The lids develop from mesenchyme except for the epidermis of the skin and the

epithelium of the conjunctiva, which are derivatives of surface ectoderm. The lid
buds are first seen at 6 weeks growing in front of the eye, where they meet and
fuse by 8 weeks. They separate during the fifth month. The lashes and meibomian
and other lid glands develop as downgrowths from the epidermis.

The lacrimal and accessory lacrimal glands develop from the conjunctival
epithelium. The structures of the lacrimal drainage system (canaliculi, lacrimal sac,
and nasolacrimal duct) are also surface ectodermal derivatives, which develop
from a solid epithelial cord that becomes buried between the maxillary and nasal
processes of the developing facial structures. This cord canalizes just before birth.

The process of eyelid fusion. A, At around week 8, the flattened periderm cells (arrowhead) undergo a
morphogenetic and proliferative change into rounded or cuboidal periderm cells. B, The leading edge of
these proliferating cells helps make contact with the advancing edge of the opposing eyelid periderm cells
until a connection is established. C, When a connection is established between both sides, these periderm
cells flatten again and form a continuous sheet ultimately covering the cornea. D, Only the periderm and
epidermal layers are involved in eyelid fusion while eyelid mesenchyme (*) remains distinct (Modified
with permission from Yu et al.32).

Maturation of the eyelids during the fetal period. A, Week 9 (40 ± 2 mm). The development of eyelid
structures begins in the 9th week immediately following eyelid fusion with mesenchymal cell
condensations and an occasional ingrowth of surface epithelium into the underlying mesenchyme, which
together contribute to the formation of some eyelid structures. The first to appear is the orbital part of the
orbicularis oculi muscle. B, By week 14 (121 ± 11 mm). The eyelid is now clearly divided into separate
layers. Rudimentary eyelashes, sebaceous, and sweat glands (*) could be seen near the eyelid margin, and
a primordial tarsal plate has formed (arrow). C, Week 20 (195 ± 15 mm). Although the eyelids are still
visibly fused, separation has already started anteriorly (*) and is visible in the middle at a microscopic
level. Meibomian gland branching is first observed and the tarsal plate has lengthened significantly. The
orbicularis oculi muscle looks more fully developed. Nearly mature eyelash follicles about to pierce the
eyelid margin are also evident. D, Week 32 (301 ± 33 mm). The eyelid has taken its nearly fully
developed appearance. Meibomian glands increase in length and are present in two-thirds of the length of
the tarsal plate. The eyelids are fully separated by now but the eyes are still visibly closed. E, Full term.
Final appearance of the eyelids at birth, which is not dissimilar from the adult counterpart. OO,
orbicularis oculi muscle; MG, Meibomian glands; TP, tarsal plate.

Lacrimal pump. A, In the relaxed state, the puncta lie in the tear lake. B, With eyelid closure, the
orbicularis oculi muscle contracts. The pretarsal orbicularis squeezes and closes the puncta and
canaliculi. The preseptal orbicularis, which inserts into the lacrimal sac, pulls the lacrimal sac
open, creating a negative pressure that draws the tears into the sac. C, With eyelid opening, the
orbicularis relaxes, the puncta open, and the lacrimal sac collapses, propelling tears down the
duct. Simultaneously, with the puncta opened, the canaliculi refill, completing the cycle.
https://www.britannica.com/science/human-eye/The-visual-
process
The work of the auxiliary structures
The protective mechanisms
The first line of protection of the eyes is provided by the lids, which prevent access of foreign
bodies and assist in the lubrication of the corneal surface. Lid closure and opening are
accomplished by the orbicularis oculi and levator palpebri muscles; the orbicularis oculi operates
on both lids, bringing their margins into close apposition in the act of lid closure. Opening results
from relaxation of the orbicularis muscle and contraction of the levator palpebri of the upper lid;
the smooth muscle of the upper lid, Müller’s muscle, or the superior palpebral muscle, also
assists in widening the lid aperture. The lower lid does not possess a muscle corresponding to the
levator of the upper lid, and the only muscle available for causing an active lowering of the lid,
required during the depression of the gaze, is the inferior palpebral muscle, which is analogous to
the muscle of Müller of the upper lid (called the superior palpebral muscle). This inferior
palpebral muscle is so directly fused with the sheaths of the ocular muscles that it provides
cooperative action, opening of the lid on downward gaze being mediated, in effect, mainly by the
inferior rectus.

Innervation
The seventh cranial nerve—the facial nerve—supplies the motor fibres for the orbicularis
muscle. The levator is innervated by the third cranial nerve—the oculomotor nerve—which also
innervates some of the extraocular muscles concerned with rotation of the eyeball, including the
superior rectus. The smooth muscle of the eyelids and orbit is activated by the sympathetic
division of the autonomic system. The secretion of epinephrine (adrenaline) during such states of
excitement as fear would also presumably cause contraction of the smooth muscle, but it seems
unlikely that this would lead to the protrusion of the eyes traditionally associated with extreme
fear. It is possible that the widening of the lid aperture occurring in this excited state and the
dilation of the pupil create the illusion of eye protrusion.

Blinking is normally an involuntary act, but it may be carried out voluntarily. The more vigorous
“full closure” of the lids involves the orbital portion of the orbicularis muscle and may be
accompanied by contraction of the facial muscles that have been described as accessory muscles
of blinking—namely, the corrugator supercilii, which on contraction pulls the eyebrows toward
the bridge of the nose, and the procerus or pyramidalis, which pulls the skin of the forehead into
horizontal folds, acting as a protection when the eyes are exposed to bright light. The more
vigorous full closure may be evoked as a reflex response.

Blink reflexes
Reflex blinking may be caused by practically any peripheral stimulus, but the two functionally
significant reflexes are (1) that resulting from stimulation of the endings of the fifth cranial nerve
in the cornea, lid, or conjunctiva—the sensory blink reflex, or corneal reflex—and (2) that
caused by bright light—the optical blink reflex. The corneal reflex is rapid (0.1 second reflex
time) and is the last to disappear in deepening anesthesia, impulses being relayed from the
nucleus of the fifth nerve to the seventh cranial nerve, which transmits the motor impulses. The
reflex is said to be under the control of a medullary centre. The optical reflex is slower; in
humans, the nervous pathway includes the visual cortex (the outer substance of the brain; the
visual centre is located in the occipital—rear—lobe).

Normal rhythm
In the waking hours, the eyes blink fairly regularly at intervals of two to 10 seconds, the actual
rate being a characteristic of the individual. The function of this is to spread the lacrimal
secretions over the cornea. It might be thought that each blink would be reflexly determined by a
corneal stimulus—drying and irritation—but extensive studies indicate that this view is incorrect.
The normal blinking rate is apparently determined by the activity of a “blinking centre” in the
globus pallidus of the caudate nucleus, a mass of neurons between the base and the outer
substance of the brain. This is not to deny that the blink rate is modified by external stimuli.

There is a strong association between blinking and the action of the extraocular muscles. Eye
movement is generally accompanied by a blink, and it is thought that this aids the eyes in
changing their fixation point.

Secretion of tears
The exposed surface of the globe (eyeball) is kept moist by the tears secreted by the lacrimal
apparatus, together with the mucous and oily secretions of the other secretory organs and cells of
the lids and conjunctiva; these have been described earlier. The secretion produces what has been
called the precorneal film, which consists of an inner layer of mucus, a middle layer of lacrimal
secretion, and an outer oily film that reduces the rate of evaporation of the underlying watery
layer. The normal daily (24-hour) rate of secretion has been estimated at about 0.75 to 1.1 grams
(0.03–0.04 ounce avoirdupois); secretion tends to decrease with age. Chemical analysis of the
tears reveals a typical body fluid with a salt concentration similar to that of blood plasma. An
interesting component is lysozyme, an enzyme that has bactericidal action by virtue of its power
of dissolving away the outer coats of many bacteria.

Tears are secreted reflexly in response to a variety of stimuli—e.g., irritative stimuli to the
cornea, conjunctiva, nasal mucosa; hot or peppery stimuli applied to the mouth and tongue; or
bright lights. In addition, tear flow occurs in association with vomiting, coughing, and yawning.
The secretion associated with emotional upset is called psychical weeping. Severing of the
sensory root of the trigeminal (fifth cranial) nerve prevents all reflex weeping, leaving psychical
weeping unaffected; similarly, the application of cocaine to the surface of the eye, which
paralyzes the sensory nerve endings, inhibits reflex weeping, even when the eye is exposed to
potent tear gases. The afferent (sensory) pathway in the reflex is thus by way of the trigeminal
nerve. The motor innervation is by way of the autonomic (involuntary) division; the
parasympathetic supply derived from the facial nerve (the seventh cranial nerve) seems to have
the dominant motor influence. Thus, drugs that mimic the parasympathetic, such as
acetylcholine, provoke secretion, and secretion may be blocked by such typical anticholinergic
drugs as atropine. Innervation of the lacrimal gland is not always complete at birth, so that the
newborn infant is generally said to cry without weeping. Because absence of reflex tearing fails
to produce any serious drying of the cornea, and surgical destruction of the main lacrimal gland
is often without serious consequences, it seems likely that the subsidiary secretion from the
accessory lacrimal glands is adequate to keep the cornea moist. The reflex secretion that
produces abundant tears may be regarded as an emergency response.

A drainage mechanism for tears is necessary only during copious secretion. The mechanism,
described as the lacrimal pump, consists of alternately negative and positive pressure in the
lacrimal sac caused by the contraction of the orbicularis muscle during blinking.

Chapter 114General Introduction151.2BLINK ANATOMYA blink consists of simultaneous

eyelid and eye movement. Two antagonistic muscles are involved in the
performance of the eyelid component of a blink; the orbicularis oculi muscle (OO
muscle) and levator palpebrae superiorus muscle (LPS muscle) (fig. 1). The OO
muscle, a flat broad elliptical sphincter-like muscle, induces eyelid closure. The
tonically active LPS muscle serves to elevate the upper eyelid. A third muscle is the
sympathetically innervated tarsal or Müller’s Muscle which can adjust the width of
the palpebral fissure and aids the LPS muscle in keeping the eyelid open. The eye
component of a blink is performed with all 6 extraocular muscles. Lower mammals
such as rabbits and cats have an additional muscle which retracts the eye into the
orbit during blinking, the retractor bulbi muscle. Reflex blinks have short circuits in
the brainstem; other blinks are evoked through projections linked to these circuits.
The current knowledge on the pathways underlying different blinks is described in
chapter 1.3. For all muscle contractions proper conduction of signals through a
nerve and muscle is imperative. Essential for efficient transfer of a signal from nerve
to muscle are well-functioning motor units. A motoneuron and the muscle fibers it
innervates constitute a motor unit. When a motoneuron enters a muscle it splits into
numerous unmyelinated branches. One neuron can therefore innervate many
muscle fibers. The synaptic contacts formed between the branches and muscle
fibers are called neuromuscular junctions. For proper innervation only one such
contact is made per muscle fiber [Schwartz and Westbrook 2000]. Each region of
the OO muscle contains motor units of different sizes. The size of the motor unit
determines the precision with which muscle force can be increased or decreased
during different types of blinks.Orbicularis oculi muscleIn the OO muscle three
separate portions have been distinguished based on anatomical as well as
functional characteristics. The pretarsal and preseptal portion, together known as
the palpebral portion, and the orbital portion are depicted in figure 1. The pretarsal
portion of the OO muscle contains relatively short muscle fibers and motor units
[Lander et al. 1996] and consists for 90% of fibers that are capable of making fast
contractions (fast twitch fibers). These fibers have a relatively low threshold and can
therefore induce fast precise eyelid closure needed for spontaneous and reflex
blinks. The orbital portion is involved in blinking, winking and more forceful eyelid
closure [Aramideh et al. 1995] and contains relatively large muscle fibers and motor
units which allows for more forceful, yet slower contractions [Gordon 1951, Lander
et al. 1996]. The preseptal portion is active during both blinking and sustained
activity. During a blink the OO motor units, predominantly in the palpebral portion,
discharge brief high frequency bursts. Levator palpebrae superioris muscle The LPS
muscle is ontogenetically an extraocular muscle that is closely related to the
superior rectus muscle. The tonically active LPS muscle has motoneurons with a
regular discharge pattern during steady eyelid position which changes linearly
related to eye and eyelid position [Fuchs 1992]. Contrary to the other extraocular
muscles the LPS muscle is not divided into an orbital and global layer. The muscle
contains three types of singly innervated fibers also found in other extraocular
muscles and the unique levator slow-twitch fiber type [Porter et al. 1989]. The LPS
muscle is connected to the eyelid by the levator aponeurosis which consists of two
layers that contain smooth muscle components in their proximal portions
[VanderWerf et al. 1993]. During blinking LPS muscle activity is inhibited. The LPS
muscle acts in synergy with the superior rectus muscle. This means when the eye
rotates upward, the eyelid is raised so vision is not blocked. Likewise, on downward
gaze, the lid comes down to protect the superior part of the eyeball. Rotations of the
eye are mediated by the extraocular muscles [Spencer and Porter 2006].Extraocular
musclesThe extraocular muscles are four recti and two oblique muscles that serve
to move the eyeball in different directions. The primary movement of the medial,
lateral, inferior, superior rectus and inferior and superior oblique muscles is
adduction, abduction, depression, elevation, excycloduction and incycloduction of
the eyeball, respectively [Burde and Feldon 1992]. Furthermore, extraocular
muscles hold the eye steady during fixation. Extraocular muscles have a
complicated make-up, in accordance with the range of movements they have to
make, varying from high velocity saccades or blinks to slow smooth pursuit
movements. In order to provide the necessary contraction speeds and fatigue
resistances the eye muscles contain several fiber types. All extraocular muscles
consist of a orbital (facing the orbital wall) and global (near the eye) layer. The
orbital layer contains a highly fatigue-resistant singly innervated fiber type and
multiple innervated type, possibly with twitch characteristics in the middle of the
muscle belly but with tonic characteristics at the proximal and distal ends of
individual fibers. The global layer contains three singly innervated, fast-twitch fiber
types and one multiply innervated fiber type [Porter and Hauser 1993, Spencer and
Porter 2006]. The extraocular muscles have small motor units (approximately 10
muscle fibers per motoneuron), which corresponds perfectly with the small
increments in muscle tension necessary for accurate eye movements [Porter et al.
1995, Spencer and Porter 2006.
Blink pathway
Neuronal structures in the brainstem, cerebrum and cerebellum regulate and
coordinate the blink. The precise projections and locations of areas involved in
blinking within these neuronal structures have only been established to a certain
extent. Seven of the cranial nerves are involved in blinking; the optic, oculomotor,
trochlear, trigeminal, abducens, facial and vestibulocochlear nerves. In table 3 a
short description is given of the 12 cranial nerves and their functions. Reflex blinks
are basal and fast reactions and are regulated in the brainstem. In the cerebrum
voluntary blinks are initiated. The cerebellum is involved in the precise timing and
coordination of blinks and plays an eminent role in associative learning of a
conditioned response. Although a conditioned blink is not the same as a reflex blink
there are arguments that the cerebellum might also be involved in reflex blinking
[Evinger personal communication]. Freed and co-workers (1981) found that
cerebellectomized rats displayed increased blink rates. Imaging studies even
showed cerebellar activation during spontaneous blinking [Evinger and Perlmutter
2003]. Most of the influence exerted by the higher order or supranuclear areas
modulates the excitability of the blink, through for instance, descending cortical
projections via the thalamus and superior colliculus (SC) via tecto-reticular
projections [Basso et al. 1996]. Supranuclear projections involved in blinking are
distributed over several regions. Imaging studies revealed that the primary motor
cortex, supplementary motor cortex, cingulated motor cortex and the central
thalamus are active during spontaneous and voluntary blinking [Evinger and
Perlmutter 2003]. Using rabies virus as a transneuronal tracer, the hypothalamus
and especially the parietal areas of the cerebral cortex were labeled as part of the
eyelid premotor circuit [Morcuende et al. 2002]. Direct projections have been
described from the motor cortex to the facial nucleus and lateral medullary reticular
formation [Jenny and Saper 1987, Kuypers 1958]. Grinevich et al. (2005) also
showed monosynaptic projections from the rat vibrissae motor cortex to facial
motoneurons using lentivirus-based axonal tracing methods. This monosynaptic
connection was, however, expected as a result of ongoing development of
specialized movements of the whiskers. Blinks do not require as much skill, though it
is possible that monosynaptic projections from the motor cortex to the facial
motoneurons involved in blinking exist. Tracing studies in the monkey showed
projections from the motor cortex to the intermediate facial motor nucleus [Morecraft
et al. 2001]. The basal ganglia can also influence reflex blinking through different
pathways [Esteban 1999].

Most experimental studies described in this thesis focus on reflex and conditioned
blinks, the pathways of these two types of blinks are discussed in more detail.
During reflex blinking the eyes and eyelids are innervated by their individual circuits
which are discussed separately. For conditioned blinks the eyes and eyelids are
partially innervated by the same pathways. The exact projections that enable this
form of associative learning are still extensively investigated although some
consensus has been reached, which is discussed in the last part of this chapter. Box
2 provides additional
information on the main
neuronal structures
involved in the blink.

How Does a Blink Work?

Involuntary blinks can be sub-
divided into spontaneous and
reflex blinks. Spontaneous
blinks occur subconsciously, are
triggered by the autonomic
nervous system and account for
the majority of the blinks
performed during the day.3
Spontaneous blinking helps to
maintain an intact pre-corneal
tear film to ensure optical
quality as well as proper re-
wetting of the ocular surface,
and helps with removal of tear
film debris.1,4,5

Reflex blinks are typically Fig. 1. This contact lens surface shows substantial drying
triggered by some kind of across the inferior portion after a partial blink. Note the
external stimulus, such as a clear transition from dark (replenished) superior to
sudden bright light, a loud noise speckled (dried) inferior portion of the lens, identifying
or a foreign body touching the where the downward movement of the blink ended.
anterior surface of the eye.1 Photo: The Centre for Ocular Research & Education
Voluntary or consciously (CORE). Click image to enlarge.
performed blinks are intentional
lid movements for a specific
purpose, for example to achieve re-wetting of the ocular surface after prolonged eye opening.
Voluntary blinking is typically used during blinking exercises that aim at altering a patient’s
blink habits for the better.5

The blinking process involves movements of both upper and lower lid, with the upper lid doing
the primary closing and opening motion, while the lower lid only exhibits a minimal upwards
and nasal movement.6 During a full eye closure, the upper eyelid touches the lower eyelid in the
temporal location first, followed by a wave-like swiping motion nasally that also assists in tear
exchange and drainage at the lacrimal puncta of the eyelids.1,4,6 

Opening and closing of the eyelids is controlled by innervation of the 3rd and 7th cranial nerves,
respectively, which innervate the levator palpebrae superioris and orbicularis oculi muscle,
respectively.2 Innervation of the levator palpebrae superioris muscle as well as Mueller’s muscle
contributes to raising the eyelid and holding it up, while the orbicularis oculi muscle closes the
lids.6,7 During a blink, the nervous system turns off the tonically active levator palpebrae
superioris, allowing the orbicularis oculi muscle to rapidly lower the upper eyelid before the
levator palpebrae superioris becomes active again and raises the lid.6 

Complete eye closure is a crucial requirement for ocular surface health, as the contact of upper
and lower lid during a complete blink promotes secretion of lipids from the meibomian glands,
which protect the tear film from evaporation.5 During a complete blink, mucins are secreted from
the tarsal goblet cells over the entire ocular surface and tear film; for incomplete blinks, this only
applies to the areas covered by the moving eyelids, thus impacting tear film integrity.5 

The presence of incomplete spontaneous blinks is therefore of concern, particularly in patients

with evaporative DED.5,8,9 Researchers recently reported a two-fold increased risk for developing
DED in patients with incomplete blinking patterns, suggesting it may be a predisposing factor
towards the eventual development of evaporative DED.8 Compared with participants with
complete blinking patterns, participants who exhibited incomplete blinks were found to have
significantly worse symptoms and signs of DED, including greater ocular surface disease index
(OSDI) scores, greater meibomian gland drop-out and poorer meibum quality, as well as reduced
lipid layer thickness and tear film stability.8
 1. Kenapa orbital fat disebut sebagai penanda operasi
2. Apakah hanya orbital fat yang dianggap sebagai “penanda operasi”
3. Disebutkan tadi, palpebra kaya akan pembuluh darah, pada saat misalnya akan
melakukan anestesi palpebra apa yang harus kita perhatikan ?
4. Tadi sempat disebutkan mengenai auskultasi pada palpebra, apakah bisa dijelaskan
bagaimana cara melakukannya
5. Apakah bisa dijelaskan Kembali mengenai fungsi palpebra dalam pompa air mata ?
6. Apakah ada fungsi dari gray line, atau hanya sebagai pembatas saja ?
7. Otot Riolan, yang terletak dekat dengan tepi kelopak mata, berkontribusi
untuk menjaga tutupnya tetap rapat.
8. bum; it pressurizes the meibomian glands as the orbicularis muscles contract with the
blink. Gland expression is controlled by the muscle of Riolan (Figure 1) at the distal end
of the gland. Riolan’s muscle prevents lipid expression, except when the eyelids touch as
the blink completes.

9. Pemeriksaan phenylephrine tadi apakah ada kontraindikasinya ?

10. Objective: To evaluate the response of ptotic upper eyelids to topical phenylephrine 10%.
Methods: The medical records of patients referred for ptosis evaluation over an 18-month
period were retrospectively reviewed. Seventy-seven ptotic upper eyelids with
aponeurotic dehiscence in 47 patients were given 1 drop of 10% phenylephrine. Margin-
to-reflex distance 1 (MRD1) and levator excursion were recorded and photography of lid
height was performed both pre- and 5 minutes post-phenylephrine testing. Results: A
total of 77 ptotic upper eyelids of 47 patients were included. In 22% of lids,
phenylephrine testing produced no response; in 18%, lid elevation of 0.5-1 mm; in 35%,
elevation of 1.5-2 mm; and in 25%, elevation of > 2 mm. Subgroup analyses revealed a
higher proportion of response in cases of mild to moderate ptosis compared with cases of
severe ptosis. The amount of levator function in these cases of aponeurotic dehiscence
did not correlate with the amount of response to phenylephrine. Conclusions: A majority
of ptotic eyelids, regardless of levator function, responded to topical phenylephrine,
which has been demonstrated to be necessary for successful Müller's muscle resection
ptosis repair. While the severity of ptosis was linked to eyelid response to phenylephrine,
the degree of levator function did not appear to affect an eyelid's response to
phenylephrine. In this study cohort, phenylephrine was shown to stimulate Müller's
muscle contraction independently of levator function.

In patients with mild to moderate upper eyelid ptosis, phenylephrine eyedrops are used to assess
whether ptosis correction is achievable with a Müller's muscle-conjunctival resection (MMCR).
As an alpha-adrenergic agonist, phenylephrine stimulates the sympathetically innervated
Müller's muscle when applied topically.

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 diabetes
 closed angle glaucoma = dilate pupil
 high blood pressure
 coronary artery disease
 abnormal heart rhythm
 hardening of the arteries due to plaque buildup
 enlarged prostate