Lifeless limbus: What's the diagnosis?

By Amelia Fong, MD

Editor’s Note: Ophthalmology Times is pleased to announce Amelia Fong, MD, of Georgetown University School of Medicine, Washington, DC, as the third-place winner of the publication’s 2015 Resident Writer’s Award Program, sponsored by Allergan. Dr. Fong’s entry is featured here.

The Ophthalmology Times Resident Writer’s Award Program is a unique recognition opportunity designed to promote excellence in ocular surface disease education. It was created to acknowledge outstanding case identification and written presentation skills in ophthalmology residents.

Amy Patel, MD, of Gavin Herbert Eye Institute, UC Irvine Health, Irvine, CA, is the first-place winner of this year’s Resident Writer’s Award Program. Dr. Patel’s winning submission-“There’s something in the water”-is featured here. Seanna Grob, MD, MAS, of Massachusetts Eye and Ear, Harvard Medical School, Boston, is the second-place winner. Dr. Grob’s entry-“Management of drug-induced cicatricial conjunctivitis and dry eye”-is featured here.To read all of the case study submissions from this year’s Ophthalmology Times Resident Writer’s Award Program, click here.

A 67-year-old African American male presented to the ophthalmology clinic after referral from an outside optometrist. He was seen previously for a 4-month history of red eye by two outside optometrists, diagnosed with filamentary keratitis, and given tobramycin/dexamethasone ophthalmic suspension 0.3%/0.05%.

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His medical history was significant for hypertension and a history of prostate cancer. His medications included hypertensive medicines and aspirin.

He denied any ocular history except soft contact lens wear for the past 24 years with average daily wear of 12 to 16 hours a day.

He denied any ocular insult, did not use eye drops prior to presentation to the optometrist, or any family history of ocular diseases. He gave no history of severe allergic reactions, rash, autoimmune diseases, radiation, or any other cancers.

Examination

At the time of presentation, ocular examination showed a best-corrected visual acuity of 20/30 in both eyes with ability to pinhole down to 20/20 in the right eye and 20/25 in the left. Pupils, motility, and IOP were unremarkable. Anterior examination revealed pannus superiorly and 1+ guttae in both eyes.

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In the left eye, opaque epithelium arising from the superior limbus was observed to cover the visual axis and involve 70% of the cornea. Similar findings were present to a lesser degree in the right eye.

Late-fluorescein staining with a “whorl-like” pattern was demonstrated in both eyes. Dilated fundoscopic examination was unremarkable bilaterally.

Discussion and diagnosis

Discussion and diagnosis

This patient exhibited classic findings of limbal stem cell deficiency (LSCD). Given his extensive contact lens history and lack of any other ocular etiologies, he was diagnosed with soft contact lens-induced limbal stem cell deficiency (SCL-LCSD).

LSCD is a well-known ophthalmologic disease. Common etiologies include Stevens-Johnson syndrome, chemical/thermal insult, radiation, mitomycin C, surgically induced, and aniridia.^1-3

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SCL-LCSD is a poorly understood cause of LCSD. Its prevalence among LCSD patients and SCL wearers is unknown with one cite stating 15% and 4%, respectively.³

Common symptoms of SCL-LCSD are decreased vision ranging from 20/25 to HM, photophobia, pain, redness, and tearing. These patients may also be asymptomatic; diagnosed during routine examination.^1-3

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Clinical findings are similar to those found in LCSD. The corneal epithelium demonstrates a dull and irregular reflex with opaque and variable thickness. A “streaming” appearance of the epithelium may be appreciated. The classic sign of late-fluorescein staining is present in all cases elicited due to the increased permeability of abnormal conjunctivalized epithelial cells.^1-3 Superior involvement is present in all patients with SCL-LCSD with some degree of bilateral involvement.

Discussion (cont.)

All patients who exhibit SCL-LCSD are found to have worn soft contact lens daily. The average use at time of diagnosis is from 14.1 to 17.6 years (range 1 to 30 years) and 10 to 16.25 hours daily.^1-3 Women are more affected than men accounting for 67% to 93%.^1-3

The pathogenesis of SCL-LCSD is poorly understood. Mechanical friction of the SCL on the limbus may induce damage to the limbal stem cells. Hypoxia from the SCL may induce destruction. Thimerosal, a preservative used in SCL disinfecting solution, has also been associated with limbal stem cell failure.⁴

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However, it is unknown why among the millions of SCL wearers, the diagnosis of SCL-LCSD is not more common. A “two-hit hypothesis” has been proposed suggesting that these patients are predisposed with co-existing ocular diseases (e.g., rosacea, conjunctivitis, low serum Vit A) or prior ocular insult (e.g., exposure to thimerosol).²

Often SCL-LCSD presents in patients with no other ocular diseases or risk factors.^1,3

Management of SCL-LCSD is similar to the treatment of LCSD with the exception of indefinite cessation of SCL wear. Mild cases may resolve or stabilize with termination of SCL wear, preservative free artificial tears, and steroid drops.

Adjunctive measures, such as warm compresses, lid scrubs, punctual occlusions, and autologous serum eye drops, may be used to promote ocular surface health.

Topical cyclosporine has been successful in continuing anti-inflammatory activity as steroids are tapered.

Other options

Vitamin A and scleral lenses have also been used with good success in recalcitrant cases.^1,5

Epithelial debridement of conjunctivalized cornea is another successfully employed technique.^6-7 Amniotic membrane has been used for partial-LCSD patients and shown to be successful in eyes with up to 330^o of LCSD involvement.^8-9

A number of other surgical options are available for SCL-LCSD.^10-11

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Conjunctival limbal autograft (CLAU) should be discouraged as both eyes almost always exhibit some extent of LSCD.

Living-related conjunctival limbal allograft (LR-CLAL) and keratolimbal allograft (KLAU- cadaveric donor) are two possible options with proven success. Both procedures, however, commit the patient to life-long use of systemic immunosuppressant.

Cultured limbal epithelial transplantation (CLET) is a relatively new promising technique. Donor epithelium may come from autologous, living-relative, cadaveric, or autologous oral mucosa epithelium and cultured to provide donor corneal epithelium. It has been used successfully in a limited number of cases.¹⁰

Stopping soft contact use

Among all these treatments, the most important is the indefinite cessation of soft contact lens use. With the cessation of SCL and artificial tears alone, 22% to 61% of SCL-LCSD resolved or stabilized.^1,5 The addition of a steroid eye drop increased the percentage to 89% to 100%.^1,3,5

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Another study reported failure of conservative treatment in all eyes with all patients requiring surgery.² Their diagnosis of SCL-LCSD, however, included only severe LCSD patients with greater than 6 clock hours of LCSD. Regardless of treatment method, visual and symptomatic prognosis is very good in this population with the majority achieving 20/30 or better vision.^1-3,5

Our patient was instructed to immediately stop contact lens wear and use preservative-free artificial tears QID and Pred Forte QID. By 2 weeks, his clinical exam stabilized, redness improved, and vision stabilized.

Conclusions

It is difficult to predict which patients will develop SCL-LCSD. Therefore, all SCL patients should be encouraged to undergo routine ophthalmologic examination. One should always consider this disease when presented with a SCL-wearing patient with vague complaints, as early and correct diagnosis may reverse the damage with conservative measures alone.

Acknowledgements

Chantal Cousineau-Krieger, MD

Joseph A. Giovannini, MD

James D. Colgain, OD

References

References

1)   Jeng BH, Halfpenny CP, Meisler DM, Stock EL. Management of focal limbal stem cell deficiency associated with soft contact lens wear. Cornea. 2011;30:18-23.

2)   Chan CC, Holland EJ. Severe limbal stem cell deficiency from contact lens wear: patient clinical features. American Journal of Ophthalmology 2013; 155(3):544-549.

3)   Martin R. Corneal conjunctivalisation in long-standing contact lens wearers. Clinical and Experimental Optometry. 2007;90:26-30.

4)   Nguyen DQ, Srinivasan S, Hiscott P, Kaye SB. Thimerosal-induced limbal stem cell failure: report of a case and review of the literature. Eye Contact Lens. 2007;33:196-198.

5)   Kim BY, Riaz KM, et al. Medically reversible limbal stem cell disease: clinical features and management strategies. Ophthalmology 2014;121:2053-2058.

6)   Dua HS, Gomes JAP, Singh A. Corneal epithelial wound healing. Br J Ophthalmol 1994;78:401-408.

7)   Dua HS. The conjunctiva in corneal wound healing. Br J Ophthalmol 1998; 82:141.

8)   Anderson DF, Ellies P, Pires RT, et al. Amniotic membrane transplantation for partial limbal stem cell deficiency. Br J Ophthalmol. 2001;85:567-575.

9)   Sangwan VS, Matalia HP, Vemuganti GK, et al. Amniotic membrane transplantation for reconstruction of corneal epithelial surface in cases of partial limbal stem cell deficiency. Indian J Ophthalmol. 2004;52:281-285.

10) Holland EJ. Management of Limbal Stem Cell Deficiency: A Historial Perspective, Past, Present, and Future. Cornea. 2015 Jul 22 [Epub ahead of print]

11) Bieber JM, Holland EJ, Neff KD. Management of Ocular Stem Cell Disease. International Ophthal Clinics 2010;50:25-34.