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Limbal Stem Cell Deficiency Associated Persistent Epithelial Defect in Turner Syndrome:
A Case Report
Stephanie Chiang, OD
Ohio Eye Alliance
This report outlines a rare case in literature describing the co-occurrence of limbal stem cell
deficiency in a Turner syndrome patient presenting with a persistent marginal ulcer and
substantial corneal thinning despite aggressive topical therapy.
I. Case history
Chief Complaint
A 41 year old caucasian female, existing patient, presented to the office for constant redness
and burning OS for the last 2 weeks. She also reports ocular irritation and photosensitivity. The
patient had the same symptoms a year ago with a history of severe keratoconjunctivitis sicca
OU. The patient notes no relief with restasis BID OU and artificial tears QID OU.
Ocular history
Keratoconjunctivitis sicca with punctal plugs 2012
No contact lens wear
Medical history
Hypertension
Scoliosis
Turner syndrome, diagnosed at age 12
Current medications
Lisinopril 10mg
Synthroid 88 mcg
Prempro 2.5 mg (conjugated estrogens plus medroxyprogesterone acetate)
Fish oil
II. Pertinent findings
Visual acuity (cc)
OD 20/25
OS 20/25
Pupils: PERRL-APD, 4mm
Confrontation visual fields: Full OD,OS
EOMs: SAFE
Anterior segment exam
Eyelids: clear OU
Conjunctiva: white and quiet OD, 2+ inferior nasal injection OS
Cornea:
OD: inferior nasal stromal opacity with overlying neovascularization, no staining or epithelial
defect
OS: inferior nasal 1mm x 1.5mm peripheral ulcer with 90% corneal thinning, +NaFL staining,
heaped limbal conjunctival vessels, no infiltrate
Anterior chamber: deep and quiet OU
Iris: flat OU
Lens: clear OU
III. Differential diagnosis
Peripheral ulcerative keratitis
Corneal melt
Corneal erosion
Bacterial/fungal keratitis
Interstitial keratitis
Neurotrophic keratopathy
Pellucid marginal degeneration
IV. Diagnosis and Discussion
Based on the appearance and epithelial defect of the left cornea, the patient was diagnosed
with a marginal corneal ulcer, likely inflammatory in nature. Furthermore, due to patient ocular
and medical history, the bilaterality of clinical findings and presentation of the cornea, the patient
is suspected to have a limbal stem cell deficiency (LSCD).
Corneal epithelium is continuously regenerated by limbal stem cells (LSC) that reside within the
basal epithelium at the limbus. Cells from the corneal surface are replaced by proliferating
epithelial cells migrating from the periphery towards the center. LSCs maintain the integrity of
the corneal surface, and the limbus functions as a physical barrier preventing conjunctival
epithelium from invading the cornea. In limbal stem cell deficiency, the corneal epithelium
cannot be renewed and is substituted by conjunctival epithelial cells. The deficiency can be
partial and sectoral or total.
Presentation and clinical manifestations of LSCD varies by the extent and severity of the
condition. Patients with LSCD present with symptoms such as decreased vision and
photophobia. In partial LSCD, a classic pattern of stippled late fluorescein staining that occurs
due to increased permeability of abnormal epithelial cells. This staining may have a vortex
pattern. Other findings consistent with limbal stem cell deficiency include epithelial thinning,
chronic inflammation, an unstable tear film, filaments or erosion over affected area. In severe
cases, corneal opacity, scarring, stromal vascularization, persistent epithelial defects and
corneal conjunctivalization are sequelae of LSCD.
LSCD can be detected clinically based on the presentation described above. However,
laboratory tests such as impression cytology (gold standard) and in vivo confocal microscopy
are necessary to confirm the diagnosis of LSCD. Impression cytology involves placing
nitrocellulose acetate filter paper on the ocular surface removing 1-2 cell layers followed by
histological, immunohistological or molecular analysis. In vivo confocal microscopy are highresolution cellular images.
A case report published in Cornea February 2014 first reported two cases of the coexistence of
LSCD and Turner syndrome. In Turner syndrome, a monosomy, a female is partly or completely
missing an X chromosome. The condition has a prevalence of 3% of female fetuses and an
incidence of 1 in 2500 live births. These individuals may have a short stature, webbed neck and
low-set ears. Typically they do not develop breasts or menstrual periods and are infertile.
What is the relation between LSCD and Turner’s? Causes of LSCD can range from congenital
intrinsic factor defects that affect the limbal stem cell environment to acquired extrinsic factors
where limbal stem cells are destroyed. For example, damage after chemical or thermal injuries,
ocular surgeries involving the limbal region, Stevens-Johnson syndrome or contact lens wear.
With the absence of a chromosome, patients with Turner syndrome suffer from deficiencies in
intrinsic factors and therefore may be without genes that code for areas influencing the limbal
stem cells. In addition, if the Turner syndrome patient suffers from dry eye, lid disease,
lagopthalmos or are contact lens wearers, the remaining viable limbal stem cells are further
deteriorated. Turner syndrome only affect females, who are also more commonly affected by
chronic ocular surface inflammation. The development of severe LSCD is multifactorial and
exacerbated by a deficient ocular surface such as the chronic keratoconjunctivitis sicca in the
reported patient.
V. Treatment, management
The patient was instructed to immediately begin polytrim q1h OS while awake and erythromycin
ung qHs OS. Discontinue Restasis and return for follow up the next day. The following day,
there was minimal improvement in clinical findings but no enlargement of the ulcer or
perforation. The patient noted a 30% improvement in symptoms since the day before with a
decreased gritty sensation but still light sensitive and red. Zylet QID OS was added and polytrim
reduced to QID OS with continuation of erythromycin qHs OS. Follow up was arranged in 3-4
days, unless symptoms worsened. Over the next two follow-ups spanning a month, the patient
reported much improvement in redness, irritation and light sensitivity despite poor response to
treatment. Vision was unaffected and topical medications were continued, remaining the same.
The epithelial defect and ulcer persisted with limited change in clinical findings and size. An
amniotic membrane graft over the cornea OS to facilitate healing is considered at the next visit If
there is no improvement in thinning.
Management of LSCD depends on the severity and etiology of the ocular surface disease. In
focal cases where the central cornea is unaffected and only partial LSCD exists, treatment is
aimed to optimize the ocular surface and the limbal stem cell environment to aid in stem cell
survival. This includes management of dry eye and meibomian gland dysfunction, long term
preservative free topical corticosteroid and discontinuing contact lens wear. More aggressive
treatment in total LSCD may be mechanical debridement of abnormal conjunctival epithelial
growth from the cornea (sequential sectoral conjunctival epitheliectomy), transplanted limbal
graft or amniotic membrane transplantation.
VI. Conclusion
The stem cells responsible for corneal epithelial renewal are presumed to reside within the
basal epithelium at the limbus. A deficiency can result in significant visual impairment or even
perforation. A Turner syndrome patient presented with extreme ocular irritation and photophobia
revealing local conjunctivalization of the corneal epithelium with stromal neovascularization in
one eye and a marginal ulcer with substantial thinning in the other, consistent with LSCD.
The few patients reported in literature indicate an association between Turner syndrome and
LSCD. Further research is indicated to better understand the relationship and genetics between
these two conditions. Patients with Turner syndrome should be examined ophthalmologically to
identify and treat ocular abnormalities to further prevent LSCD.
References
1. Djalilian, MD Ali, American Academy of Opthalmology: 10 Pearls for Ocular Surface
Disease, 2014,
http://www.aao.org/yo/newsletter/201009/article04.cfm?RenderForPrint=1&
2. Karpecki, OD Paul, Review of Optometry’s Practice Pearl of the Week, Vol 4 #2, Feb 21,
2014, http://www.revoptom.com/email/022114_pearl150_v2.html
3. Sejpal, K, Middle East African Journal of Ophthalmology: Presentation, Diagnosis and
Management of Limbal Stem Cell Deficiency, 2013 Jan-Mar; 20(1): 5-10,
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3617528/
4. Strungaru, M. Mah, D. Chan, C. Focal Limbal Stem Cell Deficiency in Turner Syndrome:
Report of Two Patients and Review of the Literature. Cornea 2014;33:207-209, February
2014