Cornea, Corneal Therapeutics
Cultivating Progress for LSCD
Clinical trials now underway could further support promise shown by cultivated limbal stem cells.
Cheryl Guttman Krader
Published: Monday, April 1, 2024
Research advances are reshaping the diagnosis and treatment of limbal stem cell deficiency (LSCD), according to Sophie X Deng MD, PhD.
Stage classification is part of the foundation for management decisions, so in diagnosis, Dr Deng said recent evidence indicates biomarkers of LSC function identified by in vivo confocal microscopy may provide more accurate information for staging than clinical examination.
She illustrated her point by presenting a case of a patient misdiagnosed with stage III LSCD based on clinical exam but found to have minimal LSCD when assessed with confocal microscopy. Dr Deng also noted using the in vivo imaging tool revealed hidden normal epithelial cells in eyes staged with total LSCD by clinical exam.
“These existing limbal epithelial cells can be retrieved by targeted biopsy and expanded in culture to achieve autologous stem cell transplantation that is favoured over the use of allogeneic cells whenever possible,” she said.
“Although both simple limbal epithelial transplantation (SLET) and cultivated limbal epithelial transplantation (CLET) can provide excellent results, cultivated LSCs might be the preferred choice for treating total LSCD, while SLET might be sufficient in eyes with less severe LSCD. Randomised controlled clinical trials using a set of standardised disease staging criteria are necessary to compare the efficacy of different therapies.”
New methods for rejuvenation
Cases of stage I LSCD require observation and optimisation of the ocular surface and might provide enough improvement of the corneal surface to avoid limbal stem cell transplantation in eyes with moderate LSCD—although Dr Deng noted promising results obtained in ongoing research indicate the possibility of treating the latter eyes with mesenchymal stem cells or growth factors that will promote the growth of residual LSCs in the future.
“It has been shown that mesenchymal stem cells and their secretome have anti-scarring properties and can promote epithelial wound healing,” she said. “Perhaps in the future, topical medications made from the extracellular vesicles/secretome of the mesenchymal stem cells might replace or reduce the need for corneal transplantation to treat corneal scarring and epithelial defects.”
Progress in LSC cultivation
CLET is not available in the United States because the cultivation process involves xenogeneic murine feeder cells and foetal bovine serum, making it more challenging to meet the FDA regulatory requirement. Research in the field of LSC transplantation also includes efforts to improve the safety of manufacturing LSCs by removing all animal products.
Dr Deng identified Dr Ula Jurkunas and colleagues as one of the teams in the US actively working on this area and cited their development of a xenobiotic- and feeder-free LSC manufacturing process that would meet FDA requirements. Dr Deng and colleagues have also been working on a new process for manufacturing LSCs and have been successful in devising a robust method with a favourable safety profile.
Recruitment is now underway for patients with severe to total LSCD for participation in a phase 1 study she is conducting investigating the safety and feasibility of expanding cultivated autologous LSCs using their manufacturing process. The preliminary data show promising safety and efficacy results. Dr Deng provided the clinicaltrials.gov ID number (NCT03957954) and asked colleagues to refer potential candidates.
Dr Deng spoke at AAO 2023 in San Francisco, US.
Sophie X Deng MD, PhD is Professor of Ophthalmology and Co-Chief Cornea Division, Stein Eye Institute, UCLA, Los Angeles, California, US. deng@jsei.ucla.edu
Latest Articles
Glaucoma Treatment Under Pressure
New techniques and technologies add to surgeons’ difficult decisions
Outside the Box, Inside the Pipeline
Researchers are tackling glaucoma diagnosis and treatment from all sides.
The EHDS Is Ready for the Green Light
If proposal is approved, Europe could see better access to, and exchange and use of, health data.
From Lab to Life: Corneal Repair Goes Cellular
Long-awaited cellular therapies for corneal endothelial disease enter the clinic.
Balancing Innovation and Safety
Ensuring access to advanced cell therapies amid regulatory overhaul.
With Eyes on Its Future, ESCRS Celebrates Its Past
Winter Meeting offers opportunities to experiment with new concepts and formats.
Best of ESCRS Winter Meeting 2024
Following the New Generation
EDOF IOLs an option for eyes with mild comorbidities, showing potential in mini-monovision strategies.
Refocus on Multifocals
Trifocal IOLs continue to improve as consensus grows regarding indications and contraindications.
Common Myths in Presbyopia Correction
Patient education key to satisfaction with refractive IOLs.