Cases of limbal stem cell deficiency (LSCD) are prevalent in the United States. Typical causes of LSCD include chemical burns and severe ocular scarring secondary to several ocular conditions, such as Stevens-Johnson syndrome.
However, cases of LSCD associated with contact lens abuse are being diagnosed more frequently than ever before.1 Furthermore, since President Obama signed an executive order in March 2009 that allows the use of federal funds for human embryonic stem cell research, the potential to treat LSCD and other sight-threatening conditions, such as AMD, has become a subject of much discussion.
An Overview of LSCD
Embryonic stem cell research in the United States has faced significant ethical and moral scrutiny. Fortunately, most of the research related to the ocular surface requires limbal stem cells from the fellow eye, cadaver eyes or existing banks of stem cells.
A diagnosis of LSCD is made if corneal epithelium damage results in a dysfunctional stem cell population. The final outcome is an inability to produce healthy epithelium.
The key signs of LSCD are clouding or conjunctivalization, epithelial alteration, or irregularity and superficial neovascularization of the cornea.2 Typically, these signs begin with the superior cornea, but they can also involve damaged areas of the limbus.3 Additionally, LSCD can cause persistent epithelial defects in the presence of these findings.4
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This patient with LSCD could benefit from stem cell transplantation. |
Symptoms of LSCD include decreased vision and persistent photophobia.5 If the irregular and cloudy epithelium is removed, the new surface typically becomes cloudy as well.
In addition to chemical burns and Stevens-Johnson syndrome, other causes of LSCD include contact lens-induced keratitis, limbitis, aniridia, multiple ocular surgeries, peripheral ulcerative disorders, chronic neurotrophic keratitis, pterygium, severe microbial keratitis, chronic bullous keratopathy and radiation therapy.2 In cases with no pathology or history of trauma, question the patient about long-standing contact lens use.
One study found that 14 of 591 contact lens patients exhibited conjunctivalization with no known cause.6 The findings revealed that 13 of the 14 patients were women with daily wear contacts who had worn lenses for an average of 17.6 years (+/-8.5 years). These patients were diagnosed with contact lens-associated LSCD.
In addition to the clinical picture, a conclusive diagnosis of LSCD can be made via impression cytology. Because the hallmark finding is conjunctivalization, the presence of goblet cells and cytokeratine-19 positive cells confirms a diagnosis of LSCD.7 Furthermore, a statistically significant percentage of patients with LSCD also have decreased corneal sensitivity.6,7
Treatment of LSCD
If applicable, treatment begins with removal of the offending agent (e.g., a contact lens), followed by initiation of intense ocular lubrication with preservative-free artificial tears and anti-inflammatory drops, such as cyclosporine or mild steroids.
Another non-surgical option that has shown some benefit is the use of autologous serum q2h while awake for one to two months.8 If there is no significant improvement after two months of therapy or the patient exhibits a severe case of LSCD, surgical options are recommended.
In a case of partial LSCD, where a segment of the limbus is damaged, the conjunctival and corneal epithelium is debrided and an amniotic membrane transplant is placed over the region.9
In more severe forms involving one eye, limbal stem cells from the fellow eye can be transplanted (conjunctival limbal autograft). Conjunctival limbal autografts pose no risk of immune rejection and may not require long-term immunosuppressant drops.10
If the entire limbus in both eyes is involved, a transplant from a cadaver (keratolimbal allograft) is recommended. Patients who receive keratolimbal allografts must be placed on long-term steroid drops, cyclosporine drops, ample lubricating drops and even autologous serum.11
Other Stem Cell Applications
Research from the U.K. has suggested that the use of contact lenses coated with stem cells can restore sight to non-long-standing contact lens patients with corneal conjunctivalization.12 This approach involves coating a contact lens with a patient’s own stem cells. Stem cells from the healthy limbal region are harvested, grown on the back surface of a contact lens, and the placed on the eye over a debrided cornea. Usually, the stem cell-coated lens remains in place for 10 days.
Early results suggest that this approach achieves a substantially faster recovery time than other stem cell transplant methods.12 In fact, the researchers reported that all patients with significant vision loss secondary to corneal clouding from LSCD experienced a restored ocular surface and improved visual acuity in less than 30 days, with no recurrence of conjunctivalization or corneal vascularization.12
Stem cells are also being studied in animal eyes to treat degenerative blindness secondary to AMD and retinitis pigmentosa (RP).13 Currently, researchers are testing experimental approaches to grow retinal stem cells that can be transplanted in the macular area to restore lost vision.14 The procedure involves patching the damaged retinal areas with stem cells that eventually transform into healthy tissue. Though this technology is at least seven years away from FDA approval, human trials of dry AMD and RP patients should begin fairly soon.
LSCD is a common diagnosis in patients with irregular epithelium and cloudy or neovascular corneas. New therapeutic options and surgical techniques that utilize limbal stem cells hold tremendous promise in combating LSCD and other vision-threatening conditions.
1. Achong RA, Caroline P. Limbal stem cell deficiency in a contact lens-related case. Optometry. 1999 Dec;11(4):191-7
2. Puangsricharern V, Tseng SC. Cytologic evidence of corneal diseases with limbal stem cell deficiency. Ophthalmology. 1995 Oct;102(10):1476-85.
3. Holland EJ, Schwartz GS. Iatrogenic limbal stem cell deficiency. Trans Am Ophthalmol Soc. 1997;95:95-107.
4. Ang LP, Tan DT. Ocular surface stem cells and disease: current concepts and clinical applications. Ann Acad Med Singapore. 2004 Sep;33(5):576-80.
5. Dua HS, Saini JS, Azuara-Blanco A, Gupta P. Limbal stem cell deficiency: concept, aetiology, clinical presentation, diagnosis and management. Indian J Ophthalmol. 2000 Jun;48(2):83-92.
6. Martin R. Corneal conjunctivalisation in long-standing contact lens wearers. Clin Exp Optom. 2007 Jan;90(1):26-30.
7. Sacchetti M. Clinical and cytological findings in limbal stem cell deficiency. Graefes Arch Clin Exp Ophthalmol. 2005 Sep;243(9):870-6.
8. Schrader S. Combination of serum eye drops with hydrogel bandage contact lenses in the treatment of persistent epithelial defects. Graefes Arch Clin Exp Ophthalmol. 2006 Oct;244(1):1345-9.
9. Kolli S, Ahmand S, Lako M, et al. Successful clinical implementation of corneal epithelial stem cell therapy for treatment of unilateral limbal stem cell deficiency. Stem Cells. 2010 Mar 31;28(3):597-610.
10. Miri A,. Long-term outcomes of autolimbal and allolimbal transplants. Ophthalmology. 2010 Jun;117(6):1207-13.
11. Tsubota K. Ocular surface management in corneal transplantation, a review. Jpn J Ophthalmol. 1999 Nov-Dec;43(6):502-8.
12. Di Girolamo N. A contact lens-based technique for expansion and transplantation of autologous epithelial progenitors for ocular surface reconstruction. Transplantation. 2009 May 27;87(10):1571-8.
13. Wang NK. Transplantation of reprogrammed embryonic stem cells improves visual function in a mouse model for retinitis pigmentosa. Transplantation. 2010 Apr 27;89(8):911-9.
14. Idelson M. Directed differentiation of human embryonic stem cells into functional RPE cells. Cell Stem Cell. 2009 Oct 2;5(4):396-408.