DƯỢC LÍ Goodman & Gilman's The Pharmacological Basis of Therapeutics 12th, 2010

Ocular Pharmacology
Jeffrey D. Henderer and
Christopher J. Rapuano
OVERVIEW OF OCULAR ANATOMY,
PHYSIOLOGY, AND BIOCHEMISTRY
The eye is a specialized sensory organ that is relatively
secluded from systemic access by the blood-retinal,
blood-aqueous, and blood-vitreous barriers; as a consequence,
the eye exhibits some unusual pharmacodynamic
and pharmacokinetic properties. Because of its anatomical
isolation, the eye offers a unique, organ-specific
pharmacological laboratory in which to study the autonomic
nervous system and the effects of inflammation
and infectious diseases. No other organ in the body is so
readily accessible or as visible for observation; however,
the eye also presents some unique challenges as well as
opportunities for drug delivery (Robinson, 1993).
Extraocular Structures
The eye is protected by the eyelids and by the orbit, a bony
cavity of the skull that has multiple fissures and foramina
that conduct nerves, muscles, and vessels (Figure 64–1). In
the orbit, connective (i.e., Tenon’s capsule) and adipose
tissues and six extraocular muscles support and align the
eyes for vision. The retrobulbar region lies immediately
behind the eye (or globe). Understanding ocular and orbital
anatomy is important for safe periocular drug delivery, including
subconjunctival, sub-Tenon’s, and retrobulbar injections.
The eyelids serve several functions. Foremost, their
dense sensory innervation and eyelashes protect the eye
from mechanical and chemical injuries. Blinking, a coordinated
movement of the orbicularis oculi, levator palpebrae,
and Müller’s muscles, serves to distribute tears over
the cornea and conjunctiva. In humans, the average blink
rate is 15-20 times/minute. The external surface of the
eyelids is covered by a thin layer of skin; the internal surface
is lined with the palpebral portion of the conjunctiva,
which is a vascularized mucous membrane continuous
with the bulbar conjunctiva. At the reflection of the
palpebral and bulbar conjunctivae is a space called the
fornix, located superiorly and inferiorly behind the upper
and lower lids, respectively. Topical medications usually
are placed in the inferior fornix, also known as the inferior
cul-de-sac.
The lacrimal system consists of secretory glandular
and excretory ductal elements (Figure 64–2). The
secretory system is composed of the main lacrimal
gland, which is located in the temporal outer portion of
the orbit, and accessory glands, also known as the
glands of Krause and Wolfring, located in the conjunctiva.
The lacrimal gland is innervated by the autonomic
nervous system (Table 64–1 and Chapter 8). The
parasympathetic innervation is clinically relevant
because a patient may complain of dry eye symptoms
while taking medications with anticholinergic side
effects, such as tricyclic antidepressants (Chapter 15),
antihistamines (Chapter 32), and drugs used in the management
of Parkinson disease (Chapter 22). Located
just posterior to the eyelashes are meibomian glands,
which secrete oils that retard evaporation of the tear
film. Abnormalities in gland function, as in acne
rosacea and meibomitis, can greatly affect tear film
stability.
Conceptually, tears constitute a trilaminar lubrication
barrier covering the conjunctiva and cornea. The
anterior layer is composed primarily of lipids secreted
by the meibomian glands. The middle aqueous layer,
produced by the main lacrimal gland and accessory
lacrimal glands, constitutes ~98% of the tear film.
Adherent to the corneal epithelium, the posterior layer
is a mixture of mucins produced by goblet cells in the
conjunctiva. Tears also contain nutrients, enzymes, and
immunoglobulins to support and protect the cornea.
The tear drainage system starts through small
puncta located on the medial aspects of both the upper
and lower eyelids (Figure 64–2). With blinking, tears