Ocular surface Ocular surface reconstruction with reconstruction with autologous mucosal autologous mucosal

membrane membrane transplantation in limbal transplantation in limbal

stem cell deficiencystem cell deficiency

Elisabeth MacdonaldElisabeth MacdonaldSuzannah DrummondSuzannah Drummond

Kanna Ramaesh Kanna Ramaesh

Authors have no financial interestAuthors have no financial interest

BackgroundBackground Corneal limbal stem cell deficiency Corneal limbal stem cell deficiency

(LSCD) causes corneal opacification (LSCD) causes corneal opacification and blindnessand blindness

Repopulation with stem cells may Repopulation with stem cells may occur by transplanting limbal tissue occur by transplanting limbal tissue from a donor source or with ex vivo from a donor source or with ex vivo expanded LSCexpanded LSC

Cultured oral mucosal epithelial cells Cultured oral mucosal epithelial cells have previously been used as an have previously been used as an alternative to limbal transplantationalternative to limbal transplantation

An Alternative ?An Alternative ?Mucous Membrane EpitheliumMucous Membrane Epithelium

Reports of cultured autologous oral mucosal Reports of cultured autologous oral mucosal epithelium for LSCD:epithelium for LSCD:

Nakamura et al. Nakamura et al. Transplantation of cultivated autologous Transplantation of cultivated autologous oral mucosal epithelial cells in patients with severe oral mucosal epithelial cells in patients with severe ocular surface disorders ocular surface disorders BJO 2004;88:1280-84BJO 2004;88:1280-84

Tsutomu et al. Tsutomu et al. Midterm results on ocular surface Midterm results on ocular surface reconstruction using cultivated autologous oral reconstruction using cultivated autologous oral mucosal epithelial transplantation mucosal epithelial transplantation Am J Ophth Am J Ophth 2006;141:2672006;141:267

Can the method be simplified by avoiding the Can the method be simplified by avoiding the cultivation step ?cultivation step ?

Is dIs direct migration from perilimbal mucous irect migration from perilimbal mucous membrane grafts (MMG) possible ?membrane grafts (MMG) possible ?

Why Mucous Membrane?Why Mucous Membrane?

Autograft materialAutograft material Readily availableReadily available

Widely used Widely used historically to replace historically to replace abnormal conjunctivaabnormal conjunctiva

11stst use 1876 by Klein use 1876 by Klein

Epithelium similar to Epithelium similar to corneal epitheliumcorneal epithelium

Denig: Textbook of Surgery 1943

Purpose and MethodsPurpose and Methods

We describe a novel surgical technique of direct oral We describe a novel surgical technique of direct oral MMG to rehabilitate LSCDMMG to rehabilitate LSCD

Direct oral MMG has not been previously Direct oral MMG has not been previously reported to restore corneal transparencyreported to restore corneal transparency

The results of 5 patients are reportThe results of 5 patients are report

LSCD was characterised by conjunctivalisation of the LSCD was characterised by conjunctivalisation of the corneal surface, corneal scarring, recurrent epithelial corneal surface, corneal scarring, recurrent epithelial defects and corneal vascularisation and later defects and corneal vascularisation and later confirmed by immunohistochemistryconfirmed by immunohistochemistry

No donor site complications occurredNo donor site complications occurred

Surgical techniqueSurgical technique A 360A 360 peritomy and peritomy and

removal of abnormal removal of abnormal epithelium and epithelium and fibrovascular tissue fibrovascular tissue covering the cornea were covering the cornea were performedperformed

A small strip of buccal oral A small strip of buccal oral mucosa was excised and mucosa was excised and the sub-stromal adipose the sub-stromal adipose tissue removedtissue removed

The mucosal membrane The mucosal membrane strips were sutured to the strips were sutured to the exposed perilimbal sclera exposed perilimbal sclera

ResultsResults Baring of the corneal stroma allowed Baring of the corneal stroma allowed

migration of mucous membrane migration of mucous membrane epitheliumepithelium

This produced transparent epithelium on the cornea in 4 This produced transparent epithelium on the cornea in 4 casescases

In one case radial corneal vessels invaded from the peripheryIn one case radial corneal vessels invaded from the periphery

Post OpPre Op

CasesCasesAge Co

morbidityPrevious ocular reconstruction surgery

Pre Op BCVA

Post Op BCVA 2yrs

Co Pathology

37 Chemical Injury

AMG HM 3/60

52 OCP 2 x failed stem cell grafts, DLK

CF 6/60 CRVO

52 OCP None CF 6/36

61 Aniridia Lamellar corneal graft

HM 6/24 Macula hypoplasia, Optic neuropathy

70 OCP Conjunctival autograft

6/36 6/12

Transparent epithelium on cornea

Epithelial cell maintenanceEpithelial cell maintenance The mucosal epithelial cells migrated from the The mucosal epithelial cells migrated from the

MMG in the perilimbal region onto the cornea to MMG in the perilimbal region onto the cornea to provide a stable corneal surfaceprovide a stable corneal surface

On slit lamp examination the migrated On slit lamp examination the migrated epithelium appeared very similar to normal epithelium appeared very similar to normal corneal epithelium and was transparentcorneal epithelium and was transparent

The epithelium over the cornea has been The epithelium over the cornea has been maintained and has behaved like ‘corneal maintained and has behaved like ‘corneal epithelium’epithelium’

The HypothesisThe Hypothesis

These are derived from resident stem cells of the oral mucosa These are derived from resident stem cells of the oral mucosa epitheliumepithelium

It is our belief that the success of the technique is due to the It is our belief that the success of the technique is due to the survival of the stem cells within the transplanted oral mucosa survival of the stem cells within the transplanted oral mucosa to the vascular perilimbal locationto the vascular perilimbal location

These cells may act as a reservoir and generate a progeny of These cells may act as a reservoir and generate a progeny of differentiated epithelial cells that cover the cornea differentiated epithelial cells that cover the cornea

Mucous membrane grafts

Progenitor cells

Success of Success of ex vivoex vivo expanded oral expanded oral mucosal epithelial transplantation mucosal epithelial transplantation is attributed to the presence of is attributed to the presence of stem cells among the transplanted stem cells among the transplanted populationpopulation

Direct MMG compared with Direct MMG compared with reported cultivated epithelial reported cultivated epithelial

techniquetechnique Duration of our results is the same or Duration of our results is the same or

longerlonger

Perilimbal vascular invasion similarPerilimbal vascular invasion similar

Advantages of our technique:Advantages of our technique: Much less expensiveMuch less expensive No need for laboratoryNo need for laboratory No risk of transmitted diseaseNo risk of transmitted disease

ConclusionConclusion New findingNew finding

Mucosal epithelium migrates from perilimbal Mucosal epithelium migrates from perilimbal grafts to produce functional corneal epitheliumgrafts to produce functional corneal epithelium

Simple and cheap techniqueSimple and cheap technique

Direct autologous perilimbal transplantation of Direct autologous perilimbal transplantation of oral mucosal tissue may be an alternative to oral mucosal tissue may be an alternative to limbal stem cell transplantation to reconstruct limbal stem cell transplantation to reconstruct the corneal surface and restore vision in the corneal surface and restore vision in selected cases of severe LSCDselected cases of severe LSCD