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Background. Noninvasive assessment of metabolic processes that sustain regeneration of human retinal visual pigments (visual cycle) is essential to improve ophthalmic diagnostics and to accelerate development of new treatments to counter retinal diseases. Fluorescent vitamin A derivatives, which are the chemical intermediates of these processes, are highly sensitive to UV light; thus, safe analyses of these processes in humans are currently beyond the reach of even the most modern ocular imaging modalities.Methods. We present a compact two-photon excited fluorescence scanning laser ophthalmoscope and spectrally resolved images of the human retina based on two-photon excitation (TPE) with near-infrared (IR) light. A custom Er:fiber laser with integrated pulse selection, along with intelligent post-processing of data, enables excitation with low laser power and precise measurement of weak signals.Results. We demonstrate spectrally resolved TPE fundus images of human subjects.Comparison of TPE data between human and mouse models of retinal diseases revealed similarity with mouse models that rapidly accumulate bisretinoid condensation products. Thus, visual cycle intermediates and toxic byproducts of this metabolic pathway can be measured and quantified by TPE imaging. Conclusion.Our work establishes a TPE instrument and measurement method for noninvasive metabolic assessment of the human retina. This approach opens the possibility for monitoring eye diseases in the earliest stages before structural damage to the retina occurs.

In the last decade, 3D printing systems have greatly evolved both in terms of processable materials and printing resolutions, becoming a top seed technology for many academic and industrial applications. Nevertheless, manufacturing polymeric materials characterized by a trabecular porosity and functionally graded architecture—where both the local porosity and chemical composition of the matrix change in the 3D space—through additive platforms remains an open technical challenge. In this study, a 3D extrusion printing strategy to tackle this problem is presented. The proposed systems are based on a flow‐focusing microfluidic printing head—to continuously generate oil‐in‐water emulsion inks—and on an agarose fluid–gel used as a temporary support bath for the deposition of the photo‐curable emulsion inks. It is demonstrated that through this strategy one can design a priori and build with high accuracy both discontinuous and continuous functionally graded polymeric foams, where both the density and composition of the materials could be varied independently within arbitrarily complex 3D architectures. This study provides new means for the synthesis of microporous, polymeric FGMs which could find applications ranging from interface tissue engineering to automotive and construction industries.