Limbal stem cells are pluripotent cells located in the limbus that constantly renew the corneal epithelium and are essential for ocular surface health throughout life.¹ Limbal stem cell deficiency (LSCD) occurs when there is a dysfunction or disproportionate loss of limbal stem cells, and the quantity of functioning limbal stem cells is lost so that normal corneal homeostasis is disrupted.^2-4

Multiple conditions cause LCSD, including autoimmune conditions, thermal and chemical burns, contact lens overwear, aniridia, medicamentosa, and ocular surgeries.⁵ LSCD can contribute to pain of the ocular surface and vision loss due to persistent epithelial defects of the cornea, corneal melts, corneal neovascularization, and corneal scarring.⁶

LSCD is challenging to treat and is related to sizable corneal morbidity. Treatment for mild cases of LSCD include supportive care, such as limiting contact lens overwear, discontinuing eye drops that contain preservatives, practicing frequent lubrication, and using punctal occlusion, serum tears, topical steroids, and scleral or bandage contact lenses.⁷ Scleral lenses remain one of the therapeutic treatment options for managing LSCD.

Treatment for moderate to severe cases often necessitates procedures for visual rehabilitation that have a high risk for adverse events. Examples are stem cell transplantation and keratoprosthesis.^8-9 LSCD is a significant public health burden due to the correlated therapeutic challenges.

A study examined the patient demographics common for LSCD and reported the frequency, identifiable etiologies, and treatment outcomes.⁷ A retrospective literature review compared the demographics and/or epidemiology of LSCD of 3 large retrospective studies from the University of Minnesota (UMN), the Cincinnati Eye Institute (CEI), and the LV Prasad Eye Institute (LV Prasad).

The average age of diagnosis was 53.2 years for the UMN cohort and 42.9 years for the CEI cohort. The median age was 24 years old in the LV Prasad cohort. A 2:1 male predominance was reported in the LV Prasad cohort. The LV Prasad and UMN cohorts described similar rates laterality of LSCD (unilateral vs bilateral); 70% of cases in the CEI cohort reported bilateral LSCD.

The main cause of LSCD was ocular burns (53.7%) in the LV Prasad cohort, congenital aniridia (30.9%) in the CEI cohort, and chemical/thermal burns (18.7%) in the UMN cohort. Solely, the UMN site described an LSCD frequencyof 4.25%.

A younger age of diagnosis, sex discrepancy, and primary etiology of ocular surface burns was found in the LV Prasad cohort. The majority of the burns were due to lime powder (chuna), which is frequently consumed with betel leaves and tobacco in parts of Asia. Chuna is the most widespread chemical in pediatric ocular chemical injuries, with a male predominance of 63%.¹⁰

LSCD is probably underdiagnosed and undertreated, which is compounded by the absence of a specific ICD-10 code. More comprehensive demographic data and prevalence estimates are required to propel research and investment in new treatment options for LSCD.

References

1. Thoft RA, Friend J. The X, Y, Z hypothesis of corneal epithelial maintenance. Invest Ophthalmol Vis Sci. 1983;24(10):1442-1443.
2. Dua HS, Azuara-Blanco A. Limbal stem cells of the corneal epithelium. Surv Ophthalmol. 2000;44(5):415-425. doi: 10.1016/s0039-6257(00)00109-0
3. Le Q, Xu J, Deng SX. The diagnosis of limbal stem cell deficiency. Ocul Surf. 2018;16(1):58-69. doi: 10.1016/j.jtos.2017.11.002
4. Deng SX, Borderie V, Chan CC, et al; The International Limbal Stem Cell Deficiency Working Group. Global consensus on definition, classification, diagnosis, and staging of limbal stem cell deficiency. Cornea. 2019;38(3):364-375. doi: 10.1097/ICO.0000000000001820
5. Missing Reference TK TK
6. Dziasko MA, Daniels JT. Anatomical features and cell-cell interactions in the human limbal epithelial stem cell niche. Ocul Surf. 2016;14(3):322-330. doi: 10.1016/j.jtos.2016.04.002
7. Fraser D, Brown MM, Hou JH. Demographics of limbal stem cell deficiency: a literature review. Eye Contact Lens. 2025 Apr 10. [Online ahead of print] doi: 10.1097/ICL.0000000000001184.
8. Deng SX, Kruse F, Gomes JAP, et al; The International Limbal Stem Cell Deficiency Working Group. Global consensus on the management of limbal stem cell deficiency. Cornea. 2020;39 (10):1291–1302. doi: 10.1097/ICO.0000000000002358
9. Bonnet C, Gonzalez S, Deng SX. Limbal stem cell therapy. Curr Opin Ophthalmol. 2024;35(4):309-314. doi: 10.1097/ICU.0000000000001061
10. Agarwal T, Vajpayee RB, Sharma N, Tandon R. Severe ocular injury resulting from chuna packets. Ophthalmology. 2006;113(6):961.e1. doi: 10.1016/j.ophtha.2006.01.042

Melissa Barnett, OD, FAAO, FSLS, is the director of optometry at the University of California, Davis. She has received remuneration from ABB, Abbvie, Alcon, Azura, Bausch + Lomb, BCLA, Bruder, Cloudbreak Pharma, CooperVision, Dompé, Epion, JJVC Vistakon, Lentechs, Ocusoft, Orasis, ScienceBased Health, STAPLE Program, Tarsus, and Théa Pharma.

This editorial content was supported via unrestricted sponsorship.