Table 2.

Major etiologies of LSCD.

Etiology	Pathophysiology and Clinical Context	Reference
Contact lens (CL) wear	LSCD in CL wearers is often asymmetric and bilateral, meaning one eye is more affected than the other. Of the estimated 125 million CL wearers worldwide, roughly 2.4–5% of contact lens wearers develop signs of LSCD. LSC niche damage is hypothesized to be multifactorial, due to hypoxia, mechanical trauma, insufficient lubrication, predisposing factors, eyelid anatomy differences, etc. Presentation of LSCD secondary to CL wear is often initially asymptomatic; subsequent symptoms are generally nonspecific, e.g., pain, photophobia, visual impairment, dryness, irritation.	[45]
Ectrodactyly-ectodermal dysplasia-clefting (EEC) syndrome	An autosomal dominant inherited illness due to heterozygous mutation in the TP63 gene, involving progressive keratinocyte loss, culminating in LSCD and eventual blindness. Ectoderm-derived structures, such as the hair, teeth, skin, and sweat glands, are often compromised. A common defect is anomaly of the Meibomian glands and subsequent instability of the tear film.	[46,47]
Chemical or thermal injury	Most prevalent in males 20–40 years. Non-surgical management (e.g., irrigation, corticosteroids + ascorbic acid, bandage CL, autologous serum, treating high intraocular pressure, tetracycline) to immediately control the inflammation will influence clinical outcomes for the ocular surface and restoration of vision. Sufficient damage to LSCs or niche disarray will culminate in LSCD. After the initial healing process, reconstructive processes can be considered.	[48]
Stevens-Johnson syndrome	SJS is a type IV hypersensitivity adverse drug reaction with a high mortality rate. associated with SJS include anticonvulsants (phenobarbital, lamogtrigine, carbamazepine), antibiotics (sulphonamides, erythromycin, cefotaxime, cloxacillin, quinolones), and non-steroidal anti-inflammatory drugs (NSAIDs). Erythema, erosion, and pseudomembranes affect the oral, ocular, and genital mucous membranes, which may result in insults to the limbal niche.	[49]
Ocular cicatricial pemphigoid (OCP)	An autoimmune ocular disease and type II hypersensitivity response that requires proper management to prevent corneal conjunctivalization, opacification, and irreversible vision loss. Characteristic symptoms included progressive symblepharon (abnormal adhesions between the conjunctiva of the inner surface of the eyelid & conjunctiva of the globe), severely dry eyes, and conjunctival scarring. Twice as prevalent in females vs. males. Topical lubricants for dry eye symptom relief can be used in combination with immunosuppression. The first-line treatment is dapsone, a sulfonamide antibiotic with anti-inflammatory and immuno-modulatory properties.	[50]
LSC transplant donor eye	Great care is taken to preserve the donor eye, which can be a patient’s healthy eye if applicable, or the eye of a suitable donor. LSCD can be induced in the donor eye if excessive limbal tissue is removed. Dissection toward the cornea is extended through the limbal PV to obtain stem cells.	[51]
LSC transplant recipient eye	Measures are taken to limit inflammation and prevent LSC graft rejection. Post-operative management of inflammation involves topical steroids, preservative-free teardrops, and antibiotics. Tarsorrhaphy (stitching the eyelids closed temporarily) after LSC transplantation can decrease susceptibility to dryness.	[51]
Congenital aniridia	Aniridia is a disease in which the iris is partially or completely absent or abnormally developed. Implicated in aniridia-associated LSCD is an abnormality in the PAX6 gene, which has a role in the development of the anterior segment of the eye. Although the corneal epithelium is normal at birth, progressive signs of LSCD become apparent in the range of 20–40 years of age.	[52]