A dry eye problem offers a solution

Sometimes solving one problem creates another. Putting up a fence in the backyard may keep the dog from running away, but it could also block the view. Upgrading to a van may provide more room for legs and luggage on road trips, but it could also make it difficult to park. And for more than 140 million people worldwide, contact lenses offer a convenient alternative to glasses to correct vision. However, for 30 to 50 percent of wearers, contact lenses themselves trigger another problem within the eye (1).

The tear film itself and tear film dynamics are very complex, and we think that the contact lens disrupts these dynamics to some extent. 
- Anat Galor, University of Miami Health System

Contact lenses can interfere with the tear film, the lubricating layer on the surface of the eye, causing contact lens-induced dry eye syndrome. “The tear film itself and tear film dynamics are very complex, and we think that the contact lens disrupts these dynamics to some extent,” said Anat Galor, an ophthalmologist and dry eye specialist at the University of Miami Health System. 

Contact lenses seem to promote faster moisture evaporation from the eye and create a barrier that impedes fluid flow to the ocular surface. While younger wearers’ tear-producing glands can often adapt to overcome dry eye symptoms, older adults may experience sensations of grittiness, burning, or irritation, leading to contact lens intolerance. Some may try to manage their conditions with regular eye drop application, gland stimulation, or pharmaceutical treatments, “but none of it is as satisfying as just putting in a contact lens and having it be comfortable like it was when you were 20,” Galor said. “There's definitely a need for more technology and more therapeutic solutions in this regard.” 

To meet this need, researchers are developing contact lenses that restore tear film dynamics to combat dry eye syndrome. Drawing on advanced concepts in material sciences and fluid mechanics, they have designed technology compatible with vision applications that can slow evaporation or direct moisture to the surface of the eye. By incorporating a solution to a major contact-associated problem within the lens itself, they hope to make long-term contact lens use a comfortable option for people of all ages. 

Evaporation and electroosmosis

Byung Hee Hong, a chemist at Seoul National University, was interested in identifying a material that could absorb harmful electromagnetic waves generated by some smart contact lens wearable devices (2). Graphene, a single layer of carbon atoms arranged in a hexagonal lattice, fit the bill, but Hong wondered if it might also reduce dryness in the eye. “The structure of graphene is so densely packed that the space within the lattice is smaller than the size of water, so it protects [against] the evaporation of water through the graphene membrane,” Hong said. Graphene is also optically transparent, mechanically durable and flexible, and biocompatible, making it well-suited for coating contact lenses.

Using a technique called chemical vapor deposition, Hong’s team flowed methane gas over a copper substrate, where the carbon in the methane assembled into graphene at 1,000°C. They then placed the substrate in a solution that dissolved the copper, leaving the graphene floating on the surface and transferred it onto the exterior of a contact lens. 

The researchers set up two vials of water on a hot plate and covered one with the graphene-coated contact lens and one with a normal lens. They weighed the vials over a period of one week and observed that the graphene coating provided a diffusion barrier, reducing the rate at which the water evaporated by approximately 30 percent (2).  

While graphene is theoretically impermeable to water, structural defects in the material can allow fluid to sneak through. To further reduce evaporation, the researchers use various synthesis techniques to prevent defects from forming or buffer for the effects of these deformations by stacking multiple layers of graphene. But “if it's too perfect, then there is some problem with the oxygen supply,” Hong said. “We need some balance between water permeation and oxygen permeation.” 

To prepare for mass production, the researchers developed another strategy for applying the graphene coating to the contact lens using a specific type of tape, which is more scalable and cost effective than the wet transfer method. They estimate the cost of adding the graphene layer to be less than one cent per lens, making it a feasible approach for disposable contact lenses.   

A graphene coating that reduces evaporation could provide one important form of protection against dry eye syndrome. “At the same time, we need to supply the water content very efficiently to the eye surface,” Hong said. “Then probably two different technologies can be combined to develop the more efficient contact lens.” 

To address this need, researchers at Tohoku University developed a contact lens that relies on electroosmotic flow to redistribute moisture within the eye (3). They designed a porous hydrogel material containing a negatively charged methacrylic acid molecule and an accompanying positively charged sodium ion. When they apply voltage across the material, the mobile sodium ions migrate upward toward the negatively charged electrode, carrying water with them. In this way, the device moves fluid from the tear reservoir behind the lower eyelid to the surface of the eye.

The researchers tested hydrogels with various methacrylic acid concentrations and found that while the highest amount gave the most effective water transport, it also yielded a brittle, breakable material. They therefore proceeded with a slightly lower percentage that preserved the strength and flexibility of a contact lens. They also identified a current density threshold for the applied voltage that could maintain upward fluid flow to the degree needed to compensate for evaporation. 

The team then tested their contact lens’s hydration capabilities using an ocular system. They placed the lens on a model of the eye featuring a surface layer of fluid with fluorescent microbeads suspended in it. The beads vibrate in wet conditions but stay still when dry, allowing the researchers to track their motion to monitor moisturization. When they did not apply any voltage, the microbeads almost completely stopped moving after one hour due to loss of moisture from natural drying. However, when they applied a current density above the threshold, the beads remained fully in motion, indicating that electroosmotic flow can maintain fluid between the contact lens and the surface of the eye. 

While these experiments relied on an external power source to generate the electrical current, contact lenses would require a built-in, wireless power supply. The researchers evaluated two types of batteries that could be integrated into the lens with flexible electronics: a magnesium-oxygen battery with metal-based electrodes and an organic “biobattery” with enzyme-based electrodes. In the latter, one enzyme catalyzes the oxidation of sugar, such as glucose found in tears, while the other catalyzes the reduction of oxygen from air. In theory, the environment of the eye provides everything the enzyme-powered battery needs to operate, but “the concentration of sugar in tears is not very high, so the magnesium-oxygen battery can generate the power more stably than the enzyme battery,” said Matsuhiko Nishizawa, a biological device researcher at Tohoku University who developed the electroosmotic lens. “But the enzyme battery is very, very safe. It’s a tradeoff.” 

The lifetime of the biobattery was approximately 12 hours. To extend its activity, the contact lens wearer could supplement the battery’s sugar source with a glucose eye drop solution. “With dropping, we’re confident that the device can work for more than one day. So, it is enough for a daily disposable device,” Nishizawa said. He hopes to further optimize and eventually commercialize the technology “to make smile the many patients with dry eye syndrome,” he said.  

Channeling microfluidics

Yangzhi Zhu, a wearable technology researcher at the Terasaki Institute for Biomedical Innovation, aimed to develop a battery-free contact lens that could beat dry eye syndrome with both safety and simplicity. “We needed to come up with a different method that is more user-friendly and biocompatible,” he said. “You don't need to introduce any external components; you just make full use of the contact lens material itself.” Zhu wondered if he could embed tiny channels into the material that would deliver fluid to the surface of the eye.

Zhu’s team set out to design a microfluidic device that could transport fluid under the standard pressure of blinking (1). Since tears cannot spontaneously flow through the channels due to the surface tension of the water, an external force is required to pump the fluid. “Eyelid pressure is a great human mechanical force that we can use in the lens,” Zhu said.  

The researchers used 3D printing to pattern high-resolution molds with different microchannel configurations and dimensions, cast them in a soft hydrogel material, and added a top capping layer to encapsulate the channels. They then tested their microfluidic lenses using a blinking eye model, which incorporates a 3D-printed artificial eyelid and eyeball that mimic the mechanical properties of the human versions. An actuator device controls the motion of the eyelid, allowing it to apply a blinking force to the hydrogel lens resting on the eyeball. 

Using the results of these experiments and mathematical simulations of fluid mechanics in various microfluidic designs, the team observed that the flow rate increased in microchannels with larger cross-sectional areas. However, the channels need to be narrow enough to fit inside a contact lens, which is only a few hundred micrometers thick. The researchers found that channels with a square cross section 200 micrometers on each side struck a middle ground between effective fluid transport and contact-compatible size.

The team added custom inlet and outlet reservoirs to the device, allowing them to track the transfer of a dyed aqueous solution from the outermost layer of the contact lens to the space between the lens and the surface of the eye. They found that applying eyelid pressures in the range of a normal blinking force (100 to 5,000 pascals) led to significantly faster fluid exchange from the inlet to the outlet reservoir compared to diffusion alone. 

The researchers then fabricated a disk with microfluidic channels in a circular arrangement, providing a prototype for an actual contact lens. Mathematical simulations revealed that the flow rate was approximately equal in the linear and curved channels. The team applied various blinking forces and found that the volume of fluid transported to the outlet reservoir increased by an order of magnitude as they escalated the eyelid pressure from 1,000 to 5,000 pascals.  

What’s more likely to make a difference for dry eyes, however, is not the exact volume transported with each blink, but the fact that fluid is continuously delivered to the surface of the eye with recurrent blinking. The researchers applied a blinking force repeatedly and observed that the outflow volume increased by nearly tenfold from 10 to 100 blinking cycles. As the average person blinks approximately 15 to 20 times per minute, blinking provides a convenient and largely involuntary way to replenish moisture.   

Ultimately, understanding the device’s ability to alleviate dry eye syndrome requires assessing its on-eye performance. To visualize the transport of transparent tears in vivo, the researchers could use a biocompatible dye or measure the thickness of the layer of fluid between the contact lens and the eye. The team plans to evaluate the lens’s effectiveness in animal studies, potentially by detecting tear-based biomarkers or ocular signs of eye dryness. They are also testing different materials for the lens to enhance its oxygen permeability and looking to make the fabrication process feasible with standard contact lens manufacturing equipment.

Galor noted that technology that redistributes tears may not be effective if the tears aren’t present in the first place. “Part of the problem when you’re older is that you just don't have the same ability to produce a tear lake. It's not that it's sitting there and not moving; it's just not there,” she said. 

Zhu agreed that the possibility of a low tear reservoir volume is an important consideration and has a plan to adapt his lens for this patient population. “We can also use the microfluidic contact lens for drug delivery. For example, we can load some drugs that can enhance tear production,” he said.  

Galor hopes that as diagnostic technology for dry eye syndrome evolves, so too will our understanding of its complex tear film dynamics and how to best overcome them. “I can't look at tear dynamics in a contact lens wearer and tell you whether it's an evaporation issue or a redistribution issue,” she said. “We don't have the tools to answer that question right now. ...But it is absolutely possible that one of these or both are viable options. They certainly make biological sense.”

With further studies to demonstrate symptom relief and wearability, these devices could make a big difference for people with contact lens-induced dry eye syndrome. “We use our eyes every day to do so many tasks and specific functions — we’re on the computer or on our phones — and it's frustrating if every time you tried to do that, your eyes feel uncomfortable. So, while these aren't blinding diseases, these are ones that cause significant visual morbidity and lost productivity,” Galor said. “Finding strategies to help patients who are suffering, I think, is a great approach, and I'm really excited to see these ideas develop.” 

References

1. 1. Zhu, Y., et al. A microfluidic contact lens to address contact lens-induced dry eye. Small  19, 2207017 (2023).
2. Lee, S. et al. Smart contact lenses with graphene coating for electromagnetic interference shielding and dehydration protection. ACS Nano  11, 5318-5324 (2017). 
3. Kusama, S., Sato, K., Yoshida, S., & Nishizawa, M. Self-moisturizing smart contact lens employing electroosmosis. Avd Mater Technol  5, 1900889 (2019).