treatment of lscd with dm

Conditions: Limbal Stem-cell Deficiency; Congenital Aniridia

Summary: limbal stem cell deficiency (lscd) is a blinding disease that accounts for an estimated 15-20% of corneal blindness worldwide. current treatments are limited. traditional corneal transplantation with penetrating keratoplasty (pkp) is ineffective in treating these patients. without a healthy population of limbal stem cells (lsc) to regenerate the corneal epithelium, standard corneal transplants will not re-epithelialize and will rapidly scar over or melt. the limbal niche is the microenvironment surrounding the lscs that is critical for maintaining their survival and proliferative potential under physiologic conditions. extracellular signals from the microenvironment are critical to the normal function and maintenance of pluripotent stem cells. identifying an effective niche replacement is thus an important focus of limbal stem cell research and critical for advancing treatments for lscd. descemet's membrane (dm), an acellular, naturally occurring, basement membrane found on the posterior surface of the cornea, is a promising niche replacement. dm is routinely isolated and transplanted intraocularly with associated donor corneal endothelium for treatment of diseases like fuchs' dystrophy and corneal bullous keratopathy that specifically affect dm and corneal endothelium. however, its application on the ocular surface has not been explored. dm is optically clear and highly resistant to collagenase digestion. this makes it very attractive as a long-term corneal on-lay and niche replacement on the surface of the eye. the anterior fetal banded layer of dm shares key compositional similarities with limbal basement membrane, which is a major component of the limbal niche. these similarities include limbus-specific extracellular matrix proteins such as collagen iv that is restricted to the α1, α2 subtypes, vitronectin, and bm40/sparc. of these, vitronectin and bm40/sparc are known to promote proliferation of lscs and induced pluripotent stem cells (ipsc) in culture. because of this, dm is a promising biological membrane for establishing a niche-like substrate on the corneal surface in patients with lscd. the purpose of this pilot study is to investigate the clinical efficacy of using dm as a corneal on-lay to promote corneal re-epithelialization in partial lscd.


Eligibility criteria:
inclusion criteria: arm 1: * partial lscd (involving less than 75% of the limbus, or \<75% of the corneal surface) * visually significant (best-corrected visually acuity 20/100 or worse) arm 2: * total/near-total lscd with recurrent erosions or peds (involving more than 75% of the limbus, or more than 75% of the corneal surface) * visually significant (best-corrected visually acuity 20/100 or worse) plus * persistent epithelial defects last \>2 weeks despite maximal medical therapy or * recurrent erosions occuring at least once every month exclusion criteria: * pregnant women * prisoners (vulnerable population) * adults lacking capacity to consent (vulnerable population) * adults unable to sign consent due to non-english speaking or illiterate (vulnerable population)

Keywords: congenital aniridia limbal stem cell deficiency descemet's membrane