Case Study:
Patient complains of long standing blurred vision, redness and pain in both
eyes
Dilraj S. Grewal, MD
History
A 55-year-old female was referred to Northwestern University Feinberg School of
Medicine by her optometrist for evaluation of blurred vision, redness and pain in both
eyes. These symptoms had been worsening over the past 10 years and were now
interfering with her job. She had been told she had a “corneal dystrophy” and had been
prescribed torbadex drops and “blink” artificial tears that she had been taking
intermittently over the past 3 months and felt they had slightly helped with her
symptoms.
Her medical history was significant for systemic hypertension, which was diagnosed
4 years earlier, primary hyperparathyroidism and depression. She denied any previous
ocular problems, and there was no family history of eye disease. Her work involved
making dental implants and she reported a history of 25 years of exposure to porcelain
dust at work.
Examination
At the time of her referral, ocular examination showed a best-corrected visual acuity
of 20/30 in her right eye and 20/60 in her left eye. Pupils, motility, IOP, confrontation
visual fields were unremarkable.
External exam was significant for floppy eyelids. Anterior segment examination of
both eyes revealed 360 degree of peripheral corneal vascularization, numerous elevated
subepithelial semi-translucent opacities involving the central and mid peripheral cornea
which exhibited negative fluorescein staining. There were peripheral punctate epithelial
erosions in the area of the peripheral vascularization. The findings were more severe in
her left eye (Figure 1). She had no evidence of facial or ocular rosacea but did have
moderate blepharitis with posterior telangiectasia and meibomian gland dysfunction.
Dilated fundus examination was unremarkable in both eyes.
Discussion and diagnosis
She was diagnosed with advanced limbal stem cell (LSC) disease and aqueous tear
deficiency. Slit-lamp photographs demonstrated a demarcation line between healthy and
unhealthy epithelium (Figure 1 left, arrow).
She was started on a systematic regimen comprising of conservative measures and
topical medical treatment. Conservative management included aggressive lubrication
with preservative-free refresh optive artificial tears, lid hygiene and warm compresses.
Medical management included prednisolone acetate ophthalmic suspension 1% (Pred
Forte, Allergan, Irvine, CA) twice a day in both eyes and nightly topical vitamin A
ointment (0.01%).
A significant clinical response was noted with evidence of regressing conjunctival
epithelial haze on review 1 month after the start of the steroid drops. At this time her
steroid drops were discontinued and she was started on topical cyclosporine, 0.05%
(Restasis; Allergan Inc, Irvine, California) in both eyes. Inferior punctal plugs (Oasis,
Glenview, CA) were also placed in both eyes at this time. At 3 months follow-up, as a
result of improvement in the ocular surface and corneal clarity, visual acuity improved in
her left eye to 20/30.
Cases with LSC deficiency occur most commonly in patients with aqueous tear film
insufficiency in the setting of chronic traumatic or toxic insults to the limbus, in
particular contact lens use or exposure to benzalkonium chloride, or as in our case longterm exposure to the micro-abrasive porcelain dust. In this setting of poor lubrication, the
force of eyelid blinking could cause repeated micro-trauma to the limbus and
cumulatively over time can lead to LSC disease. This is suggested by the presence of
LSC disease in the superior quadrant of the limbus, which was also seen in our case.
Therefore, in addition to stopping traumatic or toxic insults, optimizing the tear film with
preservative-free lubricants and aggressive treatment of the lid margin disease is one of
the primary interventions.
Previous studies describing a whorl-like or advancing wave-like epitheliopathy have been
shown in patients with similar a disease process.
1,2
An interesting clinical feature of
these cases is the mixed phenotype of the cells growing onto the cornea. In particular in
some of the early cases, before having a continuous sheet of late-staining epithelium,
there appeared to be single clones of late-staining cells that follow a whorl-like path. In
the setting of trauma or inflammation, the function of the LSCs or their niche may be
disturbed, giving rise to goblet cells that migrate onto the cornea explaining the
appearance of the late-staining epithelium on the cornea.
Medical management is aimed primarily at restoring the limbal microenvironment.
This involves a stepwise approach based on 2 fundamental strategies: (1) stopping
traumatic or toxic insults to the limbus and (2) optimizing the ocular surface environment
by improving the tear film, controlling inflammation, and promoting differentiation of
healthy epithelium. The clinically significant response to steroids in this case of LSC
disease suggests that chronic subclinical inflammation plays a significant role in the
pathogenesis of such cases of LSC disease. Topical cyclosporine was used effectively as
maintenance treatment after the inflammation had been controlled. It has been suggested
that inflammation disturbs the normal milieu of the limbal niche and leads to dysfunction
or aberrant differentiation of the LSCs, or both. 3-5
In a recent series of patients with LSC deficiency 5 Kim et al reported the outcomes
of 22 eyes of 15 patients that were treated with medical therapy. The corneal epithelial
phenotype returned to normal with only conservative measures, including lubrication and
discontinuing contact lens wear in 4 patients (4 eyes), whereas in 11 patients (18 eyes),
additional medical interventions were required after at least 3 months of conservative
therapy. Medical interventions included topical corticosteroids, topical cyclosporine,
topical vitamin A, oral doxycycline, punctal occlusion, or a combination thereof. All eyes
achieved a stable ocular surface over a mean follow-up of 15 months and visual acuity
improved from a mean of 20/42 to 20/26.
If left untreated, chronic and persistent damage to the limbal niche may lead to
permanent loss of the niche, and hence LSC deficiency, requiring surgical intervention
including superficial keratectomy and amniotic membrane transplantation, LSC
transplantation, or both.
2,6
The goal of surgical intervention is to restore the limbal
microenvironment.
As a first step, all toxic or traumatic stimuli should be discontinued, including
contact lens use and all potentially toxic eye drops. At the same time, the tear film should
be optimized using preservative-free artificial tears and aggressive treatment of
associated lid disease. Patients who did not respond to a few months of conservative
medical management should be treated with topical corticosteroids (preferably nonpreserved if available) and reassessed after a few weeks to determine the clinical
response. Topical cyclosporine can be used to maintain ongoing anti-inflammatory
activity as steroids are being tapered. After inflammation is controlled, punctal plugs or
cautery may be considered in patients with more significant aqueous deficiency.
Adjunctive measures such as topical vitamin A and autologous serum drops may be
considered to improve the tear film and epithelial health and scleral lenses can be used
for recalcitrant cases.
Conclusion
This case demonstrates many important points about the presentation, evaluation,
and management of patients with LSC deficiency. Although this condition is rare,
recognition by the ophthalmologist can be important for early identification and
treatment. A stepwise approach involving conservative measures and medical
management can result in good outcomes with significant improvement in visual acuity,
resolution of symptoms while avoiding the need for surgical intervention.
References
1.
2.
3.
4.
5.
6.
Jeng BH, Halfpenny CP, Meisler DM, Stock EL. Management of focal limbal
stem cell deficiency associated with soft contact lens wear. Cornea. Jan
2011;30(1):18-23.
D'Aversa G, Luchs JL, Fox MJ, Rosenbaum PS, Udell IJ. Advancing wave-like
epitheliopathy. Clinical features and treatment. Ophthalmology. Jun
1997;104(6):962-969.
Pajoohesh-Ganji A, Pal-Ghosh S, Tadvalkar G, Stepp MA. Corneal goblet cells
and their niche: implications for corneal stem cell deficiency. Stem cells. Sep
2012;30(9):2032-2043.
Marsh P, Pflugfelder SC. Topical nonpreserved methylprednisolone therapy for
keratoconjunctivitis sicca in Sjogren syndrome. Ophthalmology. Apr
1999;106(4):811-816.
Kim BY, Riaz KM, Bakhtiari P, et al. Medically Reversible Limbal Stem Cell
Disease: Clinical Features and Management Strategies. Ophthalmology. Jun 4
2014.
Anderson DF, Ellies P, Pires RT, Tseng SC. Amniotic membrane transplantation
for partial limbal stem cell deficiency. The British journal of ophthalmology. May
2001;85(5):567-575.
Legends
Figure 1: Slit-lamp photograph of our patient with superior limbal stem cell (LSC)
disease demonstrating significant superior corneal vascularization, a demarcation line
between healthy and unhealthy epithelium (arrow) and several sub-epithelial opacities
which are easily seen on the retro-illumination picture (right).