The cornea’s epithelium is essential for its function, serving both a protective and an optical role (Haagdorens et al, 2016). Like much of the epithelium in other parts of the body, the corneal epithelium is continually shed and replaced, in this instance from stem cells located at the limbus (Haagdorens et al, 2016). Damage to these epithelial stem cells and a decrease in their number and activity can lead to limbal stem cell deficiency (LSCD), which can have a significant impact on the health and function of the cornea (Stapleton et al, 2021). The most dramatic complication of LSCD is conjunctivalization of the corneal surface in the absence of a healthy corneal epithelium (Haagdorens et al, 2016).

Clinically, LSCD is diagnosed through a combination of history and anterior segment signs, which include persistent epithelial defects that stain with fluorescein, changes in limbal anatomy, and corneal vascularization and conjunctivalization (Stapleton et al, 2021). The deficiency can span the entire cornea or can be more localized to one section of the cornea, which is referred to as sectoral or focal stem cell deficiency. Focal LSCD typically presents with late fluorescein staining on the cornea and with epithelial projections that take on a “whorl-like” or “finger-like” appearance (Termote et al, 2017). In most instances, patients who have LSCD will not have any symptoms in early stages of the disease; but as it advances, they will have complaints of ocular discomfort and dryness (Deng et al, 2019).

Use of impression cytology can more definitively confirm an LSCD diagnosis by detecting goblet and conjunctival cells, which should not be among cells collected from the limbal area (Haagdorens et al, 2016). Imaging techniques such as in vivo confocal microscopy, in which corneal, conjunctival, and limbal epithelial cells can be imaged and differentiated from each other in vivo, or anterior segment optical coherence tomography, which shows the thickness of different layers of cells in different areas as well as where transitions occur from corneal to conjunctival epithelium, can also be employed to support LSCD diagnoses (Deng et al, 2019).

Contact Lens-Induced LSCD

Damage to the limbal stem cells that leads to LSCD can result from various etiologies, including chemical burns, radiation exposure, and immune disorders such as Stevens-Johnson syndrome and toxic epidermal necrolysis. LSCD associated with contact lens wear, also referred to as contact lens-induced keratopathy, has been reported in the literature, with up to 5% of contact lens wearers showing signs of LSCD in the absence of any other cause (Deng et al, 2019; Bhatia et al, 2009; Martin, 2007). Ophthalmologists in Australia and New Zealand surveyed over the course of 21 months reported that 21% of severe LSCD case etiologies were associated with contact lens wear, although only 26 cases in total were captured during the surveillance period (Bobba et al, 2017). Contact lens patients in this study had worn contact lenses for eight-to-10 hours a day on most days of the week for more than 10 years. Another study examining severe contact lens-associated LSCD also specifically reported long periods of lens wear overall: an average of 14 years of contact lens wear, with 78% of cases reporting 10-to-20 years of soft lens wear and with an average vision decrease to 20/78 (Chan and Holland, 2013).

From a pathogenesis perspective, contact lens-induced LSCD is thought to have multifactorial origins, with a combination of mechanical, hypoxic, toxic, and tear film factors all potentially contributing and interacting to ultimately decrease the health of the limbal stem cells (Rossen et al, 2016). For example, a change in the tear film leading to dryness may result in greater mechanical interaction between the lens and the ocular surface and to greater friction-related interactions (Rossen et al, 2016). Hypoxic stress in the limbal region can result from wear of lower-oxygen-permeable (lower-Dk) materials, particularly with higher-minus lenses (Martin, 2007). Indirectly supporting this is that discontinuation of contact lens wear or a refit with higher-Dk soft lenses or GP lenses can often alleviate some of the persistent epithelial defects or pannus associated with focal LSCD or milder forms of the disease (Martin, 2007).

Solution-related toxicity has also been discussed in the literature as affecting the limbal stem cell niche. This is partially supported by laboratory data showing cell damage or toxicity from some contact lens solution preservatives such as thimerosal (Baskin et al, 2003) and by case reports of thimerosal-induced or -associated contact lens LSCD (Nguyen et al, 2007). Indirectly supporting this, in a case series exploring lens-associated LSCD, all patients were using contact lens care solutions, and no patients were reported as daily disposable lens wearers (Termote et al, 2017). However, none of the care solutions used by patients during this case series contain thimerosal, leading authors to speculate as to whether potential previous exposure to the agent led to cumulative damage to the limbal stem cell area over time (Termote et al, 2017). Regardless, a combination of these factors likely contributes to stress and inflammation in the area and ultimately to depletion and dysfunction of these cells (Rossen et al, 2016).

Managing Lens-Induced LSCD

Mild or focal contact lens-induced LSCD generally can be managed with contact lens discontinuation, unpreserved artificial tears, and occasionally with corticosteroid use, with good prognosis and often with multiple treatment modalities used concurrently (Termote et al, 2017; Rossen et al, 2016). Treatment with these more conservative, non-surgical methods can extend for months and years if patients continue to show signs of improvement (Rossen et al, 2016). For more severe disease, most medical treatments, including artificial tears, corticosteroids, cyclosporine, oral doxycycline, and topical vitamin A ointments, are reported to be ineffective, with the majority requiring some form of limbal stem cell transplant (LSCT) (Chan and Holland, 2013).

Autologous serum has also been reported in the literature as successful in managing severe LSCD (Yeh et al, 2020). Other surgical options include mechanical scraping of the conjunctivalized epithelium (although this tends to provide only temporary relief) and amniotic membranes (Rossen et al, 2016). Contact lens-induced LSCD also tends to be a bilateral, albeit asymmetric, disease; this makes autologous limbal stem cell donation from the contralateral eye generally not recommended, as it may precipitate the disease in the fellow eye (Rossen et al, 2016).

The Role of Contact Lenses in LSCD Management

Patients who have contact lens-induced LSCD can be refit with higher-Dk lenses such as silicone hydrogels, which may allow resumption of soft lens wear. Often, this is not a viable option; signs of LSCD tend to recur, again requiring lens wear discontinuation (Rossen et al, 2016). In contrast, therapeutic use of scleral lenses may aid and repair a damaged limbal stem cell niche (Rossen et al, 2016; Schornack, 2011; Kim et al, 2014). Here, the scleral lens not only vaults the limbus and prevents further mechanical trauma, it may also allow repair and regeneration of the remaining limbal stem cells in the area (Rossen et al, 2016; Schornack, 2011).

Soft contact lenses have also been investigated for the expansion and delivery of limbal stem cells for LSCD patients (Bobba and Di Girolamo, 2016; Bobba et al, 2015; Di Girolamo et al, 2009). This technique involves harvesting of autologous limbal or conjunctival epithelial cells followed by culturing and expansion of the cells on lotrafilcon A lenses prior to wear for two weeks to facilitate stem cell transfer (Bobba and Di Girolamo, 2016). In a case series of 16 patients who had total or partial LSCD from various causes, including one case of contact lens-induced LSCD, transplantation of cells with wear of the contact lens was successful in restoring an avascular epithelial surface in 63% of patients (Bobba et al, 2015). Patients in this study had a mean follow-up of 2.5 years, with the longest follow-up period of 5.8 years. Importantly, none of these patients experienced any long-term complications with this method of transplantation.

Conclusions

It is unclear why some lens wearers develop LSCD while the vast majority do not, but practitioners should familiarize themselves with the signs of contact lens-induced LSCD. Lens-induced LSCD is amenable to treatment in its early stages, but more severe disease will generally require surgical intervention. CLS

The author thanks Associate Professor Michele Madigan for her help in improving this article.

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