JMIR Publications

ABSTRACT

Gene therapies that make the eye secrete its own drug have no fixed dose. The dose is whatever the transduced cells produce, and it is rarely measured. Visual acuity and imaging show the consequences of expression; they do not show the protein. We propose precision monitoring of vector expression (PMVX), a three-step framework. First, an anterior chamber sample taken from every treated eye before and after dosing establishes a per-eye signature: the transgene product, its free target and a pre-specified downstream pathway. Second, tears collected on Schirmer strips at the same visits are compared with the aqueous, analyte by analyte, with fellow-eye tears and plasma as controls. Third, for analytes that pass, the strip is tested as a monitor between scheduled aqueous samples. The first step rests on published methods. The second and third are a hypothesis. No study has shown that tears report an intraocular transgene, and anatomy gives reasons to doubt it. We define the terms, set gates for each stage, and state the results that would prove the tear hypothesis wrong. The aqueous reference stands either way.