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Clinical Update
COR N E A
Acute Hydrops:
Rethinking Treatment
by jean shaw, contributing writer
interviewing michael b. raizman, md, william b. trattler, md,
and pravin k. vaddavalli, md
W
© 2 011 a m e r i c a n a c a d e m y o f o p h t h a l m o l o g y
hat’s the best way to
treat acute corneal hydrops? Given that most
cases of hydrops—corneal edema resulting
from tears in the Descemet membrane—eventually resolve spontaneously, many ophthalmologists rely on
conservative management for this relatively uncommon condition associated
with keratoconus, keratoglobus, and
pellucid marginal corneal degeneration (PMCD).
More recently, however, a growing
number of cornea specialists have
been turning to a treatment approach
that promises quicker resolution of
the edema but may carry additional
risks.
A Shift in the Paradigm
Conventional treatment of hydrops
includes topical antibiotics, cycloplegics, and hypertonic saline as well as
patching and bandage soft contact
lens. When treated conservatively, the
edema tends to resolve over two to four
months, with some patients achieving
acceptable visual results and others
requiring subsequent surgery.1
The rethinking of hydrops treatment grew out of an observation taken
from cataract surgery: When the
Descemet membrane is detached after
surgery, ophthalmologists have been
using intracameral injections of air to
reattach the membrane to the corneal
stroma. In hydrops, there is a break in
the Descemet membrane that allows
aqueous humor to enter the stroma.
K e r a t o c o nu s W i t h A cu t e H y dr o p s
1
2
3
4
(1) Three days after onset of symptoms. (2) One day after intracameral C3F8
injection, the gas bubble covers the break in the Descemet membrane. (3) One
month after injection. (4) Seventy days after injection, edema has resolved, and
visual acuity is 20/40 with contact lenses.
Could an injected air bubble act as a
tamponade to prevent aqueous humor
penetration into the stroma?
This possibility prompted researchers to try using intracameral air to
treat hydrops.2 That approach was followed, in turn, by the use of intracameral injections of sulfur hexafluoride
(SF6) gas and perfluoropropane (C3F8)
gas, which also act as mechanical barriers and prevent the entry of aqueous into the corneal stroma, but their
resorption is much slower than that of
air. These gases have long been used as
a treatment for retinal detachment.
Research Overview
Intracameral air. In 2002, Miyata et
al. published a retrospective study of
intracameral air injections to treat
hydrops secondary to keratoconus.2
Of 30 eyes with acute hydrops, 21
were treated with either no therapy or
standard conservative management,
while nine received 0.1-mL injections
of filtered air.
The results: Corneal edema persisted for an average of 20 days in those
who received the injections versus
an average of 64.7 days in the control
group. Similarly, patients who received
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the air injections were able to begin
wearing hard contact lenses an average
of 33.4 days after the onset of hydrops,
while those in the control group had
to wait an average of 128.9 days. BCVA
after the hydrops subsided was similar
between the two groups, and the injections induced no complications.
Intracameral SF6 gas. In 2007,
Panda et al. reported results with the
use of intracameral SF6 gas in nine
eyes with acute hydrops secondary to
keratoconus. Another nine eyes were
treated conservatively.3
The results: Edema in the eyes that
had received the injections resolved at
four weeks versus 12 weeks in those
treated conservatively. In addition, the
mean BCVA at 12 weeks was slightly
better in the eyes treated with SF6.
Intracameral C3F8 gas. Last year,
a retrospective study of intracameral
injections of C3F8 in eyes with hydrops
secondary to keratoconus, PMCD, and
keratoglobus was published in Ophthalmology. The study group consisted
of 62 eyes of 57 patients; the control
group included 90 eyes of 82 patients
who were treated conservatively.4
The results: Edema resolved more
quickly in eyes treated with C3F8 than
in those managed conservatively. This
effect was most evident in eyes with
keratoconus; the time to resolution
averaged 57.2 days in eyes treated with
C3F8 versus an average of 104 days in
the control group. Although edema
also resolved more quickly in patients
who had PMCD or keratoglobus and
who had been treated with C3F8 than
in the controls, the advantage was not
as marked, possibly because of the
position or size of the tear in the membrane, the researchers noted.
Final BCVA was roughly the same
in the treatment and control groups,
with a higher proportion of the C3F8treated eyes with keratoconus achieving 20/40 vision or better.
Real-World Concerns
“At the moment, I am not a big fan of
using air or the retinal gases; I tend to
be a little more conservative in managing hydrops,” said Michael B. Raizman, MD, codirector of the cornea
28
j u n e
2 0 1 2
and cataract service at New England
Eye Center in Boston. However, he
knows cornea specialists who routinely
perform such intracameral injections,
“so it definitely has been accepted by
some,” Dr. Raizman noted.
For clinicians who are considering
following suit, two experts who perform the injections offer several points
to consider.
Timing of intervention. If you
choose to do intracameral injections,
how soon should you proceed? “You
want to jump in early,” said William
B. Trattler, MD, a cornea specialist
with the Center for Excellence in Eye
Care in Miami. “The goal is to get the
Descemet membrane back into position flush against the back surface of
the cornea so that it can heal. The gas
works to block fluid entry into the cornea, which results in reduced corneal
swelling. The sooner you can initiate
the treatment, the quicker the recovery.”
Choice of gas. Which option is
best—air, SF6, or C3F8? “My recommendation is to use one of the retinal
gases, as they last longer in the eye
than air,” Dr. Trattler said. Pravin K.
Vaddavalli, MD, a cornea specialist
with the LV Prasad Eye Institute in Hyderabad, India, agreed. “The thought
process behind injecting an intracameral gas bubble is to have it present in
the anterior chamber for a longer duration, leading to a sustained tamponade of the torn edges of the Descemet
membrane. An air bubble wouldn’t
suffice, as it would get absorbed too
quickly. Both C3F8 and SF6 are good
options.”
Choice of concentration. “C3F8 and
SF6 should be used in isoexpansile concentrations to prevent further expansion of the bubble after surgery,” said
Dr. Vaddavalli, a coauthor of the 2011
Ophthalmology study. “For C3F8, this
would be a concentration of 14 percent; for SF6 , it would be 18 percent.”
Dr. Trattler proceeds on a case-by-case
basis, using concentrations ranging
from 16 to 18 percent.
Choice of setting. Dr. Vaddavalli
recommended performing intracameral injections in the OR: “As the pro-
cedure involves a peripheral iridotomy
and intracameral tamponade with frequent changes in the depth of the anterior chamber, peribulbar anesthesia
in the OR would be ideal.” However,
he added, “a topical procedure could
be tried with intracameral anesthesia.”
In contrast, Dr. Trattler performs the
injections at the slit lamp.
Anterior chamber fill. “You want
to do a 70 percent fill to avoid pupillary block,” Dr. Trattler said. As Dr.
Vaddavalli noted, a complete anterior
chamber fill followed by saline exchange, as is performed in Descemet
stripping endothelial keratoplasty
(DSEK), is not advisable. “The principle behind a gas bubble to tamponade
the torn edges of the Descemet membrane is different from that in DSEK
surgery, which requires only a short
period of contact of the Descemet graft
with the posterior stroma to adhere,”
Dr. Vaddavalli said. “Following hydrops, it would be desirable to have a
constant-sized bubble in the anterior
chamber to tamponade the curled
edges of the membrane. Moreover,
an air-gas exchange or an air-fluid
exchange could have the potential of
changing the isoexpansile nature of
the gas bubble, potentially reducing its
efficacy.”
Question of risks. Potential risks
associated with intracameral injections
include the following:
• Cataracts. Dr. Raizman noted that
his primary concern with intracameral
injections is that the introduction of
air or gas into the anterior chamber
could cause cataracts. “Cataracts have
been reported after air in the anterior
chamber with DSEK in phakic patients. These tend to be young patients
who otherwise would not need cataract
surgery.” The air or gas is left in place
even longer with hydrops.
Anterior subcapsular cataracts are
a potential concern, Dr. Vaddavalli
agreed, “as most of the patients are
young.” He added, “The risk of developing an anterior subcapsular cataract
was not evaluated in our paper but
may be minimized by using miotics
to constrict the pupil during surgery.
However, reduced pupil size can in-
Cor nea
crease the risk of a pupillary block, and
this can be surmounted by performing
an intraoperative peripheral iridectomy.”
• Endothelial cell loss. “This has been
reported with both air and perfluoropropane in the anterior chamber in
a rabbit model,” Dr. Vaddavalli said.
“However, we believe the mechanical tamponade afforded by the gas
bubble in the anterior chamber reduces the endothelial redistribution
over the torn and detached Descemet
membrane, eventually minimizing
endothelial migration and resulting in
lesser endothelial cell loss compared
with eyes where no intervention is
performed.” And Dr. Trattler noted
that he has experienced no issues with
endothelial cell loss.
• Pupillary block. There is an immediate postoperative risk of pupillary block, said Dr. Vaddavalli. “This
can be avoided to a certain extent by
titrating the amount of gas injected
intracamerally and making sure the
concentration of the gas-air mixture is
in the right proportion to avoid postop
expansion of the bubble.”
Question of compliance. Theoretically, patients should remain supine for
two weeks after receiving intracameral
gas injections. “It’s not necessarily for
weeks; it’s more like a couple of days to a
week,” said Dr. Trattler. “Still, patients
aren’t always compliant, and you sometimes have to make a point of urging
them to keep their proper head position to maximize the effect of the gas.”
clinical trial, and that will be hard to
do for such a rare condition.” Indeed,
Dr. Vaddavalli and his coauthors estimate that a prospective trial to validate
the efficacy of C3F8 would require 63
patients in both the study and control groups for statistical power of
80 percent; for 90 percent power, the
number of patients jumps to 85. In the
meantime, Dr. Raizman said, “I still
advocate conservative management. I
realize that it’s frustrating for patients
to have blurry vision for a couple of
months, but that’s still the approach I
use.”
But even before a clinical trial
could be put together, it’s entirely possible that current corneal research
could take the debate over treatment
of hydrops in a completely different
direction, Dr. Raizman said. “My hope
is that, with collagen cross-linking
and other techniques, we’ll be able to
strengthen and reshape the cornea;
and then hydrops could become a
thing of the past.”
Coming in the next
1 Grewal S et al. Trans Am Ophthalmol Soc.
1999;97:187-198.
2 Miyata K et al. Am J Ophthalmol. 2002;
133(6):750-752.
3 Panda A et al. Cornea. 2007;26(9):10671069.
4 Basu S et al. Ophthalmology. 2011;118(5):
934-939.
in diagnosing normal-tension
Looking Forward
What are the odds that intracameral injections will become standard
practice? “None of the measures used
in standard medical management
have any clear indication or benefit,”
argued Dr. Vaddavalli. “A surgical
intervention to hasten the resolution
of hydrops seems the natural course
of action, as it is the only proven technique to reduce the time taken for the
hydrops to resolve.”
But to settle the issue and, especially, to define the extent of cataract
development and other risks, Dr. Raizman noted, “We need a prospective
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