The individual whose eye appears in this photograph suffers from corneal limbal stem cell deficiency (LSCD), a potentially devastating ocular condition.¹ Tears and the corneal epithelium function together as the primary refractive surface of the eye. To maintain the integrity of this unit, superficial corneal epithelial cells are constantly being shed, and new cells arising from underlying stem cells replace them.¹ Because stem cells are responsible for continuously repopulating human corneal cells, they are essential to the health and clarity of the cornea.¹ Deficiency in or loss of corneal limbal stem cells (CLSCs) may potentially devastate corneal health and clarity and may ultimately impair vision.¹

It is important to recognize and appreciate the unique and vital functions performed by the corneal epithelium. It interfaces with the tear layer to form the most powerful refractive surface of the eye.² Unlike almost all other epithelial cells, which migrate vertically from the basal layer toward the surface, CLSCs initially migrate centripetally, from the periphery (i.e., from limbal tissue toward the central cornea) and then vertically toward the corneal apex.² Corneal epithelium represents one of the most rapidly regenerating mammalian tissues, undergoing a complete turnover over the course of approximately one-to-two weeks.²

Chemical and Thermal Trauma

The extreme importance of CLSCs in maintaining the ocular surface integrity is demonstrated by the fact that in ocular thermal burns that decimate both corneal epithelial and stem cells, corneal clarity is frequently lost.³ Ocular burns, both thermal and chemical, can rapidly damage the ocular surface and potentially cause substantial vision loss.⁴ Basu et al reported that in corneal transplant procedures for thermal ocular burns, transplanted tissues that did not include stem cells typically failed, whereas procedures in which the grafted tissues included CLSCs had much better outcomes, particularly with regard to corneal clarity.³

Rama et al evaluated the use of cultivated, autologous limbal stem cells to treat 112 patients who had corneal damage resulting from a variety of chemical agents.⁴ The extent of LSCD ranged from severe (35.4% of subjects) to total (64.6% of subjects). The causative agents were most commonly burns: thermal (7), alkali (83), acidic (16), and other chemical agents (4).⁴ A total of 125 cultures were grafted in 113 eyes (112 patients).

At the end of the study, clinical outcomes were judged to be successful in 76.6% of the eyes.⁴ This study, which extended over a period of eight years, validates the potential benefits of autologous corneal transplants in individuals who have severe limbal stem cell loss.⁴

Chemical and thermal burns are well-recognized causative factors in LSCD; however, other seemingly benign factors may also cause limbal stem cell changes. In 2012, Chan and Holland described severe limbal stem cell changes relating to contact lens wear.⁵ They reviewed the charts of 12 contact lens patients (18 eyes) who had been referred for evaluation of corneal and conjunctival changes.⁵ Significant risk factors associated with this condition included female gender, soft CL wear, and extended duration of wear time. Vision in the subjects was decreased to a mean of 20/78. Findings leading to a conclusive diagnosis of corneal limbal stem cell disease included whorl-like epitheliopathy, corneal conjunctivalization, and fluorescein staining. Fourteen eyes (78%) eventually underwent limbal stem cell transplantation, and the patients were prescribed systemic immunosuppressant agents.

Our understanding of the causative role that contact lens wear plays in the development of LSCD continues to expand. In 2016, Rossen et al published the results of a literature search elaborating on this relationship.⁶ Their research revealed that up to 5% of all contact lens wearers have signs of LSCD and that 15% of LSCD is associated with contact lens wear. Individuals who have contact lens-associated LSCD often report a long-term history of daily soft lens wear, although LSCD also occurs with rigid contact lenses. The mean duration of lens wear associated with LSCD was 14.2 to 17.6 years, but in some cases, the onset occurred as early as six to 12 months after the subjects began wearing lenses.⁶

Martin evaluated clinical characteristics in long-standing contact lens wearers who presented with LSCD, 93% of whom were females.⁷ The mean duration of CL wear in these subjects was 17.6 ± 8.5 years; all of the subjects were daily wearers who had a mean wearing time of 12.5 hours per day. Only four (28.6%) reported any ocular symptoms.

Corneal LSCD is a relatively common finding that has the potential to drastically impair vision and may ultimately require surgical intervention. Because contact lens wear is strongly associated with this condition, it is important that eyecare providers recognize the early and late signs of this condition and intervene as early as possible in the course of the of the disease to preserve vision.

REFERENCES

1. Sejpal K, Bakhtiari P, Deng SX. Presentation, diagnosis and management of limbal stem cell deficiency. Middle East Afr J Ophthalmol. 2013 Jan-Mar;20:5-10.
2. Gonzales G, Sasamoto Y, Ksander BR, Frank MH, Frank NY. Limbal stem cells: identity, developmental origin and therapeutic potential. Wiley Interdiscip Rev Dev Biol. 2018 Mar;7:10.1002/wdev.303.
3. Basu S, Sureka SP, Shanbhag SS, Kethiri AR, Singh V, Sangwan VS. Simple Limbal Epithelial Transplantation: Long-Term Clinical Outcomes in 125 Cases of Unilateral Chronic Ocular Surface Burns. Ophthalmology. 2016 May;123:1000-1010.
4. Rama P, Matuska S, Paganoni G, Spinelli A, De Luca M, Pelligrini G. Limbal stem-cell therapy and long-term corneal regeneration. N Engl J Med. 2010 Jul 8;363:147-155.
5. Chan CC, Holland EJ. Severe limbal stem cell deficiency from contact lens wear: patient clinical features. Am J Ophthalmol. 2013 Mar;155:544-549.e2.
6. Rossen, J, Amram A, Milani B, et al. Contact Lens-induced Limbal Stem Cell Deficiency. Ocul Surf. 2016 Oct;14:419-434.
7. Martin R. Corneal conjunctivalization in long-standing contact lens wearers. Clin Exp Optom. 2007 Jan;90:26-30.