Direct Laser Writing of Titanium Dioxide-Laden Retinal Cone Phantoms

Adaptive optics-optical coherence tomography (AO-OCT) is a developing medical imaging modality that can spatially resolve individual photoreceptor cell and detect retinal pathologies in vivo. To date, however, a lack of standardized physical models - termed “phantoms” - that recapitulate the opto-structural properties of the retina impedes performance assessment, which could lead to inconsistencies in retinal pathology detection once AO-OCT reaches the clinic. Here we present a novel approach for manufacturing three-dimensional (3D) retinal cone outer segment (OS) phantoms via two-photon direct laser writing (DLW) of a photomaterial laden with titanium (IV) dioxide (TiO
2
) nanoparticles. The ability to directly integrate light-scattering particles into biologically relevant architectures facilitates AO-OCT visibility of phantom components. Preliminary DLW results demonstrated TiO
2
nanoparticle-laden phantoms that effectively match cone dimensions and spacing at 1°, 2.5°, 5°, and 10° retinal eccentricities. Furthermore, preliminary AO-OCT experiments revealed that individual retinal cones could be optically resolved in phantoms with center-to-center spacing less than
$4\ \mu \mathrm{m}$
. These results suggest a promising pathway to produce biologically relevant retinal phantoms to standardize clinical AO-OCT imaging performance.