Expanding Options for Stromal Supplementation

There’s never enough supply for the growing demand for corneal tissue around the world, making bioengineering and innovative intrastromal lenticular implantation enticing solutions.

This two-pronged approach to one of ophthalmology’s most pressing issues—supplementing the stroma via recreation or enhancement—is full of fascinating opportunities. According to Sayan Basu MBBS, the bioengineering approach has three potential directions to explore.

“The first is with keratocytes (mesenchymal cells), which can be targeted towards regenerating optically transparent corneal tissue through remodelling of opacity,” Dr Basu said. “The second is to examine the decellularised extracellular matrix (dECM), repairing corneal tissue via scaffolding and scarless wound healing. The third is to put these two together. This involves replacing corneal opacity with bioengineered, transparent and tectonically stable tissue.”

While bioengineering is still relatively novel in ophthalmology (from a historical perspective), lenticular implantation or epikeratophakia is not. According to Aylin Kılıç MD, while this technique is not new, doctors can unlock its full potential by using corneal allograft tissue as a novel material.

“Using corneal allograft tissue has the advantage of being fully biocompatible without foreign body reaction. It’s also shapeable, and can be prepared as rings, segments, lenticules, or inlays,” Dr Kılıç said.

“We can shape lenticular tissue precisely by using an excimer laser to create inlays and put the stroma under a flap. We can create intracorneal rings and change the shape of the cornea for keratoconus patients too.”

Engineering good patient outcomes

Human limbus-derived mesenchymal cells (hLMCs), taken from cadaveric corneo-scleral rims, are particularly advantageous, according to Dr Basu. That’s because they can create new matrices in the cornea, remove any present opacity, and produce a clear stroma.

“We examined one case involving a patient with a Hansen’s disease-derived persistent epithelial defect who had not responded to treatment with amniotic membrane grafts,” Dr Basu said. “The effect of the hLMCs treatment was so profound that there was an amount of nerve regeneration that occurred, along with stromal regeneration.”

Dr Basu said that the dECM method is even more innovative because it uses corneo-scleral rims that are “discarded from the eye bank as they are not of high optical quality.” These can then be processed and converted into dECM-derived treatments such as hydrogels.

Dr Basu added that this process is extremely efficient since multiple samples can be taken from the same donor. The resulting dECM hydrogel can then be applied rapidly to a large number of patients affected by a wide range of conditions.

The same level of efficiency can be achieved by using corneal allograft tissues too, according to Dr Kılıç. That’s because it’s reversible and can be removed or exchanged if needed, so the operating doctor can create a thinner lenticule if needed, then re-implant the lens based on the cornea’s behaviour.

“This means there are multiple clinical applications,” Dr Kılıç said. “These include cone flattening and astigmatic reduction for keratoconus, and myopia, hyperopia, and presbyopia correction with lenticules and inlays for refractive purposes.”

Life-changing 3D printing

Dr Kılıç believes surgeons can “change a patient’s life within minutes” by using novel materials such as allograft corneal tissue in intrastromal lenticular implantation. The ability to reverse implantation is valuable, as is the fact that it is flexible, allowing the shape, size, and thickness of the lens to be customised according to each patient’s needs.

“This form of biological integration with the cornea is safe, and it can use sterilised cornea tissue that’s already available today,” Dr Kılıç explained. “It can be tailored for each patient and has been clinically proven with clear long-term safety and efficiency.”

As for Dr Basu, something with less clinical provenance (given its novelty) but full of potential is 3D bioprinting using dECM hydrogel as a type of ‘ink’ to create 3D-generated constructs. Studies into 3D bioprinting are at an elementary stage, but he’s adamant that the technology shows considerable promise.

“You scan the patient’s cornea and you get your 3D model. It will then print out the substrate of the cornea, the engineered corneal substitute, and it can also carry out photo cross-linking,” Dr Basu said.

“3D bioprinting allows for the customised integration of cells in the corneal stromal scaffold. It’s affordable, highly customisable, and the human tissue alternatives it produces are optically clear and mechanically strong.”

Drs Kılıç and Basu presented at the 2025 ESCRS Annual Congress in Copenhagen.

Sayan Basu MBBS, MS is the Head of Research at the L V Prasad Eye Institute, Hyderabad, India. sayanbasu@lvpei.org

Aylin Kılıç MD is an associate professor at Biruni University and the Medical Director of the Swiss Vision Group Istanbul, Türkiye. aylinkilicdr@gmail.com