Review Article for Residents

Anatomy of cornea and ocular surface

Mittanamalli S Sridhar

Important functions of cornea in the eye include protecting the structures inside the eye, contributing to Access this article online
the refractive power of the eye, and focusing light rays on the retina with minimum scatter and optical Website:
degradation. Considerable advances have taken place in understanding the organization of collagen in the www.ijo.in
corneal stroma and its clinical significance. In this review, the structure and function of various components DOI:
of cornea and ocular surface are presented. 10.4103/ijo.IJO_646_17
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Key words: Collagen, cornea, Descemet’s membrane, endothelium, epithelium, stroma *****
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Cornea and sclera constitute the outer covering or coat of the The cornea is made up of cellular and acellular components.
eyeball. The main purpose of this coat is to protect structures The cellular components include the epithelial cells, keratocytes,
inside the eye. The cornea is a transparent avascular tissue and endothelial cells. The acellular component includes
that acts as a structural barrier and protects the eye against collagen and glycosaminoglycans. The epithelial cells are
infections.[1] Along with the tear film, it provides proper derived from epidermal ectoderm. The keratocyte and
anterior refractive surface for the eye. Cornea contributes to endothelial cells are derived from neural crest. The corneal
two‑third of the refractive power of the eye. layers include epithelium, Bowman’s layer, stroma, Descemet’s
membrane, and endothelium [Fig. 2]. Recently, a layer of cornea
The cornea is horizontally oval, measuring 11–12 mm
which is well defined, acellular in pre‑Descemet’s cornea is
horizontally and 9–11 mm vertically. The corneal horizontal
getting attention with the development of lamellar surgeries.[5]
diameter (white to white) using ORBSCAN II system has
Table 1 summarizes all layers of cornea with their functions.
revealed average corneal diameter as 11.71 ± 0.42 mm. The
average corneal diameter was 11.77 ± 0.37 in males compared The corneal epithelium is composed fairly uniformly of
to 11.64 ± 0.47 in females. The corneal diameter ranged from 5–7 layers of cells [Fig. 3]. It is about 50 µ in thickness. The
11.04–12.50 in males and 10.7–12.58 in females.[2] The limbus epithelium is uniform to provide a smooth regular surface and
is widest in superior and inferior cornea. Cornea is convex is made up of nonkeratinized stratified squamous epithelium.
and aspheric. The anterior curvature is 7.8 mm and posterior The epithelium is derived from surface ectoderm between 5
curvature is about 6.5 mm. Cornea contributes to about 40–44 and 6 weeks of gestation. The epithelium and the overlying
D of refractive power and accounts for approximately 70% of tear film have symbiotic relationship. The mucin layer of the
total refraction. The refractive index of cornea is 1.376. There tear film which is in the direct contact with corneal epithelium
is a gradual increase in thickness from central cornea to the is produced by the conjunctival goblet cells. It interacts closely
periphery[3] [Fig. 1]. Alteration in tissue thickness is due to with the corneal epithelial cells’ glycocalyx to allow hydrophilic
increase in the amount of collagen in the peripheral stroma. spreading of the tear film with each eyelid blink.
With different methods of evaluation, the central corneal
thickness in normal eyes is found to range from 551 to 565 µ Cornea epithelial cells have a lifespan of 7 to 10 days
and the peripheral corneal thickness from 612 to 640 µ.[4] The undergoing involution, apoptosis, and desquamation. The
corneal thickness is found to decrease with age. Anterior presence of high concentrations of intracytoplasmic enzyme
corneal stromal rigidity appears to be particularly important crystalline, like in lens epithelial cells, may play an important
in maintaining the corneal curvature. Anterior curvature role in maintaining optical transparency. The epithelium is
resists changes to stromal hydration much more than posterior 5–6 layers structure with three types of cells: superficial cells,
stroma.[1]
This is an open access article distributed under the terms of the Creative
Commons Attribution‑NonCommercial‑ShareAlike 3.0 License, which allows
Department of Ophthalmology, Krishna Institute of Medical Sciences,
others to remix, tweak, and build upon the work non‑commercially, as long as the
Hyderabad, Telangana, India author is credited and the new creations are licensed under the identical terms.
Correspondence to: Dr. Mittanamalli S Sridhar, Department of
Ophthalmology, Krishna Institute of Medical Sciences, Minister For reprints contact: [email protected]
Road, Secunderabad, Hyderabad ‑ 500 003, Telangana, India.
E‑mail: [email protected] Cite this article as: Sridhar MS. Anatomy of cornea and ocular surface. Indian
J Ophthalmol 2018;66:190-4.
Manuscript received: 26.07.17; Revision accepted: 20.09.17

© 2018 Indian Journal of Ophthalmology | Published by Wolters Kluwer - Medknow

 Sridhar: Anatomy of cornea
February 2018 191

Figure 2: Histopathology of cornea showing corneal epithelium, stroma,

and Descemet’s membrane

Desmosomes are present along the lateral membranes

of all epithelial cells, to keep the epithelial cells adherent to
Figure 1: Picture of cornea showing central and peripheral cornea each other. The basal cells are attached to the underlying
basement membrane by a hemidesmosomal system. The strong
attachment prevents the epithelium getting separated from the
Table 1: Corneal layers with their functions underlying layers. Abnormality of this attachment results in
Epithelium corneal erosions and nonhealing epithelial defects.
Barrier to chemicals and water Tight junctions are present only in the lateral wall of apical
Barrier to microbes cells of epithelium, providing a permeability barrier between
To provide a smooth optical surface as an internal part of tear the cells at the most superficial level.[3] Adherens junctions are
film‑cornea interface contributing to refractive power of the eye present along the lateral membrane of only the apical cells of
Langerhans cells which perform important immunological the epithelium. They maintain cellular adherence in the region
functions of tight junctions. Gap junctions are permeable channels on the
Bowman’s layer helps in maintaining the corneal shape lateral aspects of all epithelial cells, allowing the diffusion of
Stroma small molecules.
Mechanical strength to cornea The basement membrane of epithelial cells is 40–60 nm in
Transparency of cornea thickness and is made up of Type IV collagen and laminin
Main refracting lens secreted by basal cells. The basement membrane is made up
Descemet’s membrane‑resting layer for endothelial cells of lamina lucida and lamina densa. From the basal epithelial
Endothelium ‑ maintains corneal clarity by removing water from the cells, anchoring fibrils pass through the basement membrane
corneal stroma and end as anchoring plaques. The anchoring fibrils are made
up of Type VII collagen and anchoring plaque is made up of
Type I collagen [Fig. 4]. If basement membrane is damaged,
wing cells, and the basal cells. The superficial cells are 2–3 fibronectin levels increases and the process of healing can take
layers made up of flat polygonal cells. They have a diameter of up to 6 weeks.
40–60 µ with a thickness of about 2–6 µ. The microvilli on the
surface increase the surface area. The epithelial layer is made There are differences between epithelium of central and
up of large dark cells and small light cells. Desmosomes form peripheral cornea. In the central cornea, the epithelium has 5–7
the tight junction in between the superficial cells. Thawing cells layers. The basal cells are columnar. There are no melanocytes
are 2–3 layered and are named as they have wing‑like shape. or Langerhans cells. There is a smooth basal cell layer with
They express 64‑k dalton keratins. Basal cells are single layer keratan sulfate, and there are no lymphatics. In the peripheral
of the epithelium which is cuboidal or columnar. They have cornea, the epithelium is 7–10 layered. The basal cells are
abundant organelles and they are active mitotically. cuboidal. There are melanocytes and Langerhans cells. There
are undulating extensions of basal layer. There is no keratan
The surface cells maintain tight junction complexes sulfate and there are no lymphatics.
between the neighbors which prohibit tears from entering the
intercellular spaces. The deepest cell layer of the epithelium Thoft and Friend proposed the XYZ hypothesis of central
is the basal layer, which compromises the single cell layer epithelial maintenance.[6] X component denotes the basal cell
of epithelium approximately 20 µ tall. Besides the stem cells proliferation. The Y component migration of cells from peripheral
and transient amplifying cells, basal cells are the only corneal to central cornea and Z component denotes the loss of cells from
epithelial cells capable of mitosis. They are the source of wing the surface. The cells in the limbus are in two compartments. The
and superficial cells. stem cells and transient amplifying cells are in the proliferative
192 Indian Journal of Ophthalmology Volume 66 Issue 2

Figure 4: Diagram depicting the junctional complexes of the corneal

epithelium

inferior, superior, nasal, and temporal which probably originate

Figure 3: Histopathology of corneal epithelium and Bowman’s in the adjacent sclera. Collagen fibrils in the prepupillary
membrane appear to be more closely packed than in the peripheral
cornea.[9] High packing density of stress‑bearing collagen
compartment. The postmitotic cells and terminally differentiated fibrils in the prepupillary cornea seems to be necessary for
cells are in nonproliferative compartment. The palisades of Vogt maintaining corneal strength and hence curvature in a region
are undulations in basement membrane which provide increased of reduced corneal thickness.
vascularity, increased surface area for attachment, and also for Collagen fibrils within the cornea are narrower than in many
provide protection to stem cells. other connecting tissues, and there is an important factor for
Bowman’s membrane is condensation of collagen and transparency, which is a function of diameter. There are about
proteoglycans. It is a 12 µ structure and is made up of Type I 300–400 triple‑helical molecules within the cross section of the
and V collagen as well as proteoglycans. It has no regenerative fibril. Ultrastructure within the organization of the lamellar
ability. Bowman’s membrane lies just anterior to stroma and appears to vary based on the depth within the stroma. Deeper
is not a true membrane. It is acellular condensate of the most layers are more strictly organized than superficial layers. This
anterior portion of the stroma. This smooth layer helps the accounts for care of surgical dissection in a particular plane as
cornea maintains its shape. When injured, this layer does not one approaches the posterior depths of the corneal stroma.[1]
regenerate and may result in a scar. During air injection into stroma, it is a common observation
that part of the posterior stroma often adheres to the Descemet’s
The corneal stroma forms the bulk of the structural
membrane and there is a natural cleavage plane in the stroma
framework of the cornea and comprises approximately
almost 10 µ alone Descemet’s membrane.[5]
80%–85% of its thickness. Embryologically, it is the result
of second wave of neural crest migration that occurs in the A high refractive index and symmetric curvature are
7th week of gestation, after establishment of the primitive essential for optimal refractive power and minimum
endothelium. The stroma is characteristically transparent astigmatism of the cornea.[10] The architecture of the most
which is the result of precise organization of stromal fibers anterior part (100–120 µ) of the stroma prevents changes in the
and extracellular matrix (ECM). The collagen within corneal morphology of the stromal region even after extreme swelling.
fibrils is predominantly Type I. Type VI collagen and Type XII The smooth curvature at the anterior side is not affected in
collagen are also found in stroma.[7] conditions with increased corneal hydration. As the diameter
The collagen fibers are arranged in parallel bundles called of the cornea hardly changes, swelling is compensated by large
fibrils. These fibrils are packed in layers or lamellae. The stroma undulations in Descemet’s membrane at the posterior side.
of the human eye contains 200–250 distinct lamellae, each layer The corneal swelling behavior shows a gradual decrease in
arranged at right angles relative to fibers in adjacent lamella. swelling from posterior to anterior side; this seems to be related
The collagen in the stroma is laid down within lamellae. These to the organization of collagen lamellae and to the presence of
structures are of the variable thickness, in humans up to 0.2 mm different types of proteoglycan. In the posterior part keratan
broad and 2 µm thick. At the center of the human cornea, there sulfate, a more hydrophilic proteoglycan is prevalent, whereas
is approximately 200 lamellar thickness. The packing density in the anterior part dermatan sulfate, a much less hydrophilic
is higher in the anterior lamellae than in the posterior stroma. proteoglycan is prevalent. There is also an elastic fiber network
These anterior lamellae are highly interwoven and most appear within the stroma. These elastic fibers present throughout the
to insert into the Bowman’s layer.[8] The mid‑stromal lamellae stromal depth, are concentrated below the posterior‑most
are also highly interlaced. The posterior lamellae in the central keratocyte layer.
cornea are more hydrated. The posterior stromal can swell
Cornea stroma is made up of keratocytes and ECM.
easily whereas the more interwoven cannot.
The ECM is composed of collagens (Type I, III, V, VI) and
Cornea lamellae in the deepest stroma have preferred glycosaminoglycans. The glycosaminoglycans constitute
directions which appear to close to inferior superior and keratan sulfate, chondroitin sulfate, and dermatan sulfate. The
nasal‑temporal directions. X‑rays scattering also has suggested corneal stroma has keratocytes and about 300 collagen lamellae
a network of collagen lamella that enters the cornea close to the which are regularly arranged. The glycosaminoglycans
 Sridhar: Anatomy of cornea
February 2018 193

are predominantly keratan sulfate. Less contribution is by

dermatan sulfate and chondroitin sulfate. Hyaluronan is seen
in infancy.
Keratocytes are the major cell type of stroma. They are
involved in maintaining the ECM environment. They are able to
synthesize collagen molecules and glycosaminoglycans, while
also creating matrix metalloproteinases (MMPs), all important
in maintaining stromal homeostasis. Most of the keratocytes
reside in the anterior stroma.
The Descemet’s membrane is a 7 µ structure. It is made up of
Type IV collagen and laminin. Descemet’s membrane begins in
utero at the 8‑week stage. Endothelial cells continuously secrete
Descemet’s membrane. The anterior 3 µ secreted before birth Figure 5: Endothelial cell layer on the specular microscopy
has a distinctive banded appearance. Descemet’s membrane
produced after birth is unbanded and has an amorphous banks, the bubble can be inflated to pressure about 700 mmHg
ultrastructural texture. Descemet’s membrane can be up to 10 µ before it ruptures. It is also found in children.
in thickness with age. The Descemet’s membrane is elastic and
The cornea is one of the most heavily innervated and most
curls on getting severed.
sensitive tissues in the body. The sensation is derived from
The endothelium is a single layer, 5 µ thick structure [Fig. 5]. the nasociliary branch of the first division of (ophthalmic)
The cells are hexagonal and are metabolically active. of the trigeminal nerve. Thick and straight stromal nerve
There is an endothelial pump which regulates water trunks extend laterally and anteriorly to give rise to plexiform
content. Endothelium is a monolayer which appears as a arrangements of progressively thin nerve fibers at several levels
honeycomb‑like mosaic when viewed from the posterior within the stroma.[13] The nerve fibers perforate Bowman’s layer
side. In early embryogenesis, the posterior surface is and eventually form a dense nerve plexus just beneath the basal
lined with a neural crest‑derived monolayer of orderly epithelial cell layer characterized by tortuous, thin beaded
arranged cuboidal cells. The individual cells continue nerve fibers interconnected by numerous nerve elements. The
to flatten over time and stabilize at approximately 4 µ in cornea also contains autonomic sympathetic nerve fibers.
thickness is adulthood. Adjacent cells share extensive lateral
interdigitations and possess gap and tight junctions along Normal human cornea is avascular. The aqueous humor is
the lateral borders. The lateral membrane contains the high the main source of nutrients to the cornea. Blood supply is by
density of Na+ K+ ATPase pump sites. The two most important tiny vessels at the outer edge of the cornea as well as components
ion transport systems are the membrane‑bound Na+ K+ ATPase supplied by end branches of the facial and ophthalmic arteries
and the intracellular carbonic anhydrase pathway. Activity through the aqueous humor and the tear film.
in both these pathways produces the net flux of ions from
the stroma to the aqueous humor. The basal surface of the Tear film
endothelium contains numerous hemidesmosomes that The minute surface irregularities of the corneal surface
promote adhesion to Descemet’s membrane. epithelium are masked by a smooth and regular overlying
Immediately anterior to the flattened layer of endothelial tear film. The tear film is the first layer of the cornea with
cell is a discontinuous homogeneous acellular layer Descemet’s which light comes into contact. In produces lubrication
membrane. At birth, the endothelial layer is approximately and hydration to the ocular surface. It is also a source of
10 µ thick. Descemet’s membrane becomes continuous and oxygen, immunoglobulins, lysozymes, lactoferrin, and α‑ and
uniform, fusing peripheral with the trabecular beams. The β‑defensins. The tear film is traditionally told to be composed
fusion site, known as Schwalbe line, is a gonioscopic landmark of three distinct layers. The most superficial layer is composed
that defines the end of Descemet’s membrane and the start of of oily secretions of meibomian glands. Because oil is less dense
trabecular meshwork. than water, the secretions float to the top of the tear film to
form a smooth refractive surface. This oily layer also provides
Endothelial cell density continues to change throughout life, an important barrier against the evaporation of the tear film.
from second to eight decades of life. The cell density declines The aqueous middle layer of the tear film lies immediately
from 3000 to 4000 cells/mm2 to around 2600 cells/mm2 of beneath the oily layer. It is produced from the secretion of the
hexagonal cells decline from approximately from 75% to 60%. lacrimal gland which is located in the superior lateral orbit. The
Endothelial cell density at birth is 3500 cells/mm2. Human central aqueous is secreted onto the ocular surface from ducts in the
endothelial cell density decreases at an average of approximately superior fornix. There are also numerous scattered accessory
0.6% per year in normal corneas throughout adult life, into
lacrimal glands embedded within the conjunctiva stroma which
gradual increase in polymegathism and pleomorphism. [11]
contribute to this aqueous layer. The innermost mucin layer is
Endothelial cells do not regenerate in adults.[12]
produced primarily by the conjunctival goblet cells although
A deep corneal layer has been getting attention recently. It the epithelial cells of the cornea and the conjunctiva also
is a well‑defined, acellular, strong layer in the pre‑Descemet’s contribute. Current understanding is that all the three layers
cornea.[5] This layer is found to be 5–8 lamellae of collagen fibers are in the form of a gel on the ocular surface. Conjunctival
ranging from 6 to 15 µ in thickness. There are no keratocytes in goblet cells seem to be important in performing the functions
this layer, and it is impervious to air. In donor eyes from eye of debris removal and immune surveillance.[14]
194 Indian Journal of Ophthalmology Volume 66 Issue 2

Ocular surface Financial support and sponsorship

Nil.
Thoft and Friend first suggested that cornea, conjunctiva,
lacrimal glands, and lids work as an integrated unit called Conflicts of interest
ocular surface.[15] The anatomical ocular surface is composed There are no conflicts of interest.
of the mucosa that lines the globe and palpebral surfaces, the
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