Recognizing LSCD through advanced diagnostics
LSCD occurs when the limbal epithelial stem cells—or their niche—are damaged or dysfunctional. While severe cases may present with dense neovascularization and corneal opacity, more subtle presentations are common in clinical practice. Diagnosing LSCD can be particularly difficult in eyes with sectoral involvement or atypical fluorescein staining patterns. Optimally, diagnosis involves a combination of slit-lamp exam, appropriate amount of fluorescein staining, anterior segment OCT (optical coherence tomography) and in vivo confocal microscopy.
Dr. Deng emphasized the importance of applying the correct amount of fluorescein to the ocular surface. Inadequate or excessive dye can obscure the staining patterns indicative of LSCD. Confirmatory diagnostics—such as in vivo confocal microscopy—can assess basal epithelial cell density and identify conjunctival goblet cells in atypical locations. OCT imaging further helps evaluate epithelial thickness and detect subepithelial scarring.
A 2019 consensus statement from the International Limbal Stem Cell Deficiency Working Group recommends incorporating molecular or cytologic testing whenever possible to confirm LSCD before surgical intervention. These tests aid in differentiating LSCD from mimicking conditions such as dry eye disease or post-surgical ocular surface changes.
A step-by-step approach to LSCD management
Effective LSCD management begins with addressing ocular surface comorbidities. Before pursuing surgical options, clinicians should correct eyelid or conjunctival abnormalities, reduce surface inflammation and discontinue any medications causing toxicity. Preservative-free formulations are preferred, and punctal plugs may be used to improve tear film stability and support healing.
Optimizing the ocular surface can lead to significant improvement, even in cases previously deemed surgical. For example, a patient initially diagnosed with stage 2B LSCD showed substantial visual and structural recovery after managing inflammation and switching to less toxic medications, without proceeding to limbal stem cell transplant.
If LSCD persists after medical optimization, surgical intervention may be appropriate. The treatment strategy depends on disease staging and laterality. Stage 1 and early stage 2A may respond well to observation and medical therapy, particularly in unilateral cases. For more advanced or bilateral cases, limbal stem cell transplantation—either autologous or allogeneic—becomes a critical tool for ocular surface rehabilitation.
Evaluating surgical options and outcomes
Transplantation options include direct tissue transplantation (allograft or autograft), cultivated limbal epithelial cell transplantation (CLET) and mucosal grafts. Selective procedures like SLET (simple limbal epithelial transplantation) are preferred over older approaches, as they minimize donor site morbidity. Cultivated autologous limbal epithelial cells can also be effective and require smaller tissue samples, though standardized outcome measures are still under development.
Autologous transplants have shown higher success and lower complication rates than allogeneic procedures. However, long-term success remains limited, with many studies reporting outcomes ranging from 50–76%. For bilateral LSCD or cases lacking autologous donor tissue, allogeneic transplants, keratoprosthesis, or oral mucosal grafts are potential alternatives.
Dr. Deng also highlighted her team’s ongoing work in developing a xenobiotic-free, feeder-free stem cell culture system. This platform supports stem cell expansion in less than two weeks and incorporates quantitative assays to assess cell quality. A Phase I clinical trial is now underway to test the safety and feasibility of this method in treating LSCD.
Future directions in LSCD care
Emerging evidence suggests that residual limbal stem cells may exist even in eyes diagnosed with total LSCD. In vivo imaging has revealed hidden cell populations embedded in deeper stromal layers or less-accessible regions of the limbus. Understanding the resilience and plasticity of these stem cells opens new avenues for targeted therapies.
Future treatments may focus on rejuvenating residual stem cells through topical therapies or stimulating regeneration within their native niche. For patients lacking viable stem cells, expanded culture-based approaches offer the potential for more durable ocular surface reconstruction.
Regardless of the treatment path, a standardized staging and outcome system is essential to compare interventions and optimize care. As researchers refine these tools, the field moves closer to more precise and personalized LSCD management.
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About the author
Brooke Harthun, Partner Development Director