Barrier free chromatic pupillometry in children from infancy on. A novel biomarker to quantify outer and inner retinal function in inherited retinal disorders as a measure of therapeutic benefit after gene therapy.

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Retinal gene addition therapy has been and is further developed for several potentially blinding retinal dystrophies. For RPE65 deficiency a drug is expected to be soon approved by the FDA and EMA. Treatment benefit has been difficult to quantify due to still limited treatment success today, but also because of limited functional assessment methods with high enough sensitivity. One way to improve treatment success may be to treat as little degenerated retina as possible. This may mean that very young patients or even infants and toddlers will be considered for treatment in the future. Due to limited capacity and compliance new objective measures of function and morphology are therefore needed.Our aim is to develop highly reliable biomarkers of retinal function in inherited retinal dystrophies from infancy on and to correlate them with retinal morphology. We will develop, construct and test an entirely new concept of objective assessment of retinal function. The proposed method of contact- and barrier-free chromatic pupillometry enables separate stimulation of one eye or stimulation of both eyes at the same time and simultaneous recording of the pupils. It consists of a specialized remote eye-tracker to measure online pupil diameter and at the same time eye gaze and head position, necessary to correct pupil deformation induced artifacts. The subject is stimulated through an LED-based monitor using blue and red light with different backgrounds and intensities, all this without the need to fix head position. This will allow age-independent evaluation of rod, cone, and ipRPGCs mediated pupillary constriction as an indicator of their function. This is particularly important in IRDs of the LCA type where early on rod and/or cone function are below detection level with Ganzfeld electroretinography. Rod, cone, and ipRGC function as assessed with barrier-free chromatic pupillometry will be correlated to morphological data of the central retina, assessed with hand-held OCT, and analyzed with DIOCTA software. Values obtained with barrier-free pupillometry will be validated with our previously developed binocular chromatic pupillometry in older children capable of performing both methods.