15
Antiedema Drugs
Siret D. Jaanus
Osmotherapy was introduced to ocular therapeutics in
1904 with the use of oral hypertonic saline to reduce
elevated intraocular pressure.Topical ocular use of hyper-
osmotic agents has been proven clinically useful in the
treatment of corneal edema, particularly when the cause
is endothelial dysfunction.
The following discussion considers the pharmacologic
properties of hyperosmotic agents available for topical
use. Chapter 26 discusses the clinical uses of topical
osmotherapy in the management of conditions character-
ized by corneal edema.
CORNEAL EDEMA
A variety of clinical situations can give rise to corneal
edema (Box 15-1). Because the endothelium is the main
structure involved in maintaining normal corneal deturges-
cence, it plays a role in stromal hydration and compensates
for the driving force of intraocular pressure. Also, the
active transport system involved in the movement of water
and electrolytes from the cornea to the aqueous humor
must be maintained to prevent fluid retention. Endothelial
failure, a frequent cause of corneal edema, can occur due
to defects in the transport system or stromal compression
resulting from elevation of intraocular pressure, which can
induce water movement toward the epithelium.
Whenever swelling takes place, transparency is lost in
the region where the edema occurs. Because the corneal
epithelium and tear film constitute the most anterior opti-
cal surface of the eye, epithelial edema can exert a major
detrimental influence on vision because it induces ante-
rior irregular astigmatism.
It is clinically useful to consider corneal edema as
epithelial, stromal, or a combination of both. In general,
epithelial edema is more responsive to topical hyperos-
motic therapy.
TOPICAL HYPEROSMOTIC AGENTS
Topical hyperosmotic agents can be useful in dehydrating
edematous corneas. The clinical objective of topical
osmotherapy is to increase the tonicity of the tear film
and thereby enhance the rate of movement of fluid from
the cornea. All the currently available hyperosmotic
preparations are hyperosmolar to the ocular tissue fluid.
When applied to the ocular surface, water is drawn from
the cornea to the more highly osmotic tear film and is
eliminated through the usual tear flow mechanisms.
Patients with minimal to moderate epithelial edema often
achieve subjective comfort and improved vision with use
of these agents.
Various agents can reduce corneal edema,including corn
syrup, glucose, gum cellulose, sodium chloride, and glyc-
erin. Only a few of these have proved clinically useful and
acceptable to most patients. Sodium chloride and glycerin
(Table 15-1) are the preferred agents in clinical practice.
Sodium Chloride
Pharmacology
Sodium chloride is a component of all body fluids, includ-
ing tears. A solution of 0.9% is approximately isotonic
with tears. Of the various concentrations tested, 2% to 5%
formulations have proven effective, with an irritation
level acceptable to most patients. Studies comparing vari-
ous hyperosmotic agents in human subjects have
confirmed the usefulness of hypertonic sodium chloride
in the treatment of corneal edema. Use of 5% sodium
chloride in ointment form can be effective in reducing
corneal thickness and in improving vision.The maximum
reduction in corneal thickness occurs 3 to 4 hours after
instillation of the ointment (Figure 15-1).
Despite their apparent efficacy, the usefulness of
sodium chloride solutions in the treatment of edematous
corneas with a traumatized epithelium appears to be
limited. The intact corneal epithelium exhibits limited
permeability to inorganic ions. In the absence of an intact
epithelium the cornea imbibes salt solutions, which
reduces the osmotic effect. In the management of corneal
edema associated with traumatized epithelium, hyper-
tonic saline solutions may be of limited value due to their
increased ability to penetrate the epithelial barrier.
279
280 CHAPTER 15 Antiedema Drugs

Box 15-1 Causes of Corneal Edema
Endothelial
Birth trauma
Congential hereditary corneal dystrophy
Fuchs’ dystrophy
Keratoconus and hydrops
Mechanical trauma
Surgical trauma
Inflammation
Increased intraocular pressure
Acute angle-closure glaucoma
Chronic glaucoma
Adapted from Boruchoff SA. Clinical causes of corneal edema.
Int Ophthalmol Clin 1968;8:581–600.
Clinical Uses
Sodium chloride is useful for reducing corneal edema of
various etiologies, including bullous keratopathy. Generally,
one to two drops are instilled in the eye every 3 to 4 hours.
Sodium chloride ointment requires less frequent
instillation and is generally reserved for nighttime use.
Sodium chloride is commercially available in 2% and
5% solutions and as 5% ointment (see Table 15-1). In clinical
practice, the 5% concentration appears to be somewhat
more effective.
The way in which hyperosmotic preparations are
administered may affect the clinical results. Because
vision is usually worse on arising, several instillations
during the first waking hours can prove helpful. On hot
dry days, eyes may require less medication, because tear
film evaporation is enhanced.
Side Effects
Whereas isotonic saline (0.9% sodium chloride) is
nontoxic to the cornea and conjunctiva, sodium chloride,
especially at the 5% concentration, can cause discomfort
on instillation. Stinging, burning, and irritation are
common complaints, but patients generally tolerate the
therapy, especially if vision is improved. Epistaxis has
been associated with use of 2% sodium chloride solution.
The solution formulation should not be used if it changes
color or becomes cloudy.
Glycerin (Glycerol)
Pharmacology
Glycerin is a clear, colorless, syrupy liquid with a sweet
taste. It is miscible with both water and alcohol. In
contact with water, glycerin absorbs water and thereby
exerts an osmotic effect. When placed on the eye, its
hygroscopic action clears the haze of corneal epithelial
edema. Because the molecules mix readily with water, the
osmolality of the applied solution decreases rapidly as
water is imbibed from the cornea, and the clinical effect
is transient.
Clinical Uses
Topical application of glycerin in concentrations from
50% to 100% results in a significant reduction of corneal
edema within 1 to 2 minutes. Because application to the
eye is painful, a topical anesthetic must be instilled before
use. It is useful in ophthalmoscopic and gonioscopic
examination of the eye in acute angle-closure glaucoma,
bullous keratopathy, and Fuchs’ endothelial dystrophy.
Because its action is transient and application to the eye
painful, glycerin is used primarily for diagnostic purposes.

Table 15-1
Topical Hyperosmotic Preparations

Trade Name (Manufacturer) Composition

Sodium chloride
Adsorbonac Solution, 2% and 5% (Alcon)
Muro-128 Solution, 2% and 5% (Bausch & Lomb)
Muro-128 Ointment, 5% (Bausch & Lomb)
AK-NaCl 5% Ointment (Akorn)
Sochlor, 5% solution (OCuSoft)
Sochlor, 5% ointment (OCuSoft)
NaCl, povidone and other water-soluble polymer, thimerosal 0.0004%,
EDTA 0.1%
NaCl, hydroxypropylethylcellulose, methylparaben, propylparaben,
boric acid
NaCl, anhydrous lanolin, mineral oil, white petrolatum
NaCl, anhydrous lanolin, mineral oil, white petrolatum
NaCl
NaCl

Glycerin (Glycerol)
Ophthalgan* (compounded product) Anhydrous glycerin

Glucose
Glucose-40* (compounded product) Glucose 40%, usually white petrolatum, anhydrous lanolin

*Available only by prescription.

EDTA = ethylenediaminetetraacetic acid.

0 Clinical Uses
% Reduction in Corneal Thickness
4
8
12
16
20
24
0 60 120 180 240 300 360
Time (min)
Figure 15-1 Percent reduction in corneal thickness after
application of 5% sodium chloride ointment (triangles =
central; unfilled circles = nasal; filled circles = temporal).
(Modified from the American Journal of Ophthalmology
1971;71:847–853. Copyright The Ophthalmic Publishing
Company.)
In acute angle-closure glaucoma, additional glycerin may
be used as the gonioscopic bonding solution to prolong
the hyperosmotic effect during gonioscopy.
Side Effects
When applied topically to the eye without prior instilla-
tion of an anesthetic, glycerin causes significant stinging
and burning. Reflex tearing follows, and dilation of
conjunctival vessels may occur.These effects are transient,
and no significant toxic effects occur with short-term use.
Glycerin is classified as Pregnancy Category C, and it is
unknown whether it is excreted in breast milk. Safety for
use in children has not been established.
Glucose
Pharmacology
Glucose solutions ranging from 30% to 50% have been
used topically on the eye to treat corneal edema. The
dehydrating action of a 30-minute glucose bath eliminates
corneal epithelial edema and reduces corneal thickness.
The effect lasts 3 to 4 hours.
CHAPTER 15 Antiedema Drugs 281
The clinical effectiveness of 40% glucose is comparable
with that of 5% sodium chloride. Because it is difficult to
maintain sterility of the solution unless a preservative is
added, a commercial preparation containing 40% glucose
may often contain preservatives and is available in ointment
formulation (see Table 15-1).
Side Effects
After topical application glucose exhibits a low degree
of irritation and in the 30% to 50% concentrations is
420 480 540 600
nontoxic to the eye. However, some transient stinging
and irritation of the conjunctiva may occur after
instillation.
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