Moran CORE

Open source ophthalmology education for students, residents, fellows, healthcare workers, and clinicians. Produced by the Moran Eye Center in partnership with the Eccles Library

Search Moran CORE

Advancing Wavelike Epitheliopathy

Home / External Disease and Cornea / Clinical Approach to Ocular Surface Disorders

Title: Advancing Wavelike Epitheliopathy: A subtype of partial limbal stem cell deficiency

Author (s): William B. West Jr.

Photographer: Photos courtesy of Dr. Majid Moshirfar

Date: 9/3/20


 Keywords/Main Subjects: Advancing Wavelike Epitheliopathy, Partial Limbal Stem Cell Deficiency, Limbal Stem Cell Deficiency, Epitheliopathy

CORE Category:

External Disease and Cornea > Clinical Approach to Ocular Surface Disorders > Limbal Stem Cell Deficiency > Advancing Wavelike Epitheliopathy

Diagnosis: Advancing Wavelike Epitheliopathy

Description of Image:

Advancing Wavelike Epitheliopathy (AWE) is a form of ocular surface disorder that was first described by D’Aversa et. al. in 1997. It is characterized by a well-defined epithelial plaque with a rough, wavelike appearance and punctate pattern on fluorescein staining. A sub-epithelial haze may also be present. The plaque arises from the corneal limbus, most often superiorly, and expands toward the visual axis. Patients present with a history of progressive vision loss over a period of several months, as well as ocular irritation and foreign body sensation.

While the exact pathophysiology is poorly understood, AWE is presumed to be a subtype of partial limbal stem cell deficiency (PLSCD). The limbal stem cells are the progenitors of the corneal epithelium and reside at the limbus. Epithelial cells migrate from the limbus toward the center of the cornea, forming the corneal surface. In a limbal stem cell deficiency, some or all of the limbal stem cells become dysfunctional and fail to produce normal epithelium. This process most commonly results in breakdown of the epithelial layer causing surface inflammation, which in turn causes neovascularization or conjunctival invasion of the cornea.

In contrast, in AWE the epithelial surface becomes abnormal but does not break down and conjunctivalization does not usually occur. AWE has been associated with a history of ocular trauma, surgery, or chemical or toxic exposure to the ocular surface.

While the potential differential diagnosis for this disorder is broad, likely considerations include:

Initial treatment for this disease incudes conservative measures to reduce inflammation and maximize healing. These treatments include artificial tears, oral doxycycline, or topical corticosteroids. Superficial keratectomy can be used, and usually provides temporary resolution of the plaque; however, the plaque nearly always recurs. Adding topical silver nitrate, applied via cotton swab to the affected area after corneal debridement, appears to produce stable recovery. Simple limbal stem cell transplant can be performed to regenerate the corneal limbus, if silver nitrate is unsuccessful. This is usually performed by harvesting limbal stem cells from the unaffected eye (if the disease is not bilateral). Interferon alpha-2b, topical or oral cyclosporine, punctal plugs, scleral lenses, vitamin A, autologous blood serum, amniotic membrane drops, and fluorometholone may be helpful in treating AWE, as they have been used successfuly in treating other varieties of PLSCD. Topical corticosteroids have not been shown to be effective.

This video shows the left eye of a 36-year-old male with a six-month history of vision loss and foreign body sensation after LASIK. Before surgery, he had a history of chronic redness and irritation in the left eye before surgery, as well as a possible chemical injury to that eye as a child. The classic wavelike plaque can be seen advancing from the limbus both inferiorly and superiorly.


Advancing Wavelike Epitheliopathy is a type of partial limbal stem cell deficiency forming a characteristic wavy epithelial plaque that expands from the limbus toward the visual axis. It is associated with injury to the limbal stem cells and is treated with superficial keratectomy and silver nitrate or limbal stem cell transplant. Prognosis is typically excellent after treatment.


  1. D’Aversa G, Luchs JL, Fox MJ, Rosenbaum PS, Udell IJ. Advancing wave-like epitheliopathy: Clinical features and treatment. Ophthalmology [Internet]. American Academy of Ophthalmology, Inc; 1997;104(6):962–969. Available from: PMID: 9186437
  2. Rossen J, Amram A, Milani B, et al. Contact Lens-induced Limbal Stem Cell Deficiency. Ocul Surf. 2016;14(4):419-434. doi:10.1016/j.jtos.2016.06.003
  3. Kim BY, Riaz KM, Bakhtiari P, et al. Medically Reversible Limbal Stem Cell Disease: Clinical Features and Management Strategies. Ophthalmology. 2014;121(10):2053-2058. doi:10.1016/j.ophtha.2014.04.025
  4. Moshirfar M, Hastings JP. Unilateral progressive epitheliopathy after LASIK [Internet]. Journal of Cataract and Refractive Surgery. Lippincott Williams and Wilkins; 2020 [cited 2020 Aug 25]. p. 646–651. Available from: PMID: 32271301
  5. Tan JCK, Tat LT, Coroneo MT. Treatment of partial limbal stem cell deficiency with topical interferon α-2b and retinoic acid. Br J Ophthalmol. 2016;100(7):944-948. doi:10.1136/bjophthalmol-2015-307411
  6. Majid Moshirfar MD., William B. West jr., Yasmyne C. Ronquillo. Advancing Wavelike Epitheliopathy. Statpearls. 2020.
  7. William B. West jr., Yasmyne C. Ronquillo, Majid Moshirfar MD. Advancing Wavelike Epitheliopathy. Eyewiki. 2020.

Faculty Approval by: Griffin Jardine, MD


Disclosure (Financial or other):  Nothing to disclose.