Understanding Corneal Ulcer Healing Stages
A corneal ulcer is an open wound on the cornea on the surface of the eye.
In the United States alone, the annual incidence of corneal ulcers is estimated to be between 30000 and 75000.
It mostly affects the epithelium, which is the outermost layer of the cornea.
Its exposure makes it more susceptible to damage.
But fortunately, it is also the layer that heals quickly and most effectively to its pre-damage structure and function.
However, the time it takes to heal depends on the depth of the injury.
This article discusses corneal ulcer healing stages in detail for epithelial and stromal injuries.
Epithelial Wound Healing
The process of corneal epithelial healing happens in phases.
These phases occur in a set sequence but might overlap in time.
Discussed below is the process:
Latent phase
Also called the lag phase, this is the first phase of the healing process.
It is the time between the injury and the beginning of re-epithelization.
This stage of corneal wound healing is characterized by cellular remodeling and modifications to the composition of tears to facilitate healing.
There is also an increase in the production of enzymes that degrade the damaged epithelial membrane.
A decrease in cellular adhesion can also be observed, which helps enhance the movement of cells.
However, excessive levels of these enzymes might hinder the process of healing.
This phase continues for hours without any initiation of migration.
There is also
- Dismantling of intercellular junctions
- Replacement of cell-substrate junctions with weaker attachments
- Preparation of the migration process by laying down a provisional extracellular matrix
Delay in treatment can lead to complications and vision loss.
Migration
The next phase happens when cells near the edge of the wound flatten and spread.
Lamellipodia and filopodia are sent out and temporarily connected to the substrate.
Contractile elements then draw the cell forward toward the defect.
Nearby cells remain attached by desmosomes, maintaining their position in relation to each other as they slide across the denuded area.
Following this sliding/migration, a cycle continues until a single cell layer seals the defect.
The migration process happens at a constant rate but starts to slow down as the defect becomes smaller.
The process generally takes place over 24-36 hours.
But, it can vary depending on the location and size of the defect.
Proliferation and differentiation
After the migration stage is complete, the density of the epithelial cells is restored.
It occurs in conjunction with cell differentiation.
Mitosis of cells around the wound is observed to have slowed down after the migration stage.
The single layer of the cell which covers the defect then multiplies to restore the standard thickness of the epithelium.
As the cells multiply towards the center, the daughter cells also move upwards towards the superficial layers of the eye.
They also start to differentiate into wing cells and then squamous cells.
The intercellular junctions are also reformed, restoring the function of the epithelial barrier.
Hence, a new basement membrane is formed.
Epithelial reattachment
In the final phase, the epithelial firmly attaches itself to the underlying substrate.
Hemidesmosomes are responsible for this adherence of the epithelial cells to the basement membrane and the stroma.
The absence of hemidesmosomes might make the epithelium more vulnerable to sloughing and erosion.
If the basement membrane remains intact at the time of injury, this process is completed in a few days.
But if this membrane has suffered any damage, it might take months or longer to form the final attachments.
Thus, the healing speed depends on whether or not the stroma is compromised.
Stromal Wound Healing
If the ulcer progresses in depth, it might cause damage to the stroma as well.
Thus, the stroma needs to heal before the layers on top begin healing.
The stromal wound healing process involves:
- Transformation of keratocytes
- Production of fibrous material
- Tissue remodeling
Early in the healing phase, leukocytes from the conjunctival vessel are recruited to the site of injury.
They protect against any infection but also contribute to damage to the tissue.
But, evidence is present which suggests that they promote healing too.
The keratocytes nearest to the wound undergo apoptosis, and those around this area activate to become fibroblasts or myofibroblasts.
These cells then migrate to the injury site to deposit the fibrotic material to fill the defect.
This material might opacify and contract to reduce the cornea’s transparency and alter the corneal curvature.
The number of transformed keratocytes begins to fall once the wound is filled.
After this, a slow remodeling phase goes on for weeks to years, reorganizing the collagen in an attempt to restore the corneal transparency.
Takeaway
A corneal ulcer is a defect on the corneal epithelium which might involve the underlying stroma.
The epithelium, however, is the layer that heals most quickly and effectively.
This healing process happens in four stages, the duration of which depends upon the severity of the injury.
These stages occur in a sequence but might overlap in time.
Additional time might be required if the injury penetrates the deeper layers of the eye, which lie under the epithelium.
Frequently Asked Questions
Will corneal ulcers heal itself?
Corneal ulcers do not heal themselves. If left untreated, this infection can cause irritation, vision loss, and even blindness. The treatment depends on the underlying cause of the ulcer. You can read Corneal Ulcer Treatment: Options and Considerations to learn about the available treatment options.
How long does a corneal ulcer take to heal?
Most corneal ulcers heal in about two to three weeks with proper treatment. It might take longer if you have an indolent ulcer. Consult your doctor if you do not experience improvement even after receiving the treatment.
Does a corneal ulcer require surgery?
Corneal ulcers might require surgical intervention in some cases. Such incidences include ulceration being unresponsive to medical treatment and persistent or any other complication cropping up. Consult an eye doctor for the best advice on treating your corneal ulcer.
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