients with geographic atrophy (GA) has not been established. The OPTICA trial was designed as the first prospective study to validate the safety of serial ACP for longitudinal proteomics in dry AMD.
Methods
OPTICA is a phase 1, prospective, longitudinal safety study enrolling 50 subjects: Cohort 1 (N=40) with confirmed GA (FAF/SD-OCT) and Cohort 2 (N=10) age-matched controls with non-exudative AMD (age 50-89). All subjects underwent two standardized ACP procedures at Baseline and Month 1, each collecting ~100µL AH under topical anesthesia using a 30-gauge needle per published protocol. The primary endpoint was incidence of adverse events of special interest (AESI) through Month 1: endophthalmitis, sustained IOP elevation (≥10mmHg from baseline), hyphema, and lens injury. Secondary endpoints included technical success and sample viability for proteomic analysis.
Results
Enrollment reached 100% (N=50) with 100% technical success across both timepoints (100 total procedures). The primary safety endpoint was met: zero AESI occurred (0% incidence of endophthalmitis, hyphema, lens trauma, or sustained IOP elevation). No subject required IOP-lowering therapy or surgical intervention. Serial ACP was well-tolerated across all ages (50-89 years) with no withdrawals due to procedural intolerance. All 100 samples met volume thresholds for downstream high-resolution proteomic analysis.
Conclusions
OPTICA provides the first prospective validation that serial anterior chamber paracentesis is safe in patients with geographic atrophy, establishing the regulatory and clinical foundation for longitudinal AH proteomics in dry AMD. These results enable future biomarker discovery trials using repeated ocular liquid biopsy to track disease progression and therapeutic response at the molecular level.