Advances in biomechanical analysis are opening up enticing new avenues in tissue research. Experts in the field at an ARVO 2024 symposium showed the promise—from screening to treatment—that a deeper understanding of these structures may bring.
The eye plays host to a nuanced multitude of structures and tissues that researchers are only beginning to unravel and understand. Much-needed progress on understanding the component structures and materials that make up the eye and their properties has been steady, but slow.
The barriers to a comprehensive understanding of the biomechanical properties of ocular tissues are many. The eye and its components are small. There isn’t much, if any, tissue to spare. And in vivo studies are sensitive due to the essential role of sight in human life and the complex, easily disrupted web of structural interactions that enable it.
But researchers gathered for a symposium at the 2024 Annual Meeting of the Association for Research in Vision and Ophthalmology (ARVO 2024) believe that might be changing. Technologies like optical coherence elastography (OCE), Brillouin microscopy and more are blossoming—and with them, a whole host of new insights, novel biomarkers, and head-turning possibilities for screening, treatment and beyond.
Novel methods for seeing—and measuring—the eye
Manual tissue palpation is one of the oldest forms of medicine, and Dr. Kirill Larin (University of Houston, USA) is at the forefront of those trying to bring it to the modern age for use in the eye.
After explaining tissue palpation’s roots in Ancient Egypt and Greece, Dr. Larin described his vision for OCE, a modern method for, in a way, palpating the tissues of the eye to discover the secrets latent in their biomechanical properties.
In OCE, force is applied to a tissue, which is then imaged and measured to understand properties like elasticity and relative hardness and softness. “It’s embarrassingly simple,” Dr. Larin said.
“You take standard OCT imaging and you apply a force. When you apply a force, if you measure area and divide by change in the tissue structures, you can deduce its mechanical properties because if you have stiffer material, it’s going to deform less,” he said.
According to Dr. Larin, one key observation that has propelled OCE forward is the ability to use natural variations in IOP (when the heart beats, for example) as a way to induce and measure deformation. The resulting lack of a need to apply external force has opened many doors for OCE.
As a result, this technology is seeing a rush of possible new applications across ophthalmology. In LASIK, for example, the softness of the cornea can be measured preoperatively in an attempt to predict the possibility of post-LASIK corneal ectasia.
Dr. Larin also mentioned research on using OCE measurements in corneal injuries and keratoconus. He’s even used it to measure the limbus and the eye globe itself. “It allows you to do 3D imaging of tissue, and this can give you highly localized mechanical information. I personally believe there’s great promise for the future detection of different diseases and therapeutics,” he concluded.
Dr. Giuliano Scarcelli (University of Maryland, USA) spoke next about how he’s breathing new life into Brillouin microscopy, another method for imaging ocular tissue for biomechanical evaluation.
With this technique, interactions between light waves and sound waves are measured to provide useful information on the hidden structures within the eye. Dr. Scarcelli’s work on Brillouin microscopy has been gathering steam over the last few years, the results are promising.
Like with Dr. Lavin and OCE, he sees great potential for the technology in corneal ectasia and keratoconus, among others. Direct, accurate measurements of the cornea with high spatial resolution that can be performed in vivo are a holy grail of sorts in corneal biomechanics, and according to Dr. Scarcelli, Brillouin microscopy just might be the ticket.
Deep dives on the lens and mechanobiology of glaucoma
After these scintillating new tools and their potential were put on display, the spotlight shifted to advancements in our current knowledge of the biomechanics of the eye and its tissues. Dr. Catherine Cheng (Indiana University Bloomington, USA) presented her work on understanding the nuanced, deep structures of the lens in mouse eyes.
At issue for Dr. Cheng’s group were the determining factors in lens stiffness and resilience. They found that the contributing factors in lens stiffness were the complex interdigitations between fiber cells, cytoskeletal networks, like the f-actin networks and intermediate filament networks, and the integrity of the lens capsule.
On the other hand, the contributors to lens resilience were different. The cytoskeletal networks like f-actin may be involved, Dr. Cheng said, and there may be a correlation with lens nucleus size, though more research is needed. The lens capsule also might be involved, though Dr. Cheng said this depends on the severity of the defect.
One of her findings though, aroused heightened interest. “Most importantly, we found that the Y-suture actually plays a really important role in lens elasticity,” she said. “Actually, the mispatterning of the cells and the misalignment of the Y-suture causes the lens to be more resilient.”
For Dr. C. Ross Ethier (Georgia Institute of Technology, USA), it is glaucoma that has drawn the kind of specialized attention that Dr. Cheng’s group placed on lens biomechanics. His presentation was full of insights on the mechanobiology of the human’s eye’s apparent self-regulation of IOP homeostasis.
Dr. Ethier’s lab has taken full advantage of technologies like the aforementioned Brillouin microscopy and OCE, along with atomic force microscopy (AFM) to reach some fascinating conclusions.
He has found that the outflow pathway tissues, like the trabecular meshwork and the inner wall of the endothelial monolayer lining Schlemm’s canal, are stiffer in glaucomatous eyes—though the mechanobiology of the outflow pathway remains complex. The regulatory system for maintaining IOP homeostasis in healthy eyes, however, holds perhaps the most promise for Dr. Ethier.
“We have a very complex mechanobiologic regulatory system with redundancy and multiple pathways,” he said. “This is great because it offers us a lot of opportunities for therapeutic intervention, and hopefully pressure control.”
The promise of modern biomechanical analysis
The final speaker of the day, Dr. Christine Wildsoet (University of California at Berkeley, USA), brought home the most crucial theme of the session, carried over from Dr. Ethier. In the end, it’s all about helping patients, and she explained how scleral biomechanics might be opening new doors for interventions in one of the world’s most pressing areas: myopia.
Dr. Wildsoet surveyed a large amount of research on the influence of the sclera in myopia. Among these, she revisited the role of the sclera in IOP and the potential benefits from using an agent like latanoprost to control myopia.
She also mentioned research on hydrogels drugs delivered to the sclera as a potential alternative to the unpopular and highly invasive scleral buckle in failing sclera in myopic eyes. But her overall message and point of emphasis was much more general—providing a fitting end to the session.
“I think translation is a two-way street,” Dr. Wildsoet began. “We’ve got to be jumping between the clinic and basic science and back again to inform one another. Having cross-disciplinary collaboration is really valuable for getting us to think outside the box,” she concluded, pointing to the immense potential on display throughout the symposium for the integration of engineering and biomechanical evaluation into potentially life-changing innovations in ocular tissue research.
Editor’s Note: The Annual Meeting of the Association for Research in Vision and Ophthalmology (ARVO 2024) is being held from 5-9 May in Seattle, Washington, USA. Reporting for this story took place during the event.
