Afamiliar situation to any ophthalmologist is when the treatment of one condition leads to the development of another. A classic example is steroid-induced glaucoma after corneal transplantation, as this case illustrates.
OPHTHALMIC HISTORY
A 47-year-old white man with a history of keratoconus
and high myopia underwent repeat penetrating keratoplasty
(PKP) in his right eye. Incidentally, 2 weeks later, he was
also treated successfully with a single injection of bevacizumab
for a choroidal neovascular membrane in his right
central macula. Soon after the second PKP, the patient's
IOP rose into the high 20s and low 30s, for which he was
treated with brimonidine tartrate 0.1% and timolol maleate
0.5%. Despite therapy, 2 months after PKP, his IOP spiked to
40 mm Hg, presumably due to steroid response. His medication
was switched from prednisolone acetate 1% to
loteprednol etabonate 0.5%. Therapy appeared to effectively
curb the elevation in IOP until the frequency of the
steroid's dosing had to be increased to six times daily in
response to signs of possible early rejection.
After tapering the loteprednol, the patient's IOP was once again controlled and remained in the teens over the course of a year, with low dosing frequency of the loteprednol and continued use of the brimonidine and timolol. An episode of rejection again required more frequent administration of the loteprednol and triggered a steroid response to nearly 30 mm Hg. Afterward, the steroid was tapered to once daily, but the elevated IOP persisted, despite the addition of travoprost 0.004%. The patient was referred to the glaucoma clinic for management, 6 months after the most recent episode of rejection and 2 years after the repeat PKP.
GLAUCOMA EVALUATION
The patient's vision was 20/40 OD and 20/30 OS (corrected
by a hybrid contact lens in his right eye and a rigid gas
permeable contact lens in his left eye, spherical equivalent
of -12.00 D OD and -10.00 D OS). His IOP measured 26 mm
Hg OD and 15 mm Hg OS by applanation tonometry. His
right eye had a clear corneal graft with a few buried sutures,
a deep and quiet anterior chamber, a normal iris, and a clear
lens. The conjunctiva was slightly injected but mobile. The
posterior segment exhibited vitreous syneresis, myopic changes in the fundus (including a Fuchs' spot), and a slightly
large disc with peripapillary atrophy and a shallow cup
(Figure 1). The cup-to-disc ratio was in the range of 0.6. The
patient's left eye demonstrated keratoconus but otherwise
appeared similar to the right eye.
Gonioscopy revealed lightly pigmented angles that were open to the ciliary body band. Pachymetry measured 600 µm OD and 432 µm OS. Structural imaging of the optic discs yielded poor results due to corneal irregularity bilaterally, and visual field testing revealed superior depression in his right eye (Figure 2). Although it was difficult to accurately assess the extent of his glaucoma, my colleagues and I felt that the patient suffered only mild-to-moderate damage but that his IOP would need to be lowered to preserve the graft's survival and prevent glaucomatous progression.
DISCUSSION
Current Plan
Occurring in up to one-third of patients, secondary
glaucoma after PKP is a well-known phenomenon.1
Although a number of factors could be involved (including
changes in the trabecular meshwork's anatomy, inflammation,
and peripheral anterior synechiae), in this case,
steroid response was clearly implicated as the major cause,
based on the patient's well-documented history and a
wide open angle on gonioscopy. As with any case of
steroid-induced glaucoma, appropriate attempts had been
made to taper the causative agent to the extent possible
(while avoiding graft rejection) and switch to a less potent
steroid, but even milder agents can be problematic. This
patient was also placed on nearly maximal glaucoma medical
therapy, excluding carbonic anhydrase inhibitors. These agents may interfere with corneal endothelial function,
and in eyes with prior endothelial cellular loss or dysfunction,
they may induce mild corneal thickening, if not
outright decompensation on rare occasions.2,3 For the
time being, my colleagues and I have elected to avoid this
class of medications unless surgery is the only option.
Instead, we plan a trial of laser trabeculoplasty. Despite limited reports on the use of trabeculoplasty in the setting of steroid-induced glaucoma,4 this form of treatment is an option in this case. The patient's cornea is clear, and his angle is open. Moreover, we want to avoid an invasive procedure that has a high risk of causing graft failure. Although it remains to be seen how our patient will respond to laser trabeculoplasty, it is instructive to contemplate the possible next step, should he require further intervention.
Further Options
Trabeculectomy
Despite a high rate of bleb failure in the setting of PKP,
the use of mitomycin C (MMC) during trabeculectomy
has improved outcomes.5 MMC does not seem to cause
the epithelial toxicity observed with 5-fluorouracil, which
is best avoided after PKP. In this case, the conjunctiva is relatively
quiet and mobile with no signs of scarring, which
makes trabeculectomy technically feasible. The patient is
heavily dependent on his contact lenses, however, which is
a relative contraindication for trabeculectomy, because the
procedure may predispose patients to infection and the
threat of endophthalmitis. Another consideration is the
importance of avoiding hypotony and a shallow anterior
chamber, which could damage the graft. Like any intraocular
surgery, even uncomplicated trabeculectomy can lead
to graft failure.
Glaucoma Drainage Devices Drainage devices are increasingly used to treat glaucoma after PKP and provide fairly good IOP control, but it is now well known that tube shunt surgery results in an even higher rate of graft failure than trabeculectomy.6,7 Possible reasons may include mechanical forces such as direct tube-cornea touch or the creation of an open channel of inflammatory mediators between the anterior chamber and the subconjunctival space. Inserting the tube into the vitreous cavity, however, is associated with a reduced risk of graft failure compared with its insertion in the anterior chamber.8 Keeping the tip of the tube away from the cornea (eg, with placement in the sulcus) is a frequent practice at our institution. Because the eye in this case is phakic with a clear lens, the only reasonable option would be to place the tube shunt deep in the anterior chamber, close to the iris. A valved implant might be an appropriate choice to minimize the risk of hypotony.
Cyclophotocoagulation
Often regarded as a last option for many forms of
glaucoma, cyclophotocoagulation (CPC) should be considered
in the setting of corneal grafts. Like incisional
surgery, CPC can effectively lower IOP (repeat treatments
possibly being necessary),9 and it is associated
with a high rate of graft failure, up to 44%.10 The known
potential complications such as hypotony and even
phthisis, however, may not be as easily and predictably
avoided with CPC as with surgery. Nevertheless, in most
cases, conservative treatments coupled with the adequate
use of steroids can prevent significant inflammation
and should minimize the risk of graft failure. Because
this patient is phakic, a transscleral approach
would be required.
Our Choice
The patient's high myopia, dependence on contact
lenses, and native crystalline lens status pose limitations.
Otherwise, trabeculectomy with MMC might be
the best option for lowering his IOP and minimizing the
risk of graft failure should laser trabeculoplasty not
remedy the problem. In this case, placing a glaucoma
drainage device in the anterior chamber and transscleral
CPC are more viable choices, although each may carry
an increased risk of graft failure in an eye that has
already undergone two PKP procedures. Alternatively,
although no published results are available, newer glaucoma
procedures such as ab interno trabeculotomy and
canaloplasty should not be dismissed as possibilities in
these challenging situations.
Eiyass Albeiruti, MD, is an assistant professor of ophthalmology at the University of Pittsburgh in Pennsylvania. Dr. Albeiruti may be reached at (412) 647-8199; albeirutie2@upmc.edu.
