With corneal blindness affecting an estimated 12.7 million people worldwide, novel treatment approaches are required. On this interview, we speak to Professors Neil Lagali and Mehrdad Rafat about their latest research, which detailed a bioengineered corneal tissue for minimally invasive vision restoration in advanced keratoconus in two clinical cohorts. 

Please are you able to introduce yourself, tell us about your scientific background, and what inspired your latest research?

Neil Lagali: I’m trained as an engineer in physics and optics, but for the past 20 years, I actually have been performing research specializing in corneal diseases. I’m currently a Professor of Experimental Ophthalmology at Linköping University in Sweden.

This research was inspired by a desire to deal with the massive burden of worldwide corneal blindness and the present inequities in access to vision care. This has turn into much more pressing with the United Nations in 2019 adopting a resolution committing us to achieve 1.1 billion individuals with vision impairment who lack access to eye care by 2030 as a part of the Sustainable Development goals.

Mehrdad Rafat: I’m a biomedical engineer by training with a Ph.D. in Chemical & Biological Engineering from the University of Ottawa, Canada. I actually have greater than 20 years of experience in Biomaterials and Tissue Engineering. The unmet need for corneal implants to treat corneal blindness inspired me to tackle this research and development work to assist people see or see higher.

Corneal blindness affects an estimated 12.7 million people worldwide. What are the present treatment options and their associated challenges?

Corneal transplantation is the present gold-standard treatment option for corneal blindness. When corneal transplants fail, prosthetic devices might be utilized in essentially the most severe cases, but those cases are relatively rare. For the overwhelming majority of corneal blindness, transplantation is the one option for regaining vision.

Image Credit: Thor Balkhed/Linköping University

Nonetheless, just one cornea is offered for each 70 needed, and over half of the world’s population doesn’t have access to donor corneas. Even when a donor cornea is offered, the infrastructure needed to acquire, store and distribute it is critical. It must be tested for diseases and viruses, which can be expensive. Finally, after transplantation, there may be at all times a risk of rejection of the donor tissue, meaning that immune suppressive medications should be given to patients for at the least a yr after transplantation.

The cornea consists mainly of the protein collagen. How was the bioengineered cornea created, and what benefits does it present over donated corneas?

We also wanted to make use of collagen to create a bioengineered cornea, to mimic the natural cornea. Because there isn’t a abundant and low-cost source of human collagen, we selected to make use of collagen sourced from pig skin. This collagen is abundant, inexpensive, highly purified and already utilized in FDA-approved medical products. Briefly, the purified collagen is rehydrated and crosslinked with a non-toxic chemical crosslinker that’s water soluble and washes out of the implant. Its only effect is to bind the collagen fibers to strengthen the implant. Then, in a second step, the implant, to which a small amount of riboflavin (vitamin B2) was added, is exposed to UVA light, which photochemically binds the collagen fibers further to supply a sturdy implant, which is a hydrogel containing almost 88% water.

The advantage of the bioengineered cornea is that it doesn’t contain impurities, human cells, or cellular material; due to this fact, it has a much lower risk for rejection than donated corneas. It might probably even be customized to the scale, thickness, and shape of the recipient. It’s packaged and sterile, might be shipped anywhere on this planet at room temperature, and might be stored for as much as two years before use in a normal refrigerator.

Donor tissue should be procured and transplanted inside two weeks and requires specialized eye banks and medicines to maintain the tissue viable, which represents a high cost and infrastructure requirement, that’s unfortunately not available in lots of developing countries. Finally, donated corneas are very scarce, whereas the bioengineered implant can, in theory, be mass produced.

You furthermore may developed a novel method for treating keratoconus. Please could you tell us about this disease, your latest method, and the benefits it presents?

Keratoconus is a progressive disease starting in childhood and progressing throughout the teenage years. It involves a gradual breakdown of the collagen within the cornea, causing it to get weaker, thinner and lose its shape and talent to focus light. Vision gets progressively worse. The reason for keratoconus is unknown usually, and there isn’t a option to prevent it.

If not detected and treated early, it can progress to some extent where severe visual impairment and blindness occur, after which only a corneal transplant can restore vision. It’s a typical disease; nevertheless, its prevalence varies from about 0.1% of the population within the USA to as much as 2-3% of the population within the Middle East, Asia, and Australia. Which means in a rustic similar to India or China, tens of tens of millions of individuals have the disease. Unfortunately, it is just not detected or treated early in lots of countries, resulting in severe vision loss and blindness.

Image Credit: Garna Zarina/Shutterstock.com

A corneal transplant is needed for advanced stages of keratoconus when the cornea becomes too thin or irregular for preventative measures. This requires removing the whole thickness of the cornea and replacing it with a human donor cornea that’s then sewn into place. Since the transplant is foreign human tissue containing cells, the patient must receive immunosuppressive eye drops for at the least a yr and are available back to the clinic several times to regulate, replace, and take away the sutures. Even then, vision is just not optimal and requires further corrective refractive procedures.

In cases where the cornea remains to be transparent, our method keeps the patient’s own cornea, only making a small incision inside it and inserting our bioengineered implant. The implant doesn’t have cells, so it doesn’t trigger an immune response, and only an 8-week course of immune suppression eye drops is required. No sutures are needed, and the procedure might be performed in a single hospital visit. The wound healing may be very fast, and vision improves almost immediately. We showed that this procedure has the potential to present 20/20 vision to initially blind patients without using donor tissue. It is usually a procedure that is less complicated to perform than standard transplantation, which we hope will allow it to be adopted in less specialized centers.

Lots of those that need corneal implants live in developing countries. How essential was it to you to think about economics when developing this implant?

Economics was a significant consideration after we used collagen derived from pig skin as a byproduct from the food industry. This ensures an inexpensive, abundant, and sustainable source of collagen that may translate into low-cost corneal implants that might be mass-produced and distributed to places where the burden of corneal blindness is highest. We also considered economics when developing our implantation technique, which is easier than current transplantation methods and doesn’t require extensive medications or many follow-up hospital visits.

Image Credit: Thor Balkhed/Linköping University

Other eye diseases, like cataracts, cause a high incidence of blindness. Is there the chance that similar implants could possibly be used to treat other eye diseases?

Our work demonstrates the feasibility of implanting a biomaterial in the attention and its stability in the long run to revive lost function. Although we haven’t tested the approach for other eye diseases, the principle has now been demonstrated. Cataracts might be treated with existing artificial implants; the challenge is to make the procedure more available globally and at a low price. Availability and price were key requirements that led us to develop the bioengineered corneal tissue and implantation method we now report.

How do you foresee biomaterials influencing healthcare and medicine in the long run?

Biomaterials can potentially restore lost function through substitute or partial or full regeneration of tissues within the body. They might be combined with cells or drugs to attain maximal therapeutic effects. Besides providing a big supply of well-defined tissues for transplantation without the necessity for donor tissue, we also foresee that biomaterials shall be a part of the arsenal in treating disease in the long run when combined with appropriate medical knowledge, techniques, and therapeutic substances. We’re entering an accelerating research phase where many teams worldwide are making breakthroughs in tissue and organ repair with the assistance of biomaterials. We expect that the usage of biomaterials in medicine will proceed to grow.

What’s next for yourself and your research?

We plan to conduct randomized clinical trials with a bigger variety of patients. So we’re working on obtaining funding for that. Once we are able to show this works in a randomized trial, then we’ll apply for authorization to market the bioengineered implant as a product. Within the meantime, we’re performing basic and clinical research to expand the appliance of the fabric to other eye conditions.

Where can readers find more information?

About Neil Lagali

Neil Lagali is currently Professor of Experimental Ophthalmology at Linköping University, specializing in cornea and diseases of the ocular surface. The Lagali lab performs basic science in cell culture and molecular biology and evaluation of latest biomaterials, biomedical devices, and experimental substances in existing and latest models of eye disease. In close collaboration with ophthalmologists, his team also performs clinical studies with a give attention to biomedical imaging, mechanisms of eye disease, and latest surgical therapy development for eye disease. His formal education is in engineering, physics, optics, and photonics, after which he worked within the fiber optic telecommunications industry in Canada and the USA. Through the past 20 years, he has been working in the sphere of biomedical research and ophthalmology specifically. He has led large EU-funded research consortia and networks (www.arrestblindness.eu, www.aniridia-net.eu), holds quite a few patents, and has published over 100 papers in the sphere of cornea research. He’s currently associate editor for the journals Scientific Reports and The Ocular Surface.

About Mehrdad Rafat

Mehrdad Rafat is currently an Adjunct Associate Professor of Tissue Engineering on the Department of Biomedical Engineering at Linköping University in Sweden and the co-founder and  CEO of Linkocare Life Sciences AB, the start-up company that has manufactured the bioengineered corneas utilized in the present study, and NaturaLens AB, a latest start-up mandated to develop natural contact lenses for treating myopia in dry eye patients in collaboration with the European Institute of Innovation and Technology (EIT-Health).

He’s an experienced entrepreneur with a demonstrated history of working in higher education, government agencies, and industry in Canada, US, and Sweden. Expert in Biomaterials, Tissue Engineering, and Ophthalmic Medical Devices with strong educational background with a Ph.D. degree in Chemical & Biological Engineering from the University of Ottawa, Canada, and postdoctoral fellowships at Health Canada and Ottawa Health Research Institute. I actually have founded successful life science spin-off firms out of my academic research including LinkoCare and NaturaLens AB.