C L I N I C A L A N D E X P E R I M E N T A L

OPTOMETRY
REVIEW

Corneal oedema and its medical treatment

Clin Exp Optom 2013; 96: 529535 DOI:10.1111/cxo.12060

Ciro Costagliola* MD Corneal oedema is a common sign of acute or protracted corneal disease of various
Vito Romano* MD aetiologies. In this paper, we review the causes and pathophysiological bases of corneal
Eliana Forbice MD oedema, as well as discussing the goals and modalities of its medical treatment. Corneal
Martina Angi MD oedema, if adequately understood and appropriately treated, generally shows a good
Arduino Pascotto* prognosis.
Tiziana Boccia*
Francesco Semeraro MD
* Eye Clinic, Department of Health Sciences,
University of Molise, Campobasso, Italy

Eye Clinic, Department of Ophthalmology,

University of Brescia, Brescia, Italy
E-mail: elianaforbice@email.it

Submitted: 10 April 2012

Revised: 1 November 2012
Accepted for publication: 20 November
2012

Key words: corneal dystrophy, corneal oedema, endothelial pump, stromal swelling pressure

The cornea protects the eye from the envi-
ronment and pathogens, as well as having an
important role in the transmission and
refraction of light, guaranteed by numerous
mechanisms that regulate corneal hydration
and maintain its transparency. Many proc-
esses work together to accomplish this task,
including properly functioning epithelium
and endothelium and a healthy interaction
between stromal structural components,
such as collagen and proteoglycans.
When one of these delicate processes is
altered, extracellular fluid accumulates in-
side the cornea leading to corneal oedema,
with loss of transparency. Corneal oedema
is a common sign of acute or protracted
corneal disease of various aetiologies.
Cogan1 emphasised that two distinct
phenomena encompass the term corneal
oedema: stromal oedema and epithelial
oedema. Both may occur independently,
produce different symptoms and have differ-
ent causes (Table 1).
Making a differential diagnosis of corneal
oedema can be very challenging but under-
standing its normal physiology, together
with an accurate medical history, a full clini-
cal examination and some specific ancillary
tests, will usually lead to the correct diagno-
sis and treatment. Usually oedema is revers-
ible, disappearing when the underlying
disease is cured. However, chronic oedema
requires symptomatic treatment and is
usually the result of irreversible damage to
the endothelium. Medical treatment aims at
improving visual acuity and reducing dis-
comfort. The present review discusses the
pathophysiology and treatment of corneal
oedema.
PATHOPHYSIOLOGY
Corneal transparency is primarily depend-
ent on the ability of the cornea to remain
in a dehydrated state. Ideally, the human
cornea maintains a 78 per cent hydration
level. Any major deviation can lead to
corneal opacity, as it has an inherent ten-
dency to imbibe water and swell. As corneal
swelling causes an increase in corneal thick-
ness, corneal thickness and hydration are
linearly related.
There are five primary factors that play a
role in corneal hydration, namely, stromal
swelling pressure, barrier function of the
epithelium and the endothelium, endothe-
lial pump, tear evaporation and intraocular
pressure.2
Stromal swelling pressure
The state of corneal hydration can increase
up to 98 per cent, when the cornea is placed
in an aqueous medium, with proportional
increase in its thickness. Stromal proteogly-
cans associated with collagen bind water and
create a strong inward pressure gradient
called swelling pressure. Stromal swelling
is due to interfibrillary imbibition of
water, not to swelling of collagen fibrils. If
glycosaminoglycans are removed from the
stroma, a marked reduction in swelling
occurs, indicating that glycosaminoglycans
are the major cause of this hydration
phenomenon.3
Histologically, ultrastructurally and bio-
chemically, there are differences between
the anterior third and posterior two-thirds of
the cornea. The anterior stroma contains
less water than the posterior. The cause
of such differences is a greater amount of
glucose in the posterior stroma, as well as
an uneven distribution of proteoglycans
throughout the cornea. Dermatan sulphate

2013 The Authors Clinical and Experimental Optometry 96.6 November 2013
Clinical and Experimental Optometry 2013 Optometrists Association Australia 529
Corneal oedema Costagliola, Romano, Forbice, Angi, Pascotto, Boccia and Semeraro
Acute
Acute glaucoma
Hydrops in keratoconus
Trauma
Chemical burns
Infections
Chronic
Chronic glaucoma
Fuchs corneal dystrophy (FECD)
Posterior polymorphous corneal dystrophy (PPCD)
Congenital hereditary endothelial corneal dystrophy (CHED)
X-linked endothelial corneal dystrophy (XECD)
Table 1. Acute versus chronic causes of corneal failure
is found mainly in the anterior portion of
the cornea, while more keratan sulphate
is present in the posterior part. Dermatan
sulphate has a greater ability to retain water
but low capacity to absorb it, while keratan
sulphate has the opposite properties. This
explains why corneal swelling is predomi-
nant in the posterior cornea and resolves
quickly, when the endothelial pump func-
tion restarts after transient damage.4
Epithelium and
endothelium barrier
Physical barriers are formed by the epithelial
and endothelial cells connected by tight
junctions, visible by electron microscopy5
and antibody staining against proteins, such
as ZO-1 and occludins.67 These tight junc-
tions regulate the flow of electrolytes and
fluid through the cornea. The epithelium
offers twice the resistance to water flow com-
pared to the endothelium and the electro-
lyte resistance is 200 times higher in the
epithelium than endothelium.8
In the absence of corneal epithelium, the
stroma is capable of increasing in thickness
by 150 per cent after only four to six hours
of contact with aqueous tears and toxic sub-
stances.9 Multiple factors can damage the
epithelium and endothelium and lead to
corneal oedema.
Factors influencing the barrier include:
1. endothelial damage, mechanical or
chemical
2. dystrophy
3. calcium free solutions
4. oxidation of intracellular glutathione
5. pH
6. preservatives
Clinical and Experimental Optometry 96.6 November 2013
530
Endothelial pump
The most important influence on cor-
neal deturgescence is the presence of an
active metabolic pump in the endothelium.
The endothelium pump function ensures,
through active transport, the passage of fluid
out of the corneal stroma into the aqueous
humour. These active processes require
oxygen and energy in the form of adenosine
triphosphate. Deprivation of either, as in
contact lens-induced hypoxia, may result
in corneal oedema. Dactinomycin, ouabain
and oligomycin are potent pump inhibitors.
Treatment with ouabain causes stromal
oedema.1011
Endothelial cells are not capable of signifi-
cant mitotic activity. Cell density is approxi-
mately 3,500 cells per mm2 at birth and this
number decreases with age, trauma, inflam-
mation and other disease processes. Eyes
with endothelial cell counts below 500 cells
per mm2 are at risk for the development of
corneal oedema. Endothelial cell morphol-
ogy, particularly size and shape, also appears
to correlate with pump function.12
Tear evaporation
The role of tear evaporation in maintaining
corneal dehydration is controversial. ONeal
and Polse13 proved that the recovery rate
from hypoxic corneal oedema is significantly
more rapid with opened versus closed eyes.
Bourassa, Benjamin and Boltz14 suggested
that tear evaporation is not a significant
mechanism for maintaining corneal dehy-
dration.14 Nevertheless, it is known that if
corneal function is already compromised,
evaporation can be a factor in maintaining
epithelial dehydration, as is observed in the
Clinical and Experimental Optometry 2013 Optometrists Association Australia
diurnal variations of visual acuity in patients
with the early stage Fuchs endothelial dys-
trophy. Lack of evaporation may account for
as much as a five per cent increase in corneal
thickness during sleep.
Intraocular pressure
Intraocular pressure (IOP) can also have an
effect on corneal stromal hydration.15 Both
chronic and acute high IOP may result in
corneal oedema and impaired vision, the
first by endothelial damage and the second
by acute angle closure.
Ytteborg and Dohlman16 showed that
when the imbibition pressure becomes posi-
tive and IOP exceeds the stromal pressure
corneal epithelial oedema results.15,16
The oedema may also result from a
reduced stromal pressure, as in the case of
stromal dystrophies, even with normal IOP.
In summary, the correct state of corneal
hydration maintenance results from the epi-
thelial and endothelial barrier functions and
from active water transport throughout the
endothelial pump. Endothelial dysfunction
and physiological conditions that exceed the
endothelial barrier or pump capacity have as
a common denominator, the appearance of
endothelial or stromal oedema.
CAUSES
The management of corneal oedema must
be based on a clear understanding of the
different physical and fluid dynamic mecha-
nisms responsible for its occurrence, the
goal of the treatment being eradication
of the underlying aetiology. The causes
of corneal oedema leading to loss of the
physical barrier, loss of pump function or
increased IOP, can be classified into four
groups: mechanical, toxic, dystrophic and
inflammatory (Table 2).
Mechanical causes
The mechanical causes can be further
divided into traumatic and glaucomatous.
The traumatic causes could be incidental
(for example, misapplication of the obstetric
forceps, foreign body) or surgical. In non-
penetrating trauma, damage is limited and
often the oedema resolves quickly. Con-
versely, penetrating trauma can produce
irreversible damage that leads to a loss of
endothelial cells.
Several factors may cause corneal damage
during surgery, primarily the technique
chosen and secondarily, the materials
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Mechanical causes Dystrophic causes
Trauma Fuchs corneal dystrophy
Accidental (FECD)
Surgical
Elevated IOP Posterior polymorphous
corneal dystrophy (PPCD)
Congenital hereditary
endothelial corneal
dystrophy (CHED)
X-linked endothelial
corneal dystrophy
IOP: Intraocular pressure
Table 2. Causes of corneal failure
employed or the eventual use of intra-
operative drugs. The experience and ability
of the surgeon can greatly affect the extent
of endothelial damage. During cataract
surgery, temporary corneal oedema may
occur due to a dysfunctional endothelial
layer caused by ultrasonic vibration, phacoe-
mulsifier tip trauma to the endothelium,
Desemets detachment, prolonged phacoe-
mulsification time, prolonged surgery time
and the need for anterior vitrectomy and
irrigation/aspiration or infusion of toxic
medications into the anterior chamber.
Epithelial oedema and sloughing can occur
due to excessive use of a topical anaesthetic.
If damage is mild, the corneal oedema is
transient, as occurs in striate keratopathy
after surgery on the anterior segment. If
damage is severe, the endothelial functional
reserve decreases until the onset of corneal
decompensation and consequent bullous
keratopathy.
The choice of materials, as well as their
shape and size, can cause endothelial
damage. For example, the main complica-
tion with anterior chamber phakic intraocu-
lar lenses is the loss of corneal endothelial
cells or damage to endothelial integrity.
A precise pre-operative examination (bio-
microscopy, pachymetry and endothelial
microscopy) should exclude patients with a
low corneal endothelial cell count or shallow
anterior chamber, as the risk of damaging
corneal endothelial cells increases as the dis-
tance between the phakic intraocular lens
(pIOL) and the endothelium decreases.
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Clinical and Experimental Optometry 2013 Optometrists Association Australia
Corneal oedema Costagliola, Romano, Forbice, Angi, Pascotto, Boccia and Semeraro
Inflammatory causes Toxic causes
Primary endothelitis Irrigating solution
to enhance intraocular surgery and its
Uveitis Miotics
Stromal viral keratitis Mydriatics
Trabeculitis Preservatives
Accidental toxins
(lime etc.)
Silicone oil
Exact pre-operative examination should
exclude patients with low corneal endothe-
lial cell counts or with shallow anterior
chambers. Meticulous long-term follow-up
of each patient with an anterior chamber
pIOL is necessary to detect patients who
have significant damage to the endothelium
and to explant the pIOL whenever clinically
necessary. Ali and colleagues17 reported an
early post-operative loss of 3.8 per cent of
corneal endothelial cells, gradually decreas-
ing to about 0.5 per cent per year after the
second post-operative year.
In glaucoma, the more the stroma absorbs
water, the greater the increase in intraocular
pressure. This corneal hyperhydration
accounts for the corneal oedema observed
during an attack of acute glaucoma. Corneal
failure can occur if the causative hypertonic
state results in a severe permanent reduction
in endothelial functional capacity.18 In fact,
corneal oedema is one of the classic signs
of an acute attack of glaucoma. Corneal
oedema may occur early in the course of
acute angle-closure glaucoma or in the
secondary open-angle glaucomas, such as
inflammatory glaucoma and neovascular
glaucoma, which may be present in any eye
with a long-standing elevation of IOP.19
Toxic causes
Toxicity is another important cause of
corneal failure. The toxic effects of medici-
nal substances injected into the anterior
chamber are reversible or irreversible
depending on the substance, concentration
Clinical and Experimental Optometry 96.6 November 2013
and contact time. Surgical solutions and
drugs are important in ocular surgery. These
include irrigating solutions, viscoelastic
substances, mydriatics, miotics and a
growing number of other agents designed
outcome. Potential for damage to the
corneal endothelium and other tissues is
related to chemical composition, pH, osmo-
lality of the irrigating solutions, volume of
irrigation solution, anterior chamber depth
and phacoemulsification time and energy.
CLINICAL SYNDROMES
Toxic endothelial cell destruction syn-
drome, a disease entity described by
Breebaart and colleagues20 and Nuyts
and colleagues,21 has been characterised
as having star-shaped Desemets folds, a
twofold increase in corneal thickness and a
visual acuity of counting fingers occurring
within a few post-operative days. The origin
of corneal oedema is related to the break-
down of the endothelial barrier function
and therefore, steroids are minimally effec-
tive to ineffective on the repair process.20
Toxic anterior segment syndrome
(TASS) has a similar aetiology to the toxic
endothelial cell destruction syndrome but
the symptoms are different. Although both
have corneal oedema one to two days
after surgery, it is less pronounced in
TASS, which is also associated with marked
intraocular inflammation, sometimes lead-
ing to hypopyon formation. Toxic anterior
segment syndrome can resemble endoph-
thalmitis; however, the presence of corneal
oedema, the timing, the impairment of iris
sphincter function and the increased IOP
to a level between 40 to 70 mmHg help the
diagnosis.
PRESERVATIVES
Benzalkonium chloride (BAC) is highly
toxic and topical applications of two per cent
can cause corneal and conjunctival necro-
sis.22 Intraocular use of 0.05% BAC causes
irreversible endothelial necrosis, whereas
0.01% BAC causes reversible corneal
oedema in healthy rabbit23 and human
eyes.24
The threshold for physiologic and
ultrastructural alterations of the endothe-
lium is 0.0001%25 and the highest safe
intraocular concentration is 0.001%.26
These numbers were generated from
rabbit experiments and therefore, the rec-
ommendation is to avoid preservatives for
531
Corneal oedema Costagliola, Romano, Forbice, Angi, Pascotto, Boccia and Semeraro
intraocular use in humans as much as possi-
ble, no matter what the concentration.
INTRAOCULAR ANTIBIOTICS
Gentamycin sulphate, vancomycin or
both have historically been used as intra-
ocular antibiotics;27,28 however, concerns
about vancomycin-resistant organisms
and aminoglycoside-related macular toxicity
have favoured the introduction of cefo-
taxime, a third-generation cephalosporin
that has broad Gram-negative coverage
and sufficient activity against Gram-positive
organisms. No evidence of toxicity was
found when 0.25% cefotaxime solution was
instilled into the anterior chamber and
there was no significant endothelial damage
in terms of cell density or morphology after
three months.29
INTRAOCULAR INDOCYANINE GREEN
Intraocular indocyanine green has been
used to stain both the internal limiting mem-
brane in vitreoretinal surgery and the ante-
rior capsule in cataract surgery. Holley and
colleagues30 studied the effects of intraocu-
lar indocyanine green on the human and
rabbit corneal endothelium. They showed
that human cornea exposed to intraocular
indocyanine green had no corneal endothe-
lial ultrastructural damage observed by scan-
ning and transmission electron microscopy.
STERILISATION DETERGENTS
A relatively new issue that will need to
be addressed by ophthalmic surgeons and
operating room personnel is enzymatic
detergent-related toxicity to the corneal
endothelium. Because ethylene oxide is now
considered an occupational carcinogen and
reproductive toxin by the National Institute
for Occupational Safety and Health, Centers
for Disease Control and Prevention,31,32
there has been a greater demand for better
and safer alternatives. Enzymatic detergents
are supposed to be the answer. They contain
subtilisin, an exotoxin, and alpha amylase
enzymes that are deactivated when exposed
to temperatures exceeding 140C. Nowadays
most autoclaves reach maximal tempera-
tures of 120C to 130C33 and hence, if
surgical instruments are not rinsed thor-
oughly, residual active detergents are intro-
duced into the eye and can be toxic for the
corneal endothelium. In vitro experiments
on both human and rabbit corneas have
shown a dose-related increase in corneal
thickness and corneal endothelial ultra-
structural damage when exposed to enzy-
matic detergents.
Clinical and Experimental Optometry 96.6 November 2013
532
Dystrophic causes
Fuchs endothelial corneal dystrophy was
first described by Fuchs34 in 1910, as bilateral
corneal stromal and epithelial oedema in
elderly patients. Fuchs dystrophy is a slowly
progressive disease with initial onset in the
fifth through seventh decades of life. Fifty
per cent of the time, there is family cluster-
ing with an autosomal dominant inheritance
pattern.3539 Females are predisposed to
Fuchs dystrophy and develop corneal guttae
2.5 times more frequently than males, pro-
gressing to corneal oedema 5.7 times more
often than males. The initial manifestation
in Fuchs dystrophy is central corneal guttae.
The guttae appear as dark spots on the
posterior corneal surface by direct illumi-
nation and are highlighted in retroillu-
mination, where they resemble dewdrops.
Pigment dusting is often present on the
endothelium and may be difficult to differ-
entiate from guttae. Patients at this early
stage of the disease are not symptomatic.
Over time, the guttae spread peripherally
and may also coalesce centrally, producing a
beaten-metal appearance associated with
increased pigmentation. Desemets mem-
brane becomes visibly thickened, grey and
irregular. In the even more advanced stage,
fibrous thickening of Desemets membrane
masks the presence of guttae, that are
then described as buried guttae.40 Corneal
oedema begins in the posterior stroma adja-
cent to Desemets membrane and just
behind Bowmans layer, causing a fine grey
haze best seen with sclerotic scatter. In addi-
tion, swelling of the corneal stroma can
produce fine vertical wrinkles or striae in
Desemets membrane. Microcystic epithe-
lial oedema may follow and is seen as a stip-
pled pattern that stands out in sclerotic
scatter. Using fluorescein stain, the micro-
cystic pattern is highlighted as a disruption
in the tear film. At this point, the patients
vision will be reduced, most prominently in
the morning. Progressive stromal oedema
results in a ground-glass appearance, with
marked thickening of the central cornea.
The epithelial microcystic changes may
coalesce to form bullae, which can lead to
epithelial erosions and fingerprint lines.
Irregularity of the corneal surface and
stromal haze further reduce vision. Confocal
microscopy has aided in the diagnosis
of advanced Fuchs endothelial dystrophy,
where corneal oedema may obscure visuali-
sation of the endothelium.41 In end-stage
disease, infrequently seen today because of
Clinical and Experimental Optometry 2013 Optometrists Association Australia
improved success with corneal transplanta-
tion, avascular subepithelial fibrous scarring
occurs between the epithelium and Bow-
mans layer, best seen with tangential
illumination. Peripheral superficial corneal
neovascularisation can also occur. Subepi-
thelial scarring may eliminate the recurrent
erosions but the irregularity of the surface
and the loss of transparency further reduce
vision.
Inflammatory causes
Inflammation of either the cornea or the
anterior chamber from the iris and/or the
trabecular meshwork, can lead to deposition
of leukocytes on the endothelium, giving
origin to keratic precipitates. These can
form a variety of patterns, according to the
underlying disease,42 including diffuse
non-specific spattering (ankylosing spond-
ylitis),43 focal aggregation (herpes simplex
keratitis) and central, inferior, elliptical
or triangular pattern44 (sarcoid uveitis). The
endothelium can also becomes directly
target by inflammatory processes, such as
in allograft reactions, where antigens on
the endothelial cell surface stimulate the
immune reaction.45
Whatever the origin, once polymorpho-
nuclear and mononuclear leukocytes
adhere to the endothelial cell surface, they
penetrate between the cells and migrate
between Desemets membrane and the
endothelium. If the inflammatory process
is mild to moderate or is appropriately
treated, the leukocytes migrate back into
the anterior chamber and the endothelial
monolayer recovers functional viability
with resolution of the corneal oedema. If
the inflammatory process is more severe
and prolonged or is inadequately treated,
endothelial cells show increasing vascuolisa-
tion, separation from Desemets mem-
brane, desquamation into the anterior
chamber and death, resulting in persisting
corneal oedema.
Desemets membrane is remarkably
resistant to the proteolytic enzymes elabo-
rated by microorganisms, leukocytes and
epithelial cells. It resists destruction in the
presence of severe keratitis, iridocyclitis
and endophthalmitis, and acts as a barrier
that prevents the passage of leukocytes and
most microorganisms between the anterior
chamber and the corneal stroma.46 Fungi
are an exception; many elaborate enzymes
enable them to penetrate Desemets mem-
brane. Inflammation directed specifically at
2013 The Authors

Desemets membrane may also occur but it
is rare.
TREATMENT
The treatment of corneal oedema depends
on the specific cause and the symptoms of
the individual patient. This can vary from no
treatment in an asymptomatic patient with
early Fuchs dystrophy to keratoplasty in a
patient with painful bullous keratopathy and
significant visual loss. A stepwise approach to
the treatment of corneal oedema is the best
approach to follow. In the case of secondary
oedema (inflammation, infection, trauma,
glaucoma et cetera) treatment must be
directed at eliminating the underlying
aetiology.
Control of associated
abnormalities
INFLAMMATION / INFECTION
Topical corticosteroids are effective and
useful in reducing anterior segment inflam-
mation and consequently corneal oedema.
Dexamethasone suppresses the new lym-
phatic vessel growth. These findings identify
a novel mechanism of glucocorticoid action,
the suppression of corneal lymphangio-
genesis, through the suppression of
macrophage infiltration, pro-inflammatory
cytokine expression and direct inhibition of
proliferation of lymphatic endothelial cells.
The steroids block corneal lymphangiogen-
esis, which is the main risk factor for immune
rejections after corneal transplantation and
herpetic stromal keratitis.47,48 The topical
corticosteroid regimen used in herpetic
stromal keratitis reduces persistence or
progression of stromal inflammation.49 The
different anti-lymphangiogenic potency of
these drugs should be taken into account
when using steroids in clinical practice.
While older corticosteroids, such as dexam-
ethasone and prednisolone acetate, offer
good anti-inflammatory efficacy, clinically
significant increases in IOP (10 mmHg or
more) are often associated with their use.
Loteprednol etabonate offers potent anti-
inflammatory efficacy but with decreased
impact on IOP.50 Several researchers have
investigated the effect of corticosteroids on
endothelial cell function, suggesting that
they may induce activation of the pump
function.5153 They can also be beneficial in
corneal oedema, due to non-viral infections
once the infectious component is well under
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Clinical and Experimental Optometry 2013 Optometrists Association Australia
Corneal oedema Costagliola, Romano, Forbice, Angi, Pascotto, Boccia and Semeraro
control. In a multicentre clinical trial com-
paring prednisolone sodium phosphate,
1.0%, to placebo as adjunctive therapy for
the treatment of bacterial corneal ulcers,
they found no overall difference in visual
acuity after three months and no safety con-
cerns with adjunctive corticosteroid therapy
for bacterial corneal ulcers.54 Similarly, Pseu-
domonas aeruginosa corneal ulcers do not
appear to respond better to treatment than
other bacterial ulcers.55
INTRAOCULAR PRESSURE
Both acute and chronic increase in IOP can
lead to corneal oedema. In such cases,
decreasing the IOP can improve or resolve
the corneal oedema and prevent further
damage to endothelial cells.
Among the pressure-lowering agents,
carbonic anhydrase inhibitors deserve
special attention for their relationship with
corneal oedema. Inhibition of corneal car-
bonic anhydrase pumps may decrease the
outflow of fluid from stroma to aqueous,
leading to corneal oedema. This class of
pressure-lowering agents should be used
with caution in eyes with compromised
corneal endothelium.
Management of primary
corneal oedema
HYPERTONIC AGENTS
Mild oedema can be treated with hypertonic
eye drops and ointment, aimed at increasing
the tonicity of the tear film and drawing fluid
out of the cornea and into the tears by osmo-
sis;56,57 however, for an osmotic gradient to
occur, the epithelium has to be intact and to
function as a semi-permeable membrane
that allows water but not electrolytes to pass.
Moreover, this treatment is most effective for
epithelial oedema, as stromal oedema is
usually caused by endothelial dysfunction.
In selected patients, vision and comfort can
often be improved for months and occasion-
ally years with this therapy.
Hypertonic solution, such as five per cent
sodium chloride drops or ointment, can be
also used for the symptomatic medical treat-
ment of more advanced chronic corneal
oedema with epithelial bullae. These solutes
penetrate the epithelium poorly and there-
fore, can attract the more easily diffusible
water from the epithelial bullae. Sooner
or later the oedema progresses and may
require surgical treatment. We prefer to
Clinical and Experimental Optometry 96.6 November 2013
instil the ointment at bedtime to prevent
visual problems when instilled during the
day.
Another solution is an emulsion of
polyoxyethylene, which is a surface active
agent that has one hydrophilic and one
hydrophobic part on the molecule and
probably extracts water from the epithelium
by osmosis. Silicone oil (350 centistokes)
smooths the irregular corneal surface and
has a mollifying effect that is clinically useful
in epithelial oedema when instilled several
times a day.
Anhydrous glycerine is another hyper-
tonic preparation that can have a dramatic
but transient effect on corneal oedema. As it
is the most effective dehydrating agent used,
it causes considerable stinging on applica-
tion and gives rise to chronic conjunctival
injection and photophobia. It is so irritating
that it should be instilled after application
of a topical anaesthetic. This agent is very
useful for diagnostic purposes, as it allows
better visualisation of the corneal layers and
the anterior chamber. In the case of corneal
damage by ultraviolet light, treatment
should be accompanied by ascorbic acid, as
it is a potent antioxidant that neutralises free
radicals.58
BANDAGE CONTACT LENS
Placement of an extended-wear bandage
contact lens on the cornea can provide relief
from the discomfort of bullous keratopathy
and is used in the setting of poor visual
potential or when surgical intervention
is not recommended or is delayed. The
contact lens chosen should have high
oxygen transmissibility. The use of a silicone
hydrogel or rigid gas-permeable lens is safe
and effective for the treatment of bullous
keratopathy,59 although theoretically, the
rigid gas-permeable lenses provide more
total oxygen to the entire cornea.60 The
comfort provided by this modality must be
weighed against the risk of contact lens-
induced infectious corneal ulcer. Regular
follow-up visits reduce the risk of complica-
tions. In suspected cases, we use broad-
spectrum fortified antibiotic drops after
appropriate laboratory workup. As a pre-
ventive measure, you can use an antibiotic
against Gram-negative organisms once per
day but we do not recommend it because it
can create resistance. In one study, antibiotic
use reduced the microbiota on the lids but
did not affect the microbiota of the throat or
change resistance to the antibiotic.61 In addi-
tion, the use of the lens on a cornea with an
533
Corneal oedema Costagliola, Romano, Forbice, Angi, Pascotto, Boccia and Semeraro
already compromised endothelium should
be entertained judiciously as a therapeutic
modality.
EVAPORATION
Some patients note that their vision is worse
in the morning than in the evening. As the
improvement during the day is due to evapo-
ration, some patients may get relief in the
morning by using a hair dryer and blowing it
across the anterior surface of their corneas.
Other patients notice that dry desert air
improves their symptoms, whereas humid
conditions exacerbate the problem. Any
measure to accelerate evaporation usually
improves vision in early cases of corneal
oedema.62
PREVENTION
Post-operative corneal oedema in patients
with Fuchs endothelial dystrophy can be
prevented by accurate patient selection.
Recommended pre-operative evaluations in
patients with cataract and corneal guttae
include endothelial cell count and pachym-
etry. An endothelial cell count of less than
1,000 cells/mm2 should raise concern about
the possibility of corneal decompensation
with intraocular surgery. A corneal thickness
of over 640 mm also increases the risk for
persistent corneal oedema. Other factors to
consider to prevent corneal oedema after
cataract surgery include the surgeons
skill, the phacoemulsification time and
energy, trauma from the phacoemulsifier
and retained viscoelastic fragments of the
lens.
For post-cataract therapy, the choice of a
steroid, which does not penetrate into the
anterior chamber could lead to corneal
oedema and spikes in IOP after cataract
surgery, and should be avoided because they
can damage the endothelium.
The hardness of the core, especially for
patients with shallow anterior chambers,
should be considered prior to cataract
surgery. In addition, patients should be
encouraged to undergo cataract surgery
before the increased hardness of the lens,
which may increase the chances of a success-
ful intervention.
In patients with pseudoexfoliation or
endothelial abnormalities, the volume of
irrigation / aspiration should be minimised.
It is also important to consider the clinical
signs in the decision-making process, such as
blurring in the morning or evidence of epi-
thelial oedema on slitlamp examination.
Clinical and Experimental Optometry 96.6 November 2013
534
In conclusion, corneal oedema is a
frequent finding with diverse clinical con-
ditions. Treatment varies according to its
severity and aetiology. Techniques for the
visualisation of corneal endothelial mor-
phology can greatly minimise oedema in
high-risk surgical cases and can also docu-
ment the efficacy of therapy in all types of
oedema.
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