ophthalmology

1. Anatomy and Physiology of
cornea
Dr.Lhacha Wangdi
1st year Resident
Department of Ophthalmology
JDWNRH/KGUMSB

2. Outline
Gross anatomy of cornea
-Surface anatomy
-clinical application
Microanatomy of cornea
-anatomy of ultra structure
Physiology of corneal tissue

3. Introduction
 Word cornea originated from Latin word-Cornu
(horn) Cornea tela(horny tissue)
 Transparent avascular tissue with a convex
anterior surface & concave posterior surface.
 Main function is OPTICAL
 Other functions are:
-STRUCTURAL INTEGRITTY
-PROTECTION FOR THE EYE

4. Gross anatomy of cornea
 Covers the anterior scleral foramen
 Limbus is transition zone between
cornea and sclera
 The cornea protrudes slightly beyond
the scleral globe because of the
different curvatures of the two
structures
 Radius of curvature (cornea)–6.7-
9.4mm whereas scleral-11.5mm
 Cornea appears elliptical in shape
measuring 11-12mm horizontally
and 10-11mm vertically
Surface area:
 About 1.3 cm² (one-sixth of the
globe)
11-12mm
10-11mm
limbus

5. Corneal thickness
 Posterior surface of cornea is
curved more than anterior
surface
 Central zone- 0.52mm
 Paracentral zone- 0.52-
0.57mm(outer diameter-7-8mm)
 Periphery zone- 0.63-0.67mm
 The thinnest zone is 1.50mm
temporal to the geographic
center about 0.505-0.51mm
 In endothelial/ epithelial cell
dysfunction, corneal becomes
unusually thick due to stromal
edma
 Thick cornea will give false IOP
reading

6. Surface anatomy- cornea
 Cornea is not a true sphere
 It has a central spherical (optical
zone-4mm)with uniform flattening
towards the periphery –prolate
shape
 Flattening is more extensive nasally
and superiorly Surface cornea is divided into three
zones-
1. Central zone of 1-2mm-spherical(red
area)
2. Paracentral zone of 3-4mm around the
central zone with progressive flattening
3. Peripheral zone which is flattened more.
Clinical application-
1. Topographic
information of
cornea is important
in contact lens fitting
2. Flattening of cornea
at periphery helps to
reduce the spherical
aberration of optical
system
3. Alteration of the uniform curvature of
cornea will induce astimatism

7. Spherical aberration
 In total spherical object
peripheral parallel rays of
light refract more and
focus in front of ideal
image point.
 Effects- blurred vision
 Spherical aberration is
minimized by aspheric
(prolate) shapes of eye
surfaces- due to peripheral
flattening

8. Cornea as a optical system
 Main function of cornea- optical( refraction of light for clear
vision)
 Contributed by its special characteristics;
1. Transparency
2.Avascularity
3. Controlled hydration
4. High refractive power
 The optical power of the cornea=42.0 D
 Is equal to 2/3 of the total optical power of the human eye (57 –
62 D)
Refractive power of cornea=(refractive index of cornea-refractive index of
air)
(radius of curvature of cornea) Refractive index of cornea is more -Cornea- 1.33765
-Air- 1.000
 Radius of curvature is inversely proportional to curvature:
- Anterior surface – about 7.8
mm
-Post. Surface – about 6.5 mm

9. Microanatomy of cornea
 Cornea has five defined layers
1. Epithelium and basal lamina-
5% of thickness
2. Bowman’s layer
3. Stroma-90% of total
thickness
4. Descemet’s Membrane
5. Endothelium –single cellular
layer (germinal layer)

10. Composition of cornea
 Water: 78 %
 Collagen: 15 %
of which: Type-I : 50-55 %
Type-III : 1 %
Type-IV : 8-10 %
Type-VI : 25-30 %
 Other protein: 5 %
 Ground substances
-Keratan sulphate: 0.7 %
-Condroitin/dermatan sulphate: 0.3 %
 Hyaluronic acid: +
 Salts: 1 %

11. Embryonic origin of cornea
 Clinical significance-cell line originating from surface ectoderm has
regenerative capacity whereas those from neural crest has little regenerative
capacity
 Disease affecting other organ such as in atopic dermatitis may cause
keratitis due to similar embryonic origin
Epithelium-Derived from
surface ectoderm
Bowmans layer-
mesenchyme(neural crest
cell)
Endothelium-
mesenchyme(neural crest
cell) 1st wave
Stroma -
mesenchyme(neural crest
cell) 2nd wave
descemet’s – synthesised
by endothelium

12. Epithelium
 Derived from surface ectoderm
 Constitutes of 5-6 layers of cell accounting for about
5% of corneal thickness-(0.05mm/50um)
 Its has three cell layers
1. Apical cells-
nonkeratinised
Squamous epithelium
2. Wing cells- 2-3 layers of
polygonal cell
3. Basal columnar cells
(germinative layer)
Nonepithelial cells-
histocytes, macrophages, lymphocytes, antigen presenting langerhans cells are also
present which becomes more numeruous during keratitis

13. Ultrastructure of epithelium
 Apical cells layers consists
of 2-3 layers of flattened
hexagonal cells
 Surface cells contain
microvilli & microplicae
coated with 300-nm thick
glycocalyx/glycoprotein
(buffy cell coat)
 The mucin layer of tear binds with glycocalyx and
helps in uniform spreading of tear film,

14. Ctn…
Epithelial cells are adhered
together by tight junctions –
1. Tight junctions & desmosomes
– surface cells
2. Desmosomes – wings &
superficial cells
3. Desmosomes &
Hemidesmosomes – in basal
cells
4. Cells are anchored to deeper
tissue by anchoring proteins
 Functions-
1. Maintains corneal homeostasis(impermeable to Na ions & confer
semipermeable membrane properties to the epithelium)
2. Mechanical barrier – protective function against infection/toxins
3. Tight junction ensure corneal transparency
4. Anchor epithelial cells to basal lamina and bowmans layer
Anchoring protein
desmosome
hemidesmosomes

15. Basal lamina  Fibrous layer consisting of 1V
collagen and glycoprotein.
 Secreted by the basal cells
 0.5 - 1 μm wide
 Ultra structurally it is distinguished
in to two parts
1. Lamina lucida (superficial)-
electron lucen zone
2. Lamina densa (deep electron
dense zone)
3. Anchored to bowman’s layer with
numerous anchoring fillaments
 Lipid solvent, stromal oedema and inflamation may loosened
the cohesion between Bowman’s zone,lamina and epithelial
cells-– eg mucus filaments due to epithelial instability
 With old age, in diabetes and in some corneal disorders it
becomes thickened and multilamellar

16. Epithelial regeneration
 The epithelium is constantly in a
state of turn-over with exfoliating
apical cells being replaced by
underlying wing cells-weekly
 Basals cells are only epithelial
cells capable of mitosis
 During normal apical cell
exfoliation basal cells
proliferates and replace lost
cells in 7-14 days
 Loss of basal cells and defective regeneration will lead to
corneal scar formation
Apical cells
loss

17. Wound healing
 During epithelial
defect either due to
infection/trauma/infla
mation there are
extended
proliferation and
differentiation of
basal cells
 If Boman’s layer is
intact the epithelium
is regenerated in 7-
14 days

18. Cellular events
Repair of corneal epithelial injury like
abration/infection follows a distinctive
sequence of events-
1. Cells at wound edge retract,
thicken and lose attachment,
produce various growth factors
(egTGF-Bs)
2. Basal cells travel in an amoeboid
movement to cover the defect
3. Migration process is halted by
contact inhibition
4. They then anchor by secreting
basal lamena
5. Mitosis resumes to re-establish
epithelial thickness
6. Surface tight junctions re-
establised
7. Adhesion with Bowman’s layer
within 7 days (if basal lamina
intact)
Toxin, trauma,
infection,
inflammation
Spreading and
dedifferentiation
Cell migration
Cell proliferation
Regeneration
redifferentiation

19. Germinative cells
 It is now recognized that
the germinative region
lies at the limbus
 Limbal stem cell migrate
centrally to replace
corneal epithelial basal
cells
 The stem cells migrate at
a very slower rate (123
μm/week) to the center of
the cornea which may be
as long as a year
 Loss of limbal stem cells
will result in corneal scar
Limbal stem
cells

20. The XYZ hypothesis
 Richard A. Thoft & Judith Friend(1983) proposed on the basis
of experimental evidence that both limbal basal and corneal
basal cells are the source for corneal epithelial cells.
 The corneal epithelium is
maintained by a balance
among-
(Z)Sloughing of cells from the
corneal surface is =
(X)cell division in the basal
layer
+
(Y) Migration of basal cells
originating from the limbal stem
cells

21. Ctn..
 In normal healthy cornea there is a constant balance between;
(cell turn over=regeneration)
 Regeneration= balanced basal cell proliferation +
migration+maturation+secretion of basement
membrane+regeneration.
 Abnormality of epithelial Cell turn over and regeneration causes
epithelial opacity and haziness.
 Example, Corneal Epithelial Basement
membrane Dystrophy(EBMD) aslo
called ‘map dot finger print’/’cogan
microcystic dystrophy’
 chateractised by;
-dots/epithelail microcysts
(due to abnormal epithelium)
-fingerprint/geographic map lines
(due to thicken basement
membrane)

22. Bowman’s layer
 Modified region of anterior stroma
 8 – 14 μm thick
 Acellular homogeneous zone
 It is perforated by many nerve
axons which courses through
toward the epithelium
 Ant. surface is smooth & parallel
with corneal surface
 Posteriorly it becomes blended &
interweaved with fibrils of ant.
stroma
Functions-
1. Anchoring site for epithelial cells to ensure its stability
2. Tough acellular layer provide mechanical supports
3. Prevents stromal keratocytes from exposure to epithelial
growth factors- prevents keratocytes metaplasia to fibroblast
and scar formation

23. Ultrastructural features
 Ultrastructurally it is a
meshwork of fine collagen
fibrils of uniform size in a
ground substance
(glycoprotein &proteoglecan)
 Compact arrangement of
collagen types I, III, V, and VI
 it has great strength and
relatively resistant to trauma
both mechanical and infective
 It is acellular and lacks fibroblast therefore after injury
it is unable to regenerate- replaced by course scar
tissue

24. Stroma
 About 450- 500 μm thick (about 90% of corneal
thickness)
 Transperant and rich in collagen-predominantly of
type I collagen with types III, V, and VI also in
evidence. Proteoglycan(glycosami
noglycan)ground
substance between the
collagen fibers
 5% of stromal volume
occupied by
keratocytes which
synthesizes both
collagen and
stroma

25. Stromal lamellae
 Stroma ensure transparency
of cornea by lamellar
arrangement of collagen
bundles
 Stroma has about 200 layers
of lamellae
 Lamelae are arranged
regularly almost right angle to
each other
 Each lamellae consists of
bundle of collagen-
1. 200 – 300 bundles –
centrally
2. 500 bundles – peripherally
3. Width about 9 – 260 μm
4. Thickness about 1.15 – 2

26. Ultrastructural features
 Each lamellae comprises of a
band of collgen fibrils
arranged in parallel with each
other
 Fibrils are regularly placed
each other with center-to-
center distance of 55-60nm.
 There is a unique uniformity of
fibril diameter of 22 (±1) nm
from ant. to post.
 Regularly arranged lamellae
with uniform diameter and
seperation of collagen fibers

27. Ground substances of stroma
 The ground substance of cornea consists of proteoglycan that
run between the collagen fibers
 It constitutes approximately 10% of corneal weight
 Proteoglycan are glycosylated with glycosaminoglycan(GAGs)-
disaccharides
 GAGs include- 1. Keratin salphate
2.Chondroitin sulphate
3.Dermatan sulphate
 Function-
1. Confer hydrophilic properties of stroma
2. Maintains corneal transparency by controlled stromal
hydration by contributing fixed negative charge of stroma
(normally stroma is 78% hydrated)
3. Helps in regular spacing of collagen fibers to ensure
transparency

28. Cellular components of stroma
Keratocytes:
 Long, thin, flattened cells (maximally 2μm
thick) running parallel to corneal surface
 Position – between the lamellae
 Having long flattened nuclei, sparse
cytoplasm but contains full component of
organells
Function
1. responsible for synthesis and
maintaining of collagen & proteoglycan
substance of stoma
2. helps in corneal regeneration after injury
3. Part of corneal anti-oxidant
defense(proteinase inhibiter, inhibitors of
metalloproteinases e.t.c)Other cells-
 Lymphocytes, macrophages and polymorphonuclear
leucocytes (very rarely) also found in stroma ocationally-
becomes numerous in corneal ulcer/stromal abscess

29. Stromal transparency theory
 The cornea transmits nearly
100% of the light that enters it.
Transparency achieved by –
 Two theories –
i) Maurice (1957):
 The transparency of the stroma
is due to the lattice
arrangement of collagen fibrils.
 He explained, because of their
small diameter and regularity of
separation, back scattered light
would be almost completely
suppressed by destructive
interference

30. Ctn…
ii) Goldman et al. (1968):
 He suggest, a perfect crystalline lattice
periodicity is not always necessary for
sufficient destructive interference.
 He explained, if fibril separation(55-60nm)
and diameter(22nm)is less than a third of the
wavelength of incident light,(400-700nm) then
almost perfect transparency will ensue.
 This is the situation which obtains in normal
cornea.

31. Other factors of corneal transparency
1. Epithelial non-keratinization
2. Regular & uniform arrangement of
corneal epithelium
3. Junctions between cells & its
compactness and also tear film maintain
a homogenicity of its refractive index
4. Relative controlled hydraton of normal
cornea
5. Corneal avascularity
6. Non myelenated nerve fibres

32. Descemet’s membrane
 It is the basal lamina of corneal
endothelium
 -First appears at 2nd month of gestation
and synthesis continue throughout adult
life
 Thickness –
at birth (3-4 μm)
adult (10 – 12 μm)
It has two zones-
 Anterior 1/3 zone - developed in utero
-irregular banded zone
 Posterior 2/3 zone
-developed after birth
- Homogenous fibrillogranular
material
 It is a strong resistant sheet
 -Major protein of DM is Type IV collagen

33. Ctn….
 Due to aging ther can be
focal overproduction of basal
lamina- peripheral
excrescence called Hassal-
Henle warts
 No clinical abnormality in
corneal function
 In extensive stromal thinning
eg. in corneal ulcer
descemet’s membrane may
bulge forward to form

34. Ctn…
 The peripheral rim of DM is
the internal landmark of
corneal limbus
 It is the anterior limit of
drainage angle, is called
Schwalbe’ line
 Schwalbe’s line may
hypertrophied in congenital
anomalies and appears as
visible shelf on gonioscopy, is
called posterior
embryotoxon

35. Endothelium
 It is a single layer of
hexagonal, cuboidal cells
attached to posterior aspect of
DM
 It is nuroectodermal in origin
 Corneal endothelial cells
production is relatively fixed
 It is about 500000
(2500cells/mm2)
 Endothelial cells density –
-At birth-About 6000 cells/mm²
-26% lost in 1st year
-Further 26% lost over next 11 years
-Rate of cell loss slows and stabilizes around
middle age and then it is about 2500 cells/mm²

36. Ultrastructural features
 Single oval nucleus located centrally
 Endothelium is rich in subcellular
organeles – large number of
mitochondria, both rough and smooth
endoplasmic reticulum, free
ribozomes, these reflects that
endothelium is extremely active
metabolically
 The posterior cell membrane (Apical)
facing Anterior chamber shows 20-30
microvilli- increases absorption area
Cellular junction-
1. The anterior cell membrane (Basal) is
attached with DM by modified
hemidesmosomes
2. Ant. 2/3rd – maculae adharentes
3. Post. 1/3rd & apicolateral edges –
macculae occludentes

37. Endothelial functions
a)Maintains corneal hydration(slightly dehydrated stae-78%
hydration) by ‘pump-leak hypothesis’-
1. Providing physiological barrier to salts and
metabolites to stroma.
2. Active transport transport of bicarbonate by
Na+/K+ATPase actively removes H2O from stroma by pump
action.
 NA+/K+ATPase is located at
the endothelial cell membrane
 Using ATP, the pump actively
transport Na+, K+ and
bicarbonate to the AC
 Creats + osmotic gradient in
the aqueous
 H2O moves from stroma to

38. NA+/K+ATPase failure
 Failure of NA+/K+ATPase to
maintain corneal hydration will
cause;
- stromal edema,
-subepithelail fibrosis
-epithelial bullae
-corneal guttata
Example- Fuchs endothelial
dystrophy

39. Endothelial function ctn..
b)Injury and repair-
 Endothelial cell regeneration is not possible by mitosis
 Healing occurs by cell enlargement.
 Immediately after injury;
1.Descet’s membrane retracts
and injured endo.cell detaches.
2. fibrin clots formed at wound
3.within hours adjacent
endo.cell attenuate with
cytoplasmic processes
4.migrate to wound site
5. cellular reorganization and
enlargement- reconstitute
monolayer

40. Ctn….
 Endothelial decompensation will cause stromal
edema, reduced transparency and loss of vision
 Endothelial decompensation occurs when cells
density falls upto 500 cells/mm² .
 With advancing age
the endothelial cells
become polymorphic
in shape due to cell
enlargement during
repair

41. Corneal Nutrition & Metabolism
 Glucose, amino acid, vitamins, and other nutrients
supplied to cornea by aqueous humor, a lesser amounts
from tears or limbal vessels
 Glucose also derived from glycogen stores in corneal
epithelium
 Glucose is metabolized in cornea by three metabolic
pathways;
1. Tricarboxylic acid cycle(TCA)- epithelium &
endothelium
2. Anaerobic glycolysis- when there is lack of
O2
3. Hexose monophosphate(HMT) shunt –mainly
in endohelium

42. Ctn..
 During normal aerobic metabolism end product
of glucose- pyruvic acid is converted to H2O via
TCA cycle.
 During anaerobic state as in tight contact lens
lactic acid is produced via anaerobic glycolysis
which causes
1.Stomal acidosis,
2.Edothelial cell dysfunction
3.Corneal edema and visual impairment
 Oxygen – mainly from atmosphere through tear
film, with minor amounts supplied by the
aqueous and limbal vasculature

43. Nerve supply of Cornea
 Cornea is rich in
sensory nerve supply
derived from
ophthalmic division of
trigeminal which give
branch to;
- Nasociliary nerve and
-Ciliary nerves
(terminal branch)
 Ciliary nerve enter the pericoroidal space a short
distance behind the limbus.
 60-80 myelinated branches pass into cornea

44. Ctn…  1-2 mm from the limbus nerves
axon lose myelin sheaths and divide
into;
- anterior branche
-posterior banche
Anterior nervs (40-50) pass through
stroma and form plexus subjacent to
Bowman’s layer
 Nerve fibres then penetrate
Bowman’s layer and form
subepithelial plexus
 Fibres then divide dichotomously to
form a parallel network which run
for upto 2 mm
 Free nerve terminals finally supplies
superficial epithelial layers
 The posterior groups of nerves (40-50)
pass posteriorly to
innervate the posterior stroma excluding
Descemet’s membrane
Subepithelial
plexus
Anteriorposterior

45. Ctn…
 HSV infection of cornea
spreads along the nerve axons
 Involvement of terminal nerve
causes;
-dendritic appearance
- loss of corneal sensation
 Nerve innervation is important
to maintain balanced epithelial
cell division
 Lesion of fifth nerve will cause abnormal cell turn over
and loss of reflex tearing and leads to Neurotrophic
keratitis

47. References
 Yanoff & Duker Ophthalmology- 4th edition
 American Academy of Ophthalmology
 Jack J. Kanski Clinical ophthalmology- 7th
edition
 Oxford textbook of ophthalmology
 Journal- Association for Research in Vision
and Ophthalmology
 Duane’s clinical ophthalmology
 Images and graphics- internet sources