September 2019


Presentation Spotlight
Reviewing corneal pathologic responses

by Stefanie Petrou Binder, MD EyeWorld Contributing Writer

The four corneal layers relevant to the pathologic response: (1) epithelium, (2) subepithelial zone (basement membrane, Bowman’s layer, and anterior stroma), (3) stroma, and (4) endothelium and Descemet’s membrane

Corneal defects can be limited to the epithelium and tend to recover within 24–48 hours.

Stromal corneal defects typically occur after infections and tend to scar with or without

Epithelial bullae resulting from endothelial cell damage and edema

Corneal cyst, a focal collection of fluid, most commonly in the corneal epithelium but rarely in the other layers

Deficient limbus cells causing epithelialization
of the cornea, i.e., conjunctivalization and
epithelialization on top of the cornea
Source (all): Marie-Jose Tassignon, MD

Presenting a review on how the cornea reacts to insult in a session at the 23rd European Society of Cataract and Refractive Surgeons Winter Meeting, Marie-Jose Tassignon, MD, detailed the mechanisms of corneal pathologic change.

Corneal basics

The cornea is a highly refractive surface that covers two-thirds of the eye. It is a metabolically active, avascular tissue, covered by a tear film layer, which contains diverse cytokines that are continuously secreted by the conjunctiva and the cornea.
“The cornea is composed of approximately five layers, but for the purposes of the pathological response, I will reduce it to four: the epithelium, subepithelial zone (basement membrane, Bowman’s layer, and anterior stroma), stroma, and the endothelium and Descemet’s membrane,” Dr. Tassignon said.
The structures of the cornea can be affected by infection, inflammation, hypoxia, ischemia, trauma, chemical burns, drug toxicity, primary dystrophies, systemic metabolic diseases, secondary degenerations, genetic diseases, growth disorders such as hyperplasia and neoplasia, immunopathology, desiccation, and aging. Like most tissues, however, it manifests only a limited number of responses to a wide variety of diseases and insults, including responses like defects, fibrosis and vascularization, edema and cysts, deposits, inflammatory and immune responses, and proliferation.

Defects and deposits

Corneal defects can be limited to the epithelium and tend to recover within 24–48 hours, or affect the stroma, typically after infections, and tend to scar with or without vascularization. Defects also occur at all layers of the cornea and are associated with a partial or complete loss of corneal tissue and may be acute, recurrent, chronic, or persistent. Keratoconus is an example of a corneal defect affecting all layers.
When endothelial cells are damaged, the cornea develops edema that can evolve into bullae. Cysts are a focal collection of fluid that appear commonly in the corneal epithelium but rarely in the other layers.
“We know that we need a certain number of endothelial cells in order to have a proper metabolism of the cornea. If you have fewer than 500 cells, you will have edema and loss of transparency of the cornea,” Dr. Tassignon explained.
The cornea is susceptible to all four types of immune responses: IgE-mediated atopic or anaphylactic reactions such as in vernal keratoconjunctivitis; antibody-mediated cytotoxic reactions like with Mooren’s ulcer; immune complex deposits as with herpes simplex stromal keratitis, fungi, or other infectious keratitis; and foreign body-related delayed cell-mediated responses, such as those seen with corneal grafts.
More than 50 known drugs may leave deposits in the cornea, such as epinephrine and amiodarone in the epithelium. Ocular or systemic diseases can leave deposits of non-metabolizable material, like copper in Wilson’s disease, melanin in Descemet’s, and pigment in the endothelium in pigment dispersion syndrome.

Proliferation and limbal cell deficiency

Proliferation is associated with abnormalities of growth. Epithelial cell proliferation is seen in LASIK cases and in patients with recurrent surgeries, causing post-surgical complications. Ectopic migration refers to epithelial ingrowth under a LASIK flap or into the anterior chamber and endothelial migration across the surface of the iris.
The transitional zone between the cornea and the sclera is the richly vascularized limbus, which contains a reservoir of pluripotential stem cells. Limbal stem cell deficiency can be genetic in etiology, as with aniridia, or acquired, caused by chemical or thermal burns, UV and ionizing radiation, chronic inflammatory diseases, contact lens wear, multiple surgeries, antimetabolites, or extensive microbial infections.
“When you have deficient limbus cells, you will have epithelialization of the cornea, meaning you have conjunctivalization and epithelialization on top of the cornea, causing corneal thickening,” she noted.

Tear film

Factors affecting tear composition are either systemic or local. Systemic factors include: inborn errors of metabolism such as in Tay-Sachs disease, infections, general pathological conditions that affect the lacrimal system, and drug-related conditions affecting tear production. Local factors are infections, injury, conjunctival leakage, and tarsorrhaphy.
“The tear film is not only an important refractive element, but it also protects the cornea. You have a lot of cytokines in the tear film playing a very important role in the preservation and protection of the cornea against viruses, bacteria, external elements, and more,” Dr. Tassignon said.
Cytokines are small cell-signaling protein molecules that are secreted by numerous cells of the immune system and are a category of signaling molecules used extensively in intercellular communication. They can be classified as proteins, peptides, or glycoproteins.
“The term ‘cytokine’ encompasses a large and diverse family of regulators produced throughout the body by cells of diverse embryological origin. Unlike hormones, cytokines are not stored in glands as preformed molecules, but are rapidly synthesized and secreted by different cells mostly after stimulation. The same cytokine can be both inhibitory or excitatory, and their roles in tears are very complex,” Dr. Tassignon said.

About the doctor

Marie-Jose Tassignon, MD
Antwerp University Hospital
Antwerp, Belgium

Relevant financial interests

Tassignon: None

Contact information


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