In the currently published literature, evidence does not support any clearly superior method for limbal stem cell transplant, leading to challenges in confirming the safety and efficacy of treating limbal stem cell deficiency (LSCD), according to research published in The Ocular Surface.
Researchers conducted a systematic review examining the efficacy, safety, and cost effectiveness of cell-based therapies for the management of LSCD, a condition that can develop following severe chemical or thermal burns, contact lens-related injury, ultraviolet radiation, extensive cryotherapy, surgery to the limbus, hereditary disease, or other issues. The condition has historically been treated by transplanting limbal tissue, the research explains. Additional treatment methods, including cultured limbal epithelial autografts and cultured autologous oral mucosa stem cells, were developed in following years.
Researchers identified studies published through September 2020, attempting to answer several key questions about the treatment of unilateral and bilateral LSCD.
Ultimately, 52 studies of 1113 eyes were included in the systematic review. Individual patient data were reported in 41 of these studies, inclusive of 716 eyes; however, included data varied and only a portion of this information was included in analyzed individual patient data outcomes.
An overall patient data analysis of 471 eyes found that between 55.9% and 76.7% of cases were likely to be considered successful. The best estimated percentage of success was found with ex vivo cultivated conjunctival autograft (EVCAU), followed by ex vivo cultivated oral mucosal autograft (EVOMAU), ex vivo mesenchymal stem cell allograft (EVMSCAL), ex vivo cultivated limbal Autograft (EVLAU), and ex vivo cultivated limbal allograft (EVLAL) (76.7%, 71.4%, 70.2%, 67.1%, and 60.1%, respectively). However, investigators noted that success criteria differed substantially between studies, and these data should be interpreted with caution.
Following a sensitivity analysis limited to patients who underwent a stem cell regraft procedure, the estimated success percentage was 50.2% (95% credible interval, 33% to 65.7%) — lower compared with the main analysis estimate (66.7%).
When evaluating LogMAR best-corrected visual acuity (BCVA), a 1.05-unit improvement was expected following EVCAU transplants. The lowest expected BCVA improvement was 0.53 units, following EVMSCAL. The review did, however, provide evidence for a small but detrimental effect of age on BCVA improvement, with each additional year of age leading to a reduction in BCVA improvement by 0.007 LogMAR.
Most included studies did not report symptom relief data. Three reported that between 12.5% and 17% of patients experienced negative symptoms, including pain, burning, and photophobia following treatment. Comparatively, 8 studies reported improvement in pain, burning, dryness, or photophobia, with between 33% and 100% of patients demonstrating improvement. Quality-of-life outcomes were rarely reported, with only 5 studies providing data on these domains. A pair of studies provided limited evidence demonstrating the positive impacts of transplantation at 1 year, and 1 study reported a quality-of-life improvement in 95.6% of participants.
Of the included studies, 9 reported surgical complications. Within the individual patient data analysis, 14 studies of 279 eyes included sufficient data. The best estimates for expected percentage of postoperative complications in transplant recipients was 42.9% in EVLAL, 22.4% in EVLAU, 14.7% in EVCAU, and 13.8% in EVOMAU, respectively. Postoperative complications in recipients can be expected in 9.3% to 50.5% of patients (median estimate, 26.2%). Four studies reported graft rejection and 1 study reported immune rejection.
Limitations of this analysis include a high bias risk based on quality of reporting, the use of least-rigorous study designs, and small sample sizes across studies, due to the orphan nature of LSCD.
Future research should include more randomized controlled trials of limbal stem cell transplant recipients. Where randomized controlled trials are not feasible, researchers might consider researching larger populations through multinational, multicenter collaborative trials or registries.
“The many studies of therapies for both unilateral and bilateral limbal stem cell deficiency that we have identified are not easily synthesized and there is no clear evidence for the superiority of one therapy over another,” the research concludes. “There is great unmet need for further better designed, conducted, and reported research and investment to be able to identify the most effective and safe cell therapy to treat LSCD.”
Figueiredo FC, Glanville JM, Arber M, et al. A systematic review of cellular therapies for the treatment of limbal stem cell deficiency affecting one or both eyes. Ocul Surf. 2021;20:48-61. doi:10.1016/j.jtos.2020.12.008.