The cornea, the transparent outer layer of the eye, plays a role in focusing light and allowing clear vision. Its continuous health and transparency depend on specialized cells located at its outer edge, in an area called the limbus. These are limbal stem cells. When these cells become damaged or are present in insufficient numbers, a condition known as limbal stem cell deficiency (LSCD) develops. This deficiency can lead to substantial vision problems and discomfort, affecting the overall function and clarity of the eye’s surface.
The Role of Limbal Stem Cells and How Deficiency Occurs
Limbal stem cells are specialized adult stem cells found in the limbus, the transitional zone between the clear cornea and the opaque sclera. They continuously regenerate the corneal surface, replacing shed epithelial cells and maintaining the cornea’s transparency and avascular nature. These cells also act as a barrier, preventing conjunctival cells and blood vessels from invading the clear corneal surface.
When limbal stem cells are deficient, this barrier is compromised, leading to significant changes on the ocular surface. The conjunctiva, which normally covers the white part of the eye, grows onto the cornea in a process called conjunctivalization. This invasion is often accompanied by new blood vessel growth (neovascularization) and scar tissue, causing the cornea to become cloudy. The impaired ability of the cornea to regenerate properly can result in chronic inflammation, persistent epithelial defects, and eventually, a loss of corneal clarity and reduced vision.
Symptoms of LSCD include chronic eye pain, persistent redness, and a foreign body sensation. Light sensitivity (photophobia) and excessive tearing are also common. As the condition progresses, patients experience a gradual decline in vision.
LSCD can arise from genetic, acquired, or idiopathic causes. Common causes include chemical or thermal eye burns, severe eye trauma, and certain genetic conditions, such as aniridia, which involves an incomplete or absent iris, and is associated with a developmental abnormality of the limbus. Inflammatory diseases such as Stevens-Johnson syndrome, ocular cicatricial pemphigoid, and chronic limbitis can also lead to LSCD. Other factors linked to LSCD are complications from multiple eye surgeries, prolonged contact lens misuse, and certain medications like antimetabolites (e.g., 5-fluorouracil, mitomycin C).
Identifying Limbal Stem Cell Deficiency
Diagnosis of LSCD typically begins with a thorough clinical examination using a slit lamp microscope. The ophthalmologist looks for characteristic signs such as corneal opacification (clouding), vascularization (blood vessels growing onto the cornea), and conjunctivalization (conjunctiva extending onto the corneal surface). The absence of normal limbal anatomy, like the palisades of Vogt, also supports the diagnosis.
To confirm the diagnosis and assess the deficiency’s extent, specialized tests are used. Impression cytology is a non-invasive technique where a small sample of superficial cells is collected from the corneal surface. These cells are then examined under a microscope for the presence of goblet cells, which are typically found only in the conjunctiva, indicating conjunctivalization of the cornea. In vivo confocal microscopy provides a high-resolution view of corneal and limbal structures, allowing visualization of changes like decreased basal epithelial cell density or fibrotic tissue replacement. High-resolution optical coherence tomography (HR-OCT) is also used in diagnosing LSCD.
It is important to rule out other eye conditions with similar symptoms to ensure an accurate diagnosis. Differential diagnosis helps distinguish LSCD from other ocular surface diseases that have overlapping features but require different management.
Treatment Options for Limbal Stem Cell Deficiency
Treating limbal stem cell deficiency aims to restore a healthy corneal surface, alleviate pain, and improve vision. Strategies range from conservative management for milder cases to surgical interventions for severe forms.
Conservative management is an initial approach for less severe LSCD or as preparation for surgery. This includes regular lubricating eye drops to maintain ocular surface moisture and reduce friction. Anti-inflammatory eye drops may control inflammation and reduce symptoms. Managing underlying inflammatory conditions is also part of conservative care. Therapeutic lenses, such as scleral or bandage contact lenses, can promote healing of persistent epithelial defects, prevent new ones, and offer relief from pain and light sensitivity.
For advanced LSCD, surgical interventions often involve transplanting stem cells or supportive tissues. Amniotic membrane transplantation places a thin membrane from the human placenta on the ocular surface. This membrane provides a temporary scaffold, promoting epithelial healing, reducing inflammation, and serving as a carrier for stem cells.
Simple Limbal Epithelial Transplantation (SLET) involves taking a small biopsy of healthy limbal tissue from the patient’s unaffected eye (autologous source). This tissue is cut into smaller pieces and transplanted onto the damaged eye, often with an amniotic membrane and fibrin glue. This method minimizes rejection risk as the tissue comes from the patient.
When more cells are needed or both eyes are affected, cultivated limbal stem cell transplantation may be performed. This involves taking a small sample of healthy limbal cells from the patient or a donor, growing them in a laboratory to expand their numbers, and then transplanting the cultivated cells onto the affected eye. This approach reduces the donor tissue required from the healthy eye.
If autologous options are not feasible, such as in bilateral total LSCD, Keratolimbal Allograft (KLAL) may be considered. This involves transplanting limbal tissue from a deceased donor. Systemic immunosuppression is required to prevent rejection. Allograft long-term survival can be limited due to immune rejection, and patients require careful monitoring for complications associated with immunosuppression. Outcomes vary by LSCD severity and treatment, with long-term follow-up necessary to manage complications and monitor ocular surface health.