New Approach to Keratoconus

Patients with keratoconus and other progressive corneal diseases may soon benefit from a novel treatment involving implantation of intrastromal lenticules capable of stimulating corneal stromal regeneration, according to a study presented at the ESCRS Winter Meeting in Frankfurt.

“Fresh myopic intrastromal lenticular (FML) implantation seems to offer a safe, economical, and reliable technique that leads to increased corneal thickness, improved visual acuity, and the regeneration of healthy keratocytes, extracellular matrix, telocyte cells, and stem cells that are involved in stromal regeneration,” reported Ceren Ece Semiz MD.

FML may offer a number of advantages over current techniques to treat advanced keratoconus, which typically involve invasive surgery such as penetrating keratoplasty—carrying a high risk of complications such as infectious keratitis, tissue rejection, or even endophthalmitis.

Dr Semiz’s study included 60 eyes of 40 patients with advanced keratoconus indicated for corneal transplantation (stage 2 or 3 advanced keratoconus according to the Amsler–Krumeich classification) at the Eye Hospital Pristina, Kosovo. A lenticular implant was removed from donor patients who underwent SMILE (VisuMax; Carl Zeiss Meditec AG) surgery for refractive error correction. The lenticules extracted from the donor eyes were implanted in the 60 keratoconic eyes on the same day and followed for up to five years.

Dr Semiz highlighted key aspects of the surgery using the VisuMax femtosecond laser.

“The surgeon (Faruk Semiz MD) created a stromal pocket with a diameter of 8.00 mm, which is larger than the optical zone of the donor lenticule, and a cap thickness set to 130 μm from the corneal surface and a 2.09-mm incision according to high keratometric value,” she said.

Although intrastromal lenticule implantation has already been reported as a safe and effective surgical option for advanced keratoconus, previous studies have used lenticules preserved in eye banks or decellularised by cross-linking (CXL). The rationale behind Dr Semiz’s approach is the fresh lenticules contain extracellular matrix, keratocytes, telocytes, and stem cells—all of which play an integral role in stromal regeneration and damage repair. “Extracellular matrix provides a suitable environment for the implanted lenticule to survive, while telocytes are responsible for homeostasis, intracellular communication, and stem cell activation,” she said.

Another key consideration is the shape of the lenticule because the central part of the myopic lenticule is thick, whereas its periphery is thin.

“In the keratoplasty indicated advanced keratoconic eyes—even though the fundus examinations are normal—these eyes have high myopia due to irregular astigmatism and increased cornea elasticity,” she said. “Therefore, based on the topography the central thick part of the donor lenticule should be placed on the thinnest part of the recipient cornea to transform the conic cornea shape into an ellipsoid form.”

For histopathological, immunohistological, and electron microscope examinations, lenticular samples were randomly extracted from treated keratoconus patients several times in the one to five years after surgery. SMILE was not applied again. The extracted volume was then replaced with a new lenticule.

Electron microscope images showed disorganised and thinned collagen fibres as well as apoptotic cells in the cornea with keratoconus. In contrast, the control eyes implanted with the fresh lenticules demonstrated well-organised parallel lamellar structures.

Postoperative immunofluorescence images displayed both telocytes and stem cell-like cells. Additionally, five years after surgery, corneal biopsy samples were stained immunohistochemically with a CD34 marker to highlight progenitory cells and telocytes. An increase in progenitory and telocyte cell activity was observed, indicating stromal reorganisation and regeneration.

Dr Semiz presented at the 2024 ESCRS Winter Meeting in Frankfurt.

Ceren Ece Semiz MD is an assistant in the Department of Ophthalmology at Eye Hospital Pristina, Kosovo. cerensemiz99@gmail.com