Anatomy of limbus, Stem cell deficiency.pptx

Anatomy of limbus, Stem
cell deficiency
Dr Suhana Shrestha
MD Opthalomogy, PGY1
NAMS (NEH), 2021

CONTENTS
 INTRODUCTION
 EMBRYOLOGY
 HISTOLOGICAL LIMBUS
 ANATOMICAL LIMBUS
 PATHOLOGICAL LIMBUS
 SURGICAL LIMBUS
 BLOOD SUPPLY
 NERVE SUPPLY
 FUNCTIONS OF LIMBUS
 LIMBUS STEM CELLS
 LIMBAL STEM CELL DEFICIENCY

INTRODUCTION
 Not a distinct anatomical structure
 transition zone between the peripheral cornea and the anterior sclera
 Hence called corneoscleraljunction or corneal limbus
 defined differently: anatomists, histologists, pathologists, and clinicians/surgeons.

 Structures found at the limbus:
1. Palisades of Vogt: houses the
corneal stem cells
2. Episclera
3. Junction of corneoscleral stroma
4. Aqueous outflow apparatus
(collector channel)
 Importance
1. Corneal wound healing
2. Surgical landmark
3. Closely related to the AC angle,
site of passage of the collector
channel that links the Schlemm
canal to aqueous veins.

Transitions at the limbus
S.NO. BEFORE LIMBUS AFTER LIMBUS
1. Corneal epithelium Epithelium of bulbar
conjunctiva
2. Bowman’s Layer Lamina propria of
conjunctiva and fascial
sheath of the eyeball
(Tenon’s capsule)
3. Transparent Corneal Stroma Opaque Stroma of
sclera
4. DM Ends as Schwalbe’s line
5. Corneal endothelium Endothelium lining the
passage of TM

Embryology
 Important to review development of cornea, sclera and AC
 During the early stages in the development, cornea & sclera
have the same radius of curvature
Later part of 2nd month
 a compact layer of mesoderm develops at the periphery of
the cornea & grows posteriorly.
 Scleral condensation begins to develop in the anterior part
of eye & proceeds towards the posterior pole

Third month
 Corneal curvature becomes quite distinct from the scleral
curvature
 AC: relatively shallow
 AC angle: extremely sharp compared to an adult eye
Later part of third month
 Structures of limbus begin to appear
Schlemm’s canal is visible & is located behind the deepest
part of the angle of AC

• Fourth month:
 TM is recognizable as a wedge shaped structure
 Anterior apex of this cell mass lies between the corneal
endothelium & deeper stroma
 corneal endothelium covers most of the anterior face of
the trabecular meshwork

• Fifth month:
 Scleral spur becomes recognizable
 It lies next to posterior wall of Schlemm’s canal & curves
slightly in front of the canal

 Sixth month:
Definitive angle of AC develops as a result of atrophy &
absorption of the mesoderm
The formation of angle is a very gradual process
beginning during the 6th month & being completed just
before birth

 The TM is initially covered by an endothelial layer confluent
with corneal endothelium This membrane 'retracts' to the
cornea only in the later stages of the 3rd trimester.

CLINICAL ASPECTS
1. When the corneal endothelium crosses over the limbus,
overgrowing trabecular meshwork and iris  secondary
glaucoma.
2. Proliferation of corneal endothelial tissue has been
described in the IridoCornealEndothelial syndromes and
after trabecular trauma, especially laser trabeculoplasty.
3. Congenital glaucoma and AC dysgenesis: defect in terminal
differentiation of trabecular tissue leading to excessive
formation of meshwork collegen preventing formation of
iridocorneal angle

Histologist’s Limbus
demarcated by:
 Anterioly, a line that begins at the end of Bowman’s zone
 Extends posteriorly into the stroma in a concave arc, the
apex curving above, the midline of Schlemm’s canal
 Terminating medially to end at the inner aspect of peripheral
termination of DM or its junction with Schwalbe’s ring

Anatomist’s limbus
refers to a circumcorneal transition zone of conjunctivocorneal and sclerocorneal
junction
 Conjunctivocorneal junction:
o Above, narrow, 0.5 mm
o conjunctiva is firmly attached to underlying structure
o substantia propria ends here but conjunctival epithelium continues with that of
the cornea.
 Its characteristics are:
 epithelium 10-12 layers thick, irregularly arranged cells
 cells contain melanin
 epithelium is similar to cornea but its basal cells are arranged in a peculiar
pattern k/a palisade of Vogt, containing stem cells, more prominent superiorly
and inferiorly
In superior and inferior limbus , limbal epithelium extends more into cornea
and there is earlier termination of BM and measures around 1 mm.

 Scelocorneal junction:
 Below, wide, 1 mm
 here transparent parallel corneal lamellae become opaque, oblique and circular
scleral lamellae

Divisions of anatomical limbus
1. Superficial limbus
 Limbal conjunctival epithelium
 Conjunctival stroma
 Tenon’s capsule
 Episclera
2. Mid limbus
 Transitional corneoscleral stroma
 Intrascleral venous plexus
3. Deep limbus
 Ciliary band
 Scleral spur
 Schlemm’s canal
 Trabecular meshwork
 Schwalbe’s ring

Superficial limbus
1. Limbal epithelium:
 peripheral corneal epithelium  epithelium of the bulbar conjunctiva
 non keratinized, stratified squamous & no goblet cells
 about 10-15 cells deep
 Superficial-polyhedral cells, deep-cylindrical or cubical cells with little protoplasm &
dense nuclei dark line characteristic of limbal conjunctiva
 The basal cell membrane is of the basal epithelial cells show a marked infolding
 basal cells often contain pigment granules
 Lymphocytes & langerhan cells are seen in basal & suprabasal layers

 The conjunctival epithelium & stroma form rete ridges & papillae at the corneal
periphery
 These papillae radiate from the corneal edge into the conjunctiva to form the
palisades of vogt.
 The palisades are 0.5mm in width & 2-4mm long
 Small nerves, vessels & lymphatics run along the length of papillae

 There are approximately 36 ridges per limbal quadrant
 In heavily pigmented individuals, the palisades are outlined by golden brown
pigmentation
 They are more prominent in lower limbus
 They are attenuated, but lengthened superiorly & are undetectable in horizontal
quadrants

2. Limbal conjunctival stroma
 loose connective tissue with fibroblasts, melanocytes, macrophages, mast cells,
lymphocytes, plasma cells & an occasional PMN’s
 blood vessels, lymphatics & unmyelinated nerve fibers
 It is hypothesized that :
 Undifferentiated electron dense basal cells are the stem cells that regulate
the regeneration of the corneal epithelium whereas the larger more
differentiated basal cells are the terminal amplification cells.

 Deep to the point of epithelial transformation, the sub epithelial tissues, Tenon’s
capsule & episclera fan out; usually inconspicuous except when oedematous &
inflamed
 Bowman’s layer becomes continuous with the lamina propria of the conjunctiva
and the facial sheath of the eyeball (Tenon’s capsule)

Mid Limbus
 The substantia propria of the cornea gradually loses its uniform and orderly
arrangement and becomes the sclera
 Transitional corneoscleral stroma consists of collagen fibrils, proteoglycans &
glycoprotein
 Within the limbal zone the orderly packing of the corneal collagen gives way to
coarse interweaving of scleral fibres & the fibril diameter increases markedly from
the narrow range of fine fibril diameter in the cornea to broad range found in
sclera

 The interfibrillar distance is less constant in sclera
 Collagen fibrils run in a circular course at the limbus which is the weakest region
in the corneoscleral envelope
 So, traumatic rupture of the globe is quite common at the limbus or under a
rectus muscle at the equator because the sclera is thinnest at that positions
 There is appearance of proteoglycan – dermatan sulphate & hyaluronic acid at
the limbus & marked fall in keratan sulphate which predominates in the central
cornea

Deep limbus
i. Ciliary band:
 Represents the anterior face of ciliary body
(Schwalbe’s line, Schlemm’s canal, trabecular
meshwork) including the insertion of ciliary
muscle into the scleral spur.
 DM ends abruptly at Schwalbe’s line, and just
posterior to this the TM begins
 At the limbus, the corneal endothelium is
continuous laterally with endothelium lining
TM described above and then continues to
the anterior surface of iris

ii. Scleral spur-
 wedge shaped circular ridge
 the deep aspect of the sclerolimbal
junction
 receives the insertion of the anterior
tendon of the longitudinal ciliary
muscle on its inner aspect
 contains collagen & elastic tissue with
a circular arrangement.
 Contraction of ciliary muscle pulls the
spur posteriorly & opens up trabecular
spaces

iii. Schwalbe’s ring-
• the anterior border ring of
trabecular region
• contains circularly arranged
collagen fibers & elastic fibers.
• a sponge work of connective tissue
beams which are arranged as
superimposed perforated sheets

iv. Trabecular meshwork-
• roughly triangular in cross section
• with apex at Schwalbe’s line & base formed by scleral
spur & ciliary body.
• 3 parts:
1) Uveal portion
2) Corneoscleral meshwork
3) Juxtacanalicular tissue adjacent to
Schlemm’s canal

v. Schlem’s canal
 36 mm long, large venous channel
 formed by a continuous
monolayer of non fenestrated
endothelium & a thin connective
tissue wall
 A zone of paracanalicular tissue
separates the inner and outer walls
of schlemm’s canal from the
trabecular meshwork and sclera,
respectively

Diagnostic importance:
USG biomicroscopy :
 Termination of Bowman’s layer is indicated
by internal limit of marginal arcade of
corneal vessels seen best at upper & lower
limbus
On gonioscopy:
 Termination of Descemet’s layer
represented by the most anterior landmark
of the drainage angle, Schwalbe’s line
 Scleral limbus is less clearly defined by : A
line perpendicular to the surface passing
through the tip of scleral spur

 To understand the angle in anterior segment OCT: Glaucoma evaluation

Pathologists’ limbus
 Anterior boarder: an imaginary line joining the peripheral
termination of BM & that of DM.
 Posterior border: a line from scleral spur perpendicular to the
tangent of the external surface of the globe
Dimension
 Spreads approximately 1.5 mm posterior to the termination of the
Bowman layer in the horizontal meridian
 2.0 mm posterior in the vertical meridian, where there is greater
scleral overlap

SURGICAL LIMBUS
 2 mm wide circumcorneal transitional
zone
 between the clear cornea on one side
and opaque sclera on the other side.
 characterized by external landmarks:
- Anterior limbal border
- Mid limbal line
- Posterior limbal border
 2 zones: blue and white

 blue-gray appearance: due to the
scattering of light through the
oblique interface between cornea
and sclera

Anterior limbal border
 represented by insertion of conjunctiva into peripheral cornea
 it overlies the termination of Bowman’s membrane.
 Under microscope, anterior limbal border can be identified as a zone in clear
cornea where fine conjunctival vessels are terminating.

Blue zone
 Posterior to anterior limbal
border, there is a blue zone
which terminates in midlimbal
line.
 extends for 1 mm superiorly
and 0.8 mm inferiorly
 Under microscope, blue limbal
zone can be identified as
bluish translucent area, after
dissecting overlying
conjunctiva and tenon’s
capsule from anterior limbal
border

Mid limbal border
 overlies the Schwalbe’s line which is termination of Descemet’s membrane. It is the
junction of blue and white zone of limbus.

White zone
-starts at midlimbal line
-extends for 1 mm
-terminates in posterior
limbal border
-overlies the trabecular
meshwork.

Posterior limbal border
 a consistent external landmark that corresponds to the internal junction of cornea
and sclera overlying the trabecular meshwork in all meridians.
 overlies the scleral spur and iris root

Clinical anatomy
• Scleral incision:
 posterior to the posterior limbal border
 Disadvantage: excessive bleeding and
hyphaema
• Posterior limbal incision:
 at the white limbal zone between the
mid-limbal line and the posterior limbal
border or Scleral spur
 Underlying TM may be injured
• Mid limbal incision:
 at the mid–limbal line  corresponds to
Schwalbe’s line
 Most preferred site for incision

 Anterior limbal incision:
 in the blue limbal zone
 Traverses the DM and may
cause its stripping
 Clear corneal incision:
 in front of the anterior limbal
border
 Associated with high
induced astIgmatism
 Also greater chance of
Descement`s stripping

Arterial supply
The rich limbal vasculature is supplied by :
 Superficial marginal plexus derived from
the episcleral branches of the anterior
ciliary artery .
 These also gives off fine loops to the
palisades of vogt.

 Two sets of vessels originate from the superficial marginal plexus of the
limbus;
1) Terminal vessels: form the peripheral corneal arcade near the termination
of Bowman’s layer.
2) Recurrent vessels: form a part of peripheral arcades.
∙ These run posteriorly through the palisades to supply the peripheral
conjunctiva.
∙ The recurrent vessels anastomoses with the conjunctival vessels from the
fornices

Venous drainage
Immediately behind the limbal arcades & anterior to the episcleral arterial
circle lies the perilimbal venous circle composed of upto three
communicating parallel vessels.
These collect blood from the limbus ,marginal corneal arcades & fine
anterior conjunctival veins.
They drain into radial episcleral collecting veins & then into the veins of
rectus muscle
Clinical importance: Chemical injury to eye may manifest with limbal
ischaemia or limbal ‘blanching ‘ which is associated with most unfavourable
visual prognosis..

Nerve supply
 Limbal area is supplied by :
Branches from ciliary nerves  the branches of nasociliary nerve
arises from the ophthalmic nerve the branch of trigeminal nerve

Functions of limbus
 nourishment and oxygen for the peripheral cornea
 provides pathway for drainage of aqueous humour
 Corneal wound healing :
 Corneal epithelium is highly differentiated and renews itself rapidly, it depends
on its stem cells for continual migration and replacement.
 In the absence of limbal stem cells , epithelium wound healing is
compromised.
 Limbal stem cells deficiency may lead to invasion of the cornea by
conjunctival cells including goblet cells - a process called conjunctivalisation of
the cornea.
 Acts as a barrier against corneal neovascularization from the conjunctiva and invasion of
conjunctival cells from bulbar surface
Site for incision into AC in cataract & glaucoma surgery

XYZ Hipothesis: Corneal epithelium
 It states that for a healthy
cornea:
X + Y = Z
where
X= proliferation of limbal basal cells
by mitosis. Daughter cells move
upward from basal layer,
differentiating into wing cells
and finally into superficial cells
Y= Centripetal migration of new
basal cells into cornea from
limbus
Z= Shedding of superficial epithelial
cells.
Epithelium turn over completely
every 7-10 days

LIMBAL STEM CELLS
 Limbal epithelial stem cells are the
undifferentiated pluripotent cells
which serve as an important
source of new corneal epithelium
 found in limbal basal epithelium of
palisades of Vogt
 Only 5-15%of the cells in the
limbus are stem cells

LIFE CYCLE OF STEM CELLS
 controlled via delicate regulatory mechanisms
 progeny of these epithelial stem cells transient amplifying (TA) cells
 TA cells divide more frequently than stem cells and undergo mixed (horizontal
or vertical) proliferation

 Once TA cells reach the end of their proliferative capacity, usually when
near the center of the cornea, they become basal epithelial cells
 Terminally differentiate just once into two daughter wing cells (vertical
proliferation)

Location of stem cells at limbus

Stem cells have 3 common
characterstics:
 asymmetric cell division i.e 1 daughter cell remains a
stem cell while the other proceeds toward terminal
differentiation
 Once the daughter cell is committed toward the
differentiation pathway, the process cannot be reversed
 capable of unlimited mitosis which extends through the
life of the organism

Determinations of the location of epithelial stem cells
in the Basal Limbal Epithelium:
Presence of keratin K19
Retention of (3H) thymidine labelling for longer periods
Response to tumour promoter acetate (TPA)
presence of higher quantities of proteins, enzymes and
epithelial growth factor (EGF)
High p63 immunoreactivity, at the corneal limbus, as an
indication of the location of stem cells at the corneal limbus
Higher hTERT ( human telomerase reverse transcriptase )
immunoreactivity of limbal basal cells in culture

Circumstantial evidence for location of corneal epithelial stem cells at
the limbus:
1. Pigmented cells at the limbus migrate centripetally towards the
central cornea
2. Surgical removal of limbal region results in healing with non-
corneal epithelium
3. Limbal transplants result in regeneration with cornea like
epithelium
4. Limbal basal cells respond to central corneal wounds by
undergoing cell division as would be expected of stem cells
5. Tumour cells originate at the limbus. Ocular surface squamous
neoplasias usually have a limbal origin

Histological difference:
- Limbal epithelium consists of > 10 layers
- Conjunctival epithelium has 1 to 2 layers
- Corneal epithelium has 4 to 6 layers
Stem cells localised in the fornix region of conjunctiva and mucocutaneous junction.

Characteristics of Epithelial stem cells :
1. undifferentiated
2. Slow cycling
3. Extremely long lived
4. High proliferative potential

Defination
 characterized by a loss or deficiency of the stem cells in the limbus that are vital
for re-population of the corneal epithelium and to the barrier function of the
limbus.
 When these stem cells are lost, the corneal epithelium is unable to repair and
renew itself.

• Corneal disorders characterised by absence or malfunction of
limbal stem cells:
1. Primary disorders
2. Secondary limbal stem cell deficiency

Primary disorders:
- Congenital aniridia
- Congenital erythrokeratodermia
- Multiple endocrine deficiency
- Neuropathic keratopathy
- Peripheral inflammatory keratopathy

Secondary disorders:
- Stevens-Johnson syndrome
- Iatrogenic (surgeries at the limbal region)
- Cryotherapy
- Contact lens wear ( soft CL )
- Chemical injuries ( acid burns, alkali burns )
- Thermal injuries
- Severe microbial infection
- Ocular cicatricial pemphigoid
- Ocular surface squamous neoplasia (OSSN)

Primary Prevention for LSCD
Varies according to the underlying cause:
 Contact lens overwear can be treated with the cessation of lenses and frequent
lubrication
 Traumatic causes, either mechanical or chemical, may be avoided with the use of
eye protection.
 Treatment of the systemic inflammatory disease that can affect eye.
 Timely treatment of severe infections before they affect the limbal stem cells

Diagnosis of LSCD
 Clinical diagnosis based on the signs and symptoms of the disease along with
cytological evidence.
 Typical findings of conjunctival changes to the cornea adjacent to the limbus are a
hallmark of the disease
History:
 pain resulting from recurrent erosions and decreased vision
 Other symptoms: contact lens intolerance, photophobia, tearing, and blepharospasm.
 varies depending on the etiology
 For example, a patient with LSCD from a chemical burn or trauma will give a history of
such an event.
 Clinical observation: corneal conjunctivalization, associated with persistent epithelial
defects; loss of the limbal anatomy, irregular staining with fluorescein, etc

Examination
 progressive epitheliopathy with hazy, translucent epithelium extending centrally
from the limbus, most commonly from the superior limbus.
 Epithelial staining, from punctate changes to more confluent staining, is broadest
adjacent to the involved limbus and extends centripetally into the cornea to
varying degrees in a whorl shape.
 evidence of mild to moderate tear film dysfunction, reduced tear film break-up
time, or both
 Infectious keratitis is a common complication
 Late stages: superficial and deep vascularization, persistent epithelial defects
leading to ulceration, melting and perforation, fibrovascular pannus, and finally,
scarring, keratinization, and calcification

Limbal stem cell deficiency manifests
as:
 Conjunctivalisation
 Vascularisation
 Chronic inflammation
 Irregular epithelial surface
 Recurrent erosions
 Persistent ulcer

Conjunctivalisation :
 Ingrowth of conjunctival
on the cornea
 Manifested as:
 Vascularisation
 Poor epithelial adhesion
 Recurrent breakdown
 Chronic inflammation
 Epithelial surface irregularity

Impression cytology
 presence of goblet cells and conjunctival epithelial cells on the involved corneal
surface
 conjunctivalization of the cornea
 immunohistochemical markers of conjunctiva on impression cytology of the
corneal surface (e.g. absence of keratin CK3) confirms the diagnosis.
 if the corneal impression appears mainly acellular or contains normal corneal
epithelial cells then, it becomes less likely that LSCD exists.
 However, if the impression consists of a mixture of corneal and conjunctival
epithelial cells or mainly conjunctival epithelial cells then this is highly
confirmative of LSCD

Histopathology
 invasion and overgrowth of conjunctival epithelium, neovascularization,
disruption of the basement membrane, and prominent inflammatory cell
infiltrates.
 Pathology typically shows conjunctivalization of the cornea which can be
indicated by the presence of goblet cells in the cornea.
 However, the lack of goblet cells may be seen in approximately one-third of
patients.

In vivo confocal microscopy
 the absence of the palisades of Vogt in the affected sector
 metaplastic wing and basal epithelial cells with significantly decreased basal
epithelial cell density and subbasal nerve density
 replacement of normal limbal epithelium by vascular fibrotic tissues in late stages

Differential diagnosis
 Early ulceration or peripheral infectious keratitis
 Pterygium
 Ocular surface squamous neoplasia

Staging
Stage I- Normal corneal epithelium within the central 5 mm zone of the cornea (A:
<50% of limbal involvement; B: > 50% but <100% of limbal involvement; C: 100% of
limbal involvement)
Stage II- The central 5 mm zone of the cornea is affected (A: <50% of limbal
involvement; B: >50% but <100% of limbal involvement)
Stage III- The entire corneal surface is affected.

Management
 Early stage: symptomatic treatment
Medical therapy
 Aim: restoring the limbal microenvironment with a stepwise approach
 Basis: stopping traumatic or toxic insults to the limbus and optimizing the ocular
surface
 How?: by improving the tear film, controlling inflammation, and promoting
differentiation of healthy epithelium

Medical options
 discontinuing contact lenses
 aggressive lubrication with preservative-free artificial tears
 lid hygiene
 warm compresses

When the surface does not respond to such treatment
 nightly topical Vitamin A ointment
 short-term pulse topical corticosteroids such as methylprednisolone 1%, loteprednol
etabonate 0.5%, or 0.2%, or prednisolone acetate 1%, and cyclosporine 0.05%.
 Punctal occlusion: If significant aqueous tear film deficiency
 Patients with rosacea: oral doxycycline
Newer treatments like:
 Autologous serum eyedrops
 A bandage contact lens or the PROSE scleral lens

Medical follow up
Improvement in the ocular surface may manifest as
 decreased pain and increased visual acuity on follow-up examinations
 Progressive epitheliopathy with hazy, translucent epithelium extending centrally
from the limbus may begin to regress
 reduced pattern of epithelial staining with fluorescein
If symptoms are not improving, surgery is necessary

Surgery
 effective assessment of tear film production and eye closure is an important
prerequisite to ensure optimal surgical outcomes
 Partial or focal LSCD not responding to medical treatments: Resection of pannus
tissue and subsequent amniotic membrane transplant
 Penetrating Keratoplasty (PK) alone -not a viable option in LSCD: donor tissue
does not include limbal stem cells
 Pre-existing corneal vascularization and inflammation increase the risk of
rejection in these patients.

 Unilateral LSCD: autologous limbal stem cell transplants from unaffected
eyes
However, the removal of stem cells from the contralateral eye risks LSCD in the
donor eye
The risk of epithelial problems in the donor eye is low when less than four to
clock hours of limbal tissue and a moderate amount of conjunctiva are
 Bilateral LSCD: Allogeneic transplants from donor eyes
Living donor tissue is preferred to cadaveric donor
In these cases patient must be treated with immunosuppressive agents

Ex Vivo Cultivation:
 minimize loss of donor limbal tissue and the
possibility of inducing LSCD in the donor eye
 newer techniques
 a smaller area (generally 2mm x 2mm) of
donor cells is grown in the laboratory on
fibroblast culture medium or graft
tissue/amniotic membrane in order to
the donor cell population
 an attempt to increase success rates and
decrease epithelialization time
 Because using animal feeder cells, such as
fibroblasts, to grow explanted cells may
represent an unknown risk in the clinical
transplantation of recipients with a potentially
undetected viral transmission, xeno-free
transplants on amniotic membrane have
investigated which only use human tissues
and cells.[47]

Simple Limbal Epithelial Transplantation (SLET)
 Newer technique for unilateral disease
 seeds donor stem cells directly on amniotic membrane placed on the ocular
surface of the recipient, altogether bypassing the need for laboratory conditions
expansion
 These techniques may be combined with subsequent penetrating keratoplasty to
further improve visual outcomes, once the limbal stem cell niche has been

Newest techniques for transplanting limbal stem cells:
 hydrogel lenses and plasma polymer-coated contact lenses for in vivo culture
transfer of transplanted cells.
 still in the testing phase in animal studies and some small human studies
Other techniques besides limbal cell transplant:
 oral mucosal epithelial transplantation
 keratoprostheses, such as the modified osteo–odonto keratoprosthesis and the
Boston Keratoprosthesis (KPro) generally a last resort for total LSCD with poor
surface and tear quality

Surgical F/U
 Postoperative treatment: preservative-free topical antibiotics, topical
immunosuppressants, and frequent preservative-free artificial tears. Steroids are
rapidly tapered in autologous limbal transplantation
 Transplantation of an allograft poses a high risk of rejection even in HLA matched
recipients. Therefore, graft survival depends on systemic immunosuppression for
a prolonged, if not indefinite, period.
 Early postoperative period: the limbal explant is carefully monitored for any areas
of epithelial loss. Conjunctival epithelium can cross the explant at these sites and
gain access to the corneal surface. If conjunctival encroachment is observed,
mechanical debridement of conjunctival cells should be promptly carried out

 Watch for signs of graft rejection and treated appropriately
 Signs of rejection:
sectoral limbal injection, edema and infiltration of the graft, punctate keratopathy, and
epithelial irregularities and defects, and surface keratinization
 Risk factors for failure of graft:
blink-related microtrauma, conjunctival inflammation, increased IOP, aqueous tear–
deficient dry eye, lagophthalmos, and pathogenic symblepharon

Complications
Untreated LSCD causes:
 pain, decreased vision, and recurrent epithelial erosions  infection and loss of
vision
Post surger
 risk of rejection from allogeneic transplants

References
1. Snell’s Clinical anatomy of the Eye -2nd edition
2. Wolff’s anatomy of the Eye, 8th edition
3. Anatomy and phusiology of Eye, 3rd edition, A.K Khurana, Indu Khurana
4. BCSC External disease and cornea, Section 8,2019-2020
5. Van Buskirk EM. The anatomy of the limbus. Eye. 1989 Mar;3(2):101-8
6. Internet: EYEWIKI, eOphtha

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Anatomy of limbus, Stem cell deficiency.pptx