The cornea, the transparent front part of the eye, is crucial for focusing light and protecting the iris and lens. Its high density of nerve endings makes it highly sensitive to touch, triggering the corneal reflex—an involuntary eyelid closure. Corneal diseases, however, can lead to blindness, affecting over 10 million people worldwide. Corneal transplantation (keratoplasty) is the primary treatment, but the scarcity of donor corneas limits its application to a small fraction of patients. Artificial corneal substitutes address this scarcity, offering optical transparency, but currently lack the tactile sensation and corneal reflex functionality. Existing artificial corneas, such as the Boston keratoprosthesis (KPro), Aurolab KPro, and MICOF KPro, provide protection and light refraction but fail to replicate the tactile experience and reflexive response. The osteo-odonto-keratoprosthesis utilizes a biological approach but shares the same limitations. This research addresses this gap by developing a 'smarter' artificial cornea with integrated electronics for tactile sensation, sensory expansion, and interactive functions while maintaining the optical clarity of a natural cornea.

Existing literature highlights the need for artificial cornea substitutes due to the scarcity of donor corneas for transplantation. Studies emphasize the limitations of current artificial corneas in replicating the full functionality of the natural cornea, specifically the lack of tactile sensation and the corneal reflex. Various artificial cornea designs have been developed, including the Boston KPro and its variants, which improve vision but lack sensory feedback. The osteo-odonto-keratoprosthesis, a biological alternative, also falls short in replicating the complete sensory experience. Research on transparent and biocompatible electronics for integrating into artificial corneas is also explored, highlighting the challenge of combining functionality with optical clarity. The development of neuromorphic electronics, particularly artificial synapses, has also shown promise in creating more intelligent prosthetic devices.

This study details the creation of an artificial corneal reflex arc comprising three core components: sensor-oscillation circuits (receptors), zinc tin oxide (ZTO) artificial synapses (ASs) (processing core), and electrochromic devices (actuators). The ZTO ASs, fabricated using digitally aligned, long, continuous ZTO fibers, mimic biological synapses. Different Zn:Sn molar ratios (3:7, 1:1, and 7:3) were investigated to tune synaptic plasticity. The fabrication involved electrohydrodynamic nanowire printing of ZTO fibers onto a substrate, followed by the deposition of gold source and drain electrodes and the application of an ion gel. The characterization included scanning electron microscopy (SEM), atomic force microscopy (AFM), high-resolution transmission electron microscopy (HRTEM), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), and optical measurements to assess the structural, chemical, and optical properties of the ZTO fibers. Electrical characterization involved measuring artificial excitatory postsynaptic currents (aEPSCs) and evaluating paired-pulse facilitation (PPF), spike-number-dependent plasticity (SNDP), spike-frequency-dependent plasticity (SFDP), spike-duration-dependent plasticity (SDDP), and spike-voltage-dependent plasticity (SVDP). Density functional theory (DFT) calculations were performed to understand the relationship between ZTO fiber structure and synaptic properties. The electrochromic devices, used as actuators, consisted of ITO/PET substrates, a PEDOT:PSS electrochromic layer, and a LiClO4 gel electrolyte layer. Their optical and electrochemical properties were characterized. The complete artificial corneal reflex arc was tested under mechanical and light stimulation to simulate the corneal reflex and its variations (bilateral, ipsilateral, contralateral). A robot was used as a proof-of-concept demonstration of the artificially-intelligent cornea.

The researchers successfully fabricated a digitally aligned ZTO fiber array with high transparency (>99.89% transmittance and <0.36% haze at 550 nm) and low cost. The ZTO fibers, especially those with a 3:7 Zn:Sn molar ratio, exhibited tunable synaptic plasticity, including PPF, SNDP, SFDP, SDDP, and SVDP. The 3:7 ratio showed long-term plasticity (LTP), while 7:3 and 1:1 ratios displayed short-term plasticity (STP). This tunability enabled demonstration of encrypted communication (Morse code) and associative learning (Pavlovian conditioning). The artificial corneal reflex arc, incorporating the ZTO ASs and electrochromic actuators, successfully simulated the bilateral, ipsilateral, and contralateral corneal reflexes, providing different electrochromic responses representing different points of neural pathway damage. The integration of a light sensor allowed the system to also respond to light intensity changes, demonstrating sensory expansion and interaction with the environment; the electrochromic actuator adjusted its transmittance based on the light level. The flexible version of the artificial synapse showed excellent bending resistance. The artificially-intelligent cornea exhibited a response time that partially replicated the eyelid closure process.

This research successfully addresses the limitation of existing artificial corneas by integrating advanced electronic components for replicating the corneal reflex and expanding sensory capabilities. The tunable synaptic plasticity of the ZTO ASs opens up possibilities for developing highly adaptable and responsive visual neuroprosthetics. The ability to simulate various corneal reflex patterns provides a valuable tool for neurological examination and diagnosis. The demonstration of sensory expansion and interaction with environmental stimuli showcases the potential for creating more intelligent and integrated prosthetic devices. The high transparency and low haze of the ZTO fibers ensure that the device is optically compatible with the natural cornea. The study successfully combines materials science, electronics, and neuroscience to create a functional and bio-inspired artificial cornea.

This study demonstrates a novel artificially-intelligent cornea that replicates and expands upon the functionalities of the natural human cornea. The use of tunable ZTO artificial synapses and electrochromic devices allows for the accurate simulation of the corneal reflex and adaptation to varying light conditions. Future work should focus on improving biocompatibility, long-term stability, miniaturization, and integration to enable clinical translation for patients with corneal blindness.

The current prototype is a proof-of-concept and requires further optimization for in vivo applications. Long-term biocompatibility and stability testing in animal models are needed before clinical trials. The response time of the electrochromic device is relatively slow compared to the natural corneal reflex; further improvements in response speed are required. The size and complexity of the current device also need to be reduced for seamless integration into a corneal implant.