Deﬁ nition of the Ocular Surface 1
Section I: Anatomy and
Physiology of the Ocular Surface
2 Ocular Surface
Deﬁ nition of the Ocular Surface 3
Deﬁ nition of the Ocular Surface
Louis Tong,a Wanwen Lan and Andrea Petznick
The ocular surface is a very important part of the eye. It consists of the
conjunctiva and the cornea, together with elements such as the lacrimal
gland, lacrimal drainage apparatus and associated eyelid structures.
This part of the eye has unique properties and is associated with special
physiological mechanisms, for example tear production and drainage,
as well as predisposition to speciﬁ c diseases. Certain diseases affect
only this part of the eye, due to its functional requirement for vision,
exposed anatomical location and its proximity to the nasal mucosa and
sinuses. For these reasons, diseases such as allergic keratoconjunctivitis
affecting the ocular surface primarily are common.
This chapter summarizes important terms and root words used
in conjunction with the ocular surface in the scientific literature.
Understanding of the nomenclature is essential for any research
discussion or clinical practice related to the ocular surface.
INTRODUCTION TO THE OCULAR SURFACE
The ocular surface, an integrated unit comprising the cornea, conjunctiva,
lacrimal glands and eyelids, was ﬁ rst described by Thoft in 1987 (Thoft
1978). Gipson extended the description of the ocular surface system
in her Friedenwald lecture in 2007 (Gipson 2007): ‘the ocular surface...
includes the surface and glandular epithelia of the cornea, conjunctiva, lacrimal
gland, accessory lacrimal glands, meibomian glands and their apical (tears) and
basal (connective tissue) matrices; the eyelashes with their associated glands of
Moll and Zeis; those components of the eyelids responsible for the blink and the
Singapore Eye Research Institute, Singapore National Eye Centre, Duke-NUS Graduate Medical
School, 11 Third Hospital Avenue, 168751, Singapore.
Is this OK?
The Corresponding has not been specified here. Is that
required? If yes, kindly specify.
4 Ocular Surface
nasolacrimal duct’. Together, these components are interconnected through
a continuous epithelium, as well as the nervous, vascular, immune and
endocrine systems. Figure 1 illustrates a cross-sectional view showing some
components of the ocular surface system. The lacrimal functional unit is
deﬁ ned by the 2007 International Dry Eye Work Shop (2007) as ‘an integrated
system comprising the lacrimal glands, ocular surface (cornea, conjunctiva and
meibomian glands), lids, and the sensory and motor nerves that connect them’. The
anatomical components of the lacrimal functional unit will be described
under ‘Lacrimal glands’ below.
Figure 1 This ﬁ gure shows a cross-sectional view of the ocular surface system with the
continuous epithelium highlighted in pink and the tear ﬁ lm in blue.
General Appearance of the Ocular Surface
In the normal ocular surface, the cornea occupies the approximate centre
of the exposed surface. The outer limit of the cornea adjacent to the bulbar
conjunctiva is the limbus. At both sides of the limbus are two triangular
sclero-conjunctival areas, visualised as the white part of the sclera. When
a person is looking straight ahead, the lower eyelid height is normally 1–2
mm higher or lower than the lower corneal limbus (see section on Cornea),
whereas the superior eyelid is normally 1–2 mm higher than the visual axis
but just lower than the superior corneal limbus (Lens et al. 2007).
The upper and lower eyelids meet at the medial (inner) and lateral
(outer) canthi which are the angles of the palpebral ﬁ ssures. The medial
Color image of this figure appears in the color plate section at the end of the book.
Accessory lacrimal gland
Tear ﬁ lm
Deﬁ nition of the Ocular Surface 5
canthus is near to the nose, whereas the lateral canthus is located temporally.
The medial canthus is usually positioned slightly lower than the lateral
canthus. The positions of the canthi have signiﬁ cance in oculoplastic surgery.
They facilitate the ﬂ ow of the tear ﬁ lm from the lateral to medial direction,
and are youthful-looking aesthetically.
The eyelid or palpebral refers to a movable fold of skin, muscle and cartilage
that can be closed or opened over the eyeball. The upper and lower eyelids
form a covering over the globe protecting against excessive light or injury.
When the eyelids are open, the margins or the palpebral ﬁ ssures form an
almond-shaped structure (Lens et al. 2007).
The eyelid structure consists of four layers. The ﬁ rst or outermost
layer includes the skin, eyelashes and associated glands. The second layer
comprises the muscular layer, namely the orbicularis oculi, the circular
sphincter-like muscles responsible for closing the eyelids. The third ﬁ brous
layer, important for mechanical stability of the eyelid, consists mainly of the
tarsal plate. The innermost layer of the eyelid is the palpebral conjunctiva.
The ﬁ rst two layers are sometimes termed anterior lamella of the eyelid,
whereas the last two layers are termed posterior lamella of the eyelid. In
oculoplastic surgery, a substantial full- thickness eyelid defect may need to
have the anterior and posterior lamellae reconstructed separately, as these
lamellae have different mechanical requirements.
The orbicularis oculi are innervated by cranial nerve VII. When there
is pathology of cranial nerve VII, such as in Bell’s palsy, the eyelids may
not be able to close. On the other hand, some conditions irritate the ocular
surface, resulting in secondary blepharospasm and tonic contraction of
orbicularis muscle. The levator palpebrae muscles are innervated by a
branch of the cranial nerve III. In the event that the cranial nerve III function
is compromised, there may be drooping of the upper eyelid or, in more
extreme cases, inability to open the lid.
The fusiform lid ﬁ ssure represents the shape of a spindle. However, the
curvature of the upper eyelid ﬁ ssure is often greater than that of the lower
eyelid. Certain dynamic features of the palpebral ﬁ ssures are unique: when
the eyes are blinking or closing, the inferior eyelid moves only minimally
and almost all the movement is done by the descending sweep of the upper
lid. To facilitate this downward motion of the upper eyelid, the medial and
lateral insertions of the palpebral ligaments are lower than the level of the
pupil, and as a result, the upper eyelid is quite bowed.
6 Ocular Surface
The piriform lid ﬁ ssure (like a pear lying ﬂ at on the side) is similar
to the fusiform one, except that the maximal height of the interpalpebral
ﬁ ssures is not aligned with the vertical diameter of the cornea but slightly
lateral to that.
The mucocutaneous junction, or gray line, is located just posterior to the
eyelashes. The gray line demarcates the eyelid into anterior and posterior
lamellae, and contains the muscle of Riolan (Wulc et al. 1987, Lipham et
al. 2002). This is also called the Marx’s line and can be visualised with
ﬂ uorescein dye. Along the posterior lid margin, the single or double row
of meibomian gland oriﬁ ces is found. This forms the white line, which
corresponds to the free border of the tarsal plate, where the bulk of the
meibomian gland elements islocated.
The tarsal plate or tarsus is a thin ﬂ at plate of dense connective tissue (one
in each eyelid), which supports the eyelid structure. The tarsus extends from
the orbital septum to the lid margin. The upper tarsal plate has a D shape
structure lying on its side and is much larger than the lower tarsal plate. The
height is 11 mm centrally, whereas the corresponding height in the lower
oblong tarsus is only 5 mm. Each tarsus is about 3 cm long and 1 mm thick.
The meibomian glands (refer to ‘Tear producing glands: meibomian glands’)
are located within the tarsus (Jester et al. 1981, Obata 2002).
The eyelashes are hairs growing at the edge of the eyelids. They are
positioned in the anterior portion of the lid margin, lined by skin epithelium.
The eyelashes are surrounded by the glands of Zeis (modiﬁ ed sebaceous
glands) and the glands of Moll (modiﬁ ed sweat glands) (Stephens et al.
1989). The eyelashes help to keep foreign particles from entering the ocular
surface system, as well as increase the sensitivity of the eye to touch. Refer
to Table 1 for the terms related to the eyelids or eyeball.
Gross Anatomy and Corneal Limbus
The cornea is an avascular, transparent tissue that provides the majority
of optical power to refract the light entering the eye. It is generally ovoid
Deﬁ nition of the Ocular Surface 7
in nature, with a steeper or shorter radius of curvature in the vertical than
the horizontal plane. It occupies a central position in the ocular surface
and consists of several layers including the epithelium, stroma and
A general overview on the corneal structure is shown in Fig. 2. The
stroma is separated from the epithelium and endothelium by the Bowman’s
membrane and Descemet’s membrane respectively.
Table 1 This table summarizes words related to the eyelids or eyeball.
Eyelid-related deﬁ nitions Examples of use of term
Fusion of the upper to the lower eyelids
Blepharo- Related to the eyelid Blepharospasm
Blepharitis Eyelid inﬂ ammation Anterior,
Blepharo-conjunctiva Related to the eyelid and conjunctiva Blepharo-conjunctivitis
Enophthalmos Decreased palpebral ﬁ ssures associated
with posterior movement of the eyeball
into the orbit
Epiblepharon Congenital horizontal fold of skin over
the upper eyelid which can result in
inward-turning of the eyelashes of the
medial upper eyelid, common in people
of Asian origin
Exophthalmos Increased palpebral ﬁ ssures associated
with bulging of the eyeball from the
Intermittent, speciﬁ c
Entropion Abnormal inward-turning of the eyelid
Ectropion Abnormal outward-turning of the eyelid
Lagophthalmos Condition of inadequate eyelid closure Nocturnal, paralytic
Marx’s line Refers to the muco-cutaneous junction at
the eyelid margin
Ptosis Drooping of the eyelids Involutional or paralytic
Symblepharon Condition where the palpebral
conjunctiva of the upper or lower
eyelids fusing with the bulbar
conjunctiva of the eyeball
Trichiasis Condition where backwardly directed
lashes cause irritation, usually due to
scarring of the eyelids
8 Ocular Surface
The surgical limbus is an important landmark for surgical incisions as
well as the anatomical position of ocular surface progenitor or stem cells
important for regeneration of the corneal epithelium (Lens et al. 2007). The
surgical limbus can be differentiated into a bluish zone anteriorly, and a
more whitish zone posteriorly. The line dividing the two zones corresponds
to the Schwalbe’s line, which is the termination of the Descemet’s membrane
(see below) (Preziosi 1968).
The epithelium is the outermost layer of the cornea. The corneal epithelium
is approximately 50 µm thick (Li et al. 1997, Haque et al. 2004) and is
composed of ﬁ ve to seven cell layers. The stratiﬁ ed epithelium of the cornea
is non-keratinized and composed of several morphologically distinct layers
of cells including two to three layers of superﬁ cial ﬂ attened squamous
cells, several layers of wing cells and a single layer of columnar basal cells
(Beuerman and Pedroza 1996).
The Bowman’s layer, produced by the corneal epithelium, is a thin layer
separating the corneal epithelium from the stroma. It is usually 10–17 µm
thick (Li et al. 1997, Hayashi et al. 2002)and comprises collagen ﬁ brils found
in random distribution. Damage to the Bowman’s layer may confound
adherence of corneal epithelium to the stroma and disrupt structural
integrity of the ocular surface (Wilson and Hong 2000).
The stroma accounts for approximately 90% of the total corneal volume. It is
predominantly composed of hydrated ﬁ brils of collagen, glycoproteins (such
Figure 2 This ﬁ gure shows a schematic illustration of the different layers of the
cornea (not drawn to scale).
Color image of this figure appears in the color plate section at the end of the book.
Deﬁ nition of the Ocular Surface 9
as ﬁ bronectin and laminin) and proteoglycans (Linsenmayer et al. 1998).
It has the tendency to imbibe ﬂ uid and controlled dehydration is essential
to maintain transparency of the cornea. Damage to the cellular limiting
layers, with subsequent ﬂ uid inﬂ ux, interferes with the orderly ﬁ brillar
arrangement of the stromal lamellae increasing light scatter, resulting in loss
of transparency of the cornea (Maurice 1957). Inﬁ ltration of the cornea with
immune cells such as macrophages can also reduce corneal transparency.
The Descemet’s membrane, which is a basement membrane secreted by the
endothelium, separates the stroma from the endothelium. The Descemet’s
membrane is approximately 10 µm thick in an adult human cornea and its
thickness increases throughout life (Joyce 2003).
The corneal endothelium is a cellular monolayer of approximately 5 µm
thickness and 15 to 20 µm width (Binder et al. 1991). Endothelial cells
forming this layer are joined by interdigitations and leaky tight junctions.
In order to keep the cornea dehydrated, the endothelial cells serve as a
pump which removes ﬂ uid by active transport from the corneal stroma to
the aqueous (Maurice 1972). The number of endothelial cells in humans
decreases with age (Joyce 2003). Following injury, the non-replicative
endothelium in humans repairs the endothelial wound by enlargement
and migration of existing cells rather than mitosis (Chan-Ling et al. 1988b,
Joyce 2003). Refer to Table 2 for terms related to the cornea.
The conjunctiva is a thin, transparent tissue that lines the inner surface of
the eyelids, fusing with the eyelid epithelium at the eyelid margin and the
corneal epithelium at the limbus. It covers the sclera up to the limbus and
is continuous with the corneal epithelium. The conjunctiva consists of six
or more non-keratinized epithelial cell layers near the limbus and can be
up to 12 layers near the fornix (Wanko et al. 1964). The conjunctival fold
(cul-de-sac) is open at the palpebral ﬁ ssure and is closed when the eyelids
The conjunctiva is divided into 3 parts: The forniceal conjunctiva,
bulbar conjunctiva and palpebral conjunctiva. These will be described in
the sections below.
10 Ocular Surface
This is the part of the conjunctiva that lines the globe of the eye. It consists
of 2 parts: the limbal conjunctiva which is fused with the episclera at the
limbus, and the scleral conjunctiva which extends from the limbus to the
This is the intermediate portion of the conjunctiva which is not attached
to the eyelids or the eyeball. This lines the bottom of the conjunctival sac
(fornix) and joins the bulbar and palpebral portions.
Table 2 This table summarizes words related to the cornea.
Cornea-related deﬁ nitions Examples of use of term
Corneal degeneration Acquired age-related condition of
Fuchs’ endothelial dystrophy,
Inherited developmental disease
of the cornea
Abnormal thinning of the cornea Post-LASIK corneal ectasia
Corneal epitheliopathy Pathology of the corneal
Abnormal spots or indentations
in the corneal endothelium
Abnormal deposits in the cornea
Corneal striae/folds Abnormal lines in the cornea
Condition with a defect in
the corneal epithelium. Often
associated with infection
Bacterial keratitis, fungal
Keratitis Inﬂ ammation of the cornea Infectious, marginal keratitis
Keratoconjunctivo- Related to the cornea and the
Keratolysis Thinning or melting of cornea Paracentral, rheumatoid
Keratopathy Any disease of the cornea Band, exposure, lipid,
ﬁ lamentous keratopathy
Keratomalacia Melting of the cornea usually
related to xerosis
Is this OK?
Deﬁ nition of the Ocular Surface 11
The palpebral conjunctiva lines the posterior surface of the eyelids. It is
divided into 3 portions: the marginal conjunctiva which extends from the
margin of the eyelids to the tarsus, the subtarsal conjunctiva which extends
over the tarsal plate and the orbital conjunctiva which extends from the
tarsus to the fornix (Lens et al. 2007).
The lacrimal caruncle is the reddish structure or eminence that is found in
the medial angle of the eye. It contains sebaceous and sweat glands.
The plicasemilunaris is asmall crease of the bulbar conjunctiva found at the
medial canthus (Arends and Schramm 2004). It produces a watery/mucoid
secretion with fatty substances that traps dirt and foreign particles from the
ocular surface to form rheum. The rheum forms the crust from the canthus
during sleep. Refer to Table 3 for terms related to the conjunctiva.
Table 3 This table summarizes words related to the conjunctiva.
Conjunctiva-related deﬁ nitions Examples of use of term
Blepharoconjunctiv Related to eyelid and
Conjunctivalisation Abnormality of the cornea
where the epithelium resembles
that of the conjunctiva. Usually
related to limbal stem cell
Conjunctivitis Inﬂ ammation in the conjunctiva,
usually infectious in nature, but
sometimes due to rare immune-
Ligneous, bacterial, viral,
Keratoconjunctivitis Inﬂ ammation involving the
cornea and conjunctiva
—atopic and vernal
(dry eye disease)
A special type of conjunctivitis
where a ‘membrane’ is
visualised over the ocular
12 Ocular Surface
The sclera is a tough ﬁ brous coat of the eye composed of mainly collagen
and elastic ﬁ brous tissue. It has 3 poorly deﬁ ned layers from superﬁ cial to
deep, called the episclera, the sclera proper and the lamina fusca (Lens et
al. 2007). Refer to Table 4 for deﬁ nitions of some conditions involving the
Table 4 This table summarizes words related to the sclera.
Sclera-related deﬁ nitions
Episcleritis Inﬂ ammation of the episclera
Scleritis Inﬂ ammation of the sclera
Sclerokeratitis Inﬂ ammation of the sclera and cornea
Scleromalacia Degenerative thinning of the sclera, commonly associated
with rheumatoid arthritis and collagen diseases
THE TEAR FILM
Preocular Tear Film
The tear ﬁ lm is a mixture of ocular surface secretions from the main lacrimal
and accessory lacrimal glands, meibomian glands and the corneal and
conjunctival epithelium. The tear ﬁ lm, as part of the ocular surface system,
has several roles that include the provision of a smooth refractive surface,
protection of the ocular surface with its antibacterial and immune functions,
supply of oxygen and removal of metabolites such as carbon dioxide,
lubrication, and clearance of cells, debris and foreign bodies in conjunction
with the eyelids (Van Haeringen 1981, Tiffany 2008).
The preocular tear ﬁ lm is the ﬁ rst structure that incident light encounters
on reaching the eye; so the air-tear interface is the ﬁ rst refractive surface
for focusing of light rays. Irregularities of the tear ﬁ lm therefore affect
quality of vision. The tear ﬁ lm in human eyes is structured in three layers:
the outer lipid layer, the intermediate aqueous layer and the inner mucin
layer. However, the aqueous and mucin layers have been described as a
continuum (Chen et al. 1997, Spurr-Michaud et al. 2007). The lipid layer of
the tear ﬁ lm is secreted by the meibomian glands. This layer can be evaluated
by interferometry, and may be deranged in meibomian gland disease. There
have been studies which suggest that this layer consists of an outer layer
of neutral lipids and an inner layer of amphipathic polar lipids (Linsen
and Missotten 1990). The functions of this layer include the prevention of
aqueous tear evaporation and aiding the spreading of the tear ﬁ lm.
The aqueous layer of the tear ﬁ lm is basally secreted by the Kraus
and Wolfring accessory lacrimal glands, and reﬂ ex secretion is by the
Deﬁ nition of the Ocular Surface 13
main lacrimal gland. This layer forms the main bulk of the volume of
the tear ﬁ lm.
The mucin layer is secreted by the goblet cells and also the corneal and
conjunctival epithelial cells (Asbell and Lemp 2006). This layer merges with
the glycocalyx of the conjunctival epithelial cells. The glycocalyx, being
anterior to the corneal epithelium, holds the tear ﬁ lm on to the ocular
surface via membrane-spanning mucins attached to the microvilli and
small ﬁ laments of the outermost superﬁ cial epithelial cells (Beuerman and
Pedroza 1996, Gipson 2007).
The upper and lower tear menisci are strips of tear found on the upper and
lower lid margins respectively. They account for 75–90% of the total tear
volume on the ocular surface (Mishima et al. 1966, Holly 1985). During
blinking, tears are distributed from the menisci onto the ocular surface
(Lens et al. 2007).
The radius of curvature of the tear menisci has been found to be directly
correlated to the total tear volume (Yokoi et al. 2004), and the absence of
tear menisci is associated with dry eye disease. In ocular surface practice,
the menisci may be evaluated using the anterior segment optical coherence
tomography (Qiu et al. 2010).
Tear turnover is defined as the percentage decrease in fluorescein
concentration of tears per minute and is clinically used to assess the lacrimal
functional unit as well as tear quality (Mishima et al. 1966, Nelson 1995).
Reduced tear turnover is usually associated with ocular irritation and
inﬂ ammation (de Paiva and Pﬂ ugfelder 2004).
TEAR PRODUCING GLANDS
There are multiple factors governing tear production. Tear production may
be classiﬁ ed as basal, reﬂ ex and emotional.
The lacrimal reﬂ ex is the process where tear is produced after irritation
of the cornea and conjunctiva. This is in contrast to the basal tear production
which is constant in the resting state and added to the reﬂ ex production in
the stimulated state. Psycho-emotional tears are related to emotional states
such as sadness, anger or happiness (Murube 2009).
14 Ocular Surface
The main lacrimal gland is located in the upper, outer quadrant of the
orbit and is made up of two lobes, the palpebral and orbital lobes. It is
composed of acinar, ductal and myoepithelial cells. The main lacrimal
gland is approximately 15 to 20 mm long, 10 to 12 mm wide and 5 mm thick
(Lorber 2007). The lacrimal gland is innervated by the smallest branch of
the ophthalmic nerve, the lacrimal nerve (Burton 1992). Any stimulation
to the ocular surface activates afferent sensory nerves in the cornea and
conjunctiva, which then activate afferent sympathetic and parasympathetic
nerves that subsequently stimulate the lacrimal gland to secrete proteins,
electrolytes and water (Zoukhri 2006).
With age, the morphology of the lacrimal gland changes and inﬁ ltration
of inﬂ ammatory cells into the lacrimal gland tissue occurs. This, in turn,
leads to inﬂ ammation of the tissue and reduces protein and tear production
(Draper et al. 1998, Nagelhout et al. 2005).
Accessory Lacrimal Glands
The smaller accessory glands of Krause and Wolfring are part of the lacrimal
system and are located close to the superior fornix of the conjunctiva. Their
microanatomy is identical to that in the main lacrimal gland (Lemp and
Wolﬂ ey 1992).
The meibomian glands are large, tubuloacinar structures embedded within
the tarsal plate of the eyelids (Jester et al. 1981, Obata 2002). There are about
32 glands in the upper eyelid and 25 in the lower eyelid (Greiner et al. 1998).
The sebaceous meibomian glands consist of branched, round-shaped acini
that secrete lipids into a long single duct.
The meibomian gland lipids, also referred to as meibum, comprise waxy
esters, sterols, cholesterol, polar lipids and fatty acids which are transported
towards the ductal oriﬁ ce by blinking (Lemp and Wolﬂ ey 1992). The muscle
of Riolan at the gray line of the eyelid margin may also regulate meibomian
gland secretion. Once the lipids are secreted into the ocular surface, they
form the superﬁ cial lipid layer of the tear ﬁ lm.
Conjunctival goblet cells are specialized glandular epithelial cells. They are
integrated in the conjunctiva epithelium and secrete gel-forming mucin
(Gipson 2004). The highest density of conjunctival goblet cells in humans
Deﬁ nition of the Ocular Surface 15
is found in the nasal and nasal inferior area of the conjunctiva (Kessing
1968, Rivas et al. 1991). The number of goblet cells decreases in humans
in some conditions such asa loss of vascularisation after chemical injury,
or inﬂ ammation in the ocular surface, e.g. conjunctivitis (Tseng et al. 1984,
Grahn et al. 2005). The innermost mucin layer of the tear ﬁ lm is hydrophilic,
accounting for its adherence to the ocular surface.
The nasolacrimal drainage system consists of the lacrimal puncta,
canaliculus, lacrimal sac and nasolacrimal duct. This is the tear drainage
pathway from the lacrimal lake to the nasal cavity. The lacrimal lake is the
space or recess between the eyelids at the nasal commissure of the eye. The
tears collect from the upper and lower tear menisci and the preocular surface
into the lacrimal lake before draining into the lacrimal punctum.
The concept of the lacrimal pump is that the orbicularis oculi muscle
creates a pressure on the lacrimal sac. On relaxation, there is a negative
pressure which draws tears from the lacrimal lake into the sac via the
The lacrimal puncta are small openings located on the medial aspect of the
eyelid margins and sit on an elevated structure called the papilla lacrimalis.
The openings are usually directed posteriorly against the globe.
The lacrimal canaliculi are the tubular structures linking the lacrimal
puncta to the lacrimal sac. There is a vertical 2mm segment and a horizontal
8mm segment in each canaliculus. The upper canaliculus and the lower
canaliculus join to form the common canaliculus.
The common canaliculus enters the lacrimal sac obliquely forming the
valve of Rosenmüller, which prevents backﬂ ow of tears from the sac to
the canaliculi. Sometimes, the common canaliculus dilates slightly before
entering the lacrimal sac, forming the sinus of Maier.
This structure sits on the part of the bony orbit called the lacrimal fossa.
The superior part of the sac is the fundus and the inferior part of the sac,
16 Ocular Surface
the body, is where it extends to the osseous opening of the nasolacrimal
canal which contains the nasolacrimal duct.
The nasolacrimal duct consists of a superior (intraosseous) portion travelling
within the maxillary bone and a shorter inferior (membranous) portion
along the nasal mucosa. The duct ultimately opens into the inferior meatus
of the nasal cavity under the inferior nasal turbinate. There may be a valve
of Hasner at the opening of the nasolacrimal duct just before the tear drains
into the nasal cavity (Snell and Lemp 1998). Refer to Table 5 for terms related
to the lacrimal apparatus or unit.
Table 5 This table summarizes words related to lacrimal production and drainage.
Lacrimal-related deﬁ nitions Examples of use of term
Dacryo-adenitis Inﬂ ammation of the lacrimal
lacrimal sac abscess
Pus-ﬁ lled infected swelling in
the lacrimal sac
Dacryocystogram Imaging of the nasolacrimal
Dacryocystor-hinostomy Surgical procedure where
anastomosis is established
between nasal cavity and
Epiphora Excessive tearing onto the
face, i.e. caused by obstructed
drainage of tears
Lacrimal cysts Congenital displacement of
the lacrimal tissue resulting
in subconjunctival cysts
Swelling of the lacrimal
sac due to congenital
malformation or, if infected,
called lacrimal sac abscess
The Blood Supply of the Ocular Surface
The cornea is avascular except for the limbal area, which has a similar blood
supply as the conjunctiva. The blood supply to the conjunctiva is mainly
derived from the anterior ciliary and the palpebral artery branches. The
palpebral arteries also supply the eyelids and associated structures. The
corresponding veins drain these structures. The main lacrimal gland is
supplied by the lacrimal artery derived from the ophthalmic artery, with
veins draining to the superior ophthalmic vein (Snell and Lemp 1998).
Deﬁ nition of the Ocular Surface 17
The Lymphatics of the Ocular Surface
The conjunctival and eyelid lymphatic vessels drain to the submandibular
lymph glands medially and to the superﬁ cial preauricular nodes laterally.
After certain types of infection or inflammatory processes, corneal
lymphatics can be observed (Tang et al. 2010, Nakao et al. 2011, Zhang et
THE INNERVATION OF THE OCULAR SURFACE
The cornea is the most densely innervated structure in the human body. The
nerve branches supplying the cornea are derived from the long posterior
ciliary nerves, which are from the ophthalmic and maxillary division of the
trigeminal nerve. At the peripheral cornea, the nerves from the conjunctiva,
episclera and sclera penetrate the cornea at various depths.
The nerve ﬁ bers become unmyelinated when they penetrate the cornea
and run parallel to its surface. The corneal nerves turn abruptly 90 degrees
and proceed towards the corneal surface where they branch into the dense
subepithelial plexus (Marfurt et al. 2010). Unsheathed nerve endings arise
from the subepithelial plexus and continue superﬁ cially into the wing
and squamous cell layers of the epithelium (Beuerman and Pedroza 1996,
Müller et al. 2003).
Conjunctiva, Eyelids and Lacrimal Gland
The conjunctiva and eyelids are innervated by the ophthalmic and maxillary
branches of the trigeminal nerve (cranial nerve V). Refer to “Lacrimal gland
section” for lacrimal gland innervation.
Immune Privilege of Cornea
Since the cornea is avascular, the corneal stroma is normally not accessible
to the immune system. However, components of the innate immunity, such
as dendritic cells, have access to the limbal region. The corneal epithelial
cells possess pathogen recognition receptors, form a barrier to pathogens
and constitute an important part of innate defence of the ocular surface
In addition, components of the immune system, such as the complement
system and immunoglobulins, are present in the tear ﬁ lm, thereby exposing
the corneal epithelium to these elements of the immune system. During
18 Ocular Surface
inﬂ ammation of the cornea or when the cornea epithelium is breached by
trauma or microbes, cytokines and immune cells such as neutrophils and
macrophages will have access to the deeper layers of the cornea.
Mucosal Associated Lymphoid Tissues/Conjunctiva
Associated Lymphoid Tissues
The mucosal associated lymphoid tissue (MALT) is an important component
of the immunity in many mucosa of the body, for example, the Peyer’s
patches in the intestinal mucosa. Embedded into the palpebral conjunctiva
are lymphoid aggregates, the conjunctival associated lymphoid tissues
(CALT), which are an ocular surface form of MALT. The CALT are composed
of T and B lymphocytes, macrophages, plasma cells and dendritic cells
(Knop and Knop 2005) and serve as an induction site for immune defence
responses of the ocular surface (Astley et al. 2003, Liang et al. 2010).
The ocular surface is a well-integrated unit comprising the different parts
summarized above. Being a relatively exposed anatomical unit, the ocular
surface is prone to infections that can seriously affect the quality of lifestyle
of patients. In this chapter, we have summarized the main functions of
these different units and their associated commonly encountered clinical
diseases. We hope that this will help readers better understand the ocular
surface and its related pathology.
We would like to thank Lee Man Xin for aid in diagrams and research
relevant for the review.
Arends, G. and U. Schramm. 2004. The structure of the human semilunar plica at different
stages of its development—a morphological and morphometric study. Ann Anat 186:
Asbell, P.A. and M.A. Lemp. 2006. Dry eye disease: the clinician’s guide to diagnosis and
treatment. New York, Thieme Medical Publishers.
Astley, R.A., R.C. Kennedy and J. Chodosh. 2003. Structural and cellular architecture of
conjunctival lymphoid follicles in the baboon (Papio anubis). Exp. Eye Res. 76: 685–
Beuerman, R.W. and L. Pedroza. 1996. Ultrastructure of the human cornea. Microsc. Res.
Tech. 33: 320–335.
Binder, P.S., M.E. Rock, K.C. Schmidt and J.A. Anderson. 1991. High-voltage electron
microscopy of normal human cornea. Invest Ophthalmol. Vis. Sci. 32: 2234–2243.
Deﬁ nition of the Ocular Surface 19
Burton, H. 1992. Somatic Sensations from the eye. Adler’s Physiology of the Eye. W. M. Hart.
St. Louis, Mosby-Year Book 71–100.
Chan-Ling, T.L., A. Vannas and B.A. Holden. 1988b. Long-term changes in corneal endothelial
morphology following wounding in the cat. Invest Ophthalmol Vis. Sci. 29: 1407–1412.
Chen, H.B., S. Yamabayashi, B. Ou, Y. Tanaka, S. Ohno and S. Tsukahara. 1997. Structure
and composition of rat precorneal tear ﬁ lm. A study by an in vivo cryoﬁ xation. Invest
Ophthalmol. Vis. Sci. 38: 381–387.
de Paiva, C.S. and S.C. Pﬂ ugfelder. 2004. Tear clearance implications for ocular surface health.
Exp. Eye Res. 78: 395–397.
Draper, C.E., E. Adeghate, P.A. Lawrence, D.J. Pallot, A. Garner and J. Singh. 1998. Age-related
changes in morphology and secretory responses of male rat lacrimal gland. J. Auton.
Nerv. Syst. 69: 173–183.
Gipson, I.K. 2004. Distribution of mucins at the ocular surface. Exp. Eye Res. 78: 379–388.
Gipson, I.K. 2007. The ocular surface: the challenge to enable and protect vision: the
Friedenwald lecture. Invest Ophthalmol. Vis. Sci. 48: 4390; 4391–4398.
Grahn, B.H., S. Sisler and E. Storey. 2005. Qualitative tear ﬁ lm and conjunctival goblet cell
assessment of cats with corneal sequestra. Vet. Ophthalmol. 8: 167–170.
Greiner, J.V., T. Glonek, D.R. Korb, A.C. Whalen,E. Hebert, S.L. Hearn, J.E. Esway and C.D.
Leahy. 1998. Volume of the human and rabbit meibomian gland system. Adv. Exp. Med.
Biol. 438: 339–343.
Haque, S., D. Fonn, T. Simpson and L. Jones. 2004. Corneal and epithelial thickness changes
after 4 weeks of overnight corneal refractive therapy lens wear, measured with optical
coherence tomography. Eye Contact Lens 30: 189–193.
Hayashi, S., T. Osawa and K. Tohyama. 2002. Comparative observations on corneas, with special
reference to Bowman’s layer and Descemet’s membrane in mammals and amphibians.
J. Morphol. 254: 247–258.
Holly, F.J. 1985. Physical chemistry of the normal and disordered tear ﬁ lm. Trans. Ophthalmol.
Soc. UK 104: 374–380.
Jester, J.V., N. Nicolaides and R.E. Smith. 1981. Meibomian gland studies: histologic and
ultrastructural investigations. Invest Ophthalmol. Vis. Sci. 20: 537–547.
Joyce, N.C. 2003. Proliferative capacity of the corneal endothelium. Prog. Retin Eye Res. 22:
Kessing, S.V. 1968. Mucous gland system of the conjunctiva. A quantitative normal anatomical
study. Acta. Ophthalmol. 95: 91.
Kiel, J.W. 2010. The Ocular Circulation. San Rafael, Morgan and Claypool Publishers.
Knop, E. and N. Knop. 2005. The role of eye-associated lymphoid tissue in corneal immune
protection. J. Anat. 206: 271–285.
Lemp, M.A. and D.E. Wolﬂ ey. 1992. The Lacrimal Apparatus. Adler’s Physiology of the Eye,
Mosby Year Book 18–28.
Lens, A., S.C. Nemeth and J.K. Ledford. 2007. Ocular Anatomy and Physiology. Basic Bookshelf
for Eyecare Professionals Series, Slack Incorporated.
Li, H.F., W.M. Petroll, T. Moller-Pedersen, J.K. Maurer, H.D. Cavanagh and J.V. Jester. 1997.
Epithelial and corneal thickness measurements by in vivo confocal microscopy through
focusing (CMTF). Curr. Eye Res. 16: 214–221.
Liang, H., C. Baudouin, B. Dupas and F. Brignole-Baudouin. 2010. Live conjunctiva-associated
lymphoid tissue analysis in rabbit under inﬂ ammatory stimuli using in vivo confocal
microscopy. Invest Ophthalmol. Vis. Sci. 51: 1008–1015.
Linsen, C. and L. Missotten. 1990. Physiology of the lacrimal system. Bull. Soc. Belge Ophtalmol.
Linsenmayer, T.F., J.M. Fitch, M.K. Gordon, C.X. Cai, F. Igoe, J.K. Marchant and D.E. Birk.
1998. Development and roles of collagenous matrices in the embryonic avian cornea.
Prog. Retin Eye Res. 17: 231–265.
Lipham, W.J., H.A. Tawﬁ k and J.J. Dutton. 2002. A histologic analysis and three-dimensional
reconstruction of the muscle of Riolan. Ophthal. Plast. Reconstr. Surg. 18: 93–98.
20 Ocular Surface
Lorber, M. 2007. Gross characteristics of normal human lacrimal glands. Ocul. Surf. 5:
Marfurt, C.F., J. Cox, S. Deek and L. Dvorscak. 2010. Anatomy of the human corneal innervation.
Exp. Eye Res. 90: 478–492.
Maurice, D.M. 1957. The structure and transparency of the cornea. J. Physiol. 136: 263–286.
Maurice, D.M. 1972. The location of the ﬂ uid pump in the cornea. J. Physiol. 221: 43–54.
Mishima, S., A. Gasset, S.D. Klyce, Jr. and J.L. Baum. 1966. Determination of tear volume and
tear ﬂ ow. Invest Ophthalmol. 5: 264–276.
Müller, L.J., C.F. Marfurt, F. Kruse and T.M. Tervo. 2003. Corneal nerves: structure, contents
and function. Exp. Eye Res. 76: 521–542.
Murube, J. 2009. Hypotheses on the development of psychoemotional tearing. Ocul. Surf. 7:
Nagelhout, T.J., D.A. Gamache, L. Roberts, M.T. Brady and J.M. Yanni. 2005. Preservation of
tear ﬁ lm integrity and inhibition of corneal injury by dexamethasone in a rabbit model
of lacrimal gland inﬂ ammation-induced dry eye. J. Ocul. Pharmacol. Ther. 21: 139–148.
Nakao, S., S. Zandi, Y. Hata, S. Kawahara, R. Arita, A. Schering, D. Sun, M.I. Melhorn, Y. Ito,
N. Lara-Castillo, T. Ishibashi and A. Hafezi-Moghadam. 2011. Blood vessel endothelial
VEGFR-2 delays lymphangiogenesis: an endogenous trapping mechanism links lymph-
and angiogenesis. Blood 117: 1081–1090.
Nelson, J.D. 1995. Simultaneous evaluation of tear turnover and corneal epithelial permeability
by ﬂ uorophotometry in normal subjects and patients with keratoconjunctivitis sicca
(KCS). Trans. Am. Ophthalmol. Soc. 93: 709–753.
Obata, H. 2002. Anatomy and histopathology of human meibomian gland. Cornea 21:
Preziosi, V.A. 1968. The Periphery of Descemet’s Membrane: A Study by Light Microscopy.
Arch. Ophthalmol. 80: 197–201.
Qiu, X., L. Gong, X. Sun and H. Jin. 2011. Age-related Variations of Human Tear Meniscus
and Diagnosis of Dry Eye With Fourier-domain Anterior Segment Optical Coherence
Tomography. Cornea 30: 543–549.
Rivas, L., M.A. Oroza, A. Perez-Esteban and J. Murube-del-Castillo. 1991. Topographical
distribution of ocular surface cells by the use of impression cytology. Acta. Ophthalmol.
(Copenh) 69: 371–376.
Snell, R.S. and M.A. Lemp. 1998. Clinical Anatomy of the Eye. Malden, Blackwell Science.
Spurr-Michaud S., P. Argueso and I. Gipson 2007. Assay of mucins in human tear ﬂ uid. Exp.
Eye Res. 84: 939–950.
Stephens, L.C., T.E. Schultheiss, K.J. Vargas, D.M. Cromeens, K.N. Gray and K.K. Ang.
1989. Glands of the eyelids of rhesus monkeys (Macaca mulatta). J. Med. Primatol. 18:
Tang, X.L., J.F. Sun, X.Y. Wang, L.L. Du and P. Liu. 2010. Blocking neuropilin-2 enhances
corneal allograft survival by selectively inhibiting lymphangiogenesis on vascularized
beds. Mol. Vis. 16: 2354–2361.
The International Dry Eye Disease Workshop. 2007. The deﬁ nition and classiﬁ cation of dry
eye disease: report of the Deﬁ nition and Classiﬁ cation Subcommittee of the International
Dry Eye WorkShop. Ocul. Surf. 5: 75–92.
Thoft, R.A. 1978. Role of the ocular surface in destructive corneal disease. Trans. Ophthalmol.
Soc. UK 98: 339–342.
Tiffany, J.M. 2008. The normal tear ﬁ lm. Dev. Ophthalmol. 41: 1–20.
Tseng, S.C., L.W. Hirst, A.E. Maumenee, K.R. Kenyon, T.T. Sun and W.R. Green. 1984. Possible
mechanisms for the loss of goblet cells in mucin-deﬁ cient disorders. Ophthalmology
Van Haeringen, N.J. 1981. Clinical biochemistry of tears. Surv. Ophthalmol. 26: 84–96.
Wanko, T., B.J. Lloyd, Jr. and J. Matthews 1964. The Fine Structure of Human Conjunctiva in
the Perilimbal Zone. Invest. Ophthalmol. 3: 285–301.
Deﬁ nition of the Ocular Surface 21
Wilson, S.E. and J.W. Hong. 2000. Bowman’s layer structure and function: critical or dispensable
to corneal function? A hypothesis. Cornea 19: 417–420.
Wulc, A.E., R.M. Dryden and T. Khatchaturian. 1987. Where is the gray line? Arch. Ophthalmol.
Yokoi, N., A.J. Bron, J.M. Tiffany, K. Maruyama, A. Komuro and S. Kinoshita. 2004. Relationship
between tear volume and tear meniscus curvature. Arch. Ophthalmol. 122: 1265–1269.
Zhang, H., X. Hu, J. Tse, F. Tilahun, M. Qiu and L. Chen. 2011. Spontaneous lymphatic
vessel formation and regression in the murine cornea. Invest Ophthalmol. Vis. Sci. 52:
Zoukhri, D. 2006. Effect of inﬂ ammation on lacrimal gland function. Exp. Eye Res. 82: